Abstract

Cell imaging using low-light techniques such as bioluminescence, radioluminescence, and low-excitation fluorescence has received increased attention, particularly due to broad commercialization of highly sensitive detectors. However, the dim signals are still regarded as difficult to image using conventional microscopes, where the only low-light microscope in the market is primarily optimized for bioluminescence imaging. Here, we developed a novel modular microscope that is cost-effective and suitable for imaging different low-light luminescence modes. Results show that this microscope system features excellent aberration correction capabilities and enhanced image resolution, where bioluminescence, radioluminescence and epifluorescence images were captured and compared with the commercial bioluminescence microscope.

© 2015 Optical Society of America

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References

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2015 (3)

D. Sengupta, S. Miller, Z. Marton, F. Chin, V. Nagarkar, and G. Pratx, “Bright Lu2 O3 :Eu thin-film scintillators for high-resolution radioluminescence microscopy,” Adv. Healthc. Mater. 4(14), 2064–2070 (2015).
[Crossref] [PubMed]

K. Goda, Y. Hatta-Ohashi, R. Akiyoshi, T. Sugiyama, I. Sakai, T. Takahashi, and H. Suzuki, “Combining fluorescence and bioluminescence microscopy,” Microsc. Res. Tech. 78(8), 715–722 (2015).
[Crossref] [PubMed]

T. J. Kim, M. Kim, S. Hann, J. Trejo, and C. H. Hidrovo, “Thermal Characterization of Microheated Microchannels With Spatially Resolved Two-Color Fluorescence Thermometry,” J. Microelectromech. Syst. 24(1), 115–125 (2015).
[Crossref]

2014 (3)

K. Ogoh, R. Akiyoshi, T. May-Maw-Thet, S. Sugiyama, Y. Dosaka, Y. Hatta-Ohashi, and H. Suzuki, “Bioluminescence microscopy using a short focal-length imaging lens,” J. Microsc. 253(3), 191–197 (2014).
[Crossref] [PubMed]

R. Akiyoshi, T. Kaneuch, T. Aigaki, and H. Suzuki, “Bioluminescence imaging to track real-time armadillo promoter activity in live Drosophila embryos,” Anal. Bioanal. Chem. 406(23), 5703–5713 (2014).
[Crossref] [PubMed]

D. Lambrechts, M. Roeffaers, K. Goossens, J. Hofkens, G. Vande Velde, T. Van de Putte, J. Schrooten, and H. Van Oosterwyck, “A causal relation between bioluminescence and oxygen to quantify the cell niche,” PLoS One 9(5), e97572 (2014).
[Crossref] [PubMed]

2013 (1)

G. Pratx, K. Chen, C. Sun, M. Axente, L. Sasportas, C. Carpenter, and L. Xing, “High-Resolution Radioluminescence Microscopy of 18F-FDG Uptake by Reconstructing the β-Ionization Track,” J. Nucl. Med. 54(10), 1841–1846 (2013).
[Crossref] [PubMed]

2012 (3)

B. W. Miller, H. B. Barber, H. H. Barrett, Z. Liu, V. V. Nagarkar, and L. R. Furenlid, “Progress in BazookaSPECT: high-resolution dynamic scintigraphy with large-area imagers,” Proc. SPIE 8508, 85080F (2012).
[Crossref] [PubMed]

G. Pratx, K. Chen, C. Sun, L. Martin, C. M. Carpenter, P. D. Olcott, and L. Xing, “Radioluminescence microscopy: measuring the heterogeneous uptake of radiotracers in single living cells,” PLoS One 7(10), e46285 (2012).
[Crossref] [PubMed]

D. K. Welsh and T. Noguchi, “Cellular bioluminescence imaging,” Cold Spring Harb. Protoc. 2012(8), 070607 (2012).
[Crossref] [PubMed]

2011 (1)

C. E. Badr and B. A. Tannous, “Bioluminescence imaging: progress and applications,” Trends Biotechnol. 29(12), 624–633 (2011).
[Crossref] [PubMed]

2010 (1)

A. P. Feranchak, M. A. Lewis, C. Kresge, M. Sathe, A. Bugde, K. Luby-Phelps, P. P. Antich, and J. G. Fitz, “Initiation of purinergic signaling by exocytosis of ATP-containing vesicles in liver epithelium,” J. Biol. Chem. 285(11), 8138–8147 (2010).
[Crossref] [PubMed]

2009 (1)

D. Muzzey and A. van Oudenaarden, “Quantitative time-lapse fluorescence microscopy in single cells,” Annu. Rev. Cell Dev. Biol. 25(1), 301–327 (2009).
[Crossref] [PubMed]

2008 (1)

V. Coulon, M. Audet, V. Homburger, J. Bockaert, L. Fagni, M. Bouvier, and J. Perroy, “Subcellular imaging of dynamic protein interactions by bioluminescence resonance energy transfer,” Biophys. J. 94(3), 1001–1009 (2008).
[Crossref] [PubMed]

2007 (2)

F. Fan and K. V. Wood, “Bioluminescent assays for high-throughput screening,” Assay Drug Dev. Technol. 5(1), 127–136 (2007).
[Crossref] [PubMed]

B. W. Miller, H. B. Barber, H. H. Barrett, L. Chen, and S. J. Taylor, “Photon-counting gamma camera based on columnar CsI(Tl) optically coupled to a back-illuminated CCD,” Proc. SPIE 6510, 65100N (2007).
[Crossref] [PubMed]

2005 (1)

A. Roda, M. Guardigli, P. Pasini, M. Mirasoli, E. Michelini, and M. Musiani, “Bio-and chemiluminescence imaging in analytical chemistry,” Anal. Chim. Acta 541(1), 25–35 (2005).
[Crossref]

2003 (3)

R. Weissleder and V. Ntziachristos, “Shedding light onto live molecular targets,” Nat. Med. 9(1), 123–128 (2003).
[Crossref] [PubMed]

T. F. Massoud and S. S. Gambhir, “Molecular imaging in living subjects: seeing fundamental biological processes in a new light,” Genes Dev. 17(5), 545–580 (2003).
[Crossref] [PubMed]

C. D. Meinhart and S. T. Wereley, “The theory of diffraction-limited resolution in microparticle image velocimetry,” Meas. Sci. Technol. 14(7), 1047–1053 (2003).
[Crossref]

2002 (1)

L. F. Greer and A. A. Szalay, “Imaging of light emission from the expression of luciferases in living cells and organisms: a review,” Luminescence 17(1), 43–74 (2002).
[Crossref] [PubMed]

