Abstract

Total internal reflection fluorescence (TIRF) microscopy benefits from high-sensitivity, low background noise, low photo-toxicity and high-contrast imaging of sub-cellular structures close to the membrane surface. Although, TIRF microscopy provides high-contrast imaging it does not provide quantitative information about morphological features of the biological cells. Here, we propose an integrated waveguide chip-based TIRF microscopy and label-free quantitative phase imaging (QPI). The evanescent field present on top of a waveguide surface is used to excite the fluorescence and an upright microscope is used to collect the signal. The upright microscope is converted into a Linnik-type interferometer to sequentially extract both the quantitative phase information and TIRF images of the cells. Waveguide chip-based TIRF microscopy benefits from decoupling of illumination and collection light path, large field of view imaging and pre-aligned configuration for multi-color TIRF imaging. The proposed multi-modal microscopy is used to study inflammation caused by lipopolysaccharide (LPS) on rat macrophages. The TIRF microscopy showed that LPS inflammatory molecule disrupts the cell membrane and causes cells to significantly expand across a substrate. While, QPI module quantified changes in the sub-cellular content of the LPS challenged macrophages, showing a net decrease in its maximum phase values.

© 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

Full Article  |  PDF Article
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References

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    [Crossref] [PubMed]

2017 (2)

J.-C. Tinguely, Ø. I. Helle, and B. S. Ahluwalia, “Silicon nitride waveguide platform for fluorescence microscopy of living cells,” Opt. Express 25(22), 27678–27690 (2017).
[Crossref] [PubMed]

R. Diekmann, Ø. I. Helle, C. I. Øie, P. McCourt, T. R. Huser, M. Schüttpelz, and B. S. Ahluwalia, “Chip-based wide field-of-view nanoscopy,” Nat. Photonics 11(5), 322–328 (2017).
[Crossref]

2016 (2)

2015 (3)

B. Agnarsson, A. Lundgren, A. Gunnarsson, M. Rabe, A. Kunze, M. Mapar, L. Simonsson, M. Bally, V. P. Zhdanov, and F. Höök, “Evanescent Light-Scattering Microscopy for Label-Free Interfacial Imaging: From Single Sub-100 nm Vesicles to Live Cells,” ACS Nano 9(12), 11849–11862 (2015).
[Crossref] [PubMed]

Z. Liu, L. D. Lavis, and E. Betzig, “Imaging live-cell dynamics and structure at the single-molecule level,” Mol. Cell 58(4), 644–659 (2015).
[Crossref] [PubMed]

X. Quan, K. Nitta, O. Matoba, P. Xia, and Y. Awatsuji, “Phase and fluorescence imaging by combination of digital holographic microscopy and fluorescence microscopy,” Opt. Rev. 22(2), 349–353 (2015).
[Crossref]

2014 (1)

S. M. Lindecrantz and O. G. Hellesø, “Estimation of propagation losses for narrow strip and rib waveguides,” IEEE Photonics Technol. Lett. 26(18), 1836–1839 (2014).
[Crossref]

2013 (3)

S. Ramachandran, D. A. Cohen, A. P. Quist, and R. Lal, “High performance, LED powered, waveguide based total internal reflection microscopy,” Sci. Rep. 3(1), 2133 (2013).
[Crossref] [PubMed]

M. L. Martin-Fernandez, C. J. Tynan, and S. E. Webb, “A ‘pocket guide’ to total internal reflection fluorescence,” J. Microsc. 252(1), 16–22 (2013).
[Crossref] [PubMed]

K. Lee, K. Kim, J. Jung, J. Heo, S. Cho, S. Lee, G. Chang, Y. Jo, H. Park, and Y. Park, “Quantitative phase imaging techniques for the study of cell pathophysiology: from principles to applications,” Sensors (Basel) 13(4), 4170–4191 (2013).
[Crossref] [PubMed]

2012 (1)

M. Mir, B. Bhaduri, R. Wang, R. Zhu, and G. Popescu, “Quantitative phase imaging,” Prog. Opt. 57, 133–217 (2012).
[Crossref]

2011 (4)

2010 (1)

A. L. Mattheyses, S. M. Simon, and J. Z. Rappoport, “Imaging with total internal reflection fluorescence microscopy for the cell biologist,” J. Cell Sci. 123(21), 3621–3628 (2010).
[Crossref] [PubMed]

2009 (4)

C. S. Yelleswarapu, M. Tipping, S.-R. Kothapalli, A. Veraksa, and D. V. Rao, “Common-path multimodal optical microscopy,” Opt. Lett. 34(8), 1243–1245 (2009).
[Crossref] [PubMed]

B. Agnarsson, S. Ingthorsson, T. Gudjonsson, and K. Leosson, “Evanescent-wave fluorescence microscopy using symmetric planar waveguides,” Opt. Express 17(7), 5075–5082 (2009).
[Crossref] [PubMed]

K. N. Fish, “Total internal reflection fluorescence (TIRF) microscopy,” Curr. Protoc. Cytom. 50(1)12–18 (2009).
[Crossref]

Y. K. Jaiswal, M. K. Jaiswal, V. Agrawal, and M. M. Chaturvedi, “Bacterial endotoxin (LPS)-induced DNA damage in preimplanting embryonic and uterine cells inhibits implantation,” Fertil. Steril. 91(5Suppl), 2095–2103 (2009).
[Crossref] [PubMed]

2008 (1)

A. Hassanzadeh, M. Nitsche, S. Mittler, S. Armstrong, J. Dixon, and U. Langbein, “Waveguide evanescent field fluorescence microscopy: Thin film fluorescence intensities and its application in cell biology,” Appl. Phys. Lett. 92(23), 233503 (2008).
[Crossref]

2006 (1)

H. M. Grandin, B. Städler, M. Textor, and J. Vörös, “Waveguide excitation fluorescence microscopy: A new tool for sensing and imaging the biointerface,” Biosens. Bioelectron. 21(8), 1476–1482 (2006).
[Crossref] [PubMed]

2005 (4)

2002 (1)

