Abstract

Experiments on single cells are currently gaining more and more interest. Single cell studies often concerns the spatio-temporal distribution of fluorescent proteins inside living cells, visualized using fluorescence microscopy. In order to extract quantitative information from such experiments it is necessary to image the sample with high spatial and temporal resolution while keeping the photobleaching to a minimum. The analysis of the spatial distribution of proteins often requires stacks of images at each time point, which exposes the sample to unnecessary amounts of excitation light. In this paper we show how holographic optical tweezers combined with image analysis can be used to optimize the axial position of trapped cells in an array in order to bring the nuclei into a single imaging plane, thus eliminating the need for stacks of images and consequently reducing photobleaching. This allows more images to be collected, as well as increasing the time span and/or the time resolution in time lapse studies of single cells.

© 2009 Optical Society of America

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  1. D. Longo and J. Hasty, "Dynamics of single-cell gene expression," Mol. Syst. Biol. 2, 64 (2006).
    [CrossRef] [PubMed]
  2. D. Di Carlo and L. P. Lee, "Dynamic single-cell analysis for quantitative biology," Anal. Chem. 78, 7918-7925 (2006).
    [CrossRef] [PubMed]
  3. K. Sott, E. Eriksson, E. Petelenz, and M. Goksor, "Optical systems for single cell analyses," Expert Opin. Drug Discov. 3, 1323-1344 (2008).
    [CrossRef]
  4. M. B. Elowitz, A. J. Levine, E. D. Siggia, and P. S. Swain, "Stochastic gene expression in a single cell," Science 297, 1183-1186 (2002).
    [CrossRef] [PubMed]
  5. J. M. Raser and E. K. O’Shea, "Control of stochasticity in eukaryotic gene expression," Science 304, 1811-1814 (2004).
    [CrossRef] [PubMed]
  6. N. Q. Balaban, J. Merrin, R. Chait, L. Kowalik, and S. Leibler, "Bacterial persistence as a phenotypic switch," Science 305, 1622-1625 (2004).
    [CrossRef] [PubMed]
  7. L. Cai, C. K. Dalal, and M. B. Elowitz, "Frequency-modulated nuclear localization bursts coordinate gene regulation," Nature 455, 485-490 (2008).
    [CrossRef] [PubMed]
  8. V. Starkuviene and R. Pepperkok, "The potential of high-content high-throughput microscopy in drug discovery," B. J. Pharmacol. 152, 62-71 (2007).
    [CrossRef]
  9. D. Petranovic, and J. Nielsen, "Can yeast systems biology contribute to the understanding of human disease?," Trends Biotechnol. 26, 584-590 (2008).
    [CrossRef] [PubMed]
  10. Y. Shav-Tal, R. H. Singer, and X. Darzacq, "Imaging gene expression in single living cells," Nat. Rev. Mol. Cell Biol. 5, 855-862 (2004).
    [CrossRef] [PubMed]
  11. H. Zhang and K. K. Liu, "Optical tweezers for single cells," J. R. Soc. Interface 5, 671-690 (2008).
    [CrossRef] [PubMed]
  12. H. A. Svahn and A. van den Berg, "Single cells or large populations?," Lab Chip 7, 544-546 (2007).
    [CrossRef] [PubMed]
  13. J. Liesener, M. Reicherter, T. Haist, and H. J. Tiziani, "Multi-functional optical tweezers using computergenerated holograms," Opt. Commun. 185, 77-82 (2000).
    [CrossRef]
  14. J. E. Curtis, B. A. Koss, and D. G. Grier, "Dynamic holographic optical tweezers," Opt. Commun. 207, 169-175 (2002).
    [CrossRef]
  15. G. M. Akselrod, W. Timp, U. Mirsaidov, Q. Zhao, C. Li, R. Timp, K. Timp, P. Matsudaira, and G. Timp, "Laserguided assembly of heterotypic three-dimensional living cell microarrays," Biophys. J. 91, 3465-3473 (2006).
    [CrossRef] [PubMed]
  16. P. Jordan, J. Leach, M. Padgett, P. Blackburn, N. Isaacs, M. Goksor, D. Hanstorp, A. Wright, J. Girkin, and J. Cooper, "Creating permanent 3D arrangements of isolated cells using holographic optical tweezers," Lab Chip 5, 1224-1228 (2005).
    [CrossRef] [PubMed]
  17. E. Eriksson, J. Scrimgeour, J. Enger, and M. Goksor, "Holographic optical tweezers combined with a microfluidic device for exposing cells to fast environmental changes," SPIE Proc. 6592, P5920-9 (2007).
  18. U. Mirsaidov, J. Scrimgeour, W. Timp, K. Beck, M. Mir, P. Matsudaira, and G. Timp, "Live cell lithography: Using optical tweezers to create synthetic tissue," Lab Chip 8, 2174-2181 (2008).
    [CrossRef] [PubMed]
  19. E. Eriksson, J. Enger, B. Nordlander, N. Erjavec, K. Ramser, M. Goksor, S. Hohmann, T. Nystrom, and D. Hanstorp, "A microfluidic system in combination with optical tweezers for analyzing rapid and reversible cytological alterations in single cells upon environmental changes," Lab Chip 7, 71-76 (2007).
    [CrossRef]
  20. V. Emiliani, D. Cojoc, E. Ferrari, V. Garbin, C. Durieux, M. Coppey-Moisan, and E. Di Fabrizio, "Wave front engineering for microscopy of living cells," Opt. Express 13, 1395-1405 (2005).
    [CrossRef] [PubMed]
  21. S. Oddos, C. Dunsby, M. A. Purbhoo, A. Chauveau, D. M. Owen, M. A. A. Neil, D. M. Davis, and P. M. W. French, "High-speed high-resolution imaging of intercellular immune synapses using optical tweezers," Biophys. J. 95, L66-L68 (2008).
    [CrossRef] [PubMed]
  22. To make the hologram calculation more efficient, the algorithm was modified to update the trap intensities for all traps in a specific axial plane simultaneously, rather than looping through the number of traps individually. To achieve trapping patterns with high uniformity of the trap intensities, the number of iterations was also increased.
  23. J. Leach, K. Wulff, G. Sinclair, P. Jordan, J. Courtial, L. Thomson, G. Gibson, K. Karunwi, J. Cooper, Z. J. Laczik, and M. Padgett, "Interactive approach to optical tweezers control," Appl. Opt. 45, 897-903 (2006).
    [CrossRef] [PubMed]
  24. A. Gordon, A. Colman-Lerner, T. E. Chin, K. R. Benjamin, R. C. Yu, and R. Brent, "Single-cell quantification of molecules and rates using open-source microscope-based cytometry," Nat. Methods 4, 175-181 (2007).
    [CrossRef] [PubMed]
  25. G. Volpe, G. P. Singh, and D. Petrov, "Dynamics of a growing cell in an optical trap," Appl. Phys. Lett. 88, 231106 (2006).
    [CrossRef]
  26. J. E. Curtis, C. H. J. Schmitz, and J. P. Spatz, "Symmetry dependence of holograms for optical trapping," Opt. Lett. 30, 2086-2088 (2005).
    [CrossRef] [PubMed]
  27. M. Polin, K. Ladavac, S. H. Lee, Y. Roichman, and D. G. Grier, "Optimized holographic optical traps," Opt. Express 13, 5831-5845 (2005).
    [CrossRef] [PubMed]

