Abstract

We demonstrate an optical micro-particle size detection technique based on phase sensing by a fiber interferometer through phase-generated carrier (PGC) modulation/demodulation. Particle diameters were resolved from phase shift due to particle-induced optical scattering. Polystyrene nanoparticles, air bubbles and yeast cells in a microfluidic channel were tested using this technique, and particle diameters ranging from 0.7 to 5.5 μm can be resolved in real-time. In comparison with existing amplitude-sensing techniques which require tens of milliwatts of laser irradiance, phase-sensing through PGC can successfully utilize probe laser powers as low as 220 μW to measure the test particle sizes. We further constructed a theoretical model based on phase scattering and PGC demodulation, which obtained good agreement between experimental data and calculated phase shift as a function of particle time-of-flight. This technique may be applied to a wide range of potential applications, ranging from real-time analysis of clinically relevant cell samples, to contamination control of processing fluids used in the semiconductor industry.

© 2016 Optical Society of America

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References

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  1. O. Lazcka, F. J. Del Campo, and F. X. Muñoz, “Pathogen detection: a perspective of traditional methods and biosensors,” Biosens. Bioelectron. 22(7), 1205–1217 (2007).
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    [Crossref]
  3. I. Engelmann, D. R. Petzold, A. Kosinska, B. G. Hepkema, T. F. Schulz, and A. Heim, “Rapid quantitative PCR assays for the simultaneous detection of herpes simplex virus, varicella zoster virus, cytomegalovirus, Epstein-Barr virus, and human herpesvirus 6 DNA in blood and other clinical specimens,” J. Med. Virol. 80(3), 467–477 (2008).
    [Crossref] [PubMed]
  4. T. L. Cromeans, X. Lu, D. D. Erdman, C. D. Humphrey, and V. R. Hill, “Development of plaque assays for adenoviruses 40 and 41,” J. Virol. Methods 151(1), 140–145 (2008).
    [Crossref] [PubMed]
  5. W. Hübner, G. P. McNerney, P. Chen, B. M. Dale, R. E. Gordon, F. Y. S. Chuang, X.-D. Li, D. M. Asmuth, T. Huser, and B. K. Chen, “Quantitative 3D video microscopy of HIV transfer across T cell virological synapses,” Science 323(5922), 1743–1747 (2009).
    [Crossref] [PubMed]
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    [Crossref] [PubMed]
  7. K. Krabchi, F. Gros-Louis, J. Yan, M. Bronsard, J. Massé, J. C. Forest, and R. Drouin, “Quantification of all fetal nucleated cells in maternal blood between the 18th and 22nd weeks of pregnancy using molecular cytogenetic techniques,” Clin. Genet. 60(2), 145–150 (2001).
    [Crossref] [PubMed]
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    [Crossref]
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2015 (1)

H. Huang, Q. Li, J. Fu, J. Wu, F. Lin, and X. Wu, “Efficient subwavelength focusing of light with a long focal depth,” Nanoscale 7(39), 16504–16507 (2015).
[Crossref] [PubMed]

2011 (1)

C. Rivet, H. Lee, A. Hirsch, S. Hamilton, and H. Lu, “Microfluidics for medical diagnostics and biosensors,” Chem. Eng. Sci. 66(7), 1490–1507 (2011).
[Crossref]

2010 (1)

2009 (1)

W. Hübner, G. P. McNerney, P. Chen, B. M. Dale, R. E. Gordon, F. Y. S. Chuang, X.-D. Li, D. M. Asmuth, T. Huser, and B. K. Chen, “Quantitative 3D video microscopy of HIV transfer across T cell virological synapses,” Science 323(5922), 1743–1747 (2009).
[Crossref] [PubMed]

2008 (2)

I. Engelmann, D. R. Petzold, A. Kosinska, B. G. Hepkema, T. F. Schulz, and A. Heim, “Rapid quantitative PCR assays for the simultaneous detection of herpes simplex virus, varicella zoster virus, cytomegalovirus, Epstein-Barr virus, and human herpesvirus 6 DNA in blood and other clinical specimens,” J. Med. Virol. 80(3), 467–477 (2008).
[Crossref] [PubMed]

T. L. Cromeans, X. Lu, D. D. Erdman, C. D. Humphrey, and V. R. Hill, “Development of plaque assays for adenoviruses 40 and 41,” J. Virol. Methods 151(1), 140–145 (2008).
[Crossref] [PubMed]

2007 (1)

O. Lazcka, F. J. Del Campo, and F. X. Muñoz, “Pathogen detection: a perspective of traditional methods and biosensors,” Biosens. Bioelectron. 22(7), 1205–1217 (2007).
[Crossref] [PubMed]

2006 (1)

F. V. Ignatovich, D. Topham, and L. Novotny, “Optical detection of single nanoparticles and viruses,” IEEE J. Sel. Top. Quantum Electron. 12(6), 1292–1300 (2006).
[Crossref]

2005 (2)

D. O. Lapotko and V. P. Zharov, “Spectral evaluation of laser-induced cell damage with photothermal microscopy,” Lasers Surg. Med. 36(1), 22–30 (2005).
[Crossref] [PubMed]

D. O. Lapotko and E. Y. Lukianova, “Influence of physiological conditions on laser damage thresholds for blood, heart, and liver cells,” Lasers Surg. Med. 36(1), 13–21 (2005).
[Crossref] [PubMed]