J. Zhang, R. E. Campbell, A. Y. Ting, and R. Y. Tsien, “Creating new fluorescent probes for cell biology,” Nat. Rev. Mol. Cell Biol. 3(12), 906–918 (2002).
[Crossref] [PubMed]

2001 (1)

D. Axelrod, “Total internal reflection fluorescence microscopy in cell biology,” Traffic 2(11), 764–774 (2001).
[Crossref] [PubMed]

1998 (1)

J. S. Burmeister, L. A. Olivier, W. M. Reichert, and G. A. Truskey, “Application of total internal reflection fluorescence microscopy to study cell adhesion to biomaterials,” Biomaterials 19(4-5), 307–325 (1998).
[Crossref] [PubMed]

1989 (1)

1987 (1)

J. G. White, W. B. Amos, and M. Fordham, “An evaluation of confocal versus conventional imaging of biological structures by fluorescence light microscopy,” J. Cell Biol. 105(1), 41–48 (1987).
[Crossref] [PubMed]

1981 (1)

L. V. Johnson, M. L. Walsh, B. J. Bockus, and L. B. Chen, “Monitoring of relative mitochondrial membrane potential in living cells by fluorescence microscopy,” J. Cell Biol. 88(3), 526–535 (1981).
[Crossref] [PubMed]

1979 (1)

S. N. Vogel, S. T. Marshall, and D. L. Rosenstreich, “Analysis of the effects of lipopolysaccharide on macrophages: differential phagocytic responses of C3H/HeN and C3H/HeJ macrophages in vitro,” Infect. Immun. 25(1), 328–336 (1979).
[PubMed]

1942 (1)

C. Burch and J. Stock, “Phase-contrast microscopy,” J. Sci. Instrum. 19(5), 71–75 (1942).
[Crossref]

Agnarsson, B.

Agrawal, V.

Y. K. Jaiswal, M. K. Jaiswal, V. Agrawal, and M. M. Chaturvedi, “Bacterial endotoxin (LPS)-induced DNA damage in preimplanting embryonic and uterine cells inhibits implantation,” Fertil. Steril. 91(5Suppl), 2095–2103 (2009).
[Crossref] [PubMed]

Ahluwalia, B. S.

R. Diekmann, Ø. I. Helle, C. I. Øie, P. McCourt, T. R. Huser, M. Schüttpelz, and B. S. Ahluwalia, “Chip-based wide field-of-view nanoscopy,” Nat. Photonics 11(5), 322–328 (2017).
[Crossref]

J.-C. Tinguely, Ø. I. Helle, and B. S. Ahluwalia, “Silicon nitride waveguide platform for fluorescence microscopy of living cells,” Opt. Express 25(22), 27678–27690 (2017).
[Crossref] [PubMed]

Ahmad, A.

Amos, W. B.

J. G. White, W. B. Amos, and M. Fordham, “An evaluation of confocal versus conventional imaging of biological structures by fluorescence light microscopy,” J. Cell Biol. 105(1), 41–48 (1987).
[Crossref] [PubMed]

Armstrong, S.

A. Hassanzadeh, M. Nitsche, S. Mittler, S. Armstrong, J. Dixon, and U. Langbein, “Waveguide evanescent field fluorescence microscopy: Thin film fluorescence intensities and its application in cell biology,” Appl. Phys. Lett. 92(23), 233503 (2008).
[Crossref]

Arnfinnsdottir, N. B.

Awatsuji, Y.

X. Quan, K. Nitta, O. Matoba, P. Xia, and Y. Awatsuji, “Phase and fluorescence imaging by combination of digital holographic microscopy and fluorescence microscopy,” Opt. Rev. 22(2), 349–353 (2015).
[Crossref]

Axelrod, D.

Bally, M.

B. Agnarsson, A. Lundgren, A. Gunnarsson, M. Rabe, A. Kunze, M. Mapar, L. Simonsson, M. Bally, V. P. Zhdanov, and F. Höök, “Evanescent Light-Scattering Microscopy for Label-Free Interfacial Imaging: From Single Sub-100 nm Vesicles to Live Cells,” ACS Nano 9(12), 11849–11862 (2015).
[Crossref] [PubMed]

Betzig, E.

Z. Liu, L. D. Lavis, and E. Betzig, “Imaging live-cell dynamics and structure at the single-molecule level,” Mol. Cell 58(4), 644–659 (2015).
[Crossref] [PubMed]

Bhaduri, B.

M. Mir, B. Bhaduri, R. Wang, R. Zhu, and G. Popescu, “Quantitative phase imaging,” Prog. Opt. 57, 133–217 (2012).
[Crossref]

Bingham, P. R.

C. J. Mann, P. R. Bingham, H. K. Lin, V. C. Paquit, and S. S. Gleason, “Dual modality live cell imaging with multiple-wavelength digital holography and epi-fluorescence,” 3D Res. 2, 5 (2011).
[Crossref]

Bockus, B. J.

L. V. Johnson, M. L. Walsh, B. J. Bockus, and L. B. Chen, “Monitoring of relative mitochondrial membrane potential in living cells by fluorescence microscopy,” J. Cell Biol. 88(3), 526–535 (1981).
[Crossref] [PubMed]

Burch, C.

C. Burch and J. Stock, “Phase-contrast microscopy,” J. Sci. Instrum. 19(5), 71–75 (1942).
[Crossref]

Burmeister, J. S.

J. S. Burmeister, L. A. Olivier, W. M. Reichert, and G. A. Truskey, “Application of total internal reflection fluorescence microscopy to study cell adhesion to biomaterials,” Biomaterials 19(4-5), 307–325 (1998).
[Crossref] [PubMed]

Campbell, R. E.

J. Zhang, R. E. Campbell, A. Y. Ting, and R. Y. Tsien, “Creating new fluorescent probes for cell biology,” Nat. Rev. Mol. Cell Biol. 3(12), 906–918 (2002).
[Crossref] [PubMed]

Chang, G.

