Abstract

Confocal microscopy has several advantages over wide-field microscopy, such as out-of-focus light suppression, 3D sectioning, and compatibility with specialized detectors. While wide-field microscopy is a faster approach, multiplexed confocal schemes can be used to make confocal microscopy more suitable for high-throughput applications, such as high-content screening (HCS) commonly used in drug discovery. An increasingly powerful modality in HCS is fluorescence lifetime imaging microscopy (FLIM), which can be used to measure protein-protein interactions through Förster resonant energy transfer (FRET). FLIM-FRET for HCS combines the requirements of high throughput, high resolution and specialized time-resolving detectors, making it difficult to implement using wide-field and spinning disk confocal approaches. We developed a novel foci array scan method that can achieve uniform multiplex confocal acquisition using stationary lenslet arrays for high resolution and high throughput FLIM. Unlike traditional mirror galvanometers, which work in Fourier space between scan lenses, this scan method uses optical flats to steer a 2-dimension foci array through refraction. After integrating this scanning scheme in a multiplexing confocal FLIM system, we demonstrate it offers clear benefits over traditional mirror galvanometer scanners in scan linearity, uniformity, cost and complexity.

© 2015 Optical Society of America

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References

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2015 (1)

2014 (2)

M. D. Risi, H. Makhlouf, A. R. Rouse, A. A. Tanbakuchi, and A. F. Gmitro, “Design and performance of a multi-point scan confocal microendoscope,” Photonics 1(4), 421–431 (2014).
[Crossref]

F. Gürlitz, P. Hoyer, H. J. Falk, L. Kastrup, J. Engelhardt, and S. W. Hell, “A STED microscope designed for routine biomedical applications,” Prog. Electromagnetics Res. 147, 57–68 (2014).
[Crossref]

2013 (1)

A. Chmyrov, J. Keller, T. Grotjohann, M. Ratz, E. d’Este, S. Jakobs, C. Eggeling, and S. W. Hell, “Nanoscopy with more than 100,000 ‘doughnuts’,” Nat. Methods 10(8), 737–740 (2013).
[Crossref] [PubMed]

2012 (3)

A. Tsikouras, J. Ning, S. Ng, R. Berman, D. W. Andrews, and Q. Fang, “Streak camera crosstalk reduction using a multiple delay optical fiber bundle,” Opt. Lett. 37(2), 250–252 (2012).
[Crossref] [PubMed]

C. Cammi, A. Gulinatti, I. Rech, F. Panzeri, and M. Ghioni, “SPAD array module for multi-dimensional photon timing applications,” J. Mod. Opt. 59(2), 131–139 (2012).
[Crossref]

A. Aranovich, Q. Liu, T. Collins, F. Geng, S. Dixit, B. Leber, and D. W. Andrews, “Differences in the Mechanisms of Proapoptotic BH3 Proteins Binding to Bcl-XL and Bcl-2 Quantified in Live MCF-7 Cells,” Mol. Cell 45(6), 754–763 (2012).
[Crossref] [PubMed]

2010 (1)

M. Bickle, “The beautiful cell: high-content screening in drug discovery,” Anal. Bioanal. Chem. 398(1), 219–226 (2010).
[Crossref] [PubMed]

2008 (2)

D. M. Grant, W. Zhang, E. J. McGhee, T. D. Bunney, C. B. Talbot, S. Kumar, I. Munro, C. Dunsby, M. A. A. Neil, M. Katan, and P. M. W. French, “Multiplexed FRET to image multiple signaling events in live cells,” Biophys. J. 95(10), L69–L71 (2008).
[Crossref] [PubMed]

C. Buranachai, D. Kamiyama, A. Chiba, B. D. Williams, and R. M. Clegg, “Rapid frequency-domain FLIM spinning disk confocal microscope: lifetime resolution, image improvement and wavelet analysis,” J. Fluoresc. 18(5), 929–942 (2008).
[Crossref] [PubMed]

2007 (4)

2006 (2)

P. Lang, K. Yeow, A. Nichols, and A. Scheer, “Cellular imaging in drug discovery,” Nat. Rev. Drug Discov. 5(4), 343–356 (2006).
[Crossref] [PubMed]