2008

K. Sott, E. Eriksson, E. Petelenz, and M. Goksor, "Optical systems for single cell analyses," Expert Opin. Drug Discov. 3, 1323-1344 (2008).
[CrossRef]

L. Cai, C. K. Dalal, and M. B. Elowitz, "Frequency-modulated nuclear localization bursts coordinate gene regulation," Nature 455, 485-490 (2008).
[CrossRef] [PubMed]

D. Petranovic, and J. Nielsen, "Can yeast systems biology contribute to the understanding of human disease?," Trends Biotechnol. 26, 584-590 (2008).
[CrossRef] [PubMed]

H. Zhang and K. K. Liu, "Optical tweezers for single cells," J. R. Soc. Interface 5, 671-690 (2008).
[CrossRef] [PubMed]

U. Mirsaidov, J. Scrimgeour, W. Timp, K. Beck, M. Mir, P. Matsudaira, and G. Timp, "Live cell lithography: Using optical tweezers to create synthetic tissue," Lab Chip 8, 2174-2181 (2008).
[CrossRef] [PubMed]

S. Oddos, C. Dunsby, M. A. Purbhoo, A. Chauveau, D. M. Owen, M. A. A. Neil, D. M. Davis, and P. M. W. French, "High-speed high-resolution imaging of intercellular immune synapses using optical tweezers," Biophys. J. 95, L66-L68 (2008).
[CrossRef] [PubMed]

2007

E. Eriksson, J. Enger, B. Nordlander, N. Erjavec, K. Ramser, M. Goksor, S. Hohmann, T. Nystrom, and D. Hanstorp, "A microfluidic system in combination with optical tweezers for analyzing rapid and reversible cytological alterations in single cells upon environmental changes," Lab Chip 7, 71-76 (2007).
[CrossRef]

A. Gordon, A. Colman-Lerner, T. E. Chin, K. R. Benjamin, R. C. Yu, and R. Brent, "Single-cell quantification of molecules and rates using open-source microscope-based cytometry," Nat. Methods 4, 175-181 (2007).
[CrossRef] [PubMed]

H. A. Svahn and A. van den Berg, "Single cells or large populations?," Lab Chip 7, 544-546 (2007).
[CrossRef] [PubMed]

V. Starkuviene and R. Pepperkok, "The potential of high-content high-throughput microscopy in drug discovery," B. J. Pharmacol. 152, 62-71 (2007).
[CrossRef]

2006

D. Longo and J. Hasty, "Dynamics of single-cell gene expression," Mol. Syst. Biol. 2, 64 (2006).
[CrossRef] [PubMed]

D. Di Carlo and L. P. Lee, "Dynamic single-cell analysis for quantitative biology," Anal. Chem. 78, 7918-7925 (2006).
[CrossRef] [PubMed]

G. Volpe, G. P. Singh, and D. Petrov, "Dynamics of a growing cell in an optical trap," Appl. Phys. Lett. 88, 231106 (2006).
[CrossRef]

G. M. Akselrod, W. Timp, U. Mirsaidov, Q. Zhao, C. Li, R. Timp, K. Timp, P. Matsudaira, and G. Timp, "Laserguided assembly of heterotypic three-dimensional living cell microarrays," Biophys. J. 91, 3465-3473 (2006).
[CrossRef] [PubMed]

J. Leach, K. Wulff, G. Sinclair, P. Jordan, J. Courtial, L. Thomson, G. Gibson, K. Karunwi, J. Cooper, Z. J. Laczik, and M. Padgett, "Interactive approach to optical tweezers control," Appl. Opt. 45, 897-903 (2006).
[CrossRef] [PubMed]

2005

2004

Y. Shav-Tal, R. H. Singer, and X. Darzacq, "Imaging gene expression in single living cells," Nat. Rev. Mol. Cell Biol. 5, 855-862 (2004).
[CrossRef] [PubMed]

J. M. Raser and E. K. O’Shea, "Control of stochasticity in eukaryotic gene expression," Science 304, 1811-1814 (2004).
[CrossRef] [PubMed]

N. Q. Balaban, J. Merrin, R. Chait, L. Kowalik, and S. Leibler, "Bacterial persistence as a phenotypic switch," Science 305, 1622-1625 (2004).
[CrossRef] [PubMed]

2002

M. B. Elowitz, A. J. Levine, E. D. Siggia, and P. S. Swain, "Stochastic gene expression in a single cell," Science 297, 1183-1186 (2002).
[CrossRef] [PubMed]

J. E. Curtis, B. A. Koss, and D. G. Grier, "Dynamic holographic optical tweezers," Opt. Commun. 207, 169-175 (2002).
[CrossRef]

2000

J. Liesener, M. Reicherter, T. Haist, and H. J. Tiziani, "Multi-functional optical tweezers using computergenerated holograms," Opt. Commun. 185, 77-82 (2000).
[CrossRef]

Akselrod, G. M.