K. Lee, K. Kim, J. Jung, J. Heo, S. Cho, S. Lee, G. Chang, Y. Jo, H. Park, and Y. Park, “Quantitative phase imaging techniques for the study of cell pathophysiology: from principles to applications,” Sensors (Basel) 13(4), 4170–4191 (2013).
[Crossref] [PubMed]

Chaturvedi, M. M.

Y. K. Jaiswal, M. K. Jaiswal, V. Agrawal, and M. M. Chaturvedi, “Bacterial endotoxin (LPS)-induced DNA damage in preimplanting embryonic and uterine cells inhibits implantation,” Fertil. Steril. 91(5Suppl), 2095–2103 (2009).
[Crossref] [PubMed]

Chen, L. B.

L. V. Johnson, M. L. Walsh, B. J. Bockus, and L. B. Chen, “Monitoring of relative mitochondrial membrane potential in living cells by fluorescence microscopy,” J. Cell Biol. 88(3), 526–535 (1981).
[Crossref] [PubMed]

Chirico, G.

A. Diaspro, G. Chirico, and M. Collini, “Two-photon fluorescence excitation and related techniques in biological microscopy,” Q. Rev. Biophys. 38(2), 97–166 (2005).
[Crossref] [PubMed]

Cho, S.

K. Lee, K. Kim, J. Jung, J. Heo, S. Cho, S. Lee, G. Chang, Y. Jo, H. Park, and Y. Park, “Quantitative phase imaging techniques for the study of cell pathophysiology: from principles to applications,” Sensors (Basel) 13(4), 4170–4191 (2013).
[Crossref] [PubMed]

Chou, K. C.

Cohen, D. A.

S. Ramachandran, D. A. Cohen, A. P. Quist, and R. Lal, “High performance, LED powered, waveguide based total internal reflection microscopy,” Sci. Rep. 3(1), 2133 (2013).
[Crossref] [PubMed]

Collini, M.

A. Diaspro, G. Chirico, and M. Collini, “Two-photon fluorescence excitation and related techniques in biological microscopy,” Q. Rev. Biophys. 38(2), 97–166 (2005).
[Crossref] [PubMed]

Colomb, T.

Cuche, E.

Depeursinge, C.

Diaspro, A.

A. Diaspro, G. Chirico, and M. Collini, “Two-photon fluorescence excitation and related techniques in biological microscopy,” Q. Rev. Biophys. 38(2), 97–166 (2005).
[Crossref] [PubMed]

Diekmann, R.

R. Diekmann, Ø. I. Helle, C. I. Øie, P. McCourt, T. R. Huser, M. Schüttpelz, and B. S. Ahluwalia, “Chip-based wide field-of-view nanoscopy,” Nat. Photonics 11(5), 322–328 (2017).
[Crossref]

Dixon, J.

A. Hassanzadeh, M. Nitsche, S. Mittler, S. Armstrong, J. Dixon, and U. Langbein, “Waveguide evanescent field fluorescence microscopy: Thin film fluorescence intensities and its application in cell biology,” Appl. Phys. Lett. 92(23), 233503 (2008).
[Crossref]

Dubey, V.

Emery, Y.

Fish, K. N.

K. N. Fish, “Total internal reflection fluorescence (TIRF) microscopy,” Curr. Protoc. Cytom. 50(1)12–18 (2009).
[Crossref]

Fordham, M.

J. G. White, W. B. Amos, and M. Fordham, “An evaluation of confocal versus conventional imaging of biological structures by fluorescence light microscopy,” J. Cell Biol. 105(1), 41–48 (1987).
[Crossref] [PubMed]

Gleason, S. S.

C. J. Mann, P. R. Bingham, H. K. Lin, V. C. Paquit, and S. S. Gleason, “Dual modality live cell imaging with multiple-wavelength digital holography and epi-fluorescence,” 3D Res. 2, 5 (2011).
[Crossref]

Grandin, H. M.

H. M. Grandin, B. Städler, M. Textor, and J. Vörös, “Waveguide excitation fluorescence microscopy: A new tool for sensing and imaging the biointerface,” Biosens. Bioelectron. 21(8), 1476–1482 (2006).
[Crossref] [PubMed]

Gudjonsson, T.

Gunnarsson, A.

B. Agnarsson, A. Lundgren, A. Gunnarsson, M. Rabe, A. Kunze, M. Mapar, L. Simonsson, M. Bally, V. P. Zhdanov, and F. Höök, “Evanescent Light-Scattering Microscopy for Label-Free Interfacial Imaging: From Single Sub-100 nm Vesicles to Live Cells,” ACS Nano 9(12), 11849–11862 (2015).
[Crossref] [PubMed]

Hassanzadeh, A.

A. Hassanzadeh, M. Nitsche, S. Mittler, S. Armstrong, J. Dixon, and U. Langbein, “Waveguide evanescent field fluorescence microscopy: Thin film fluorescence intensities and its application in cell biology,” Appl. Phys. Lett. 92(23), 233503 (2008).
[Crossref]

Helle, Ø. I.

R. Diekmann, Ø. I. Helle, C. I. Øie, P. McCourt, T. R. Huser, M. Schüttpelz, and B. S. Ahluwalia, “Chip-based wide field-of-view nanoscopy,” Nat. Photonics 11(5), 322–328 (2017).
[Crossref]

J.-C. Tinguely, Ø. I. Helle, and B. S. Ahluwalia, “Silicon nitride waveguide platform for fluorescence microscopy of living cells,” Opt. Express 25(22), 27678–27690 (2017).
[Crossref] [PubMed]

Hellesø, O. G.

S. M. Lindecrantz and O. G. Hellesø, “Estimation of propagation losses for narrow strip and rib waveguides,” IEEE Photonics Technol. Lett. 26(18), 1836–1839 (2014).
[Crossref]

Heo, J.

K. Lee, K. Kim, J. Jung, J. Heo, S. Cho, S. Lee, G. Chang, Y. Jo, H. Park, and Y. Park, “Quantitative phase imaging techniques for the study of cell pathophysiology: from principles to applications,” Sensors (Basel) 13(4), 4170–4191 (2013).
[Crossref] [PubMed]

Höök, F.