L. Liu, J. Qu, Z. Lin, Z. Fu, B. Guo, and H. Niu, “Simultaneous time- and spectrum-resolved multifocal multiphoton microscopy,” Appl. Phys. B 84(3), 379–383 (2006).
[Crossref]

2005 (4)

K. Suhling, P. M. French, and D. Phillips, “Time-resolved fluorescence microscopy,” Photochem. Photobiol. Sci. 4(1), 13–22 (2005).
[Crossref] [PubMed]

S. Wachsmann-Hogiu, D. Krakow, V. T. Kirilova, D. H. Cohn, C. Bertolotto, D. Acuna, Q. Fang, N. Krivorov, and D. L. Farkas, “Multiphoton, confocal, and lifetime microscopy for molecular imaging in cartilage,” Proc. SPIE 5699, 569975 (2005).
[Crossref]

E. Wang, C. M. Babbey, and K. W. Dunn, “Performance comparison between the high-speed Yokogawa spinning disc confocal system and single-point scanning confocal systems,” J. Microsc. 218(2), 148–159 (2005).
[Crossref] [PubMed]

J. Xie, S. Huang, Z. Duan, Y. Shi, and S. Wen, “Correction of the image distortion for laser galvanometric scanning system,” Opt. Laser Technol. 37(4), 305–311 (2005).
[Crossref]

2003 (4)

L. Sacconi, E. Froner, R. Antolini, M. R. Taghizadeh, A. Choudhury, and F. S. Pavone, “Multiphoton multifocal microscopy exploiting a diffractive optical element,” Opt. Lett. 28(20), 1918–1920 (2003).
[Crossref] [PubMed]

W. B. Amos and J. G. White, “How the confocal laser scanning microscope entered biological research,” Biol. Cell 95(6), 335–342 (2003).
[Crossref] [PubMed]

A. V. Agronskaia, L. Tertoolen, and H. C. Gerritsen, “High frame rate fluorescence lifetime imaging,” J. Phys. D Appl. Phys. 36(14), 1655–1662 (2003).
[Crossref]

W. R. Zipfel, R. M. Williams, and W. W. Webb, “Nonlinear magic: multiphoton microscopy in the biosciences,” Nat. Biotechnol. 21(11), 1369–1377 (2003).
[Crossref] [PubMed]

2002 (1)

S. E. Webb, Y. Gu, S. Lévêque-Fort, J. Siegel, M. J. Cole, K. Dowling, R. Jones, P. M. French, M. A. A. Neil, R. Juškaitis, L. O. D. Sucharov, T. Wilson, and M. J. Lever, “A wide-field time-domain fluorescence lifetime imaging microscope with optical sectioning,” Rev. Sci. Instrum. 73(4), 1898–1907 (2002).
[Crossref]

2001 (1)

T. Nielsen, M. Fricke, D. Hellweg, and P. Andresen, “High efficiency beam splitter for multifocal multiphoton microscopy,” J. Microsc. 201(3), 368–376 (2001).
[Crossref] [PubMed]

2000 (1)

M. Straub, P. Lodemann, P. Holroyd, R. Jahn, and S. W. Hell, “Live cell imaging by multifocal multiphoton microscopy,” Eur. J. Cell Biol. 79(10), 726–734 (2000).
[Crossref] [PubMed]

1994 (1)

1989 (1)

D. M. Shotton, “Confocal scanning optical microscopy and its applications for biological specimens,” J. Cell Sci. 94, 175–206 (1989).

Acuna, D.

S. Wachsmann-Hogiu, D. Krakow, V. T. Kirilova, D. H. Cohn, C. Bertolotto, D. Acuna, Q. Fang, N. Krivorov, and D. L. Farkas, “Multiphoton, confocal, and lifetime microscopy for molecular imaging in cartilage,” Proc. SPIE 5699, 569975 (2005).
[Crossref]

Agronskaia, A. V.

A. V. Agronskaia, L. Tertoolen, and H. C. Gerritsen, “High frame rate fluorescence lifetime imaging,” J. Phys. D Appl. Phys. 36(14), 1655–1662 (2003).
[Crossref]

Ameer-Beg, S. M.

Amos, W. B.

W. B. Amos and J. G. White, “How the confocal laser scanning microscope entered biological research,” Biol. Cell 95(6), 335–342 (2003).
[Crossref] [PubMed]

Anand, P.

