Abstract

The streak camera is a picosecond resolution photodetector with parallel input capability; however, the degree of multiplexing is limited by crosstalk and temporal uncertainty in the sweeping field. We introduced a fixed time delay between adjacent fibers to reduce crosstalk in the synchroscan mode. The fixed delay and a tunable electronic delay between the input pulse and the synchroscan unit allows robust separation modes between the streaks, while spatial and temporal nonlinearities can be calibrated in. The efficacy of the design is demonstrated through a 100-fold multiplexed confocal fluorescence lifetime imaging microscope in live cells.

© 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

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References

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    [Crossref] [PubMed]
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    [Crossref] [PubMed]

2018 (2)

J. Liang, L. Zhu, and L. V. Wang, “Single-shot real-time femtosecond imaging of temporal focusing,” Light Sci. Appl. 7(1), 42 (2018).
[Crossref] [PubMed]

J. Kale, E. J. Osterlund, and D. W. Andrews, “BCL-2 family proteins: changing partners in the dance towards death,” Cell Death Differ. 25(1), 65–80 (2018).
[Crossref] [PubMed]

2017 (5)

H. Sparks, F. Görlitz, D. J. Kelly, S. C. Warren, P. A. Kellett, E. Garcia, A. K. L. Dymoke-Bradshaw, J. D. Hares, M. A. A. Neil, C. Dunsby, and P. M. W. French, “Characterisation of new gated optical image intensifiers for fluorescence lifetime imaging,” Rev. Sci. Instrum. 88(1), 013707 (2017).
[Crossref] [PubMed]

M. Ossiander, F. Siegrist, V. Shirvanyan, R. Pazourek, A. Sommer, T. Latka, A. Guggenmos, S. Nagele, J. Feist, J. Burgdörfer, R. Kienberger, and M. Schultze, “Attosecond correlation dynamics,” Nat. Phys. 13(3), 280–285 (2017).
[Crossref]

T. Gaumnitz, A. Jain, Y. Pertot, M. Huppert, I. Jordan, F. Ardana-Lamas, and H. J. Wörner, “Streaking of 43-attosecond soft-X-ray pulses generated by a passively CEP-stable mid-infrared driver,” Opt. Express 25(22), 27506–27518 (2017).
[Crossref] [PubMed]

I. Gorgisyan, R. Ischebeck, C. Erny, A. Dax, L. Patthey, C. Pradervand, L. Sala, C. Milne, H. T. Lemke, C. P. Hauri, T. Katayama, S. Owada, M. Yabashi, T. Togashi, R. Abela, L. Rivkin, and P. Juranić, “THz streak camera method for synchronous arrival time measurement of two-color hard X-ray FEL pulses,” Opt. Express 25(3), 2080–2091 (2017).
[Crossref] [PubMed]

K. Rieger, A. Caldwell, O. Reimann, R. Tarkeshian, and P. Muggli, “GHz modulation detection using a streak camera: Suitability of streak cameras in the AWAKE experiment,” Rev. Sci. Instrum. 88(2), 025110 (2017).
[Crossref] [PubMed]

2016 (2)

P. Drap and J. Lefèvre, “An exact formula for calculating inverse radial lens distortions,” Sensors (Basel) 16(6), 1–18 (2016).
[Crossref] [PubMed]

G. Satat, B. Heshmat, D. Raviv, and R. Raskar, “All Photons Imaging Through Volumetric Scattering,” Sci. Rep. 6(1), 33946 (2016).
[Crossref] [PubMed]

2015 (1)

2014 (3)

M. Liu, M. Jia, H. Pan, L. Li, M. Chang, H. Ren, F. Argoul, S. Zhang, and J. Xu, “Instrument response standard in time-resolved fluorescence spectroscopy at visible wavelength: quenched fluorescein sodium,” Appl. Spectrosc. 68(5), 577–583 (2014).
[Crossref] [PubMed]

F. Mérola, A. Fredj, D. B. Betolngar, C. Ziegler, M. Erard, and H. Pasquier, “Newly engineered cyan fluorescent proteins with enhanced performances for live cell FRET imaging,” Biotechnol. J. 9(2), 180–191 (2014).
[Crossref] [PubMed]

A. H. Al-hamdani, H. G. Rashid, and Z. R. Ghayib, “Improvement of laser to fiber coupling efficiency,” Arpn 9(11), 2286–2291 (2014).