B. Agnarsson, A. Lundgren, A. Gunnarsson, M. Rabe, A. Kunze, M. Mapar, L. Simonsson, M. Bally, V. P. Zhdanov, and F. Höök, “Evanescent Light-Scattering Microscopy for Label-Free Interfacial Imaging: From Single Sub-100 nm Vesicles to Live Cells,” ACS Nano 9(12), 11849–11862 (2015).
[Crossref] [PubMed]

Huser, T. R.

R. Diekmann, Ø. I. Helle, C. I. Øie, P. McCourt, T. R. Huser, M. Schüttpelz, and B. S. Ahluwalia, “Chip-based wide field-of-view nanoscopy,” Nat. Photonics 11(5), 322–328 (2017).
[Crossref]

Ingthorsson, S.

Jaiswal, M. K.

Y. K. Jaiswal, M. K. Jaiswal, V. Agrawal, and M. M. Chaturvedi, “Bacterial endotoxin (LPS)-induced DNA damage in preimplanting embryonic and uterine cells inhibits implantation,” Fertil. Steril. 91(5Suppl), 2095–2103 (2009).
[Crossref] [PubMed]

Jaiswal, Y. K.

Y. K. Jaiswal, M. K. Jaiswal, V. Agrawal, and M. M. Chaturvedi, “Bacterial endotoxin (LPS)-induced DNA damage in preimplanting embryonic and uterine cells inhibits implantation,” Fertil. Steril. 91(5Suppl), 2095–2103 (2009).
[Crossref] [PubMed]

Jo, Y.

K. Lee, K. Kim, J. Jung, J. Heo, S. Cho, S. Lee, G. Chang, Y. Jo, H. Park, and Y. Park, “Quantitative phase imaging techniques for the study of cell pathophysiology: from principles to applications,” Sensors (Basel) 13(4), 4170–4191 (2013).
[Crossref] [PubMed]

Johnson, L. V.

L. V. Johnson, M. L. Walsh, B. J. Bockus, and L. B. Chen, “Monitoring of relative mitochondrial membrane potential in living cells by fluorescence microscopy,” J. Cell Biol. 88(3), 526–535 (1981).
[Crossref] [PubMed]

Jonsdottir, A. B.

Jung, J.

K. Lee, K. Kim, J. Jung, J. Heo, S. Cho, S. Lee, G. Chang, Y. Jo, H. Park, and Y. Park, “Quantitative phase imaging techniques for the study of cell pathophysiology: from principles to applications,” Sensors (Basel) 13(4), 4170–4191 (2013).
[Crossref] [PubMed]

Kim, K.

K. Lee, K. Kim, J. Jung, J. Heo, S. Cho, S. Lee, G. Chang, Y. Jo, H. Park, and Y. Park, “Quantitative phase imaging techniques for the study of cell pathophysiology: from principles to applications,” Sensors (Basel) 13(4), 4170–4191 (2013).
[Crossref] [PubMed]

Kothapalli, S.-R.

Kunze, A.

B. Agnarsson, A. Lundgren, A. Gunnarsson, M. Rabe, A. Kunze, M. Mapar, L. Simonsson, M. Bally, V. P. Zhdanov, and F. Höök, “Evanescent Light-Scattering Microscopy for Label-Free Interfacial Imaging: From Single Sub-100 nm Vesicles to Live Cells,” ACS Nano 9(12), 11849–11862 (2015).
[Crossref] [PubMed]

Lal, R.

S. Ramachandran, D. A. Cohen, A. P. Quist, and R. Lal, “High performance, LED powered, waveguide based total internal reflection microscopy,” Sci. Rep. 3(1), 2133 (2013).
[Crossref] [PubMed]

Langbein, U.

A. Hassanzadeh, M. Nitsche, S. Mittler, S. Armstrong, J. Dixon, and U. Langbein, “Waveguide evanescent field fluorescence microscopy: Thin film fluorescence intensities and its application in cell biology,” Appl. Phys. Lett. 92(23), 233503 (2008).
[Crossref]

Lavis, L. D.

Z. Liu, L. D. Lavis, and E. Betzig, “Imaging live-cell dynamics and structure at the single-molecule level,” Mol. Cell 58(4), 644–659 (2015).
[Crossref] [PubMed]

Lee, K.

K. Lee, K. Kim, J. Jung, J. Heo, S. Cho, S. Lee, G. Chang, Y. Jo, H. Park, and Y. Park, “Quantitative phase imaging techniques for the study of cell pathophysiology: from principles to applications,” Sensors (Basel) 13(4), 4170–4191 (2013).
[Crossref] [PubMed]

Lee, S.

K. Lee, K. Kim, J. Jung, J. Heo, S. Cho, S. Lee, G. Chang, Y. Jo, H. Park, and Y. Park, “Quantitative phase imaging techniques for the study of cell pathophysiology: from principles to applications,” Sensors (Basel) 13(4), 4170–4191 (2013).
[Crossref] [PubMed]

Leosson, K.

Leung, B. O.

Lin, H. K.

C. J. Mann, P. R. Bingham, H. K. Lin, V. C. Paquit, and S. S. Gleason, “Dual modality live cell imaging with multiple-wavelength digital holography and epi-fluorescence,” 3D Res. 2, 5 (2011).
[Crossref]

Lindecrantz, S. M.

S. M. Lindecrantz and O. G. Hellesø, “Estimation of propagation losses for narrow strip and rib waveguides,” IEEE Photonics Technol. Lett. 26(18), 1836–1839 (2014).
[Crossref]

Liu, Z.

Z. Liu, L. D. Lavis, and E. Betzig, “Imaging live-cell dynamics and structure at the single-molecule level,” Mol. Cell 58(4), 644–659 (2015).
[Crossref] [PubMed]

Lundgren, A.

B. Agnarsson, A. Lundgren, A. Gunnarsson, M. Rabe, A. Kunze, M. Mapar, L. Simonsson, M. Bally, V. P. Zhdanov, and F. Höök, “Evanescent Light-Scattering Microscopy for Label-Free Interfacial Imaging: From Single Sub-100 nm Vesicles to Live Cells,” ACS Nano 9(12), 11849–11862 (2015).
[Crossref] [PubMed]

Magistretti, P.