G. M. Akselrod, W. Timp, U. Mirsaidov, Q. Zhao, C. Li, R. Timp, K. Timp, P. Matsudaira, and G. Timp, "Laserguided assembly of heterotypic three-dimensional living cell microarrays," Biophys. J. 91, 3465-3473 (2006).
[CrossRef] [PubMed]

Balaban, N. Q.

N. Q. Balaban, J. Merrin, R. Chait, L. Kowalik, and S. Leibler, "Bacterial persistence as a phenotypic switch," Science 305, 1622-1625 (2004).
[CrossRef] [PubMed]

Beck, K.

U. Mirsaidov, J. Scrimgeour, W. Timp, K. Beck, M. Mir, P. Matsudaira, and G. Timp, "Live cell lithography: Using optical tweezers to create synthetic tissue," Lab Chip 8, 2174-2181 (2008).
[CrossRef] [PubMed]

Benjamin, K. R.

A. Gordon, A. Colman-Lerner, T. E. Chin, K. R. Benjamin, R. C. Yu, and R. Brent, "Single-cell quantification of molecules and rates using open-source microscope-based cytometry," Nat. Methods 4, 175-181 (2007).
[CrossRef] [PubMed]

Blackburn, P.

P. Jordan, J. Leach, M. Padgett, P. Blackburn, N. Isaacs, M. Goksor, D. Hanstorp, A. Wright, J. Girkin, and J. Cooper, "Creating permanent 3D arrangements of isolated cells using holographic optical tweezers," Lab Chip 5, 1224-1228 (2005).
[CrossRef] [PubMed]

Brent, R.

A. Gordon, A. Colman-Lerner, T. E. Chin, K. R. Benjamin, R. C. Yu, and R. Brent, "Single-cell quantification of molecules and rates using open-source microscope-based cytometry," Nat. Methods 4, 175-181 (2007).
[CrossRef] [PubMed]

Cai, L.

L. Cai, C. K. Dalal, and M. B. Elowitz, "Frequency-modulated nuclear localization bursts coordinate gene regulation," Nature 455, 485-490 (2008).
[CrossRef] [PubMed]

Chait, R.

N. Q. Balaban, J. Merrin, R. Chait, L. Kowalik, and S. Leibler, "Bacterial persistence as a phenotypic switch," Science 305, 1622-1625 (2004).
[CrossRef] [PubMed]

Chauveau, A.

S. Oddos, C. Dunsby, M. A. Purbhoo, A. Chauveau, D. M. Owen, M. A. A. Neil, D. M. Davis, and P. M. W. French, "High-speed high-resolution imaging of intercellular immune synapses using optical tweezers," Biophys. J. 95, L66-L68 (2008).
[CrossRef] [PubMed]

Chin, T. E.

A. Gordon, A. Colman-Lerner, T. E. Chin, K. R. Benjamin, R. C. Yu, and R. Brent, "Single-cell quantification of molecules and rates using open-source microscope-based cytometry," Nat. Methods 4, 175-181 (2007).
[CrossRef] [PubMed]

Cojoc, D.

Colman-Lerner, A.

A. Gordon, A. Colman-Lerner, T. E. Chin, K. R. Benjamin, R. C. Yu, and R. Brent, "Single-cell quantification of molecules and rates using open-source microscope-based cytometry," Nat. Methods 4, 175-181 (2007).
[CrossRef] [PubMed]

Cooper, J.

J. Leach, K. Wulff, G. Sinclair, P. Jordan, J. Courtial, L. Thomson, G. Gibson, K. Karunwi, J. Cooper, Z. J. Laczik, and M. Padgett, "Interactive approach to optical tweezers control," Appl. Opt. 45, 897-903 (2006).
[CrossRef] [PubMed]

P. Jordan, J. Leach, M. Padgett, P. Blackburn, N. Isaacs, M. Goksor, D. Hanstorp, A. Wright, J. Girkin, and J. Cooper, "Creating permanent 3D arrangements of isolated cells using holographic optical tweezers," Lab Chip 5, 1224-1228 (2005).
[CrossRef] [PubMed]

Coppey-Moisan, M.

Courtial, J.

Curtis, J. E.

J. E. Curtis, C. H. J. Schmitz, and J. P. Spatz, "Symmetry dependence of holograms for optical trapping," Opt. Lett. 30, 2086-2088 (2005).
[CrossRef] [PubMed]

J. E. Curtis, B. A. Koss, and D. G. Grier, "Dynamic holographic optical tweezers," Opt. Commun. 207, 169-175 (2002).
[CrossRef]

Dalal, C. K.

L. Cai, C. K. Dalal, and M. B. Elowitz, "Frequency-modulated nuclear localization bursts coordinate gene regulation," Nature 455, 485-490 (2008).
[CrossRef] [PubMed]

Darzacq, X.

Y. Shav-Tal, R. H. Singer, and X. Darzacq, "Imaging gene expression in single living cells," Nat. Rev. Mol. Cell Biol. 5, 855-862 (2004).
[CrossRef] [PubMed]

Davis, D. M.

S. Oddos, C. Dunsby, M. A. Purbhoo, A. Chauveau, D. M. Owen, M. A. A. Neil, D. M. Davis, and P. M. W. French, "High-speed high-resolution imaging of intercellular immune synapses using optical tweezers," Biophys. J. 95, L66-L68 (2008).
[CrossRef] [PubMed]

Di Carlo, D.