2004 (2)

L. M. Fu, R. J. Yang, C. H. Lin, Y. J. Pan, and G. B. Lee, “Electrokinetically driven micro flow cytometers with integrated fiber optics for on-line cell/particle detection,” Anal. Chim. Acta 507(1), 163–169 (2004).
[Crossref]

M. Cristofanilli, G. T. Budd, M. J. Ellis, A. Stopeck, J. Matera, M. C. Miller, J. M. Reuben, G. V. Doyle, W. J. Allard, L. W. Terstappen, and D. F. Hayes, “Circulating tumor cells, disease progression, and survival in metastatic breast cancer,” N. Engl. J. Med. 351(8), 781–791 (2004).
[Crossref] [PubMed]

2001 (1)

K. Krabchi, F. Gros-Louis, J. Yan, M. Bronsard, J. Massé, J. C. Forest, and R. Drouin, “Quantification of all fetal nucleated cells in maternal blood between the 18th and 22nd weeks of pregnancy using molecular cytogenetic techniques,” Clin. Genet. 60(2), 145–150 (2001).
[Crossref] [PubMed]

1998 (1)

J. J. Chalmers, M. Zborowski, L. Sun, and L. Moore, “Flow through, immunomagnetic cell separation,” Biotechnol. Prog. 14(1), 141–148 (1998).
[Crossref] [PubMed]

1996 (1)

H. M. Davey and D. B. Kell, “Flow cytometry and cell sorting of heterogeneous microbial populations: the importance of single-cell analyses,” Microbiol. Rev. 60(4), 641–696 (1996).
[PubMed]

1982 (2)

A. Dandridge, A. Tveten, and T. Giallorenzi, “Homodyne demodulation scheme for fibre-optic sensors using phase generated carrier,” IEEE J. Quantum Electron. 18(10), 1647–1653 (1982).
[Crossref]

T. G. Giallorenzi, J. A. Bucaro, A. Dandridge, G. H. Sigel, J. H. Cole, S. C. Rashleigh, and R. G. Priest, “Optical fiber sensor technology,” IEEE J. Quantum Electron. 18(4), 626–665 (1982).
[Crossref]

Allard, W. J.

M. Cristofanilli, G. T. Budd, M. J. Ellis, A. Stopeck, J. Matera, M. C. Miller, J. M. Reuben, G. V. Doyle, W. J. Allard, L. W. Terstappen, and D. F. Hayes, “Circulating tumor cells, disease progression, and survival in metastatic breast cancer,” N. Engl. J. Med. 351(8), 781–791 (2004).
[Crossref] [PubMed]

Asmuth, D. M.

W. Hübner, G. P. McNerney, P. Chen, B. M. Dale, R. E. Gordon, F. Y. S. Chuang, X.-D. Li, D. M. Asmuth, T. Huser, and B. K. Chen, “Quantitative 3D video microscopy of HIV transfer across T cell virological synapses,” Science 323(5922), 1743–1747 (2009).
[Crossref] [PubMed]

Bronsard, M.

K. Krabchi, F. Gros-Louis, J. Yan, M. Bronsard, J. Massé, J. C. Forest, and R. Drouin, “Quantification of all fetal nucleated cells in maternal blood between the 18th and 22nd weeks of pregnancy using molecular cytogenetic techniques,” Clin. Genet. 60(2), 145–150 (2001).
[Crossref] [PubMed]

Bucaro, J. A.

T. G. Giallorenzi, J. A. Bucaro, A. Dandridge, G. H. Sigel, J. H. Cole, S. C. Rashleigh, and R. G. Priest, “Optical fiber sensor technology,” IEEE J. Quantum Electron. 18(4), 626–665 (1982).
[Crossref]

Budd, G. T.

M. Cristofanilli, G. T. Budd, M. J. Ellis, A. Stopeck, J. Matera, M. C. Miller, J. M. Reuben, G. V. Doyle, W. J. Allard, L. W. Terstappen, and D. F. Hayes, “Circulating tumor cells, disease progression, and survival in metastatic breast cancer,” N. Engl. J. Med. 351(8), 781–791 (2004).
[Crossref] [PubMed]

Chalmers, J. J.

J. J. Chalmers, M. Zborowski, L. Sun, and L. Moore, “Flow through, immunomagnetic cell separation,” Biotechnol. Prog. 14(1), 141–148 (1998).
[Crossref] [PubMed]

Chen, B. K.

W. Hübner, G. P. McNerney, P. Chen, B. M. Dale, R. E. Gordon, F. Y. S. Chuang, X.-D. Li, D. M. Asmuth, T. Huser, and B. K. Chen, “Quantitative 3D video microscopy of HIV transfer across T cell virological synapses,” Science 323(5922), 1743–1747 (2009).
[Crossref] [PubMed]

Chen, L.

Chen, P.

W. Hübner, G. P. McNerney, P. Chen, B. M. Dale, R. E. Gordon, F. Y. S. Chuang, X.-D. Li, D. M. Asmuth, T. Huser, and B. K. Chen, “Quantitative 3D video microscopy of HIV transfer across T cell virological synapses,” Science 323(5922), 1743–1747 (2009).
[Crossref] [PubMed]

Chuang, F. Y. S.