Magistretti, P. J.

Mann, C. J.

C. J. Mann, P. R. Bingham, H. K. Lin, V. C. Paquit, and S. S. Gleason, “Dual modality live cell imaging with multiple-wavelength digital holography and epi-fluorescence,” 3D Res. 2, 5 (2011).
[Crossref]

Mapar, M.

B. Agnarsson, A. Lundgren, A. Gunnarsson, M. Rabe, A. Kunze, M. Mapar, L. Simonsson, M. Bally, V. P. Zhdanov, and F. Höök, “Evanescent Light-Scattering Microscopy for Label-Free Interfacial Imaging: From Single Sub-100 nm Vesicles to Live Cells,” ACS Nano 9(12), 11849–11862 (2015).
[Crossref] [PubMed]

Marquet, P.

Marshall, S. T.

S. N. Vogel, S. T. Marshall, and D. L. Rosenstreich, “Analysis of the effects of lipopolysaccharide on macrophages: differential phagocytic responses of C3H/HeN and C3H/HeJ macrophages in vitro,” Infect. Immun. 25(1), 328–336 (1979).
[PubMed]

Martin-Fernandez, M. L.

M. L. Martin-Fernandez, C. J. Tynan, and S. E. Webb, “A ‘pocket guide’ to total internal reflection fluorescence,” J. Microsc. 252(1), 16–22 (2013).
[Crossref] [PubMed]

Matoba, O.

X. Quan, K. Nitta, O. Matoba, P. Xia, and Y. Awatsuji, “Phase and fluorescence imaging by combination of digital holographic microscopy and fluorescence microscopy,” Opt. Rev. 22(2), 349–353 (2015).
[Crossref]

Mattheyses, A. L.

A. L. Mattheyses, S. M. Simon, and J. Z. Rappoport, “Imaging with total internal reflection fluorescence microscopy for the cell biologist,” J. Cell Sci. 123(21), 3621–3628 (2010).
[Crossref] [PubMed]

McCourt, P.

R. Diekmann, Ø. I. Helle, C. I. Øie, P. McCourt, T. R. Huser, M. Schüttpelz, and B. S. Ahluwalia, “Chip-based wide field-of-view nanoscopy,” Nat. Photonics 11(5), 322–328 (2017).
[Crossref]

Mehta, D. S.

Mir, M.

M. Mir, B. Bhaduri, R. Wang, R. Zhu, and G. Popescu, “Quantitative phase imaging,” Prog. Opt. 57, 133–217 (2012).
[Crossref]

Mittler, S.

A. Hassanzadeh, M. Nitsche, S. Mittler, S. Armstrong, J. Dixon, and U. Langbein, “Waveguide evanescent field fluorescence microscopy: Thin film fluorescence intensities and its application in cell biology,” Appl. Phys. Lett. 92(23), 233503 (2008).
[Crossref]

Nitsche, M.

A. Hassanzadeh, M. Nitsche, S. Mittler, S. Armstrong, J. Dixon, and U. Langbein, “Waveguide evanescent field fluorescence microscopy: Thin film fluorescence intensities and its application in cell biology,” Appl. Phys. Lett. 92(23), 233503 (2008).
[Crossref]

Nitta, K.

X. Quan, K. Nitta, O. Matoba, P. Xia, and Y. Awatsuji, “Phase and fluorescence imaging by combination of digital holographic microscopy and fluorescence microscopy,” Opt. Rev. 22(2), 349–353 (2015).
[Crossref]

Øie, C. I.

R. Diekmann, Ø. I. Helle, C. I. Øie, P. McCourt, T. R. Huser, M. Schüttpelz, and B. S. Ahluwalia, “Chip-based wide field-of-view nanoscopy,” Nat. Photonics 11(5), 322–328 (2017).
[Crossref]

Olivier, L. A.

J. S. Burmeister, L. A. Olivier, W. M. Reichert, and G. A. Truskey, “Application of total internal reflection fluorescence microscopy to study cell adhesion to biomaterials,” Biomaterials 19(4-5), 307–325 (1998).
[Crossref] [PubMed]

Paquit, V. C.

C. J. Mann, P. R. Bingham, H. K. Lin, V. C. Paquit, and S. S. Gleason, “Dual modality live cell imaging with multiple-wavelength digital holography and epi-fluorescence,” 3D Res. 2, 5 (2011).
[Crossref]

Park, H.

K. Lee, K. Kim, J. Jung, J. Heo, S. Cho, S. Lee, G. Chang, Y. Jo, H. Park, and Y. Park, “Quantitative phase imaging techniques for the study of cell pathophysiology: from principles to applications,” Sensors (Basel) 13(4), 4170–4191 (2013).
[Crossref] [PubMed]

Park, Y.

K. Lee, K. Kim, J. Jung, J. Heo, S. Cho, S. Lee, G. Chang, Y. Jo, H. Park, and Y. Park, “Quantitative phase imaging techniques for the study of cell pathophysiology: from principles to applications,” Sensors (Basel) 13(4), 4170–4191 (2013).
[Crossref] [PubMed]

Popescu, G.

M. Mir, B. Bhaduri, R. Wang, R. Zhu, and G. Popescu, “Quantitative phase imaging,” Prog. Opt. 57, 133–217 (2012).
[Crossref]

Quan, X.

X. Quan, K. Nitta, O. Matoba, P. Xia, and Y. Awatsuji, “Phase and fluorescence imaging by combination of digital holographic microscopy and fluorescence microscopy,” Opt. Rev. 22(2), 349–353 (2015).
[Crossref]

Quist, A. P.

S. Ramachandran, D. A. Cohen, A. P. Quist, and R. Lal, “High performance, LED powered, waveguide based total internal reflection microscopy,” Sci. Rep. 3(1), 2133 (2013).
[Crossref] [PubMed]

Rabe, M.