D. Di Carlo and L. P. Lee, "Dynamic single-cell analysis for quantitative biology," Anal. Chem. 78, 7918-7925 (2006).
[CrossRef] [PubMed]

Di Fabrizio, E.

Dunsby, C.

S. Oddos, C. Dunsby, M. A. Purbhoo, A. Chauveau, D. M. Owen, M. A. A. Neil, D. M. Davis, and P. M. W. French, "High-speed high-resolution imaging of intercellular immune synapses using optical tweezers," Biophys. J. 95, L66-L68 (2008).
[CrossRef] [PubMed]

Durieux, C.

Elowitz, M. B.

L. Cai, C. K. Dalal, and M. B. Elowitz, "Frequency-modulated nuclear localization bursts coordinate gene regulation," Nature 455, 485-490 (2008).
[CrossRef] [PubMed]

M. B. Elowitz, A. J. Levine, E. D. Siggia, and P. S. Swain, "Stochastic gene expression in a single cell," Science 297, 1183-1186 (2002).
[CrossRef] [PubMed]

Emiliani, V.

Enger, J.

E. Eriksson, J. Enger, B. Nordlander, N. Erjavec, K. Ramser, M. Goksor, S. Hohmann, T. Nystrom, and D. Hanstorp, "A microfluidic system in combination with optical tweezers for analyzing rapid and reversible cytological alterations in single cells upon environmental changes," Lab Chip 7, 71-76 (2007).
[CrossRef]

Eriksson, E.

K. Sott, E. Eriksson, E. Petelenz, and M. Goksor, "Optical systems for single cell analyses," Expert Opin. Drug Discov. 3, 1323-1344 (2008).
[CrossRef]

E. Eriksson, J. Enger, B. Nordlander, N. Erjavec, K. Ramser, M. Goksor, S. Hohmann, T. Nystrom, and D. Hanstorp, "A microfluidic system in combination with optical tweezers for analyzing rapid and reversible cytological alterations in single cells upon environmental changes," Lab Chip 7, 71-76 (2007).
[CrossRef]

Erjavec, N.

E. Eriksson, J. Enger, B. Nordlander, N. Erjavec, K. Ramser, M. Goksor, S. Hohmann, T. Nystrom, and D. Hanstorp, "A microfluidic system in combination with optical tweezers for analyzing rapid and reversible cytological alterations in single cells upon environmental changes," Lab Chip 7, 71-76 (2007).
[CrossRef]

Ferrari, E.

French, P. M. W.

S. Oddos, C. Dunsby, M. A. Purbhoo, A. Chauveau, D. M. Owen, M. A. A. Neil, D. M. Davis, and P. M. W. French, "High-speed high-resolution imaging of intercellular immune synapses using optical tweezers," Biophys. J. 95, L66-L68 (2008).
[CrossRef] [PubMed]

Garbin, V.

Gibson, G.

Girkin, J.

P. Jordan, J. Leach, M. Padgett, P. Blackburn, N. Isaacs, M. Goksor, D. Hanstorp, A. Wright, J. Girkin, and J. Cooper, "Creating permanent 3D arrangements of isolated cells using holographic optical tweezers," Lab Chip 5, 1224-1228 (2005).
[CrossRef] [PubMed]

Goks¨or, M.

K. Sott, E. Eriksson, E. Petelenz, and M. Goksor, "Optical systems for single cell analyses," Expert Opin. Drug Discov. 3, 1323-1344 (2008).
[CrossRef]

Goksor, M.

E. Eriksson, J. Enger, B. Nordlander, N. Erjavec, K. Ramser, M. Goksor, S. Hohmann, T. Nystrom, and D. Hanstorp, "A microfluidic system in combination with optical tweezers for analyzing rapid and reversible cytological alterations in single cells upon environmental changes," Lab Chip 7, 71-76 (2007).
[CrossRef]

P. Jordan, J. Leach, M. Padgett, P. Blackburn, N. Isaacs, M. Goksor, D. Hanstorp, A. Wright, J. Girkin, and J. Cooper, "Creating permanent 3D arrangements of isolated cells using holographic optical tweezers," Lab Chip 5, 1224-1228 (2005).
[CrossRef] [PubMed]

Gordon, A.

A. Gordon, A. Colman-Lerner, T. E. Chin, K. R. Benjamin, R. C. Yu, and R. Brent, "Single-cell quantification of molecules and rates using open-source microscope-based cytometry," Nat. Methods 4, 175-181 (2007).
[CrossRef] [PubMed]

Grier, D. G.

M. Polin, K. Ladavac, S. H. Lee, Y. Roichman, and D. G. Grier, "Optimized holographic optical traps," Opt. Express 13, 5831-5845 (2005).
[CrossRef] [PubMed]

J. E. Curtis, B. A. Koss, and D. G. Grier, "Dynamic holographic optical tweezers," Opt. Commun. 207, 169-175 (2002).
[CrossRef]

Haist, T.

J. Liesener, M. Reicherter, T. Haist, and H. J. Tiziani, "Multi-functional optical tweezers using computergenerated holograms," Opt. Commun. 185, 77-82 (2000).
[CrossRef]

Hanstorp, D.

E. Eriksson, J. Enger, B. Nordlander, N. Erjavec, K. Ramser, M. Goksor, S. Hohmann, T. Nystrom, and D. Hanstorp, "A microfluidic system in combination with optical tweezers for analyzing rapid and reversible cytological alterations in single cells upon environmental changes," Lab Chip 7, 71-76 (2007).
[CrossRef]

P. Jordan, J. Leach, M. Padgett, P. Blackburn, N. Isaacs, M. Goksor, D. Hanstorp, A. Wright, J. Girkin, and J. Cooper, "Creating permanent 3D arrangements of isolated cells using holographic optical tweezers," Lab Chip 5, 1224-1228 (2005).
[CrossRef] [PubMed]

Hasty, J.