W. Hübner, G. P. McNerney, P. Chen, B. M. Dale, R. E. Gordon, F. Y. S. Chuang, X.-D. Li, D. M. Asmuth, T. Huser, and B. K. Chen, “Quantitative 3D video microscopy of HIV transfer across T cell virological synapses,” Science 323(5922), 1743–1747 (2009).
[Crossref] [PubMed]

Cole, J. H.

T. G. Giallorenzi, J. A. Bucaro, A. Dandridge, G. H. Sigel, J. H. Cole, S. C. Rashleigh, and R. G. Priest, “Optical fiber sensor technology,” IEEE J. Quantum Electron. 18(4), 626–665 (1982).
[Crossref]

Cristofanilli, M.

M. Cristofanilli, G. T. Budd, M. J. Ellis, A. Stopeck, J. Matera, M. C. Miller, J. M. Reuben, G. V. Doyle, W. J. Allard, L. W. Terstappen, and D. F. Hayes, “Circulating tumor cells, disease progression, and survival in metastatic breast cancer,” N. Engl. J. Med. 351(8), 781–791 (2004).
[Crossref] [PubMed]

Cromeans, T. L.

T. L. Cromeans, X. Lu, D. D. Erdman, C. D. Humphrey, and V. R. Hill, “Development of plaque assays for adenoviruses 40 and 41,” J. Virol. Methods 151(1), 140–145 (2008).
[Crossref] [PubMed]

Dale, B. M.

W. Hübner, G. P. McNerney, P. Chen, B. M. Dale, R. E. Gordon, F. Y. S. Chuang, X.-D. Li, D. M. Asmuth, T. Huser, and B. K. Chen, “Quantitative 3D video microscopy of HIV transfer across T cell virological synapses,” Science 323(5922), 1743–1747 (2009).
[Crossref] [PubMed]

Dandridge, A.

A. Dandridge, A. Tveten, and T. Giallorenzi, “Homodyne demodulation scheme for fibre-optic sensors using phase generated carrier,” IEEE J. Quantum Electron. 18(10), 1647–1653 (1982).
[Crossref]

T. G. Giallorenzi, J. A. Bucaro, A. Dandridge, G. H. Sigel, J. H. Cole, S. C. Rashleigh, and R. G. Priest, “Optical fiber sensor technology,” IEEE J. Quantum Electron. 18(4), 626–665 (1982).
[Crossref]

Davey, H. M.

H. M. Davey and D. B. Kell, “Flow cytometry and cell sorting of heterogeneous microbial populations: the importance of single-cell analyses,” Microbiol. Rev. 60(4), 641–696 (1996).
[PubMed]

Del Campo, F. J.

O. Lazcka, F. J. Del Campo, and F. X. Muñoz, “Pathogen detection: a perspective of traditional methods and biosensors,” Biosens. Bioelectron. 22(7), 1205–1217 (2007).
[Crossref] [PubMed]

Doyle, G. V.

M. Cristofanilli, G. T. Budd, M. J. Ellis, A. Stopeck, J. Matera, M. C. Miller, J. M. Reuben, G. V. Doyle, W. J. Allard, L. W. Terstappen, and D. F. Hayes, “Circulating tumor cells, disease progression, and survival in metastatic breast cancer,” N. Engl. J. Med. 351(8), 781–791 (2004).
[Crossref] [PubMed]

Drouin, R.

K. Krabchi, F. Gros-Louis, J. Yan, M. Bronsard, J. Massé, J. C. Forest, and R. Drouin, “Quantification of all fetal nucleated cells in maternal blood between the 18th and 22nd weeks of pregnancy using molecular cytogenetic techniques,” Clin. Genet. 60(2), 145–150 (2001).
[Crossref] [PubMed]

Ellis, M. J.

M. Cristofanilli, G. T. Budd, M. J. Ellis, A. Stopeck, J. Matera, M. C. Miller, J. M. Reuben, G. V. Doyle, W. J. Allard, L. W. Terstappen, and D. F. Hayes, “Circulating tumor cells, disease progression, and survival in metastatic breast cancer,” N. Engl. J. Med. 351(8), 781–791 (2004).
[Crossref] [PubMed]

Engelmann, I.

I. Engelmann, D. R. Petzold, A. Kosinska, B. G. Hepkema, T. F. Schulz, and A. Heim, “Rapid quantitative PCR assays for the simultaneous detection of herpes simplex virus, varicella zoster virus, cytomegalovirus, Epstein-Barr virus, and human herpesvirus 6 DNA in blood and other clinical specimens,” J. Med. Virol. 80(3), 467–477 (2008).
[Crossref] [PubMed]

Erdman, D. D.

T. L. Cromeans, X. Lu, D. D. Erdman, C. D. Humphrey, and V. R. Hill, “Development of plaque assays for adenoviruses 40 and 41,” J. Virol. Methods 151(1), 140–145 (2008).
[Crossref] [PubMed]

Forest, J. C.

K. Krabchi, F. Gros-Louis, J. Yan, M. Bronsard, J. Massé, J. C. Forest, and R. Drouin, “Quantification of all fetal nucleated cells in maternal blood between the 18th and 22nd weeks of pregnancy using molecular cytogenetic techniques,” Clin. Genet. 60(2), 145–150 (2001).
[Crossref] [PubMed]

Fu, J.