2013 (2)

M. Wahl, T. Röhlicke, H. J. Rahn, R. Erdmann, G. Kell, A. Ahlrichs, M. Kernbach, A. W. Schell, and O. Benson, “Integrated multichannel photon timing instrument with very short dead time and high throughput,” Rev. Sci. Instrum. 84(4), 043102 (2013).
[Crossref] [PubMed]

V. Masilamani, B. B. Das, J. Secor, M. AlSalhi, S. Devanesan, S. Prasad, D. Rabah, and R. R. Alfano, “Optical biopsy of benign and malignant tissue by time resolved spectroscopy,” Technol. Cancer Res. Treat. 12(6), 559–563 (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]

Q. Liu, B. Leber, and D. W. Andrews, “Interactions of pro-apoptotic BH3 proteins with anti-apoptotic Bcl-2 family proteins measured in live MCF-7 cells using FLIM FRET,” Cell Cycle 11(19), 3536–3542 (2012).
[Crossref] [PubMed]

D. D. Li, S. Ameer-Beg, J. Arlt, D. Tyndall, R. Walker, D. R. Matthews, V. Visitkul, J. Richardson, and R. K. Henderson, “Time-domain fluorescence lifetime imaging techniques suitable for solid-state imaging sensor arrays,” Sensors (Basel) 12(5), 5650–5669 (2012).
[Crossref] [PubMed]

2011 (1)

2010 (2)

2009 (1)

2008 (2)

Y. Yuan, T. Papaioannou, and Q. Fang, “Single-shot acquisition of time-resolved fluorescence spectra using a multiple delay optical fiber bundle,” Opt. Lett. 33(8), 791–793 (2008).
[Crossref] [PubMed]

V. K. Ramanujan, J. A. Jo, G. Cantu, and B. A. Herman, “Spatially resolved fluorescence lifetime mapping of enzyme kinetics in living cells,” J. Microsc. 230(Pt 3), 329–338 (2008).
[Crossref] [PubMed]

2005 (1)

P. Schreiber, S. Kudaev, P. Dannberg, and U. D. Zeitner, “Homogeneous LED-illumination using microlens arrays,” Proc. SPIE 5942(59420K), 59420K (2005).
[Crossref]

2004 (2)

C. T. Silbernagel, P. Torres, and D. H. Kalantar, “A Method for Analyzing High Resolution, Time Domain, Streak Camera Calibration Data PULSE,” Proc. SPIE 5559, 435–442 (2004).
[Crossref]

J. Qu, J. Li, and H. Niu, “Fluorescence lifetime imaging microscopy based on a synchroscan streak camera,” Proc. SPIE 5324, 250 (2004).
[Crossref]

2003 (2)

R. V. Krishnan, A. Masuda, V. E. Centonze, and B. Herman, “Quantitative imaging of protein-protein interactions by multiphoton fluorescence lifetime imaging microscopy using a streak camera,” J. Biomed. Opt. 8(3), 362–367 (2003).
[Crossref] [PubMed]

C. V. Zint, W. Uhring, M. Torregrossa, B. Cunin, and P. Poulet, “Streak camera: a multidetector for diffuse optical tomography,” Appl. Opt. 42(16), 3313–3320 (2003).
[Crossref] [PubMed]

1999 (1)

T. Glanzmann, J. P. Ballini, H. van den Bergh, and G. Wagnières, “Time-resolved spectrofluorometer for clinical tissue characterization during endoscopy,” Rev. Sci. Instrum. 70(10), 4067–4077 (1999).
[Crossref]

1995 (1)

M. M. Martin, L. Lindqvist, R. Sjöback, J. Nygren, and M. Kubista, “Absorption and fluorescence properties of fluorescein,” J. Lumin. 51(6), L7–L21 (1995).