Anand, U.

Andresen, P.

T. Nielsen, M. Fricke, D. Hellweg, and P. Andresen, “High efficiency beam splitter for multifocal multiphoton microscopy,” J. Microsc. 201(3), 368–376 (2001).
[Crossref] [PubMed]

Andrews, D. W.

A. Aranovich, Q. Liu, T. Collins, F. Geng, S. Dixit, B. Leber, and D. W. Andrews, “Differences in the Mechanisms of Proapoptotic BH3 Proteins Binding to Bcl-XL and Bcl-2 Quantified in Live MCF-7 Cells,” Mol. Cell 45(6), 754–763 (2012).
[Crossref] [PubMed]

A. Tsikouras, J. Ning, S. Ng, R. Berman, D. W. Andrews, and Q. Fang, “Streak camera crosstalk reduction using a multiple delay optical fiber bundle,” Opt. Lett. 37(2), 250–252 (2012).
[Crossref] [PubMed]

Antolini, R.

Aranovich, A.

A. Aranovich, Q. Liu, T. Collins, F. Geng, S. Dixit, B. Leber, and D. W. Andrews, “Differences in the Mechanisms of Proapoptotic BH3 Proteins Binding to Bcl-XL and Bcl-2 Quantified in Live MCF-7 Cells,” Mol. Cell 45(6), 754–763 (2012).
[Crossref] [PubMed]

Babbey, C. M.

E. Wang, C. M. Babbey, and K. W. Dunn, “Performance comparison between the high-speed Yokogawa spinning disc confocal system and single-point scanning confocal systems,” J. Microsc. 218(2), 148–159 (2005).
[Crossref] [PubMed]

Bahlmann, K.

Barber, P.

Benham, C.

Benninger, R. K. P.

Berman, R.

Bertolotto, C.

S. Wachsmann-Hogiu, D. Krakow, V. T. Kirilova, D. H. Cohn, C. Bertolotto, D. Acuna, Q. Fang, N. Krivorov, and D. L. Farkas, “Multiphoton, confocal, and lifetime microscopy for molecular imaging in cartilage,” Proc. SPIE 5699, 569975 (2005).
[Crossref]

Bickle, M.

M. Bickle, “The beautiful cell: high-content screening in drug discovery,” Anal. Bioanal. Chem. 398(1), 219–226 (2010).
[Crossref] [PubMed]

Buehler, C.

Bunney, T. D.

D. M. Grant, W. Zhang, E. J. McGhee, T. D. Bunney, C. B. Talbot, S. Kumar, I. Munro, C. Dunsby, M. A. A. Neil, M. Katan, and P. M. W. French, “Multiplexed FRET to image multiple signaling events in live cells,” Biophys. J. 95(10), L69–L71 (2008).
[Crossref] [PubMed]

Buranachai, C.

C. Buranachai, D. Kamiyama, A. Chiba, B. D. Williams, and R. M. Clegg, “Rapid frequency-domain FLIM spinning disk confocal microscope: lifetime resolution, image improvement and wavelet analysis,” J. Fluoresc. 18(5), 929–942 (2008).
[Crossref] [PubMed]

Cammi, C.

C. Cammi, A. Gulinatti, I. Rech, F. Panzeri, and M. Ghioni, “SPAD array module for multi-dimensional photon timing applications,” J. Mod. Opt. 59(2), 131–139 (2012).
[Crossref]

Chiba, A.

C. Buranachai, D. Kamiyama, A. Chiba, B. D. Williams, and R. M. Clegg, “Rapid frequency-domain FLIM spinning disk confocal microscope: lifetime resolution, image improvement and wavelet analysis,” J. Fluoresc. 18(5), 929–942 (2008).
[Crossref] [PubMed]

Chmyrov, A.

A. Chmyrov, J. Keller, T. Grotjohann, M. Ratz, E. d’Este, S. Jakobs, C. Eggeling, and S. W. Hell, “Nanoscopy with more than 100,000 ‘doughnuts’,” Nat. Methods 10(8), 737–740 (2013).
[Crossref] [PubMed]

Choudhury, A.

Clegg, R. M.