H. Huang, Q. Li, J. Fu, J. Wu, F. Lin, and X. Wu, “Efficient subwavelength focusing of light with a long focal depth,” Nanoscale 7(39), 16504–16507 (2015).
[Crossref] [PubMed]

Fu, L. M.

L. M. Fu, R. J. Yang, C. H. Lin, Y. J. Pan, and G. B. Lee, “Electrokinetically driven micro flow cytometers with integrated fiber optics for on-line cell/particle detection,” Anal. Chim. Acta 507(1), 163–169 (2004).
[Crossref]

Giallorenzi, T.

A. Dandridge, A. Tveten, and T. Giallorenzi, “Homodyne demodulation scheme for fibre-optic sensors using phase generated carrier,” IEEE J. Quantum Electron. 18(10), 1647–1653 (1982).
[Crossref]

Giallorenzi, T. G.

T. G. Giallorenzi, J. A. Bucaro, A. Dandridge, G. H. Sigel, J. H. Cole, S. C. Rashleigh, and R. G. Priest, “Optical fiber sensor technology,” IEEE J. Quantum Electron. 18(4), 626–665 (1982).
[Crossref]

Gordon, R. E.

W. Hübner, G. P. McNerney, P. Chen, B. M. Dale, R. E. Gordon, F. Y. S. Chuang, X.-D. Li, D. M. Asmuth, T. Huser, and B. K. Chen, “Quantitative 3D video microscopy of HIV transfer across T cell virological synapses,” Science 323(5922), 1743–1747 (2009).
[Crossref] [PubMed]

Gros-Louis, F.

K. Krabchi, F. Gros-Louis, J. Yan, M. Bronsard, J. Massé, J. C. Forest, and R. Drouin, “Quantification of all fetal nucleated cells in maternal blood between the 18th and 22nd weeks of pregnancy using molecular cytogenetic techniques,” Clin. Genet. 60(2), 145–150 (2001).
[Crossref] [PubMed]

Hamilton, S.

C. Rivet, H. Lee, A. Hirsch, S. Hamilton, and H. Lu, “Microfluidics for medical diagnostics and biosensors,” Chem. Eng. Sci. 66(7), 1490–1507 (2011).
[Crossref]

Hayes, D. F.

M. Cristofanilli, G. T. Budd, M. J. Ellis, A. Stopeck, J. Matera, M. C. Miller, J. M. Reuben, G. V. Doyle, W. J. Allard, L. W. Terstappen, and D. F. Hayes, “Circulating tumor cells, disease progression, and survival in metastatic breast cancer,” N. Engl. J. Med. 351(8), 781–791 (2004).
[Crossref] [PubMed]

Heim, A.

I. Engelmann, D. R. Petzold, A. Kosinska, B. G. Hepkema, T. F. Schulz, and A. Heim, “Rapid quantitative PCR assays for the simultaneous detection of herpes simplex virus, varicella zoster virus, cytomegalovirus, Epstein-Barr virus, and human herpesvirus 6 DNA in blood and other clinical specimens,” J. Med. Virol. 80(3), 467–477 (2008).
[Crossref] [PubMed]

Hepkema, B. G.

I. Engelmann, D. R. Petzold, A. Kosinska, B. G. Hepkema, T. F. Schulz, and A. Heim, “Rapid quantitative PCR assays for the simultaneous detection of herpes simplex virus, varicella zoster virus, cytomegalovirus, Epstein-Barr virus, and human herpesvirus 6 DNA in blood and other clinical specimens,” J. Med. Virol. 80(3), 467–477 (2008).
[Crossref] [PubMed]

Hill, V. R.

T. L. Cromeans, X. Lu, D. D. Erdman, C. D. Humphrey, and V. R. Hill, “Development of plaque assays for adenoviruses 40 and 41,” J. Virol. Methods 151(1), 140–145 (2008).
[Crossref] [PubMed]

Hirsch, A.

C. Rivet, H. Lee, A. Hirsch, S. Hamilton, and H. Lu, “Microfluidics for medical diagnostics and biosensors,” Chem. Eng. Sci. 66(7), 1490–1507 (2011).
[Crossref]

Huang, H.

H. Huang, Q. Li, J. Fu, J. Wu, F. Lin, and X. Wu, “Efficient subwavelength focusing of light with a long focal depth,” Nanoscale 7(39), 16504–16507 (2015).
[Crossref] [PubMed]

Hübner, W.

W. Hübner, G. P. McNerney, P. Chen, B. M. Dale, R. E. Gordon, F. Y. S. Chuang, X.-D. Li, D. M. Asmuth, T. Huser, and B. K. Chen, “Quantitative 3D video microscopy of HIV transfer across T cell virological synapses,” Science 323(5922), 1743–1747 (2009).
[Crossref] [PubMed]

Humphrey, C. D.

T. L. Cromeans, X. Lu, D. D. Erdman, C. D. Humphrey, and V. R. Hill, “Development of plaque assays for adenoviruses 40 and 41,” J. Virol. Methods 151(1), 140–145 (2008).
[Crossref] [PubMed]

Huser, T.

W. Hübner, G. P. McNerney, P. Chen, B. M. Dale, R. E. Gordon, F. Y. S. Chuang, X.-D. Li, D. M. Asmuth, T. Huser, and B. K. Chen, “Quantitative 3D video microscopy of HIV transfer across T cell virological synapses,” Science 323(5922), 1743–1747 (2009).
[Crossref] [PubMed]

Ignatovich, F. V.