1991 (1)

A. Kusumi, A. Tsuji, M. Murata, Y. Sako, A. C. Yoshizawa, S. Kagiwada, T. Hayakawa, S. Ohnishi, and S. Ohnishi, “Development of a Streak-Camera-Based Time-Resolved Microscope Fluorimeter and Its Application to Studies of Membrane Fusion in Single Cells,” Biochemistry 30(26), 6517–6527 (1991).
[Crossref] [PubMed]

1985 (1)

G. Jones, W. R. Jackson, C. Y. Choi, and W. R. Bergmark, “Solvent effects on emission yield and lifetime for coumarin laser dyes. Requirements for a rotatory decay mechanism,” J. Phys. Chem. 89(2), 294–300 (1985).
[Crossref]

1983 (1)

J. Campillo and S. L. Shapiro, “Picosecond Streak Camera Fluorometry—A Review,” IEEE J. Quantum Electron. 19(4), 585–603 (1983).
[Crossref]

Abela, R.

Ahlrichs, A.

M. Wahl, T. Röhlicke, H. J. Rahn, R. Erdmann, G. Kell, A. Ahlrichs, M. Kernbach, A. W. Schell, and O. Benson, “Integrated multichannel photon timing instrument with very short dead time and high throughput,” Rev. Sci. Instrum. 84(4), 043102 (2013).
[Crossref] [PubMed]

Alfano, R. R.

V. Masilamani, B. B. Das, J. Secor, M. AlSalhi, S. Devanesan, S. Prasad, D. Rabah, and R. R. Alfano, “Optical biopsy of benign and malignant tissue by time resolved spectroscopy,” Technol. Cancer Res. Treat. 12(6), 559–563 (2013).
[Crossref] [PubMed]

Al-hamdani, A. H.

A. H. Al-hamdani, H. G. Rashid, and Z. R. Ghayib, “Improvement of laser to fiber coupling efficiency,” Arpn 9(11), 2286–2291 (2014).

AlSalhi, M.

V. Masilamani, B. B. Das, J. Secor, M. AlSalhi, S. Devanesan, S. Prasad, D. Rabah, and R. R. Alfano, “Optical biopsy of benign and malignant tissue by time resolved spectroscopy,” Technol. Cancer Res. Treat. 12(6), 559–563 (2013).
[Crossref] [PubMed]

Ameer-Beg, S.

D. D. Li, S. Ameer-Beg, J. Arlt, D. Tyndall, R. Walker, D. R. Matthews, V. Visitkul, J. Richardson, and R. K. Henderson, “Time-domain fluorescence lifetime imaging techniques suitable for solid-state imaging sensor arrays,” Sensors (Basel) 12(5), 5650–5669 (2012).
[Crossref] [PubMed]

Andrews, D. W.

J. Kale, E. J. Osterlund, and D. W. Andrews, “BCL-2 family proteins: changing partners in the dance towards death,” Cell Death Differ. 25(1), 65–80 (2018).
[Crossref] [PubMed]

A. Tsikouras, R. Berman, D. W. Andrews, and Q. Fang, “High-speed multifocal array scanning using refractive window tilting,” Biomed. Opt. Express 6(10), 3737–3747 (2015).
[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]

Q. Liu, B. Leber, and D. W. Andrews, “Interactions of pro-apoptotic BH3 proteins with anti-apoptotic Bcl-2 family proteins measured in live MCF-7 cells using FLIM FRET,” Cell Cycle 11(19), 3536–3542 (2012).
[Crossref] [PubMed]

Ardana-Lamas, F.

Argoul, F.

Arlt, J.

D. D. Li, S. Ameer-Beg, J. Arlt, D. Tyndall, R. Walker, D. R. Matthews, V. Visitkul, J. Richardson, and R. K. Henderson, “Time-domain fluorescence lifetime imaging techniques suitable for solid-state imaging sensor arrays,” Sensors (Basel) 12(5), 5650–5669 (2012).
[Crossref] [PubMed]

Ballini, J. P.