B. Agnarsson, A. Lundgren, A. Gunnarsson, M. Rabe, A. Kunze, M. Mapar, L. Simonsson, M. Bally, V. P. Zhdanov, and F. Höök, “Evanescent Light-Scattering Microscopy for Label-Free Interfacial Imaging: From Single Sub-100 nm Vesicles to Live Cells,” ACS Nano 9(12), 11849–11862 (2015).
[Crossref] [PubMed]

Ramachandran, S.

S. Ramachandran, D. A. Cohen, A. P. Quist, and R. Lal, “High performance, LED powered, waveguide based total internal reflection microscopy,” Sci. Rep. 3(1), 2133 (2013).
[Crossref] [PubMed]

Rao, D. V.

Rappaz, B.

Rappoport, J. Z.

A. L. Mattheyses, S. M. Simon, and J. Z. Rappoport, “Imaging with total internal reflection fluorescence microscopy for the cell biologist,” J. Cell Sci. 123(21), 3621–3628 (2010).
[Crossref] [PubMed]

Reichert, W. M.

J. S. Burmeister, L. A. Olivier, W. M. Reichert, and G. A. Truskey, “Application of total internal reflection fluorescence microscopy to study cell adhesion to biomaterials,” Biomaterials 19(4-5), 307–325 (1998).
[Crossref] [PubMed]

Rosenstreich, D. L.

S. N. Vogel, S. T. Marshall, and D. L. Rosenstreich, “Analysis of the effects of lipopolysaccharide on macrophages: differential phagocytic responses of C3H/HeN and C3H/HeJ macrophages in vitro,” Infect. Immun. 25(1), 328–336 (1979).
[PubMed]

Schneckenburger, H.

H. Schneckenburger, “Total internal reflection fluorescence microscopy: technical innovations and novel applications,” Curr. Opin. Biotechnol. 16(1), 13–18 (2005).
[Crossref] [PubMed]

Schüttpelz, M.

R. Diekmann, Ø. I. Helle, C. I. Øie, P. McCourt, T. R. Huser, M. Schüttpelz, and B. S. Ahluwalia, “Chip-based wide field-of-view nanoscopy,” Nat. Photonics 11(5), 322–328 (2017).
[Crossref]

Simon, S. M.

A. L. Mattheyses, S. M. Simon, and J. Z. Rappoport, “Imaging with total internal reflection fluorescence microscopy for the cell biologist,” J. Cell Sci. 123(21), 3621–3628 (2010).
[Crossref] [PubMed]

Simonsson, L.

B. Agnarsson, A. Lundgren, A. Gunnarsson, M. Rabe, A. Kunze, M. Mapar, L. Simonsson, M. Bally, V. P. Zhdanov, and F. Höök, “Evanescent Light-Scattering Microscopy for Label-Free Interfacial Imaging: From Single Sub-100 nm Vesicles to Live Cells,” ACS Nano 9(12), 11849–11862 (2015).
[Crossref] [PubMed]

Singh, G.

Singh, V.

Städler, B.

H. M. Grandin, B. Städler, M. Textor, and J. Vörös, “Waveguide excitation fluorescence microscopy: A new tool for sensing and imaging the biointerface,” Biosens. Bioelectron. 21(8), 1476–1482 (2006).
[Crossref] [PubMed]

Stock, J.

C. Burch and J. Stock, “Phase-contrast microscopy,” J. Sci. Instrum. 19(5), 71–75 (1942).
[Crossref]

Stout, A. L.

Textor, M.

H. M. Grandin, B. Städler, M. Textor, and J. Vörös, “Waveguide excitation fluorescence microscopy: A new tool for sensing and imaging the biointerface,” Biosens. Bioelectron. 21(8), 1476–1482 (2006).
[Crossref] [PubMed]

Ting, A. Y.

J. Zhang, R. E. Campbell, A. Y. Ting, and R. Y. Tsien, “Creating new fluorescent probes for cell biology,” Nat. Rev. Mol. Cell Biol. 3(12), 906–918 (2002).
[Crossref] [PubMed]

Tinguely, J.-C.

Tipping, M.

Truskey, G. A.

J. S. Burmeister, L. A. Olivier, W. M. Reichert, and G. A. Truskey, “Application of total internal reflection fluorescence microscopy to study cell adhesion to biomaterials,” Biomaterials 19(4-5), 307–325 (1998).
[Crossref] [PubMed]

Tsien, R. Y.

J. Zhang, R. E. Campbell, A. Y. Ting, and R. Y. Tsien, “Creating new fluorescent probes for cell biology,” Nat. Rev. Mol. Cell Biol. 3(12), 906–918 (2002).
[Crossref] [PubMed]

Tynan, C. J.

M. L. Martin-Fernandez, C. J. Tynan, and S. E. Webb, “A ‘pocket guide’ to total internal reflection fluorescence,” J. Microsc. 252(1), 16–22 (2013).
[Crossref] [PubMed]

Veraksa, A.

Vogel, S. N.

S. N. Vogel, S. T. Marshall, and D. L. Rosenstreich, “Analysis of the effects of lipopolysaccharide on macrophages: differential phagocytic responses of C3H/HeN and C3H/HeJ macrophages in vitro,” Infect. Immun. 25(1), 328–336 (1979).
[PubMed]

Vörös, J.

H. M. Grandin, B. Städler, M. Textor, and J. Vörös, “Waveguide excitation fluorescence microscopy: A new tool for sensing and imaging the biointerface,” Biosens. Bioelectron. 21(8), 1476–1482 (2006).
[Crossref] [PubMed]

Walsh, M. L.

L. V. Johnson, M. L. Walsh, B. J. Bockus, and L. B. Chen, “Monitoring of relative mitochondrial membrane potential in living cells by fluorescence microscopy,” J. Cell Biol. 88(3), 526–535 (1981).
[Crossref] [PubMed]

Wang, R.

M. Mir, B. Bhaduri, R. Wang, R. Zhu, and G. Popescu, “Quantitative phase imaging,” Prog. Opt. 57, 133–217 (2012).
[Crossref]

Webb, S. E.