D. Longo and J. Hasty, "Dynamics of single-cell gene expression," Mol. Syst. Biol. 2, 64 (2006).
[CrossRef] [PubMed]

Hohmann, S.

E. Eriksson, J. Enger, B. Nordlander, N. Erjavec, K. Ramser, M. Goksor, S. Hohmann, T. Nystrom, and D. Hanstorp, "A microfluidic system in combination with optical tweezers for analyzing rapid and reversible cytological alterations in single cells upon environmental changes," Lab Chip 7, 71-76 (2007).
[CrossRef]

Isaacs, N.

P. Jordan, J. Leach, M. Padgett, P. Blackburn, N. Isaacs, M. Goksor, D. Hanstorp, A. Wright, J. Girkin, and J. Cooper, "Creating permanent 3D arrangements of isolated cells using holographic optical tweezers," Lab Chip 5, 1224-1228 (2005).
[CrossRef] [PubMed]

Jordan, P.

J. Leach, K. Wulff, G. Sinclair, P. Jordan, J. Courtial, L. Thomson, G. Gibson, K. Karunwi, J. Cooper, Z. J. Laczik, and M. Padgett, "Interactive approach to optical tweezers control," Appl. Opt. 45, 897-903 (2006).
[CrossRef] [PubMed]

P. Jordan, J. Leach, M. Padgett, P. Blackburn, N. Isaacs, M. Goksor, D. Hanstorp, A. Wright, J. Girkin, and J. Cooper, "Creating permanent 3D arrangements of isolated cells using holographic optical tweezers," Lab Chip 5, 1224-1228 (2005).
[CrossRef] [PubMed]

Karunwi, K.

Koss, B. A.

J. E. Curtis, B. A. Koss, and D. G. Grier, "Dynamic holographic optical tweezers," Opt. Commun. 207, 169-175 (2002).
[CrossRef]

Kowalik, L.

N. Q. Balaban, J. Merrin, R. Chait, L. Kowalik, and S. Leibler, "Bacterial persistence as a phenotypic switch," Science 305, 1622-1625 (2004).
[CrossRef] [PubMed]

Laczik, Z. J.

Ladavac, K.

Leach, J.

J. Leach, K. Wulff, G. Sinclair, P. Jordan, J. Courtial, L. Thomson, G. Gibson, K. Karunwi, J. Cooper, Z. J. Laczik, and M. Padgett, "Interactive approach to optical tweezers control," Appl. Opt. 45, 897-903 (2006).
[CrossRef] [PubMed]

P. Jordan, J. Leach, M. Padgett, P. Blackburn, N. Isaacs, M. Goksor, D. Hanstorp, A. Wright, J. Girkin, and J. Cooper, "Creating permanent 3D arrangements of isolated cells using holographic optical tweezers," Lab Chip 5, 1224-1228 (2005).
[CrossRef] [PubMed]

Lee, L. P.

D. Di Carlo and L. P. Lee, "Dynamic single-cell analysis for quantitative biology," Anal. Chem. 78, 7918-7925 (2006).
[CrossRef] [PubMed]

Lee, S. H.

Leibler, S.

N. Q. Balaban, J. Merrin, R. Chait, L. Kowalik, and S. Leibler, "Bacterial persistence as a phenotypic switch," Science 305, 1622-1625 (2004).
[CrossRef] [PubMed]

Levine, A. J.

M. B. Elowitz, A. J. Levine, E. D. Siggia, and P. S. Swain, "Stochastic gene expression in a single cell," Science 297, 1183-1186 (2002).
[CrossRef] [PubMed]

Li, C.

G. M. Akselrod, W. Timp, U. Mirsaidov, Q. Zhao, C. Li, R. Timp, K. Timp, P. Matsudaira, and G. Timp, "Laserguided assembly of heterotypic three-dimensional living cell microarrays," Biophys. J. 91, 3465-3473 (2006).
[CrossRef] [PubMed]

Liesener, J.

J. Liesener, M. Reicherter, T. Haist, and H. J. Tiziani, "Multi-functional optical tweezers using computergenerated holograms," Opt. Commun. 185, 77-82 (2000).
[CrossRef]

Liu, K. K.

H. Zhang and K. K. Liu, "Optical tweezers for single cells," J. R. Soc. Interface 5, 671-690 (2008).
[CrossRef] [PubMed]

Longo, D.

D. Longo and J. Hasty, "Dynamics of single-cell gene expression," Mol. Syst. Biol. 2, 64 (2006).
[CrossRef] [PubMed]

Matsudaira, P.

U. Mirsaidov, J. Scrimgeour, W. Timp, K. Beck, M. Mir, P. Matsudaira, and G. Timp, "Live cell lithography: Using optical tweezers to create synthetic tissue," Lab Chip 8, 2174-2181 (2008).
[CrossRef] [PubMed]

G. M. Akselrod, W. Timp, U. Mirsaidov, Q. Zhao, C. Li, R. Timp, K. Timp, P. Matsudaira, and G. Timp, "Laserguided assembly of heterotypic three-dimensional living cell microarrays," Biophys. J. 91, 3465-3473 (2006).
[CrossRef] [PubMed]

Merrin, J.

N. Q. Balaban, J. Merrin, R. Chait, L. Kowalik, and S. Leibler, "Bacterial persistence as a phenotypic switch," Science 305, 1622-1625 (2004).
[CrossRef] [PubMed]

Mir, M.

U. Mirsaidov, J. Scrimgeour, W. Timp, K. Beck, M. Mir, P. Matsudaira, and G. Timp, "Live cell lithography: Using optical tweezers to create synthetic tissue," Lab Chip 8, 2174-2181 (2008).
[CrossRef] [PubMed]

Mirsaidov, U.