C. Buranachai, D. Kamiyama, A. Chiba, B. D. Williams, and R. M. Clegg, “Rapid frequency-domain FLIM spinning disk confocal microscope: lifetime resolution, image improvement and wavelet analysis,” J. Fluoresc. 18(5), 929–942 (2008).
[Crossref] [PubMed]

Coelho, S.

Cohn, D. H.

S. Wachsmann-Hogiu, D. Krakow, V. T. Kirilova, D. H. Cohn, C. Bertolotto, D. Acuna, Q. Fang, N. Krivorov, and D. L. Farkas, “Multiphoton, confocal, and lifetime microscopy for molecular imaging in cartilage,” Proc. SPIE 5699, 569975 (2005).
[Crossref]

Cole, M. J.

S. E. Webb, Y. Gu, S. Lévêque-Fort, J. Siegel, M. J. Cole, K. Dowling, R. Jones, P. M. French, M. A. A. Neil, R. Juškaitis, L. O. D. Sucharov, T. Wilson, and M. J. Lever, “A wide-field time-domain fluorescence lifetime imaging microscope with optical sectioning,” Rev. Sci. Instrum. 73(4), 1898–1907 (2002).
[Crossref]

Collins, T.

A. Aranovich, Q. Liu, T. Collins, F. Geng, S. Dixit, B. Leber, and D. W. Andrews, “Differences in the Mechanisms of Proapoptotic BH3 Proteins Binding to Bcl-XL and Bcl-2 Quantified in Live MCF-7 Cells,” Mol. Cell 45(6), 754–763 (2012).
[Crossref] [PubMed]

d’Este, E.

A. Chmyrov, J. Keller, T. Grotjohann, M. Ratz, E. d’Este, S. Jakobs, C. Eggeling, and S. W. Hell, “Nanoscopy with more than 100,000 ‘doughnuts’,” Nat. Methods 10(8), 737–740 (2013).
[Crossref] [PubMed]

Davis, D. M.

De Beule, P. A. A.

Devauges, V.

Dixit, S.

A. Aranovich, Q. Liu, T. Collins, F. Geng, S. Dixit, B. Leber, and D. W. Andrews, “Differences in the Mechanisms of Proapoptotic BH3 Proteins Binding to Bcl-XL and Bcl-2 Quantified in Live MCF-7 Cells,” Mol. Cell 45(6), 754–763 (2012).
[Crossref] [PubMed]

Dowling, K.

S. E. Webb, Y. Gu, S. Lévêque-Fort, J. Siegel, M. J. Cole, K. Dowling, R. Jones, P. M. French, M. A. A. Neil, R. Juškaitis, L. O. D. Sucharov, T. Wilson, and M. J. Lever, “A wide-field time-domain fluorescence lifetime imaging microscope with optical sectioning,” Rev. Sci. Instrum. 73(4), 1898–1907 (2002).
[Crossref]

Duan, Z.

J. Xie, S. Huang, Z. Duan, Y. Shi, and S. Wen, “Correction of the image distortion for laser galvanometric scanning system,” Opt. Laser Technol. 37(4), 305–311 (2005).
[Crossref]

Dunn, K. W.

E. Wang, C. M. Babbey, and K. W. Dunn, “Performance comparison between the high-speed Yokogawa spinning disc confocal system and single-point scanning confocal systems,” J. Microsc. 218(2), 148–159 (2005).
[Crossref] [PubMed]

Dunsby, C.

Dutton, N.

Eggeling, C.

A. Chmyrov, J. Keller, T. Grotjohann, M. Ratz, E. d’Este, S. Jakobs, C. Eggeling, and S. W. Hell, “Nanoscopy with more than 100,000 ‘doughnuts’,” Nat. Methods 10(8), 737–740 (2013).
[Crossref] [PubMed]

Engelhardt, J.

F. Gürlitz, P. Hoyer, H. J. Falk, L. Kastrup, J. Engelhardt, and S. W. Hell, “A STED microscope designed for routine biomedical applications,” Prog. Electromagnetics Res. 147, 57–68 (2014).
[Crossref]

Esposito, A.

Falk, H. J.