F. V. Ignatovich, D. Topham, and L. Novotny, “Optical detection of single nanoparticles and viruses,” IEEE J. Sel. Top. Quantum Electron. 12(6), 1292–1300 (2006).
[Crossref]

Kell, D. B.

H. M. Davey and D. B. Kell, “Flow cytometry and cell sorting of heterogeneous microbial populations: the importance of single-cell analyses,” Microbiol. Rev. 60(4), 641–696 (1996).
[PubMed]

Kosinska, A.

I. Engelmann, D. R. Petzold, A. Kosinska, B. G. Hepkema, T. F. Schulz, and A. Heim, “Rapid quantitative PCR assays for the simultaneous detection of herpes simplex virus, varicella zoster virus, cytomegalovirus, Epstein-Barr virus, and human herpesvirus 6 DNA in blood and other clinical specimens,” J. Med. Virol. 80(3), 467–477 (2008).
[Crossref] [PubMed]

Krabchi, K.

K. Krabchi, F. Gros-Louis, J. Yan, M. Bronsard, J. Massé, J. C. Forest, and R. Drouin, “Quantification of all fetal nucleated cells in maternal blood between the 18th and 22nd weeks of pregnancy using molecular cytogenetic techniques,” Clin. Genet. 60(2), 145–150 (2001).
[Crossref] [PubMed]

Lapotko, D. O.

D. O. Lapotko and V. P. Zharov, “Spectral evaluation of laser-induced cell damage with photothermal microscopy,” Lasers Surg. Med. 36(1), 22–30 (2005).
[Crossref] [PubMed]

D. O. Lapotko and E. Y. Lukianova, “Influence of physiological conditions on laser damage thresholds for blood, heart, and liver cells,” Lasers Surg. Med. 36(1), 13–21 (2005).
[Crossref] [PubMed]

Lazcka, O.

O. Lazcka, F. J. Del Campo, and F. X. Muñoz, “Pathogen detection: a perspective of traditional methods and biosensors,” Biosens. Bioelectron. 22(7), 1205–1217 (2007).
[Crossref] [PubMed]

Lee, G. B.

L. M. Fu, R. J. Yang, C. H. Lin, Y. J. Pan, and G. B. Lee, “Electrokinetically driven micro flow cytometers with integrated fiber optics for on-line cell/particle detection,” Anal. Chim. Acta 507(1), 163–169 (2004).
[Crossref]

Lee, H.

C. Rivet, H. Lee, A. Hirsch, S. Hamilton, and H. Lu, “Microfluidics for medical diagnostics and biosensors,” Chem. Eng. Sci. 66(7), 1490–1507 (2011).
[Crossref]

Li, Q.

H. Huang, Q. Li, J. Fu, J. Wu, F. Lin, and X. Wu, “Efficient subwavelength focusing of light with a long focal depth,” Nanoscale 7(39), 16504–16507 (2015).
[Crossref] [PubMed]

Li, S.

Li, X.-D.

W. Hübner, G. P. McNerney, P. Chen, B. M. Dale, R. E. Gordon, F. Y. S. Chuang, X.-D. Li, D. M. Asmuth, T. Huser, and B. K. Chen, “Quantitative 3D video microscopy of HIV transfer across T cell virological synapses,” Science 323(5922), 1743–1747 (2009).
[Crossref] [PubMed]

Lin, C. H.

L. M. Fu, R. J. Yang, C. H. Lin, Y. J. Pan, and G. B. Lee, “Electrokinetically driven micro flow cytometers with integrated fiber optics for on-line cell/particle detection,” Anal. Chim. Acta 507(1), 163–169 (2004).
[Crossref]

Lin, F.

H. Huang, Q. Li, J. Fu, J. Wu, F. Lin, and X. Wu, “Efficient subwavelength focusing of light with a long focal depth,” Nanoscale 7(39), 16504–16507 (2015).
[Crossref] [PubMed]

Lin, Q.

Lu, H.

C. Rivet, H. Lee, A. Hirsch, S. Hamilton, and H. Lu, “Microfluidics for medical diagnostics and biosensors,” Chem. Eng. Sci. 66(7), 1490–1507 (2011).
[Crossref]

Lu, X.

T. L. Cromeans, X. Lu, D. D. Erdman, C. D. Humphrey, and V. R. Hill, “Development of plaque assays for adenoviruses 40 and 41,” J. Virol. Methods 151(1), 140–145 (2008).
[Crossref] [PubMed]

Lukianova, E. Y.

D. O. Lapotko and E. Y. Lukianova, “Influence of physiological conditions on laser damage thresholds for blood, heart, and liver cells,” Lasers Surg. Med. 36(1), 13–21 (2005).
[Crossref] [PubMed]

Massé, J.

K. Krabchi, F. Gros-Louis, J. Yan, M. Bronsard, J. Massé, J. C. Forest, and R. Drouin, “Quantification of all fetal nucleated cells in maternal blood between the 18th and 22nd weeks of pregnancy using molecular cytogenetic techniques,” Clin. Genet. 60(2), 145–150 (2001).
[Crossref] [PubMed]

Matera, J.