2000 (1)

A. Roda, P. Pasini, M. Guardigli, M. Baraldini, M. Musiani, and M. Mirasoli, “Bio- and chemiluminescence in bioanalysis,” Fresenius J. Anal. Chem. 366(6-7), 752–759 (2000).
[Crossref] [PubMed]

1998 (1)

D. W. Piston, “Choosing objective lenses: the importance of numerical aperture and magnification in digital optical microscopy,” Biol. Bull. 195(1), 1–4 (1998).
[Crossref] [PubMed]

1997 (1)

C. H. Contag, S. D. Spilman, P. R. Contag, M. Oshiro, B. Eames, P. Dennery, D. K. Stevenson, and D. A. Benaron, “Visualizing gene expression in living mammals using a bioluminescent reporter,” Photochem. Photobiol. 66(4), 523–531 (1997).
[Crossref] [PubMed]

1990 (1)

C. E. Hooper, R. E. Ansorge, H. M. Browne, and P. Tomkins, “CCD imaging of luciferase gene expression in single mammalian cells,” J. Biolumin. Chemilumin. 5(2), 123–130 (1990).
[Crossref] [PubMed]

1986 (1)

H. Broda, V. D. Gooch, W. Taylor, N. Aiuto, and J. W. Hastings, “Acquisition of circadian bioluminescence data in Gonyaulax and an effect of the measurement procedure on the period of the rhythm,” J. Biol. Rhythms 1(3), 251–263 (1986).
[Crossref] [PubMed]

1980 (1)

G. Reynolds and D. Taylor, “Image intensification applied to light microscopy,” Bioscience 30(9), 586–592 (1980).
[Crossref]

1968 (1)

G. Laustriat, “The luminescence decay of organic scintillators,” Mol. Cryst. 4(1–4), 127–145 (1968).
[Crossref]

1963 (1)

J. W. Hastings and Q. H. Gibson, “Intermediates in the bioluminescent oxidation of reduced flavin mononucleotide,” J. Biol. Chem. 238(7), 2537–2554 (1963).
[PubMed]

Aigaki, T.

R. Akiyoshi, T. Kaneuch, T. Aigaki, and H. Suzuki, “Bioluminescence imaging to track real-time armadillo promoter activity in live Drosophila embryos,” Anal. Bioanal. Chem. 406(23), 5703–5713 (2014).
[Crossref] [PubMed]

Aiuto, N.

H. Broda, V. D. Gooch, W. Taylor, N. Aiuto, and J. W. Hastings, “Acquisition of circadian bioluminescence data in Gonyaulax and an effect of the measurement procedure on the period of the rhythm,” J. Biol. Rhythms 1(3), 251–263 (1986).
[Crossref] [PubMed]

Akiyoshi, R.

K. Goda, Y. Hatta-Ohashi, R. Akiyoshi, T. Sugiyama, I. Sakai, T. Takahashi, and H. Suzuki, “Combining fluorescence and bioluminescence microscopy,” Microsc. Res. Tech. 78(8), 715–722 (2015).
[Crossref] [PubMed]

R. Akiyoshi, T. Kaneuch, T. Aigaki, and H. Suzuki, “Bioluminescence imaging to track real-time armadillo promoter activity in live Drosophila embryos,” Anal. Bioanal. Chem. 406(23), 5703–5713 (2014).
[Crossref] [PubMed]

K. Ogoh, R. Akiyoshi, T. May-Maw-Thet, S. Sugiyama, Y. Dosaka, Y. Hatta-Ohashi, and H. Suzuki, “Bioluminescence microscopy using a short focal-length imaging lens,” J. Microsc. 253(3), 191–197 (2014).
[Crossref] [PubMed]

Ansorge, R. E.

C. E. Hooper, R. E. Ansorge, H. M. Browne, and P. Tomkins, “CCD imaging of luciferase gene expression in single mammalian cells,” J. Biolumin. Chemilumin. 5(2), 123–130 (1990).
[Crossref] [PubMed]

Antich, P. P.

A. P. Feranchak, M. A. Lewis, C. Kresge, M. Sathe, A. Bugde, K. Luby-Phelps, P. P. Antich, and J. G. Fitz, “Initiation of purinergic signaling by exocytosis of ATP-containing vesicles in liver epithelium,” J. Biol. Chem. 285(11), 8138–8147 (2010).
[Crossref] [PubMed]

Audet, M.

V. Coulon, M. Audet, V. Homburger, J. Bockaert, L. Fagni, M. Bouvier, and J. Perroy, “Subcellular imaging of dynamic protein interactions by bioluminescence resonance energy transfer,” Biophys. J. 94(3), 1001–1009 (2008).
[Crossref] [PubMed]

Axente, M.

G. Pratx, K. Chen, C. Sun, M. Axente, L. Sasportas, C. Carpenter, and L. Xing, “High-Resolution Radioluminescence Microscopy of 18F-FDG Uptake by Reconstructing the β-Ionization Track,” J. Nucl. Med. 54(10), 1841–1846 (2013).
[Crossref] [PubMed]

Badr, C. E.

C. E. Badr and B. A. Tannous, “Bioluminescence imaging: progress and applications,” Trends Biotechnol. 29(12), 624–633 (2011).
[Crossref] [PubMed]

Baraldini, M.

A. Roda, P. Pasini, M. Guardigli, M. Baraldini, M. Musiani, and M. Mirasoli, “Bio- and chemiluminescence in bioanalysis,” Fresenius J. Anal. Chem. 366(6-7), 752–759 (2000).
[Crossref] [PubMed]

Barber, H. B.

B. W. Miller, H. B. Barber, H. H. Barrett, Z. Liu, V. V. Nagarkar, and L. R. Furenlid, “Progress in BazookaSPECT: high-resolution dynamic scintigraphy with large-area imagers,” Proc. SPIE 8508, 85080F (2012).
[Crossref] [PubMed]

B. W. Miller, H. B. Barber, H. H. Barrett, L. Chen, and S. J. Taylor, “Photon-counting gamma camera based on columnar CsI(Tl) optically coupled to a back-illuminated CCD,” Proc. SPIE 6510, 65100N (2007).
[Crossref] [PubMed]

Barrett, H. H.