F. Gürlitz, P. Hoyer, H. J. Falk, L. Kastrup, J. Engelhardt, and S. W. Hell, “A STED microscope designed for routine biomedical applications,” Prog. Electromagnetics Res. 147, 57–68 (2014).
[Crossref]

Fang, Q.

A. Tsikouras, J. Ning, S. Ng, R. Berman, D. W. Andrews, and Q. Fang, “Streak camera crosstalk reduction using a multiple delay optical fiber bundle,” Opt. Lett. 37(2), 250–252 (2012).
[Crossref] [PubMed]

S. Wachsmann-Hogiu, D. Krakow, V. T. Kirilova, D. H. Cohn, C. Bertolotto, D. Acuna, Q. Fang, N. Krivorov, and D. L. Farkas, “Multiphoton, confocal, and lifetime microscopy for molecular imaging in cartilage,” Proc. SPIE 5699, 569975 (2005).
[Crossref]

Fantini, S.

Farkas, D. L.

S. Wachsmann-Hogiu, D. Krakow, V. T. Kirilova, D. H. Cohn, C. Bertolotto, D. Acuna, Q. Fang, N. Krivorov, and D. L. Farkas, “Multiphoton, confocal, and lifetime microscopy for molecular imaging in cartilage,” Proc. SPIE 5699, 569975 (2005).
[Crossref]

French, P. M.

K. Suhling, P. M. French, and D. Phillips, “Time-resolved fluorescence microscopy,” Photochem. Photobiol. Sci. 4(1), 13–22 (2005).
[Crossref] [PubMed]

S. E. Webb, Y. Gu, S. Lévêque-Fort, J. Siegel, M. J. Cole, K. Dowling, R. Jones, P. M. French, M. A. A. Neil, R. Juškaitis, L. O. D. Sucharov, T. Wilson, and M. J. Lever, “A wide-field time-domain fluorescence lifetime imaging microscope with optical sectioning,” Rev. Sci. Instrum. 73(4), 1898–1907 (2002).
[Crossref]

French, P. M. W.

Fricke, M.

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Ghioni, M.

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C. Cammi, A. Gulinatti, I. Rech, F. Panzeri, and M. Ghioni, “SPAD array module for multi-dimensional photon timing applications,” J. Mod. Opt. 59(2), 131–139 (2012).
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M. Straub, P. Lodemann, P. Holroyd, R. Jahn, and S. W. Hell, “Live cell imaging by multifocal multiphoton microscopy,” Eur. J. Cell Biol. 79(10), 726–734 (2000).
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Henderson, R. K.

Holroyd, P.

M. Straub, P. Lodemann, P. Holroyd, R. Jahn, and S. W. Hell, “Live cell imaging by multifocal multiphoton microscopy,” Eur. J. Cell Biol. 79(10), 726–734 (2000).
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F. Gürlitz, P. Hoyer, H. J. Falk, L. Kastrup, J. Engelhardt, and S. W. Hell, “A STED microscope designed for routine biomedical applications,” Prog. Electromagnetics Res. 147, 57–68 (2014).
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J. Xie, S. Huang, Z. Duan, Y. Shi, and S. Wen, “Correction of the image distortion for laser galvanometric scanning system,” Opt. Laser Technol. 37(4), 305–311 (2005).
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Kumar, S.

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Leber, B.

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S. E. Webb, Y. Gu, S. Lévêque-Fort, J. Siegel, M. J. Cole, K. Dowling, R. Jones, P. M. French, M. A. A. Neil, R. Juškaitis, L. O. D. Sucharov, T. Wilson, and M. J. Lever, “A wide-field time-domain fluorescence lifetime imaging microscope with optical sectioning,” Rev. Sci. Instrum. 73(4), 1898–1907 (2002).
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Lin, Z.