U. Mirsaidov, J. Scrimgeour, W. Timp, K. Beck, M. Mir, P. Matsudaira, and G. Timp, "Live cell lithography: Using optical tweezers to create synthetic tissue," Lab Chip 8, 2174-2181 (2008).
[CrossRef] [PubMed]

G. M. Akselrod, W. Timp, U. Mirsaidov, Q. Zhao, C. Li, R. Timp, K. Timp, P. Matsudaira, and G. Timp, "Laserguided assembly of heterotypic three-dimensional living cell microarrays," Biophys. J. 91, 3465-3473 (2006).
[CrossRef] [PubMed]

Neil, M. A. A.

S. Oddos, C. Dunsby, M. A. Purbhoo, A. Chauveau, D. M. Owen, M. A. A. Neil, D. M. Davis, and P. M. W. French, "High-speed high-resolution imaging of intercellular immune synapses using optical tweezers," Biophys. J. 95, L66-L68 (2008).
[CrossRef] [PubMed]

Nielsen, J.

D. Petranovic, and J. Nielsen, "Can yeast systems biology contribute to the understanding of human disease?," Trends Biotechnol. 26, 584-590 (2008).
[CrossRef] [PubMed]

Nordlander, B.

E. Eriksson, J. Enger, B. Nordlander, N. Erjavec, K. Ramser, M. Goksor, S. Hohmann, T. Nystrom, and D. Hanstorp, "A microfluidic system in combination with optical tweezers for analyzing rapid and reversible cytological alterations in single cells upon environmental changes," Lab Chip 7, 71-76 (2007).
[CrossRef]

Nystrom, T.

E. Eriksson, J. Enger, B. Nordlander, N. Erjavec, K. Ramser, M. Goksor, S. Hohmann, T. Nystrom, and D. Hanstorp, "A microfluidic system in combination with optical tweezers for analyzing rapid and reversible cytological alterations in single cells upon environmental changes," Lab Chip 7, 71-76 (2007).
[CrossRef]

O’Shea, E. K.

J. M. Raser and E. K. O’Shea, "Control of stochasticity in eukaryotic gene expression," Science 304, 1811-1814 (2004).
[CrossRef] [PubMed]

Oddos, S.

S. Oddos, C. Dunsby, M. A. Purbhoo, A. Chauveau, D. M. Owen, M. A. A. Neil, D. M. Davis, and P. M. W. French, "High-speed high-resolution imaging of intercellular immune synapses using optical tweezers," Biophys. J. 95, L66-L68 (2008).
[CrossRef] [PubMed]

Owen, D. M.

S. Oddos, C. Dunsby, M. A. Purbhoo, A. Chauveau, D. M. Owen, M. A. A. Neil, D. M. Davis, and P. M. W. French, "High-speed high-resolution imaging of intercellular immune synapses using optical tweezers," Biophys. J. 95, L66-L68 (2008).
[CrossRef] [PubMed]

Padgett, M.

J. Leach, K. Wulff, G. Sinclair, P. Jordan, J. Courtial, L. Thomson, G. Gibson, K. Karunwi, J. Cooper, Z. J. Laczik, and M. Padgett, "Interactive approach to optical tweezers control," Appl. Opt. 45, 897-903 (2006).
[CrossRef] [PubMed]

P. Jordan, J. Leach, M. Padgett, P. Blackburn, N. Isaacs, M. Goksor, D. Hanstorp, A. Wright, J. Girkin, and J. Cooper, "Creating permanent 3D arrangements of isolated cells using holographic optical tweezers," Lab Chip 5, 1224-1228 (2005).
[CrossRef] [PubMed]

Pepperkok, R.

V. Starkuviene and R. Pepperkok, "The potential of high-content high-throughput microscopy in drug discovery," B. J. Pharmacol. 152, 62-71 (2007).
[CrossRef]

Petelenz, E.

K. Sott, E. Eriksson, E. Petelenz, and M. Goksor, "Optical systems for single cell analyses," Expert Opin. Drug Discov. 3, 1323-1344 (2008).
[CrossRef]

Petranovic, D.

D. Petranovic, and J. Nielsen, "Can yeast systems biology contribute to the understanding of human disease?," Trends Biotechnol. 26, 584-590 (2008).
[CrossRef] [PubMed]

Petrov, D.

G. Volpe, G. P. Singh, and D. Petrov, "Dynamics of a growing cell in an optical trap," Appl. Phys. Lett. 88, 231106 (2006).
[CrossRef]

Polin, M.

Purbhoo, M. A.

S. Oddos, C. Dunsby, M. A. Purbhoo, A. Chauveau, D. M. Owen, M. A. A. Neil, D. M. Davis, and P. M. W. French, "High-speed high-resolution imaging of intercellular immune synapses using optical tweezers," Biophys. J. 95, L66-L68 (2008).
[CrossRef] [PubMed]

Ramser, K.

E. Eriksson, J. Enger, B. Nordlander, N. Erjavec, K. Ramser, M. Goksor, S. Hohmann, T. Nystrom, and D. Hanstorp, "A microfluidic system in combination with optical tweezers for analyzing rapid and reversible cytological alterations in single cells upon environmental changes," Lab Chip 7, 71-76 (2007).
[CrossRef]

Raser, J. M.

J. M. Raser and E. K. O’Shea, "Control of stochasticity in eukaryotic gene expression," Science 304, 1811-1814 (2004).
[CrossRef] [PubMed]

Reicherter, M.

J. Liesener, M. Reicherter, T. Haist, and H. J. Tiziani, "Multi-functional optical tweezers using computergenerated holograms," Opt. Commun. 185, 77-82 (2000).
[CrossRef]

Roichman, Y.

Schmitz, C. H. J.

Scrimgeour, J.

U. Mirsaidov, J. Scrimgeour, W. Timp, K. Beck, M. Mir, P. Matsudaira, and G. Timp, "Live cell lithography: Using optical tweezers to create synthetic tissue," Lab Chip 8, 2174-2181 (2008).
[CrossRef] [PubMed]

Shav-Tal, Y.