B. W. Miller, H. B. Barber, H. H. Barrett, Z. Liu, V. V. Nagarkar, and L. R. Furenlid, “Progress in BazookaSPECT: high-resolution dynamic scintigraphy with large-area imagers,” Proc. SPIE 8508, 85080F (2012).
[Crossref] [PubMed]

B. W. Miller, H. B. Barber, H. H. Barrett, L. Chen, and S. J. Taylor, “Photon-counting gamma camera based on columnar CsI(Tl) optically coupled to a back-illuminated CCD,” Proc. SPIE 6510, 65100N (2007).
[Crossref] [PubMed]

Benaron, D. A.

C. H. Contag, S. D. Spilman, P. R. Contag, M. Oshiro, B. Eames, P. Dennery, D. K. Stevenson, and D. A. Benaron, “Visualizing gene expression in living mammals using a bioluminescent reporter,” Photochem. Photobiol. 66(4), 523–531 (1997).
[Crossref] [PubMed]

Bockaert, J.

V. Coulon, M. Audet, V. Homburger, J. Bockaert, L. Fagni, M. Bouvier, and J. Perroy, “Subcellular imaging of dynamic protein interactions by bioluminescence resonance energy transfer,” Biophys. J. 94(3), 1001–1009 (2008).
[Crossref] [PubMed]

Bouvier, M.

V. Coulon, M. Audet, V. Homburger, J. Bockaert, L. Fagni, M. Bouvier, and J. Perroy, “Subcellular imaging of dynamic protein interactions by bioluminescence resonance energy transfer,” Biophys. J. 94(3), 1001–1009 (2008).
[Crossref] [PubMed]

Broda, H.

H. Broda, V. D. Gooch, W. Taylor, N. Aiuto, and J. W. Hastings, “Acquisition of circadian bioluminescence data in Gonyaulax and an effect of the measurement procedure on the period of the rhythm,” J. Biol. Rhythms 1(3), 251–263 (1986).
[Crossref] [PubMed]

Browne, H. M.

C. E. Hooper, R. E. Ansorge, H. M. Browne, and P. Tomkins, “CCD imaging of luciferase gene expression in single mammalian cells,” J. Biolumin. Chemilumin. 5(2), 123–130 (1990).
[Crossref] [PubMed]

Bugde, A.

A. P. Feranchak, M. A. Lewis, C. Kresge, M. Sathe, A. Bugde, K. Luby-Phelps, P. P. Antich, and J. G. Fitz, “Initiation of purinergic signaling by exocytosis of ATP-containing vesicles in liver epithelium,” J. Biol. Chem. 285(11), 8138–8147 (2010).
[Crossref] [PubMed]

Carpenter, C.

G. Pratx, K. Chen, C. Sun, M. Axente, L. Sasportas, C. Carpenter, and L. Xing, “High-Resolution Radioluminescence Microscopy of 18F-FDG Uptake by Reconstructing the β-Ionization Track,” J. Nucl. Med. 54(10), 1841–1846 (2013).
[Crossref] [PubMed]

Carpenter, C. M.

G. Pratx, K. Chen, C. Sun, L. Martin, C. M. Carpenter, P. D. Olcott, and L. Xing, “Radioluminescence microscopy: measuring the heterogeneous uptake of radiotracers in single living cells,” PLoS One 7(10), e46285 (2012).
[Crossref] [PubMed]

Chen, K.

G. Pratx, K. Chen, C. Sun, M. Axente, L. Sasportas, C. Carpenter, and L. Xing, “High-Resolution Radioluminescence Microscopy of 18F-FDG Uptake by Reconstructing the β-Ionization Track,” J. Nucl. Med. 54(10), 1841–1846 (2013).
[Crossref] [PubMed]

G. Pratx, K. Chen, C. Sun, L. Martin, C. M. Carpenter, P. D. Olcott, and L. Xing, “Radioluminescence microscopy: measuring the heterogeneous uptake of radiotracers in single living cells,” PLoS One 7(10), e46285 (2012).
[Crossref] [PubMed]

Chen, L.

B. W. Miller, H. B. Barber, H. H. Barrett, L. Chen, and S. J. Taylor, “Photon-counting gamma camera based on columnar CsI(Tl) optically coupled to a back-illuminated CCD,” Proc. SPIE 6510, 65100N (2007).
[Crossref] [PubMed]

Chin, F.

D. Sengupta, S. Miller, Z. Marton, F. Chin, V. Nagarkar, and G. Pratx, “Bright Lu2 O3 :Eu thin-film scintillators for high-resolution radioluminescence microscopy,” Adv. Healthc. Mater. 4(14), 2064–2070 (2015).
[Crossref] [PubMed]

Contag, C. H.

C. H. Contag, S. D. Spilman, P. R. Contag, M. Oshiro, B. Eames, P. Dennery, D. K. Stevenson, and D. A. Benaron, “Visualizing gene expression in living mammals using a bioluminescent reporter,” Photochem. Photobiol. 66(4), 523–531 (1997).
[Crossref] [PubMed]

Contag, P. R.

C. H. Contag, S. D. Spilman, P. R. Contag, M. Oshiro, B. Eames, P. Dennery, D. K. Stevenson, and D. A. Benaron, “Visualizing gene expression in living mammals using a bioluminescent reporter,” Photochem. Photobiol. 66(4), 523–531 (1997).
[Crossref] [PubMed]

Coulon, V.

V. Coulon, M. Audet, V. Homburger, J. Bockaert, L. Fagni, M. Bouvier, and J. Perroy, “Subcellular imaging of dynamic protein interactions by bioluminescence resonance energy transfer,” Biophys. J. 94(3), 1001–1009 (2008).
[Crossref] [PubMed]

Dennery, P.

C. H. Contag, S. D. Spilman, P. R. Contag, M. Oshiro, B. Eames, P. Dennery, D. K. Stevenson, and D. A. Benaron, “Visualizing gene expression in living mammals using a bioluminescent reporter,” Photochem. Photobiol. 66(4), 523–531 (1997).
[Crossref] [PubMed]

Dosaka, Y.

K. Ogoh, R. Akiyoshi, T. May-Maw-Thet, S. Sugiyama, Y. Dosaka, Y. Hatta-Ohashi, and H. Suzuki, “Bioluminescence microscopy using a short focal-length imaging lens,” J. Microsc. 253(3), 191–197 (2014).
[Crossref] [PubMed]

Eames, B.

C. H. Contag, S. D. Spilman, P. R. Contag, M. Oshiro, B. Eames, P. Dennery, D. K. Stevenson, and D. A. Benaron, “Visualizing gene expression in living mammals using a bioluminescent reporter,” Photochem. Photobiol. 66(4), 523–531 (1997).
[Crossref] [PubMed]

Fagni, L.