L. Liu, J. Qu, Z. Lin, Z. Fu, B. Guo, and H. Niu, “Simultaneous time- and spectrum-resolved multifocal multiphoton microscopy,” Appl. Phys. B 84(3), 379–383 (2006).
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L. Liu, J. Qu, Z. Lin, Z. Fu, B. Guo, and H. Niu, “Simultaneous time- and spectrum-resolved multifocal multiphoton microscopy,” Appl. Phys. B 84(3), 379–383 (2006).
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M. Straub, P. Lodemann, P. Holroyd, R. Jahn, and S. W. Hell, “Live cell imaging by multifocal multiphoton microscopy,” Eur. J. Cell Biol. 79(10), 726–734 (2000).
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M. D. Risi, H. Makhlouf, A. R. Rouse, A. A. Tanbakuchi, and A. F. Gmitro, “Design and performance of a multi-point scan confocal microendoscope,” Photonics 1(4), 421–431 (2014).
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E. B. van Munster, J. Goedhart, G. J. Kremers, E. M. M. Manders, and T. W. J. Gadella., “Combination of a spinning disc confocal unit with frequency-domain fluorescence lifetime imaging microscopy,” Cytometry A 71(4), 207–214 (2007).
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D. M. Grant, W. Zhang, E. J. McGhee, T. D. Bunney, C. B. Talbot, S. Kumar, I. Munro, C. Dunsby, M. A. A. Neil, M. Katan, and P. M. W. French, “Multiplexed FRET to image multiple signaling events in live cells,” Biophys. J. 95(10), L69–L71 (2008).
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Munro, I.

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Nedivi, E.

Neil, M. A. A.

D. M. Grant, W. Zhang, E. J. McGhee, T. D. Bunney, C. B. Talbot, S. Kumar, I. Munro, C. Dunsby, M. A. A. Neil, M. Katan, and P. M. W. French, “Multiplexed FRET to image multiple signaling events in live cells,” Biophys. J. 95(10), L69–L71 (2008).
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Ng, T.

Nichols, A.

P. Lang, K. Yeow, A. Nichols, and A. Scheer, “Cellular imaging in drug discovery,” Nat. Rev. Drug Discov. 5(4), 343–356 (2006).
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T. Nielsen, M. Fricke, D. Hellweg, and P. Andresen, “High efficiency beam splitter for multifocal multiphoton microscopy,” J. Microsc. 201(3), 368–376 (2001).
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Niu, H.

L. Liu, J. Qu, Z. Lin, Z. Fu, B. Guo, and H. Niu, “Simultaneous time- and spectrum-resolved multifocal multiphoton microscopy,” Appl. Phys. B 84(3), 379–383 (2006).
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Panzeri, F.

C. Cammi, A. Gulinatti, I. Rech, F. Panzeri, and M. Ghioni, “SPAD array module for multi-dimensional photon timing applications,” J. Mod. Opt. 59(2), 131–139 (2012).
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Ratz, M.

A. Chmyrov, J. Keller, T. Grotjohann, M. Ratz, E. d’Este, S. Jakobs, C. Eggeling, and S. W. Hell, “Nanoscopy with more than 100,000 ‘doughnuts’,” Nat. Methods 10(8), 737–740 (2013).
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C. Cammi, A. Gulinatti, I. Rech, F. Panzeri, and M. Ghioni, “SPAD array module for multi-dimensional photon timing applications,” J. Mod. Opt. 59(2), 131–139 (2012).
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M. D. Risi, H. Makhlouf, A. R. Rouse, A. A. Tanbakuchi, and A. F. Gmitro, “Design and performance of a multi-point scan confocal microendoscope,” Photonics 1(4), 421–431 (2014).
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M. D. Risi, H. Makhlouf, A. R. Rouse, A. A. Tanbakuchi, and A. F. Gmitro, “Design and performance of a multi-point scan confocal microendoscope,” Photonics 1(4), 421–431 (2014).
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Scheer, A.