T. Glanzmann, J. P. Ballini, H. van den Bergh, and G. Wagnières, “Time-resolved spectrofluorometer for clinical tissue characterization during endoscopy,” Rev. Sci. Instrum. 70(10), 4067–4077 (1999).
[Crossref]

Benson, O.

M. Wahl, T. Röhlicke, H. J. Rahn, R. Erdmann, G. Kell, A. Ahlrichs, M. Kernbach, A. W. Schell, and O. Benson, “Integrated multichannel photon timing instrument with very short dead time and high throughput,” Rev. Sci. Instrum. 84(4), 043102 (2013).
[Crossref] [PubMed]

Bergmark, W. R.

G. Jones, W. R. Jackson, C. Y. Choi, and W. R. Bergmark, “Solvent effects on emission yield and lifetime for coumarin laser dyes. Requirements for a rotatory decay mechanism,” J. Phys. Chem. 89(2), 294–300 (1985).
[Crossref]

Berman, R.

Betolngar, D. B.

F. Mérola, A. Fredj, D. B. Betolngar, C. Ziegler, M. Erard, and H. Pasquier, “Newly engineered cyan fluorescent proteins with enhanced performances for live cell FRET imaging,” Biotechnol. J. 9(2), 180–191 (2014).
[Crossref] [PubMed]

Burgdörfer, J.

M. Ossiander, F. Siegrist, V. Shirvanyan, R. Pazourek, A. Sommer, T. Latka, A. Guggenmos, S. Nagele, J. Feist, J. Burgdörfer, R. Kienberger, and M. Schultze, “Attosecond correlation dynamics,” Nat. Phys. 13(3), 280–285 (2017).
[Crossref]

Caldwell, A.

K. Rieger, A. Caldwell, O. Reimann, R. Tarkeshian, and P. Muggli, “GHz modulation detection using a streak camera: Suitability of streak cameras in the AWAKE experiment,” Rev. Sci. Instrum. 88(2), 025110 (2017).
[Crossref] [PubMed]

Campillo, J.

J. Campillo and S. L. Shapiro, “Picosecond Streak Camera Fluorometry—A Review,” IEEE J. Quantum Electron. 19(4), 585–603 (1983).
[Crossref]

Cantu, G.

V. K. Ramanujan, J. A. Jo, G. Cantu, and B. A. Herman, “Spatially resolved fluorescence lifetime mapping of enzyme kinetics in living cells,” J. Microsc. 230(Pt 3), 329–338 (2008).
[Crossref] [PubMed]

Centonze, V. E.

R. V. Krishnan, A. Masuda, V. E. Centonze, and B. Herman, “Quantitative imaging of protein-protein interactions by multiphoton fluorescence lifetime imaging microscopy using a streak camera,” J. Biomed. Opt. 8(3), 362–367 (2003).
[Crossref] [PubMed]

Chang, M.

Choi, C. Y.

G. Jones, W. R. Jackson, C. Y. Choi, and W. R. Bergmark, “Solvent effects on emission yield and lifetime for coumarin laser dyes. Requirements for a rotatory decay mechanism,” J. Phys. Chem. 89(2), 294–300 (1985).
[Crossref]

Chromy, B. A.

T. A. Laurence and B. A. Chromy, “Efficient maximum likelihood estimator fitting of histograms,” Nat. Methods 7(5), 338–339 (2010).
[Crossref] [PubMed]

Cunin, B.

Dannberg, P.

P. Schreiber, S. Kudaev, P. Dannberg, and U. D. Zeitner, “Homogeneous LED-illumination using microlens arrays,” Proc. SPIE 5942(59420K), 59420K (2005).
[Crossref]

Das, B. B.

V. Masilamani, B. B. Das, J. Secor, M. AlSalhi, S. Devanesan, S. Prasad, D. Rabah, and R. R. Alfano, “Optical biopsy of benign and malignant tissue by time resolved spectroscopy,” Technol. Cancer Res. Treat. 12(6), 559–563 (2013).
[Crossref] [PubMed]

Dax, A.