V. Coulon, M. Audet, V. Homburger, J. Bockaert, L. Fagni, M. Bouvier, and J. Perroy, “Subcellular imaging of dynamic protein interactions by bioluminescence resonance energy transfer,” Biophys. J. 94(3), 1001–1009 (2008).
[Crossref] [PubMed]

Fan, F.

F. Fan and K. V. Wood, “Bioluminescent assays for high-throughput screening,” Assay Drug Dev. Technol. 5(1), 127–136 (2007).
[Crossref] [PubMed]

Feranchak, A. P.

A. P. Feranchak, M. A. Lewis, C. Kresge, M. Sathe, A. Bugde, K. Luby-Phelps, P. P. Antich, and J. G. Fitz, “Initiation of purinergic signaling by exocytosis of ATP-containing vesicles in liver epithelium,” J. Biol. Chem. 285(11), 8138–8147 (2010).
[Crossref] [PubMed]

Fitz, J. G.

A. P. Feranchak, M. A. Lewis, C. Kresge, M. Sathe, A. Bugde, K. Luby-Phelps, P. P. Antich, and J. G. Fitz, “Initiation of purinergic signaling by exocytosis of ATP-containing vesicles in liver epithelium,” J. Biol. Chem. 285(11), 8138–8147 (2010).
[Crossref] [PubMed]

Furenlid, L. R.

B. W. Miller, H. B. Barber, H. H. Barrett, Z. Liu, V. V. Nagarkar, and L. R. Furenlid, “Progress in BazookaSPECT: high-resolution dynamic scintigraphy with large-area imagers,” Proc. SPIE 8508, 85080F (2012).
[Crossref] [PubMed]

Gambhir, S. S.

T. F. Massoud and S. S. Gambhir, “Molecular imaging in living subjects: seeing fundamental biological processes in a new light,” Genes Dev. 17(5), 545–580 (2003).
[Crossref] [PubMed]

Gibson, Q. H.

J. W. Hastings and Q. H. Gibson, “Intermediates in the bioluminescent oxidation of reduced flavin mononucleotide,” J. Biol. Chem. 238(7), 2537–2554 (1963).
[PubMed]

Goda, K.

K. Goda, Y. Hatta-Ohashi, R. Akiyoshi, T. Sugiyama, I. Sakai, T. Takahashi, and H. Suzuki, “Combining fluorescence and bioluminescence microscopy,” Microsc. Res. Tech. 78(8), 715–722 (2015).
[Crossref] [PubMed]

Gooch, V. D.

H. Broda, V. D. Gooch, W. Taylor, N. Aiuto, and J. W. Hastings, “Acquisition of circadian bioluminescence data in Gonyaulax and an effect of the measurement procedure on the period of the rhythm,” J. Biol. Rhythms 1(3), 251–263 (1986).
[Crossref] [PubMed]

Goossens, K.

D. Lambrechts, M. Roeffaers, K. Goossens, J. Hofkens, G. Vande Velde, T. Van de Putte, J. Schrooten, and H. Van Oosterwyck, “A causal relation between bioluminescence and oxygen to quantify the cell niche,” PLoS One 9(5), e97572 (2014).
[Crossref] [PubMed]

Greer, L. F.

L. F. Greer and A. A. Szalay, “Imaging of light emission from the expression of luciferases in living cells and organisms: a review,” Luminescence 17(1), 43–74 (2002).
[Crossref] [PubMed]

Guardigli, M.

A. Roda, M. Guardigli, P. Pasini, M. Mirasoli, E. Michelini, and M. Musiani, “Bio-and chemiluminescence imaging in analytical chemistry,” Anal. Chim. Acta 541(1), 25–35 (2005).
[Crossref]

A. Roda, P. Pasini, M. Guardigli, M. Baraldini, M. Musiani, and M. Mirasoli, “Bio- and chemiluminescence in bioanalysis,” Fresenius J. Anal. Chem. 366(6-7), 752–759 (2000).
[Crossref] [PubMed]

Hann, S.

T. J. Kim, M. Kim, S. Hann, J. Trejo, and C. H. Hidrovo, “Thermal Characterization of Microheated Microchannels With Spatially Resolved Two-Color Fluorescence Thermometry,” J. Microelectromech. Syst. 24(1), 115–125 (2015).
[Crossref]

Hastings, J. W.

H. Broda, V. D. Gooch, W. Taylor, N. Aiuto, and J. W. Hastings, “Acquisition of circadian bioluminescence data in Gonyaulax and an effect of the measurement procedure on the period of the rhythm,” J. Biol. Rhythms 1(3), 251–263 (1986).
[Crossref] [PubMed]

J. W. Hastings and Q. H. Gibson, “Intermediates in the bioluminescent oxidation of reduced flavin mononucleotide,” J. Biol. Chem. 238(7), 2537–2554 (1963).
[PubMed]

Hatta-Ohashi, Y.

K. Goda, Y. Hatta-Ohashi, R. Akiyoshi, T. Sugiyama, I. Sakai, T. Takahashi, and H. Suzuki, “Combining fluorescence and bioluminescence microscopy,” Microsc. Res. Tech. 78(8), 715–722 (2015).
[Crossref] [PubMed]

K. Ogoh, R. Akiyoshi, T. May-Maw-Thet, S. Sugiyama, Y. Dosaka, Y. Hatta-Ohashi, and H. Suzuki, “Bioluminescence microscopy using a short focal-length imaging lens,” J. Microsc. 253(3), 191–197 (2014).
[Crossref] [PubMed]

Hidrovo, C. H.

T. J. Kim, M. Kim, S. Hann, J. Trejo, and C. H. Hidrovo, “Thermal Characterization of Microheated Microchannels With Spatially Resolved Two-Color Fluorescence Thermometry,” J. Microelectromech. Syst. 24(1), 115–125 (2015).
[Crossref]

Hofkens, J.

D. Lambrechts, M. Roeffaers, K. Goossens, J. Hofkens, G. Vande Velde, T. Van de Putte, J. Schrooten, and H. Van Oosterwyck, “A causal relation between bioluminescence and oxygen to quantify the cell niche,” PLoS One 9(5), e97572 (2014).
[Crossref] [PubMed]

Homburger, V.

V. Coulon, M. Audet, V. Homburger, J. Bockaert, L. Fagni, M. Bouvier, and J. Perroy, “Subcellular imaging of dynamic protein interactions by bioluminescence resonance energy transfer,” Biophys. J. 94(3), 1001–1009 (2008).
[Crossref] [PubMed]

Hooper, C. E.