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M. Straub, P. Lodemann, P. Holroyd, R. Jahn, and S. W. Hell, “Live cell imaging by multifocal multiphoton microscopy,” Eur. J. Cell Biol. 79(10), 726–734 (2000).
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S. E. Webb, Y. Gu, S. Lévêque-Fort, J. Siegel, M. J. Cole, K. Dowling, R. Jones, P. M. French, M. A. A. Neil, R. Juškaitis, L. O. D. Sucharov, T. Wilson, and M. J. Lever, “A wide-field time-domain fluorescence lifetime imaging microscope with optical sectioning,” Rev. Sci. Instrum. 73(4), 1898–1907 (2002).
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M. D. Risi, H. Makhlouf, A. R. Rouse, A. A. Tanbakuchi, and A. F. Gmitro, “Design and performance of a multi-point scan confocal microendoscope,” Photonics 1(4), 421–431 (2014).
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S. Wachsmann-Hogiu, D. Krakow, V. T. Kirilova, D. H. Cohn, C. Bertolotto, D. Acuna, Q. Fang, N. Krivorov, and D. L. Farkas, “Multiphoton, confocal, and lifetime microscopy for molecular imaging in cartilage,” Proc. SPIE 5699, 569975 (2005).
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J. Xie, S. Huang, Z. Duan, Y. Shi, and S. Wen, “Correction of the image distortion for laser galvanometric scanning system,” Opt. Laser Technol. 37(4), 305–311 (2005).
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S. E. Webb, Y. Gu, S. Lévêque-Fort, J. Siegel, M. J. Cole, K. Dowling, R. Jones, P. M. French, M. A. A. Neil, R. Juškaitis, L. O. D. Sucharov, T. Wilson, and M. J. Lever, “A wide-field time-domain fluorescence lifetime imaging microscope with optical sectioning,” Rev. Sci. Instrum. 73(4), 1898–1907 (2002).
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P. Lang, K. Yeow, A. Nichols, and A. Scheer, “Cellular imaging in drug discovery,” Nat. Rev. Drug Discov. 5(4), 343–356 (2006).
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Appl. Phys. B (1)

L. Liu, J. Qu, Z. Lin, Z. Fu, B. Guo, and H. Niu, “Simultaneous time- and spectrum-resolved multifocal multiphoton microscopy,” Appl. Phys. B 84(3), 379–383 (2006).
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Biol. Cell (1)

W. B. Amos and J. G. White, “How the confocal laser scanning microscope entered biological research,” Biol. Cell 95(6), 335–342 (2003).
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Biomed. Opt. Express (1)

Biophys. J. (1)

D. M. Grant, W. Zhang, E. J. McGhee, T. D. Bunney, C. B. Talbot, S. Kumar, I. Munro, C. Dunsby, M. A. A. Neil, M. Katan, and P. M. W. French, “Multiplexed FRET to image multiple signaling events in live cells,” Biophys. J. 95(10), L69–L71 (2008).
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Cytometry A (1)

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Figures (5)

Fig. 1
Fig. 1

(a) Beam propagation of a foci array member din from the normal axis of the lens. The solid line path shows how the beam propagates when the mirror is at its initial position, 45° to each lens. The dashed line shows the beam path when the mirror has been tilted by φ. The lateral displacement is highlighted as ∆d. (b) Plot of the deflection experienced by different foci (f1, f2, f3) in a mirror galvanometer scanner. The curve shows an extreme case of non-linear response of deflection with tilt angle. Since the input foci are collimated at different angles relative to the mirror, they will experience different segments of the deflection response. Each red spot represents a different focal point when the galvo is in a neutral 45° position. The red line shows the range of motion of each output focal point as the galvanometer is tilted from −5° to + 5°. The deflection range for each focal point over this same angle range is highlighted in blue, showing a larger range for the outer focal points compared to the central focal point.

Fig. 2
Fig. 2

Beam propagation through a tilted glass. The solid line shows how the beam propagates when the window is normal to direction of propagation. The dashed line shows the beam path when the window has been tilted by φ.

Fig. 3
Fig. 3

Instrument setup for multiplexed FLIM, using window galvanometer scanners.

Fig. 4
Fig. 4

(a) Experimental setup for testing the linearity and uniformity of the window tilt scanning scheme. (b) Readout images of single beam spot as the differential voltage across the galvanometer is changed. (c) Plot of the relative vertical position of 24 foci as they are scanned, with 95% confidence intervals included for each data point.

Fig. 5
Fig. 5

Intensity (left) and lifetime (right) reconstructions of Convallaria sampled after a 30x30 raster scan with the window galvanometers. Dark regions outlined in white indicate the scan regions of channels that were not collected due to dead fibers in the fiber array.

Equations (3)

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

Δ d = f tan 2 ϕ 2 f ϕ .
Δ d = f tan ( tan 1 ( d i n f ) + 2 ϕ ) d i n 2 f ϕ .
Δ d = t [ tan ϕ tan ( sin 1 ( sin ϕ n ) ) ] cos ϕ ϕ t ( n 1 n ) .

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