M. Cristofanilli, G. T. Budd, M. J. Ellis, A. Stopeck, J. Matera, M. C. Miller, J. M. Reuben, G. V. Doyle, W. J. Allard, L. W. Terstappen, and D. F. Hayes, “Circulating tumor cells, disease progression, and survival in metastatic breast cancer,” N. Engl. J. Med. 351(8), 781–791 (2004).
[Crossref] [PubMed]

McNerney, G. P.

W. Hübner, G. P. McNerney, P. Chen, B. M. Dale, R. E. Gordon, F. Y. S. Chuang, X.-D. Li, D. M. Asmuth, T. Huser, and B. K. Chen, “Quantitative 3D video microscopy of HIV transfer across T cell virological synapses,” Science 323(5922), 1743–1747 (2009).
[Crossref] [PubMed]

Miller, M. C.

M. Cristofanilli, G. T. Budd, M. J. Ellis, A. Stopeck, J. Matera, M. C. Miller, J. M. Reuben, G. V. Doyle, W. J. Allard, L. W. Terstappen, and D. F. Hayes, “Circulating tumor cells, disease progression, and survival in metastatic breast cancer,” N. Engl. J. Med. 351(8), 781–791 (2004).
[Crossref] [PubMed]

Moore, L.

J. J. Chalmers, M. Zborowski, L. Sun, and L. Moore, “Flow through, immunomagnetic cell separation,” Biotechnol. Prog. 14(1), 141–148 (1998).
[Crossref] [PubMed]

Muñoz, F. X.

O. Lazcka, F. J. Del Campo, and F. X. Muñoz, “Pathogen detection: a perspective of traditional methods and biosensors,” Biosens. Bioelectron. 22(7), 1205–1217 (2007).
[Crossref] [PubMed]

Novotny, L.

F. V. Ignatovich, D. Topham, and L. Novotny, “Optical detection of single nanoparticles and viruses,” IEEE J. Sel. Top. Quantum Electron. 12(6), 1292–1300 (2006).
[Crossref]

Pan, Y. J.

L. M. Fu, R. J. Yang, C. H. Lin, Y. J. Pan, and G. B. Lee, “Electrokinetically driven micro flow cytometers with integrated fiber optics for on-line cell/particle detection,” Anal. Chim. Acta 507(1), 163–169 (2004).
[Crossref]

Petzold, D. R.

I. Engelmann, D. R. Petzold, A. Kosinska, B. G. Hepkema, T. F. Schulz, and A. Heim, “Rapid quantitative PCR assays for the simultaneous detection of herpes simplex virus, varicella zoster virus, cytomegalovirus, Epstein-Barr virus, and human herpesvirus 6 DNA in blood and other clinical specimens,” J. Med. Virol. 80(3), 467–477 (2008).
[Crossref] [PubMed]

Priest, R. G.

T. G. Giallorenzi, J. A. Bucaro, A. Dandridge, G. H. Sigel, J. H. Cole, S. C. Rashleigh, and R. G. Priest, “Optical fiber sensor technology,” IEEE J. Quantum Electron. 18(4), 626–665 (1982).
[Crossref]

Rashleigh, S. C.

T. G. Giallorenzi, J. A. Bucaro, A. Dandridge, G. H. Sigel, J. H. Cole, S. C. Rashleigh, and R. G. Priest, “Optical fiber sensor technology,” IEEE J. Quantum Electron. 18(4), 626–665 (1982).
[Crossref]

Reuben, J. M.

M. Cristofanilli, G. T. Budd, M. J. Ellis, A. Stopeck, J. Matera, M. C. Miller, J. M. Reuben, G. V. Doyle, W. J. Allard, L. W. Terstappen, and D. F. Hayes, “Circulating tumor cells, disease progression, and survival in metastatic breast cancer,” N. Engl. J. Med. 351(8), 781–791 (2004).
[Crossref] [PubMed]

Rivet, C.

C. Rivet, H. Lee, A. Hirsch, S. Hamilton, and H. Lu, “Microfluidics for medical diagnostics and biosensors,” Chem. Eng. Sci. 66(7), 1490–1507 (2011).
[Crossref]

Schulz, T. F.

I. Engelmann, D. R. Petzold, A. Kosinska, B. G. Hepkema, T. F. Schulz, and A. Heim, “Rapid quantitative PCR assays for the simultaneous detection of herpes simplex virus, varicella zoster virus, cytomegalovirus, Epstein-Barr virus, and human herpesvirus 6 DNA in blood and other clinical specimens,” J. Med. Virol. 80(3), 467–477 (2008).
[Crossref] [PubMed]

Sigel, G. H.

T. G. Giallorenzi, J. A. Bucaro, A. Dandridge, G. H. Sigel, J. H. Cole, S. C. Rashleigh, and R. G. Priest, “Optical fiber sensor technology,” IEEE J. Quantum Electron. 18(4), 626–665 (1982).
[Crossref]

Stopeck, A.

M. Cristofanilli, G. T. Budd, M. J. Ellis, A. Stopeck, J. Matera, M. C. Miller, J. M. Reuben, G. V. Doyle, W. J. Allard, L. W. Terstappen, and D. F. Hayes, “Circulating tumor cells, disease progression, and survival in metastatic breast cancer,” N. Engl. J. Med. 351(8), 781–791 (2004).
[Crossref] [PubMed]

Sun, L.