C. E. Hooper, R. E. Ansorge, H. M. Browne, and P. Tomkins, “CCD imaging of luciferase gene expression in single mammalian cells,” J. Biolumin. Chemilumin. 5(2), 123–130 (1990).
[Crossref] [PubMed]

Kaneuch, T.

R. Akiyoshi, T. Kaneuch, T. Aigaki, and H. Suzuki, “Bioluminescence imaging to track real-time armadillo promoter activity in live Drosophila embryos,” Anal. Bioanal. Chem. 406(23), 5703–5713 (2014).
[Crossref] [PubMed]

Kim, M.

T. J. Kim, M. Kim, S. Hann, J. Trejo, and C. H. Hidrovo, “Thermal Characterization of Microheated Microchannels With Spatially Resolved Two-Color Fluorescence Thermometry,” J. Microelectromech. Syst. 24(1), 115–125 (2015).
[Crossref]

Kim, T. J.

T. J. Kim, M. Kim, S. Hann, J. Trejo, and C. H. Hidrovo, “Thermal Characterization of Microheated Microchannels With Spatially Resolved Two-Color Fluorescence Thermometry,” J. Microelectromech. Syst. 24(1), 115–125 (2015).
[Crossref]

Kresge, C.

A. P. Feranchak, M. A. Lewis, C. Kresge, M. Sathe, A. Bugde, K. Luby-Phelps, P. P. Antich, and J. G. Fitz, “Initiation of purinergic signaling by exocytosis of ATP-containing vesicles in liver epithelium,” J. Biol. Chem. 285(11), 8138–8147 (2010).
[Crossref] [PubMed]

Lambrechts, D.

D. Lambrechts, M. Roeffaers, K. Goossens, J. Hofkens, G. Vande Velde, T. Van de Putte, J. Schrooten, and H. Van Oosterwyck, “A causal relation between bioluminescence and oxygen to quantify the cell niche,” PLoS One 9(5), e97572 (2014).
[Crossref] [PubMed]

Laustriat, G.

G. Laustriat, “The luminescence decay of organic scintillators,” Mol. Cryst. 4(1–4), 127–145 (1968).
[Crossref]

Lewis, M. A.

A. P. Feranchak, M. A. Lewis, C. Kresge, M. Sathe, A. Bugde, K. Luby-Phelps, P. P. Antich, and J. G. Fitz, “Initiation of purinergic signaling by exocytosis of ATP-containing vesicles in liver epithelium,” J. Biol. Chem. 285(11), 8138–8147 (2010).
[Crossref] [PubMed]

Liu, Z.

B. W. Miller, H. B. Barber, H. H. Barrett, Z. Liu, V. V. Nagarkar, and L. R. Furenlid, “Progress in BazookaSPECT: high-resolution dynamic scintigraphy with large-area imagers,” Proc. SPIE 8508, 85080F (2012).
[Crossref] [PubMed]

Luby-Phelps, K.

A. P. Feranchak, M. A. Lewis, C. Kresge, M. Sathe, A. Bugde, K. Luby-Phelps, P. P. Antich, and J. G. Fitz, “Initiation of purinergic signaling by exocytosis of ATP-containing vesicles in liver epithelium,” J. Biol. Chem. 285(11), 8138–8147 (2010).
[Crossref] [PubMed]

Martin, L.

G. Pratx, K. Chen, C. Sun, L. Martin, C. M. Carpenter, P. D. Olcott, and L. Xing, “Radioluminescence microscopy: measuring the heterogeneous uptake of radiotracers in single living cells,” PLoS One 7(10), e46285 (2012).
[Crossref] [PubMed]

Marton, Z.

D. Sengupta, S. Miller, Z. Marton, F. Chin, V. Nagarkar, and G. Pratx, “Bright Lu2 O3 :Eu thin-film scintillators for high-resolution radioluminescence microscopy,” Adv. Healthc. Mater. 4(14), 2064–2070 (2015).
[Crossref] [PubMed]

Massoud, T. F.

T. F. Massoud and S. S. Gambhir, “Molecular imaging in living subjects: seeing fundamental biological processes in a new light,” Genes Dev. 17(5), 545–580 (2003).
[Crossref] [PubMed]

May-Maw-Thet, T.

K. Ogoh, R. Akiyoshi, T. May-Maw-Thet, S. Sugiyama, Y. Dosaka, Y. Hatta-Ohashi, and H. Suzuki, “Bioluminescence microscopy using a short focal-length imaging lens,” J. Microsc. 253(3), 191–197 (2014).
[Crossref] [PubMed]

Meinhart, C. D.

C. D. Meinhart and S. T. Wereley, “The theory of diffraction-limited resolution in microparticle image velocimetry,” Meas. Sci. Technol. 14(7), 1047–1053 (2003).
[Crossref]

Michelini, E.

A. Roda, M. Guardigli, P. Pasini, M. Mirasoli, E. Michelini, and M. Musiani, “Bio-and chemiluminescence imaging in analytical chemistry,” Anal. Chim. Acta 541(1), 25–35 (2005).
[Crossref]

Miller, B. W.

B. W. Miller, H. B. Barber, H. H. Barrett, Z. Liu, V. V. Nagarkar, and L. R. Furenlid, “Progress in BazookaSPECT: high-resolution dynamic scintigraphy with large-area imagers,” Proc. SPIE 8508, 85080F (2012).
[Crossref] [PubMed]

B. W. Miller, H. B. Barber, H. H. Barrett, L. Chen, and S. J. Taylor, “Photon-counting gamma camera based on columnar CsI(Tl) optically coupled to a back-illuminated CCD,” Proc. SPIE 6510, 65100N (2007).
[Crossref] [PubMed]

Miller, S.

D. Sengupta, S. Miller, Z. Marton, F. Chin, V. Nagarkar, and G. Pratx, “Bright Lu2 O3 :Eu thin-film scintillators for high-resolution radioluminescence microscopy,” Adv. Healthc. Mater. 4(14), 2064–2070 (2015).
[Crossref] [PubMed]

Mirasoli, M.

A. Roda, M. Guardigli, P. Pasini, M. Mirasoli, E. Michelini, and M. Musiani, “Bio-and chemiluminescence imaging in analytical chemistry,” Anal. Chim. Acta 541(1), 25–35 (2005).
[Crossref]

A. Roda, P. Pasini, M. Guardigli, M. Baraldini, M. Musiani, and M. Mirasoli, “Bio- and chemiluminescence in bioanalysis,” Fresenius J. Anal. Chem. 366(6-7), 752–759 (2000).
[Crossref] [PubMed]

Musiani, M.