Devanesan, S.

V. Masilamani, B. B. Das, J. Secor, M. AlSalhi, S. Devanesan, S. Prasad, D. Rabah, and R. R. Alfano, “Optical biopsy of benign and malignant tissue by time resolved spectroscopy,” Technol. Cancer Res. Treat. 12(6), 559–563 (2013).
[Crossref] [PubMed]

Drap, P.

P. Drap and J. Lefèvre, “An exact formula for calculating inverse radial lens distortions,” Sensors (Basel) 16(6), 1–18 (2016).
[Crossref] [PubMed]

Dunsby, C.

H. Sparks, F. Görlitz, D. J. Kelly, S. C. Warren, P. A. Kellett, E. Garcia, A. K. L. Dymoke-Bradshaw, J. D. Hares, M. A. A. Neil, C. Dunsby, and P. M. W. French, “Characterisation of new gated optical image intensifiers for fluorescence lifetime imaging,” Rev. Sci. Instrum. 88(1), 013707 (2017).
[Crossref] [PubMed]

Dymoke-Bradshaw, A. K. L.

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R. V. Krishnan, A. Masuda, V. E. Centonze, and B. Herman, “Quantitative imaging of protein-protein interactions by multiphoton fluorescence lifetime imaging microscopy using a streak camera,” J. Biomed. Opt. 8(3), 362–367 (2003).
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A. Kusumi, A. Tsuji, M. Murata, Y. Sako, A. C. Yoshizawa, S. Kagiwada, T. Hayakawa, S. Ohnishi, and S. Ohnishi, “Development of a Streak-Camera-Based Time-Resolved Microscope Fluorimeter and Its Application to Studies of Membrane Fusion in Single Cells,” Biochemistry 30(26), 6517–6527 (1991).
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Pazourek, R.

M. Ossiander, F. Siegrist, V. Shirvanyan, R. Pazourek, A. Sommer, T. Latka, A. Guggenmos, S. Nagele, J. Feist, J. Burgdörfer, R. Kienberger, and M. Schultze, “Attosecond correlation dynamics,” Nat. Phys. 13(3), 280–285 (2017).
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V. Masilamani, B. B. Das, J. Secor, M. AlSalhi, S. Devanesan, S. Prasad, D. Rabah, and R. R. Alfano, “Optical biopsy of benign and malignant tissue by time resolved spectroscopy,” Technol. Cancer Res. Treat. 12(6), 559–563 (2013).
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V. K. Ramanujan, J. A. Jo, G. Cantu, and B. A. Herman, “Spatially resolved fluorescence lifetime mapping of enzyme kinetics in living cells,” J. Microsc. 230(Pt 3), 329–338 (2008).
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Rashid, H. G.

A. H. Al-hamdani, H. G. Rashid, and Z. R. Ghayib, “Improvement of laser to fiber coupling efficiency,” Arpn 9(11), 2286–2291 (2014).

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G. Satat, B. Heshmat, D. Raviv, and R. Raskar, “All Photons Imaging Through Volumetric Scattering,” Sci. Rep. 6(1), 33946 (2016).
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Richardson, J.

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M. Ossiander, F. Siegrist, V. Shirvanyan, R. Pazourek, A. Sommer, T. Latka, A. Guggenmos, S. Nagele, J. Feist, J. Burgdörfer, R. Kienberger, and M. Schultze, “Attosecond correlation dynamics,” Nat. Phys. 13(3), 280–285 (2017).
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M. M. Martin, L. Lindqvist, R. Sjöback, J. Nygren, and M. Kubista, “Absorption and fluorescence properties of fluorescein,” J. Lumin. 51(6), L7–L21 (1995).

Sommer, A.