M. L. Martin-Fernandez, C. J. Tynan, and S. E. Webb, “A ‘pocket guide’ to total internal reflection fluorescence,” J. Microsc. 252(1), 16–22 (2013).
[Crossref] [PubMed]

White, J. G.

J. G. White, W. B. Amos, and M. Fordham, “An evaluation of confocal versus conventional imaging of biological structures by fluorescence light microscopy,” J. Cell Biol. 105(1), 41–48 (1987).
[Crossref] [PubMed]

Xia, P.

X. Quan, K. Nitta, O. Matoba, P. Xia, and Y. Awatsuji, “Phase and fluorescence imaging by combination of digital holographic microscopy and fluorescence microscopy,” Opt. Rev. 22(2), 349–353 (2015).
[Crossref]

Yelleswarapu, C. S.

Zhang, J.

J. Zhang, R. E. Campbell, A. Y. Ting, and R. Y. Tsien, “Creating new fluorescent probes for cell biology,” Nat. Rev. Mol. Cell Biol. 3(12), 906–918 (2002).
[Crossref] [PubMed]

Zhdanov, V. P.

B. Agnarsson, A. Lundgren, A. Gunnarsson, M. Rabe, A. Kunze, M. Mapar, L. Simonsson, M. Bally, V. P. Zhdanov, and F. Höök, “Evanescent Light-Scattering Microscopy for Label-Free Interfacial Imaging: From Single Sub-100 nm Vesicles to Live Cells,” ACS Nano 9(12), 11849–11862 (2015).
[Crossref] [PubMed]

Zhu, R.

M. Mir, B. Bhaduri, R. Wang, R. Zhu, and G. Popescu, “Quantitative phase imaging,” Prog. Opt. 57, 133–217 (2012).
[Crossref]

3D Res. (1)

C. J. Mann, P. R. Bingham, H. K. Lin, V. C. Paquit, and S. S. Gleason, “Dual modality live cell imaging with multiple-wavelength digital holography and epi-fluorescence,” 3D Res. 2, 5 (2011).
[Crossref]

ACS Nano (1)

B. Agnarsson, A. Lundgren, A. Gunnarsson, M. Rabe, A. Kunze, M. Mapar, L. Simonsson, M. Bally, V. P. Zhdanov, and F. Höök, “Evanescent Light-Scattering Microscopy for Label-Free Interfacial Imaging: From Single Sub-100 nm Vesicles to Live Cells,” ACS Nano 9(12), 11849–11862 (2015).
[Crossref] [PubMed]

Appl. Opt. (2)

Appl. Phys. Lett. (1)

A. Hassanzadeh, M. Nitsche, S. Mittler, S. Armstrong, J. Dixon, and U. Langbein, “Waveguide evanescent field fluorescence microscopy: Thin film fluorescence intensities and its application in cell biology,” Appl. Phys. Lett. 92(23), 233503 (2008).
[Crossref]

Appl. Spectrosc. (1)

Biomaterials (1)

J. S. Burmeister, L. A. Olivier, W. M. Reichert, and G. A. Truskey, “Application of total internal reflection fluorescence microscopy to study cell adhesion to biomaterials,” Biomaterials 19(4-5), 307–325 (1998).
[Crossref] [PubMed]

Biosens. Bioelectron. (1)

H. M. Grandin, B. Städler, M. Textor, and J. Vörös, “Waveguide excitation fluorescence microscopy: A new tool for sensing and imaging the biointerface,” Biosens. Bioelectron. 21(8), 1476–1482 (2006).
[Crossref] [PubMed]

Curr. Opin. Biotechnol. (1)

H. Schneckenburger, “Total internal reflection fluorescence microscopy: technical innovations and novel applications,” Curr. Opin. Biotechnol. 16(1), 13–18 (2005).
[Crossref] [PubMed]

Curr. Protoc. Cytom. (1)

K. N. Fish, “Total internal reflection fluorescence (TIRF) microscopy,” Curr. Protoc. Cytom. 50(1)12–18 (2009).
[Crossref]

Fertil. Steril. (1)

Y. K. Jaiswal, M. K. Jaiswal, V. Agrawal, and M. M. Chaturvedi, “Bacterial endotoxin (LPS)-induced DNA damage in preimplanting embryonic and uterine cells inhibits implantation,” Fertil. Steril. 91(5Suppl), 2095–2103 (2009).
[Crossref] [PubMed]

IEEE Photonics Technol. Lett. (1)

S. M. Lindecrantz and O. G. Hellesø, “Estimation of propagation losses for narrow strip and rib waveguides,” IEEE Photonics Technol. Lett. 26(18), 1836–1839 (2014).
[Crossref]

Infect. Immun. (1)

S. N. Vogel, S. T. Marshall, and D. L. Rosenstreich, “Analysis of the effects of lipopolysaccharide on macrophages: differential phagocytic responses of C3H/HeN and C3H/HeJ macrophages in vitro,” Infect. Immun. 25(1), 328–336 (1979).
[PubMed]

J. Cell Biol. (2)

J. G. White, W. B. Amos, and M. Fordham, “An evaluation of confocal versus conventional imaging of biological structures by fluorescence light microscopy,” J. Cell Biol. 105(1), 41–48 (1987).
[Crossref] [PubMed]

L. V. Johnson, M. L. Walsh, B. J. Bockus, and L. B. Chen, “Monitoring of relative mitochondrial membrane potential in living cells by fluorescence microscopy,” J. Cell Biol. 88(3), 526–535 (1981).
[Crossref] [PubMed]

J. Cell Sci. (1)

A. L. Mattheyses, S. M. Simon, and J. Z. Rappoport, “Imaging with total internal reflection fluorescence microscopy for the cell biologist,” J. Cell Sci. 123(21), 3621–3628 (2010).
[Crossref] [PubMed]

J. Microsc. (1)

M. L. Martin-Fernandez, C. J. Tynan, and S. E. Webb, “A ‘pocket guide’ to total internal reflection fluorescence,” J. Microsc. 252(1), 16–22 (2013).
[Crossref] [PubMed]

J. Sci. Instrum. (1)

C. Burch and J. Stock, “Phase-contrast microscopy,” J. Sci. Instrum. 19(5), 71–75 (1942).
[Crossref]

Mol. Cell (1)