A. Roda, M. Guardigli, P. Pasini, M. Mirasoli, E. Michelini, and M. Musiani, “Bio-and chemiluminescence imaging in analytical chemistry,” Anal. Chim. Acta 541(1), 25–35 (2005).
[Crossref]

A. Roda, P. Pasini, M. Guardigli, M. Baraldini, M. Musiani, and M. Mirasoli, “Bio- and chemiluminescence in bioanalysis,” Fresenius J. Anal. Chem. 366(6-7), 752–759 (2000).
[Crossref] [PubMed]

Muzzey, D.

D. Muzzey and A. van Oudenaarden, “Quantitative time-lapse fluorescence microscopy in single cells,” Annu. Rev. Cell Dev. Biol. 25(1), 301–327 (2009).
[Crossref] [PubMed]

Nagarkar, V.

D. Sengupta, S. Miller, Z. Marton, F. Chin, V. Nagarkar, and G. Pratx, “Bright Lu2 O3 :Eu thin-film scintillators for high-resolution radioluminescence microscopy,” Adv. Healthc. Mater. 4(14), 2064–2070 (2015).
[Crossref] [PubMed]

Nagarkar, V. V.

B. W. Miller, H. B. Barber, H. H. Barrett, Z. Liu, V. V. Nagarkar, and L. R. Furenlid, “Progress in BazookaSPECT: high-resolution dynamic scintigraphy with large-area imagers,” Proc. SPIE 8508, 85080F (2012).
[Crossref] [PubMed]

Noguchi, T.

D. K. Welsh and T. Noguchi, “Cellular bioluminescence imaging,” Cold Spring Harb. Protoc. 2012(8), 070607 (2012).
[Crossref] [PubMed]

Ntziachristos, V.

R. Weissleder and V. Ntziachristos, “Shedding light onto live molecular targets,” Nat. Med. 9(1), 123–128 (2003).
[Crossref] [PubMed]

Ogoh, K.

K. Ogoh, R. Akiyoshi, T. May-Maw-Thet, S. Sugiyama, Y. Dosaka, Y. Hatta-Ohashi, and H. Suzuki, “Bioluminescence microscopy using a short focal-length imaging lens,” J. Microsc. 253(3), 191–197 (2014).
[Crossref] [PubMed]

Olcott, P. D.

G. Pratx, K. Chen, C. Sun, L. Martin, C. M. Carpenter, P. D. Olcott, and L. Xing, “Radioluminescence microscopy: measuring the heterogeneous uptake of radiotracers in single living cells,” PLoS One 7(10), e46285 (2012).
[Crossref] [PubMed]

Oshiro, M.

C. H. Contag, S. D. Spilman, P. R. Contag, M. Oshiro, B. Eames, P. Dennery, D. K. Stevenson, and D. A. Benaron, “Visualizing gene expression in living mammals using a bioluminescent reporter,” Photochem. Photobiol. 66(4), 523–531 (1997).
[Crossref] [PubMed]

Pasini, P.

A. Roda, M. Guardigli, P. Pasini, M. Mirasoli, E. Michelini, and M. Musiani, “Bio-and chemiluminescence imaging in analytical chemistry,” Anal. Chim. Acta 541(1), 25–35 (2005).
[Crossref]

A. Roda, P. Pasini, M. Guardigli, M. Baraldini, M. Musiani, and M. Mirasoli, “Bio- and chemiluminescence in bioanalysis,” Fresenius J. Anal. Chem. 366(6-7), 752–759 (2000).
[Crossref] [PubMed]

Perroy, J.

V. Coulon, M. Audet, V. Homburger, J. Bockaert, L. Fagni, M. Bouvier, and J. Perroy, “Subcellular imaging of dynamic protein interactions by bioluminescence resonance energy transfer,” Biophys. J. 94(3), 1001–1009 (2008).
[Crossref] [PubMed]

Piston, D. W.

D. W. Piston, “Choosing objective lenses: the importance of numerical aperture and magnification in digital optical microscopy,” Biol. Bull. 195(1), 1–4 (1998).
[Crossref] [PubMed]

Pratx, G.

D. Sengupta, S. Miller, Z. Marton, F. Chin, V. Nagarkar, and G. Pratx, “Bright Lu2 O3 :Eu thin-film scintillators for high-resolution radioluminescence microscopy,” Adv. Healthc. Mater. 4(14), 2064–2070 (2015).
[Crossref] [PubMed]

G. Pratx, K. Chen, C. Sun, M. Axente, L. Sasportas, C. Carpenter, and L. Xing, “High-Resolution Radioluminescence Microscopy of 18F-FDG Uptake by Reconstructing the β-Ionization Track,” J. Nucl. Med. 54(10), 1841–1846 (2013).
[Crossref] [PubMed]

G. Pratx, K. Chen, C. Sun, L. Martin, C. M. Carpenter, P. D. Olcott, and L. Xing, “Radioluminescence microscopy: measuring the heterogeneous uptake of radiotracers in single living cells,” PLoS One 7(10), e46285 (2012).
[Crossref] [PubMed]

Reynolds, G.

G. Reynolds and D. Taylor, “Image intensification applied to light microscopy,” Bioscience 30(9), 586–592 (1980).
[Crossref]

Roda, A.

A. Roda, M. Guardigli, P. Pasini, M. Mirasoli, E. Michelini, and M. Musiani, “Bio-and chemiluminescence imaging in analytical chemistry,” Anal. Chim. Acta 541(1), 25–35 (2005).
[Crossref]

A. Roda, P. Pasini, M. Guardigli, M. Baraldini, M. Musiani, and M. Mirasoli, “Bio- and chemiluminescence in bioanalysis,” Fresenius J. Anal. Chem. 366(6-7), 752–759 (2000).
[Crossref] [PubMed]

Roeffaers, M.

D. Lambrechts, M. Roeffaers, K. Goossens, J. Hofkens, G. Vande Velde, T. Van de Putte, J. Schrooten, and H. Van Oosterwyck, “A causal relation between bioluminescence and oxygen to quantify the cell niche,” PLoS One 9(5), e97572 (2014).
[Crossref] [PubMed]

Sakai, I.