J. J. Chalmers, M. Zborowski, L. Sun, and L. Moore, “Flow through, immunomagnetic cell separation,” Biotechnol. Prog. 14(1), 141–148 (1998).
[Crossref] [PubMed]

Terstappen, L. W.

M. Cristofanilli, G. T. Budd, M. J. Ellis, A. Stopeck, J. Matera, M. C. Miller, J. M. Reuben, G. V. Doyle, W. J. Allard, L. W. Terstappen, and D. F. Hayes, “Circulating tumor cells, disease progression, and survival in metastatic breast cancer,” N. Engl. J. Med. 351(8), 781–791 (2004).
[Crossref] [PubMed]

Topham, D.

F. V. Ignatovich, D. Topham, and L. Novotny, “Optical detection of single nanoparticles and viruses,” IEEE J. Sel. Top. Quantum Electron. 12(6), 1292–1300 (2006).
[Crossref]

Tveten, A.

A. Dandridge, A. Tveten, and T. Giallorenzi, “Homodyne demodulation scheme for fibre-optic sensors using phase generated carrier,” IEEE J. Quantum Electron. 18(10), 1647–1653 (1982).
[Crossref]

Wu, J.

H. Huang, Q. Li, J. Fu, J. Wu, F. Lin, and X. Wu, “Efficient subwavelength focusing of light with a long focal depth,” Nanoscale 7(39), 16504–16507 (2015).
[Crossref] [PubMed]

Wu, X.

H. Huang, Q. Li, J. Fu, J. Wu, F. Lin, and X. Wu, “Efficient subwavelength focusing of light with a long focal depth,” Nanoscale 7(39), 16504–16507 (2015).
[Crossref] [PubMed]

L. Chen, Q. Lin, S. Li, and X. Wu, “Optical accelerometer based on high-order diffraction beam interference,” Appl. Opt. 49(14), 2658–2664 (2010).
[Crossref]

Yan, J.

K. Krabchi, F. Gros-Louis, J. Yan, M. Bronsard, J. Massé, J. C. Forest, and R. Drouin, “Quantification of all fetal nucleated cells in maternal blood between the 18th and 22nd weeks of pregnancy using molecular cytogenetic techniques,” Clin. Genet. 60(2), 145–150 (2001).
[Crossref] [PubMed]

Yang, R. J.

L. M. Fu, R. J. Yang, C. H. Lin, Y. J. Pan, and G. B. Lee, “Electrokinetically driven micro flow cytometers with integrated fiber optics for on-line cell/particle detection,” Anal. Chim. Acta 507(1), 163–169 (2004).
[Crossref]

Zborowski, M.

J. J. Chalmers, M. Zborowski, L. Sun, and L. Moore, “Flow through, immunomagnetic cell separation,” Biotechnol. Prog. 14(1), 141–148 (1998).
[Crossref] [PubMed]

Zharov, V. P.

D. O. Lapotko and V. P. Zharov, “Spectral evaluation of laser-induced cell damage with photothermal microscopy,” Lasers Surg. Med. 36(1), 22–30 (2005).
[Crossref] [PubMed]

Anal. Chim. Acta (1)

L. M. Fu, R. J. Yang, C. H. Lin, Y. J. Pan, and G. B. Lee, “Electrokinetically driven micro flow cytometers with integrated fiber optics for on-line cell/particle detection,” Anal. Chim. Acta 507(1), 163–169 (2004).
[Crossref]

Appl. Opt. (1)

Biosens. Bioelectron. (1)

O. Lazcka, F. J. Del Campo, and F. X. Muñoz, “Pathogen detection: a perspective of traditional methods and biosensors,” Biosens. Bioelectron. 22(7), 1205–1217 (2007).
[Crossref] [PubMed]

Biotechnol. Prog. (1)

J. J. Chalmers, M. Zborowski, L. Sun, and L. Moore, “Flow through, immunomagnetic cell separation,” Biotechnol. Prog. 14(1), 141–148 (1998).
[Crossref] [PubMed]

Chem. Eng. Sci. (1)

C. Rivet, H. Lee, A. Hirsch, S. Hamilton, and H. Lu, “Microfluidics for medical diagnostics and biosensors,” Chem. Eng. Sci. 66(7), 1490–1507 (2011).
[Crossref]

Clin. Genet. (1)

K. Krabchi, F. Gros-Louis, J. Yan, M. Bronsard, J. Massé, J. C. Forest, and R. Drouin, “Quantification of all fetal nucleated cells in maternal blood between the 18th and 22nd weeks of pregnancy using molecular cytogenetic techniques,” Clin. Genet. 60(2), 145–150 (2001).
[Crossref] [PubMed]

IEEE J. Quantum Electron. (2)

A. Dandridge, A. Tveten, and T. Giallorenzi, “Homodyne demodulation scheme for fibre-optic sensors using phase generated carrier,” IEEE J. Quantum Electron. 18(10), 1647–1653 (1982).
[Crossref]

T. G. Giallorenzi, J. A. Bucaro, A. Dandridge, G. H. Sigel, J. H. Cole, S. C. Rashleigh, and R. G. Priest, “Optical fiber sensor technology,” IEEE J. Quantum Electron. 18(4), 626–665 (1982).
[Crossref]

IEEE J. Sel. Top. Quantum Electron. (1)