Y. Shav-Tal, R. H. Singer, and X. Darzacq, "Imaging gene expression in single living cells," Nat. Rev. Mol. Cell Biol. 5, 855-862 (2004).
[CrossRef] [PubMed]

Siggia, E. D.

M. B. Elowitz, A. J. Levine, E. D. Siggia, and P. S. Swain, "Stochastic gene expression in a single cell," Science 297, 1183-1186 (2002).
[CrossRef] [PubMed]

Sinclair, G.

Singer, R. H.

Y. Shav-Tal, R. H. Singer, and X. Darzacq, "Imaging gene expression in single living cells," Nat. Rev. Mol. Cell Biol. 5, 855-862 (2004).
[CrossRef] [PubMed]

Singh, G. P.

G. Volpe, G. P. Singh, and D. Petrov, "Dynamics of a growing cell in an optical trap," Appl. Phys. Lett. 88, 231106 (2006).
[CrossRef]

Sott, K.

K. Sott, E. Eriksson, E. Petelenz, and M. Goksor, "Optical systems for single cell analyses," Expert Opin. Drug Discov. 3, 1323-1344 (2008).
[CrossRef]

Spatz, J. P.

Starkuviene, V.

V. Starkuviene and R. Pepperkok, "The potential of high-content high-throughput microscopy in drug discovery," B. J. Pharmacol. 152, 62-71 (2007).
[CrossRef]

Svahn, H. A.

H. A. Svahn and A. van den Berg, "Single cells or large populations?," Lab Chip 7, 544-546 (2007).
[CrossRef] [PubMed]

Swain, P. S.

M. B. Elowitz, A. J. Levine, E. D. Siggia, and P. S. Swain, "Stochastic gene expression in a single cell," Science 297, 1183-1186 (2002).
[CrossRef] [PubMed]

Thomson, L.

Timp, G.

U. Mirsaidov, J. Scrimgeour, W. Timp, K. Beck, M. Mir, P. Matsudaira, and G. Timp, "Live cell lithography: Using optical tweezers to create synthetic tissue," Lab Chip 8, 2174-2181 (2008).
[CrossRef] [PubMed]

G. M. Akselrod, W. Timp, U. Mirsaidov, Q. Zhao, C. Li, R. Timp, K. Timp, P. Matsudaira, and G. Timp, "Laserguided assembly of heterotypic three-dimensional living cell microarrays," Biophys. J. 91, 3465-3473 (2006).
[CrossRef] [PubMed]

Timp, K.

G. M. Akselrod, W. Timp, U. Mirsaidov, Q. Zhao, C. Li, R. Timp, K. Timp, P. Matsudaira, and G. Timp, "Laserguided assembly of heterotypic three-dimensional living cell microarrays," Biophys. J. 91, 3465-3473 (2006).
[CrossRef] [PubMed]

Timp, R.

G. M. Akselrod, W. Timp, U. Mirsaidov, Q. Zhao, C. Li, R. Timp, K. Timp, P. Matsudaira, and G. Timp, "Laserguided assembly of heterotypic three-dimensional living cell microarrays," Biophys. J. 91, 3465-3473 (2006).
[CrossRef] [PubMed]

Timp, W.

U. Mirsaidov, J. Scrimgeour, W. Timp, K. Beck, M. Mir, P. Matsudaira, and G. Timp, "Live cell lithography: Using optical tweezers to create synthetic tissue," Lab Chip 8, 2174-2181 (2008).
[CrossRef] [PubMed]

G. M. Akselrod, W. Timp, U. Mirsaidov, Q. Zhao, C. Li, R. Timp, K. Timp, P. Matsudaira, and G. Timp, "Laserguided assembly of heterotypic three-dimensional living cell microarrays," Biophys. J. 91, 3465-3473 (2006).
[CrossRef] [PubMed]

Tiziani, H. J.

J. Liesener, M. Reicherter, T. Haist, and H. J. Tiziani, "Multi-functional optical tweezers using computergenerated holograms," Opt. Commun. 185, 77-82 (2000).
[CrossRef]

van den Berg, A.

H. A. Svahn and A. van den Berg, "Single cells or large populations?," Lab Chip 7, 544-546 (2007).
[CrossRef] [PubMed]

Volpe, G.

G. Volpe, G. P. Singh, and D. Petrov, "Dynamics of a growing cell in an optical trap," Appl. Phys. Lett. 88, 231106 (2006).
[CrossRef]

Wright, A.

P. Jordan, J. Leach, M. Padgett, P. Blackburn, N. Isaacs, M. Goksor, D. Hanstorp, A. Wright, J. Girkin, and J. Cooper, "Creating permanent 3D arrangements of isolated cells using holographic optical tweezers," Lab Chip 5, 1224-1228 (2005).
[CrossRef] [PubMed]

Wulff, K.

Yu, R. C.

A. Gordon, A. Colman-Lerner, T. E. Chin, K. R. Benjamin, R. C. Yu, and R. Brent, "Single-cell quantification of molecules and rates using open-source microscope-based cytometry," Nat. Methods 4, 175-181 (2007).
[CrossRef] [PubMed]

Zhang, H.

H. Zhang and K. K. Liu, "Optical tweezers for single cells," J. R. Soc. Interface 5, 671-690 (2008).
[CrossRef] [PubMed]

Zhao, Q.

G. M. Akselrod, W. Timp, U. Mirsaidov, Q. Zhao, C. Li, R. Timp, K. Timp, P. Matsudaira, and G. Timp, "Laserguided assembly of heterotypic three-dimensional living cell microarrays," Biophys. J. 91, 3465-3473 (2006).
[CrossRef] [PubMed]

Anal. Chem.

D. Di Carlo and L. P. Lee, "Dynamic single-cell analysis for quantitative biology," Anal. Chem. 78, 7918-7925 (2006).
[CrossRef] [PubMed]

Appl. Opt.

Appl. Phys. Lett.