K. Goda, Y. Hatta-Ohashi, R. Akiyoshi, T. Sugiyama, I. Sakai, T. Takahashi, and H. Suzuki, “Combining fluorescence and bioluminescence microscopy,” Microsc. Res. Tech. 78(8), 715–722 (2015).
[Crossref] [PubMed]

Sasportas, L.

G. Pratx, K. Chen, C. Sun, M. Axente, L. Sasportas, C. Carpenter, and L. Xing, “High-Resolution Radioluminescence Microscopy of 18F-FDG Uptake by Reconstructing the β-Ionization Track,” J. Nucl. Med. 54(10), 1841–1846 (2013).
[Crossref] [PubMed]

Sathe, M.

A. P. Feranchak, M. A. Lewis, C. Kresge, M. Sathe, A. Bugde, K. Luby-Phelps, P. P. Antich, and J. G. Fitz, “Initiation of purinergic signaling by exocytosis of ATP-containing vesicles in liver epithelium,” J. Biol. Chem. 285(11), 8138–8147 (2010).
[Crossref] [PubMed]

Schrooten, J.

D. Lambrechts, M. Roeffaers, K. Goossens, J. Hofkens, G. Vande Velde, T. Van de Putte, J. Schrooten, and H. Van Oosterwyck, “A causal relation between bioluminescence and oxygen to quantify the cell niche,” PLoS One 9(5), e97572 (2014).
[Crossref] [PubMed]

Sengupta, D.

D. Sengupta, S. Miller, Z. Marton, F. Chin, V. Nagarkar, and G. Pratx, “Bright Lu2 O3 :Eu thin-film scintillators for high-resolution radioluminescence microscopy,” Adv. Healthc. Mater. 4(14), 2064–2070 (2015).
[Crossref] [PubMed]

Spilman, S. D.

C. H. Contag, S. D. Spilman, P. R. Contag, M. Oshiro, B. Eames, P. Dennery, D. K. Stevenson, and D. A. Benaron, “Visualizing gene expression in living mammals using a bioluminescent reporter,” Photochem. Photobiol. 66(4), 523–531 (1997).
[Crossref] [PubMed]

Stevenson, D. K.

C. H. Contag, S. D. Spilman, P. R. Contag, M. Oshiro, B. Eames, P. Dennery, D. K. Stevenson, and D. A. Benaron, “Visualizing gene expression in living mammals using a bioluminescent reporter,” Photochem. Photobiol. 66(4), 523–531 (1997).
[Crossref] [PubMed]

Sugiyama, S.

K. Ogoh, R. Akiyoshi, T. May-Maw-Thet, S. Sugiyama, Y. Dosaka, Y. Hatta-Ohashi, and H. Suzuki, “Bioluminescence microscopy using a short focal-length imaging lens,” J. Microsc. 253(3), 191–197 (2014).
[Crossref] [PubMed]

Sugiyama, T.

K. Goda, Y. Hatta-Ohashi, R. Akiyoshi, T. Sugiyama, I. Sakai, T. Takahashi, and H. Suzuki, “Combining fluorescence and bioluminescence microscopy,” Microsc. Res. Tech. 78(8), 715–722 (2015).
[Crossref] [PubMed]

Sun, C.

G. Pratx, K. Chen, C. Sun, M. Axente, L. Sasportas, C. Carpenter, and L. Xing, “High-Resolution Radioluminescence Microscopy of 18F-FDG Uptake by Reconstructing the β-Ionization Track,” J. Nucl. Med. 54(10), 1841–1846 (2013).
[Crossref] [PubMed]

G. Pratx, K. Chen, C. Sun, L. Martin, C. M. Carpenter, P. D. Olcott, and L. Xing, “Radioluminescence microscopy: measuring the heterogeneous uptake of radiotracers in single living cells,” PLoS One 7(10), e46285 (2012).
[Crossref] [PubMed]

Suzuki, H.

K. Goda, Y. Hatta-Ohashi, R. Akiyoshi, T. Sugiyama, I. Sakai, T. Takahashi, and H. Suzuki, “Combining fluorescence and bioluminescence microscopy,” Microsc. Res. Tech. 78(8), 715–722 (2015).
[Crossref] [PubMed]

R. Akiyoshi, T. Kaneuch, T. Aigaki, and H. Suzuki, “Bioluminescence imaging to track real-time armadillo promoter activity in live Drosophila embryos,” Anal. Bioanal. Chem. 406(23), 5703–5713 (2014).
[Crossref] [PubMed]

K. Ogoh, R. Akiyoshi, T. May-Maw-Thet, S. Sugiyama, Y. Dosaka, Y. Hatta-Ohashi, and H. Suzuki, “Bioluminescence microscopy using a short focal-length imaging lens,” J. Microsc. 253(3), 191–197 (2014).
[Crossref] [PubMed]

Szalay, A. A.

L. F. Greer and A. A. Szalay, “Imaging of light emission from the expression of luciferases in living cells and organisms: a review,” Luminescence 17(1), 43–74 (2002).
[Crossref] [PubMed]

Takahashi, T.

K. Goda, Y. Hatta-Ohashi, R. Akiyoshi, T. Sugiyama, I. Sakai, T. Takahashi, and H. Suzuki, “Combining fluorescence and bioluminescence microscopy,” Microsc. Res. Tech. 78(8), 715–722 (2015).
[Crossref] [PubMed]

Tannous, B. A.

C. E. Badr and B. A. Tannous, “Bioluminescence imaging: progress and applications,” Trends Biotechnol. 29(12), 624–633 (2011).
[Crossref] [PubMed]

Taylor, D.

G. Reynolds and D. Taylor, “Image intensification applied to light microscopy,” Bioscience 30(9), 586–592 (1980).
[Crossref]

Taylor, S. J.

B. W. Miller, H. B. Barber, H. H. Barrett, L. Chen, and S. J. Taylor, “Photon-counting gamma camera based on columnar CsI(Tl) optically coupled to a back-illuminated CCD,” Proc. SPIE 6510, 65100N (2007).
[Crossref] [PubMed]

Taylor, W.

H. Broda, V. D. Gooch, W. Taylor, N. Aiuto, and J. W. Hastings, “Acquisition of circadian bioluminescence data in Gonyaulax and an effect of the measurement procedure on the period of the rhythm,” J. Biol. Rhythms 1(3), 251–263 (1986).
[Crossref] [PubMed]

Tomkins, P.

C. E. Hooper, R. E. Ansorge, H. M. Browne, and P. Tomkins, “CCD imaging of luciferase gene expression in single mammalian cells,” J. Biolumin. Chemilumin. 5(2), 123–130 (1990).
[Crossref] [PubMed]

Trejo, J.