F. V. Ignatovich, D. Topham, and L. Novotny, “Optical detection of single nanoparticles and viruses,” IEEE J. Sel. Top. Quantum Electron. 12(6), 1292–1300 (2006).
[Crossref]

J. Med. Virol. (1)

I. Engelmann, D. R. Petzold, A. Kosinska, B. G. Hepkema, T. F. Schulz, and A. Heim, “Rapid quantitative PCR assays for the simultaneous detection of herpes simplex virus, varicella zoster virus, cytomegalovirus, Epstein-Barr virus, and human herpesvirus 6 DNA in blood and other clinical specimens,” J. Med. Virol. 80(3), 467–477 (2008).
[Crossref] [PubMed]

J. Virol. Methods (1)

T. L. Cromeans, X. Lu, D. D. Erdman, C. D. Humphrey, and V. R. Hill, “Development of plaque assays for adenoviruses 40 and 41,” J. Virol. Methods 151(1), 140–145 (2008).
[Crossref] [PubMed]

Lasers Surg. Med. (2)

D. O. Lapotko and V. P. Zharov, “Spectral evaluation of laser-induced cell damage with photothermal microscopy,” Lasers Surg. Med. 36(1), 22–30 (2005).
[Crossref] [PubMed]

D. O. Lapotko and E. Y. Lukianova, “Influence of physiological conditions on laser damage thresholds for blood, heart, and liver cells,” Lasers Surg. Med. 36(1), 13–21 (2005).
[Crossref] [PubMed]

Microbiol. Rev. (1)

H. M. Davey and D. B. Kell, “Flow cytometry and cell sorting of heterogeneous microbial populations: the importance of single-cell analyses,” Microbiol. Rev. 60(4), 641–696 (1996).
[PubMed]

N. Engl. J. Med. (1)

M. Cristofanilli, G. T. Budd, M. J. Ellis, A. Stopeck, J. Matera, M. C. Miller, J. M. Reuben, G. V. Doyle, W. J. Allard, L. W. Terstappen, and D. F. Hayes, “Circulating tumor cells, disease progression, and survival in metastatic breast cancer,” N. Engl. J. Med. 351(8), 781–791 (2004).
[Crossref] [PubMed]

Nanoscale (1)

H. Huang, Q. Li, J. Fu, J. Wu, F. Lin, and X. Wu, “Efficient subwavelength focusing of light with a long focal depth,” Nanoscale 7(39), 16504–16507 (2015).
[Crossref] [PubMed]

Science (1)

W. Hübner, G. P. McNerney, P. Chen, B. M. Dale, R. E. Gordon, F. Y. S. Chuang, X.-D. Li, D. M. Asmuth, T. Huser, and B. K. Chen, “Quantitative 3D video microscopy of HIV transfer across T cell virological synapses,” Science 323(5922), 1743–1747 (2009).
[Crossref] [PubMed]

Other (1)

J. Jiang, T. Liu, Y. Zhang, L. Liu, Y. Wang, and P. Long, “Demodulation and multiplexing of optical fiber EFPI sensors,” in Photonics North (ISOP, 2004), 242–246.

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Figures (5)

Fig. 1
Fig. 1 Schematic of setup for optical detection of micrometer-size particles. A DFB laser diode emits a probe signal split by a 2 × 1 fiber power splitter. One output of the splitter is mounted on a piezoelectric ceramic vibrator driven by a sinusoidal reference signal generator to produce a PGC modulation signal. A photodiode connected to the other port of the 2 × 1 fiber power splitter collects the returned interference signal, which was then amplified and stored in a digital oscilloscope.
Fig. 2
Fig. 2 Detailed schematic of optical detection of micrometer-size particles in a microfluidic channel. As the taper fiber being vibrated back and forth, a PGC modulation signal was emitted into the microfluidic channel. After passing through the sample, the probe beam was reflected by a gold-plated micro reflector, and was partially collected by the same taper fiber for interference.
Fig. 3
Fig. 3 Experimental signal waveforms on the digital oscilloscope and corresponding screengrabs of the video recorded with a test particle scanned through the signal beam.
Fig. 4
Fig. 4 Red curves refer to the phase shift of the PGC modulation waveform while blue curves refer to the collected signal intensity as the test particle passed through. Solid curves stand for experimental data while dotted curves represent theoretical calculations.
Fig. 5
Fig. 5 Measured phase shift values (black: air bubbles, red: polystyrene nanospheres, blue: yeast cells) as a function of the particles’ diameters, while the solid curves show theoretical calculations.

Equations (4)

Equations on this page are rendered with MathJax. Learn more.

I 1 =( E ref + E sig )( E ref + E sig )* = I 0 { 2+2cos[ φMsin( ω 0 t+ φ 0 ) ] }
I 2 =( E ref + r 2 E sig + E s )( E ref + r 2 E sig + E s )* = I 0 { 1+ r 1 2 + r 2 2 +2 r 1 r 2 cos(ψ)+2 r 1 cos[ φψMsin( ω 0 t+ φ 0 ) ] +2 r 2 cos[ φMsin( ω 0 t+ φ 0 ) ] }
σ=2π 2(n n s )d 1.55
θ=σ r 1 r 1 + r 2 r 1 =a r r g(x)dx r 2 =1 r r g(x)dx

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