Z. Liu, L. D. Lavis, and E. Betzig, “Imaging live-cell dynamics and structure at the single-molecule level,” Mol. Cell 58(4), 644–659 (2015).
[Crossref] [PubMed]

Nat. Photonics (1)

R. Diekmann, Ø. I. Helle, C. I. Øie, P. McCourt, T. R. Huser, M. Schüttpelz, and B. S. Ahluwalia, “Chip-based wide field-of-view nanoscopy,” Nat. Photonics 11(5), 322–328 (2017).
[Crossref]

Nat. Rev. Mol. Cell Biol. (1)

J. Zhang, R. E. Campbell, A. Y. Ting, and R. Y. Tsien, “Creating new fluorescent probes for cell biology,” Nat. Rev. Mol. Cell Biol. 3(12), 906–918 (2002).
[Crossref] [PubMed]

Opt. Express (5)

Opt. Lett. (3)

Opt. Rev. (1)

X. Quan, K. Nitta, O. Matoba, P. Xia, and Y. Awatsuji, “Phase and fluorescence imaging by combination of digital holographic microscopy and fluorescence microscopy,” Opt. Rev. 22(2), 349–353 (2015).
[Crossref]

Prog. Opt. (1)

M. Mir, B. Bhaduri, R. Wang, R. Zhu, and G. Popescu, “Quantitative phase imaging,” Prog. Opt. 57, 133–217 (2012).
[Crossref]

Q. Rev. Biophys. (1)

A. Diaspro, G. Chirico, and M. Collini, “Two-photon fluorescence excitation and related techniques in biological microscopy,” Q. Rev. Biophys. 38(2), 97–166 (2005).
[Crossref] [PubMed]

Sci. Rep. (1)

S. Ramachandran, D. A. Cohen, A. P. Quist, and R. Lal, “High performance, LED powered, waveguide based total internal reflection microscopy,” Sci. Rep. 3(1), 2133 (2013).
[Crossref] [PubMed]

Sensors (Basel) (1)

K. Lee, K. Kim, J. Jung, J. Heo, S. Cho, S. Lee, G. Chang, Y. Jo, H. Park, and Y. Park, “Quantitative phase imaging techniques for the study of cell pathophysiology: from principles to applications,” Sensors (Basel) 13(4), 4170–4191 (2013).
[Crossref] [PubMed]

Traffic (1)

D. Axelrod, “Total internal reflection fluorescence microscopy in cell biology,” Traffic 2(11), 764–774 (2001).
[Crossref] [PubMed]

Other (1)

D. B. Murphy and M. W. Davidson, “Differential interference contrast microscopy and modulation contrast microscopy,” Fundamentals of Light Microscopy and Electronic Imaging, 2nd ed. 173–197 (2012).

Supplementary Material (1)

NameDescription
» Visualization 1       Excitation of multiple modes inside the optical waveguide and resulting TIRF image obtained from superposition of 250 images.

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Figures (7)

Fig. 1
Fig. 1 Schematic diagram of the integrated TIRF and QPI setup. The green dotted box is for TIRF imaging module and sample is positioned on the top surface of waveguide (BS- Beam-splitter, L- lens, MO-microscope objective, SMF-single mode fiber). Figure 1(a) shows the schematic diagram of Ta2O5 rib waveguide geometry on Si substrate.
Fig. 2
Fig. 2 Measurement of the spatial and temporal phase sensitivity of QPM while employing on the standard mirror (a) Interferogram obtained while using standard flat mirror as a test specimen (b) spatial, and (c) temporal phase noise of the experimental setup, (d) Interferogram of standard strip waveguide of 50 nm height, (e) phase image and (f) corresponding recovered height map which is approximately 50nm.
Fig. 3
Fig. 3 Multi-modal imaging of a CMDR-labeled MCC13 cell. (a) Epi-fluorescence image, (b) chip-based TIRF image, and (c) 2D phase map of the same cell.
Fig. 4
Fig. 4 Excitation of multiple modes inside the optical waveguide, which show generation of non-uniform evanescent field and thus resulting in non-uniform illumination of the specimen (a) Fluorescence images at different position of coupling objective by translating along x axis and (b) Resulting TIRF image obtained from superposition of 250 images by averaging them on intensity basis. Associated Visualization 1.
Fig. 5
Fig. 5 (a) Waveguide-chip illumination enables TIRF imaging of CMG-labeled macrophages over extraordinarily large field of view (5X magnification). TIRF and phase images of the same selected region of interest with (b-c) 20X magnification and (d-e) with 60X magnification objective lenses respectively. As TIRF illumination is provided by the waveguide-chip, the illumination light path of TIFR and phase modules are decoupled, enabling easy switching between the objective lens of different magnification. The arrow in (a) show the direction of light coupling.
Fig. 6
Fig. 6 (a) TIRF image and (b) quantitative phase image of unchallenged macrophages. (c) TIRF and (d) quantitative phase image of LPS-challenged macrophages.
Fig. 7
Fig. 7 Whisker box of maximum phase of the control and the LPS-challenged macrophages obtained by processing over 1000 macrophages. The central red lines indicate the median, and bottom and top sides of blue box indicate the 25th and 75th percentiles, respectively. The black lines extended vertically from blue boxes specify extreme data points without outliers

Equations (7)

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θ c = sin 1 ( n 2 n 1 )
I e ( z ) = I 0 exp ( z d )
d = λ 4 π n 1 2 sin 2 θ n 2 2
H ( x , y ) = | E r ( x , y ) + E s ( x , y ) | 2
= | E ( x , y ) r | 2 + | E s ( x , y ) | 2 + | E s ( x , y ) | | E r * ( x , y ) | exp [ i ( ϕ ( x , y ) ) ]
ϕ ( x , y ) = arc tan Im ( H f i l t ( x , y ) ) Re ( H f i l t ( x , y ) )
ϕ ( x , y ) = 2 π λ ( n s ( x , y ) n m ( x , y ) ) * 2 h ( x , y )

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