T. J. Kim, M. Kim, S. Hann, J. Trejo, and C. H. Hidrovo, “Thermal Characterization of Microheated Microchannels With Spatially Resolved Two-Color Fluorescence Thermometry,” J. Microelectromech. Syst. 24(1), 115–125 (2015).
[Crossref]

Van de Putte, T.

D. Lambrechts, M. Roeffaers, K. Goossens, J. Hofkens, G. Vande Velde, T. Van de Putte, J. Schrooten, and H. Van Oosterwyck, “A causal relation between bioluminescence and oxygen to quantify the cell niche,” PLoS One 9(5), e97572 (2014).
[Crossref] [PubMed]

Van Oosterwyck, H.

D. Lambrechts, M. Roeffaers, K. Goossens, J. Hofkens, G. Vande Velde, T. Van de Putte, J. Schrooten, and H. Van Oosterwyck, “A causal relation between bioluminescence and oxygen to quantify the cell niche,” PLoS One 9(5), e97572 (2014).
[Crossref] [PubMed]

van Oudenaarden, A.

D. Muzzey and A. van Oudenaarden, “Quantitative time-lapse fluorescence microscopy in single cells,” Annu. Rev. Cell Dev. Biol. 25(1), 301–327 (2009).
[Crossref] [PubMed]

Vande Velde, G.

D. Lambrechts, M. Roeffaers, K. Goossens, J. Hofkens, G. Vande Velde, T. Van de Putte, J. Schrooten, and H. Van Oosterwyck, “A causal relation between bioluminescence and oxygen to quantify the cell niche,” PLoS One 9(5), e97572 (2014).
[Crossref] [PubMed]

Weissleder, R.

R. Weissleder and V. Ntziachristos, “Shedding light onto live molecular targets,” Nat. Med. 9(1), 123–128 (2003).
[Crossref] [PubMed]

Welsh, D. K.

D. K. Welsh and T. Noguchi, “Cellular bioluminescence imaging,” Cold Spring Harb. Protoc. 2012(8), 070607 (2012).
[Crossref] [PubMed]

Wereley, S. T.

C. D. Meinhart and S. T. Wereley, “The theory of diffraction-limited resolution in microparticle image velocimetry,” Meas. Sci. Technol. 14(7), 1047–1053 (2003).
[Crossref]

Wood, K. V.

F. Fan and K. V. Wood, “Bioluminescent assays for high-throughput screening,” Assay Drug Dev. Technol. 5(1), 127–136 (2007).
[Crossref] [PubMed]

Xing, L.

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Figures (9)

Fig. 1
Fig. 1 (a) Schematic diagram of a typical ininity-corrected system and (b) graphical representation of Eq. (2b). The solid line represents the value of the f = 50mm, NA = 0.2 tube lens (Nikon λ 4 × objective) and the dotted line represents f·NA of the f = 36mm, NA = 0.2 lens (LV200 tube lens).
Fig. 2
Fig. 2 Schematic diagram of the low-light luminescence microscope (LLM) setup. The microscope can capture three distinct types of images: (a) low-excitation fluorescence imaging if dichroic mirror is inserted, (b) bioluminescence imaging if dichroic mirror is removed and (c) radioluminescence imaging if scintillating crystal is placed above cell during bioluminescence mode.
Fig. 3
Fig. 3 Schematic diagram depicting the reduction in effective NA of an objective lens coupled to tube lens with a small pupil diameter.
Fig. 4
Fig. 4 Comparison of image brightness with different microscope lens and tube lens manufacturer combinations based on Eq. (1). The tube lens specifications used for the LV200 (or LLM36) is f = 36mm and NA = 0.2 and for the LLM50 (Nikon λ 4 × lens) is f = 50mm and NA = 0.2. The square symbols (■,□) represent the magnification with the standard commercial microscopes for Olympus and Nikon, respectively (4 × , 10 × and 20 × ). Since the tube lens focal length for the Nikon λ is longer than the LV200 tube lens, the LLM50 has a higher magnification than the LV200 if the same microscope objective is used.
Fig. 5
Fig. 5 (a) Example of raw scintillation image. The individual tracks are evaluated and analyzed throughout the entire image stack. (b) Violin plot of histograms representing number of photons captured with different tube lens – microscope objective combinations. The widths of the violin plot have been normalized to facilitate visual comparison of the brightness performance (actual widths vary as the number of counts increases drastically with lower magnification or greater field of view).
Fig. 6
Fig. 6 Images of target grids captured with Olympus 40 × oil immersion objective lens fitted in (a) LLM50, (b) LLM36 and (c) LV200 system. The images are layered with virtual grids (green lines). Since the EMCCD in the LV200 is 1024 × 1024 pixels, the actual image area is ~2.6 times larger than (a) and (b).
Fig. 7
Fig. 7 Radioluminescence images of MDA-MB-231 cells captured using (a) LLM50, (b) LLM36 and (c) LV200. Red color represents higher radioactive decay from the cells. The top row represents raw scintillation counts and the bottom represents the radioluminescence data smoothed with Gaussian filter and overlaid onto a micrograph of the MDA-MB-231 cells.
Fig. 8
Fig. 8 Bioluminescence image of 4T1 cells using (a) LLM50, (b) LLM36 and (c) LV200. While the cell sizes are highly heterogeneous, the image shows that the LLM50 demonstrates a sharp bioluminescence image. The grayscale bar represents the number of photons per μm2.
Fig. 9
Fig. 9 GFP images of 4T1 cells captured using (a) LLM50 (epiluminescence illumination), (b) LLM36 (epiluminescence illumination) and (b) LV200 (transillumination). Intensity scale optimized for each image separately.

Tables (3)

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Table 1 Comparison chart of the low-light microscope specifications

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Table 2 Numerical aperture evaluation of different microscope objective manufacturers

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Table 3 Effective magnification using a 100 μm × 100 μm square target grid

Equations (8)

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

B= ( NA M effective ) 2 T 10 4 ,
M= f tube f objective ,
( fNA ) tube ( f ( NA/n ) 1 (NA/n) 2 ) objective ,
D tube =2 f tube tan( sin 1 ( N A tube n tube ) ),
N A obj,new = n obj sin( tan 1 ( D tube 2 f obj ) ),
#Photons= C N ( I D ¯ ) G Analog G EM QE ,
B= ( N A 2 M effective ) 2 T 10 4 .
d tot = λn N A 2 + ne MNA .

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