M. Ossiander, F. Siegrist, V. Shirvanyan, R. Pazourek, A. Sommer, T. Latka, A. Guggenmos, S. Nagele, J. Feist, J. Burgdörfer, R. Kienberger, and M. Schultze, “Attosecond correlation dynamics,” Nat. Phys. 13(3), 280–285 (2017).
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M. Wahl, T. Röhlicke, H. J. Rahn, R. Erdmann, G. Kell, A. Ahlrichs, M. Kernbach, A. W. Schell, and O. Benson, “Integrated multichannel photon timing instrument with very short dead time and high throughput,” Rev. Sci. Instrum. 84(4), 043102 (2013).
[Crossref] [PubMed]

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[Crossref] [PubMed]

K. Rieger, A. Caldwell, O. Reimann, R. Tarkeshian, and P. Muggli, “GHz modulation detection using a streak camera: Suitability of streak cameras in the AWAKE experiment,” Rev. Sci. Instrum. 88(2), 025110 (2017).
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Figures (6)

Fig. 1
Fig. 1 (a) Optical setup of the multifocal confocal streak system. (b) Schematic illustrating inward (left) and outward (right) scanning modes. The generated streaks in both modes are illustrated above, with a blue-red pseudoscale (left) representing intensity of generated streaks in that image. The sinusoidal sweeping voltage profile is shown below each image; black and white triangles indicate the start of the streaks from alternating fibers, blue and red lines indicate the near-linear section of the sweep profile, which is used to generate the streaks in the above image. The black and white arrows in the image above correspond to arrows indicated on the sinusoidal profile below.
Fig. 2
Fig. 2 (a) Normalized intensity map of a single streak. The black line shows the normalized intensity profile of the maximum intensity point on the streak perpendicular to the sweeping direction. The red dashed lines indicate the positions of the two adjacent streak to the central streak in inward scanning mode. The cyan solid lines indicate the positions of two streaks adjacent to the central streak in the outward scanning mode. This profile is used to determine the crosstalk as a function of distance away from the streak (in pixels). (b) Examples indicating corresponding location of the streaks of interest (yellow arrow) and the adjacent streaks (red dash lines and cyan solid lines). Pixel size: 6.5μm
Fig. 3
Fig. 3 (a) Left and right sweep time maps generated by interpolating the simulated grid using a delay generator. (b) Lag time map generated by taking each map and subtracting the time axis for the central horizontal line. Transient time asymmetry is observed when comparing the left map to the right map. Pixel size: 6.5μm
Fig. 4
Fig. 4 (a) Sample streaks for quenched fluorescein (IRF), Coumarin-6 and Fluorescein are shown above. Corresponding linearized lifetime decays for the average of several of these streaks is plotted below. The IRF has a second hump, which is a characteristic of the pulsed diode laser operated at high power [26]. These humps were excluded from the delay experiments used to generate the time maps. (b) Fluorescence lifetime image of Coumarin-6 and Fluorescein solutions. Images were acquired at room temperature using a 10 × 10 confocal scan. The dark squares are a result of dead fibers and were excluded from the analysis.
Fig. 5
Fig. 5 Confocal images for live MCF-7 cells expressing mCerulean3-Bcl-XL. Images of the same sample were acquired using our multiplexed streak system (left), compared images acquired on an ISS-Alba in single point confocal mode (middle) and wide field mode (right). Dark squares in the streak image indicate the positions of the dead fibers, mentioned in Fig. 4. Scalar bar: 15μm.
Fig. 6
Fig. 6 Intensity weighted lifetime maps generated by fitting extracted lifetimes from data acquired on the streak microscope. Scalar bar: 15μm. (a) Confocal FLIM images of Convallaria and (b) live MCF-7 cells expressing mCerulean3-Bcl-XL. 3 × 3 binning was used for the Convallaria FLIM cube, while 7 × 7 binning was used for the MCF-7 FLIM cube.

Equations (4)

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t = T cos - 1 ( x - c A ) 2 π
I i d e a l 1 sin ( cos 1 ( c x A ) )
I a c t u a l I i d e a l ( x ) P S F ( x )
[ x d y d ] = [ x y ] [ k 1 r 2 + k 2 r 4 + k 3 r 6 k 1 r 2 + k 2 r 4 + k 3 r 6 ]

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