G. Volpe, G. P. Singh, and D. Petrov, "Dynamics of a growing cell in an optical trap," Appl. Phys. Lett. 88, 231106 (2006).
[CrossRef]

B. J. Pharmacol.

V. Starkuviene and R. Pepperkok, "The potential of high-content high-throughput microscopy in drug discovery," B. J. Pharmacol. 152, 62-71 (2007).
[CrossRef]

Biophys. J.

G. M. Akselrod, W. Timp, U. Mirsaidov, Q. Zhao, C. Li, R. Timp, K. Timp, P. Matsudaira, and G. Timp, "Laserguided assembly of heterotypic three-dimensional living cell microarrays," Biophys. J. 91, 3465-3473 (2006).
[CrossRef] [PubMed]

S. Oddos, C. Dunsby, M. A. Purbhoo, A. Chauveau, D. M. Owen, M. A. A. Neil, D. M. Davis, and P. M. W. French, "High-speed high-resolution imaging of intercellular immune synapses using optical tweezers," Biophys. J. 95, L66-L68 (2008).
[CrossRef] [PubMed]

Expert Opin. Drug Discov.

K. Sott, E. Eriksson, E. Petelenz, and M. Goksor, "Optical systems for single cell analyses," Expert Opin. Drug Discov. 3, 1323-1344 (2008).
[CrossRef]

J. R. Soc. Interface

H. Zhang and K. K. Liu, "Optical tweezers for single cells," J. R. Soc. Interface 5, 671-690 (2008).
[CrossRef] [PubMed]

Lab Chip

H. A. Svahn and A. van den Berg, "Single cells or large populations?," Lab Chip 7, 544-546 (2007).
[CrossRef] [PubMed]

P. Jordan, J. Leach, M. Padgett, P. Blackburn, N. Isaacs, M. Goksor, D. Hanstorp, A. Wright, J. Girkin, and J. Cooper, "Creating permanent 3D arrangements of isolated cells using holographic optical tweezers," Lab Chip 5, 1224-1228 (2005).
[CrossRef] [PubMed]

U. Mirsaidov, J. Scrimgeour, W. Timp, K. Beck, M. Mir, P. Matsudaira, and G. Timp, "Live cell lithography: Using optical tweezers to create synthetic tissue," Lab Chip 8, 2174-2181 (2008).
[CrossRef] [PubMed]

E. Eriksson, J. Enger, B. Nordlander, N. Erjavec, K. Ramser, M. Goksor, S. Hohmann, T. Nystrom, and D. Hanstorp, "A microfluidic system in combination with optical tweezers for analyzing rapid and reversible cytological alterations in single cells upon environmental changes," Lab Chip 7, 71-76 (2007).
[CrossRef]

Mol. Syst. Biol.

D. Longo and J. Hasty, "Dynamics of single-cell gene expression," Mol. Syst. Biol. 2, 64 (2006).
[CrossRef] [PubMed]

Nat. Methods

A. Gordon, A. Colman-Lerner, T. E. Chin, K. R. Benjamin, R. C. Yu, and R. Brent, "Single-cell quantification of molecules and rates using open-source microscope-based cytometry," Nat. Methods 4, 175-181 (2007).
[CrossRef] [PubMed]

Nat. Rev. Mol. Cell Biol.

Y. Shav-Tal, R. H. Singer, and X. Darzacq, "Imaging gene expression in single living cells," Nat. Rev. Mol. Cell Biol. 5, 855-862 (2004).
[CrossRef] [PubMed]

Nature

L. Cai, C. K. Dalal, and M. B. Elowitz, "Frequency-modulated nuclear localization bursts coordinate gene regulation," Nature 455, 485-490 (2008).
[CrossRef] [PubMed]

Opt. Commun.

J. Liesener, M. Reicherter, T. Haist, and H. J. Tiziani, "Multi-functional optical tweezers using computergenerated holograms," Opt. Commun. 185, 77-82 (2000).
[CrossRef]

J. E. Curtis, B. A. Koss, and D. G. Grier, "Dynamic holographic optical tweezers," Opt. Commun. 207, 169-175 (2002).
[CrossRef]

Opt. Express

Opt. Lett.

Science

M. B. Elowitz, A. J. Levine, E. D. Siggia, and P. S. Swain, "Stochastic gene expression in a single cell," Science 297, 1183-1186 (2002).
[CrossRef] [PubMed]

J. M. Raser and E. K. O’Shea, "Control of stochasticity in eukaryotic gene expression," Science 304, 1811-1814 (2004).
[CrossRef] [PubMed]

N. Q. Balaban, J. Merrin, R. Chait, L. Kowalik, and S. Leibler, "Bacterial persistence as a phenotypic switch," Science 305, 1622-1625 (2004).
[CrossRef] [PubMed]

Trends Biotechnol.

D. Petranovic, and J. Nielsen, "Can yeast systems biology contribute to the understanding of human disease?," Trends Biotechnol. 26, 584-590 (2008).
[CrossRef] [PubMed]

Other

E. Eriksson, J. Scrimgeour, J. Enger, and M. Goksor, "Holographic optical tweezers combined with a microfluidic device for exposing cells to fast environmental changes," SPIE Proc. 6592, P5920-9 (2007).

To make the hologram calculation more efficient, the algorithm was modified to update the trap intensities for all traps in a specific axial plane simultaneously, rather than looping through the number of traps individually. To achieve trapping patterns with high uniformity of the trap intensities, the number of iterations was also increased.

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Figures (6)

Fig. 1.
Fig. 1.

(a) Illustration of how budding yeast cells align in optical traps with nuclei in different planes in a 2D array of traps, depending on size, shape etc. All nuclei (or other organelles of interest) of the cells in the array will thus not be imaged correctly. (b) Using HOTs it is possible to individually adjust the axial position of each individual trap, such that the nuclei of the cells always coincides with the imaging plane.

Fig. 2.
Fig. 2.

Schematic drawing of the holographic optical tweezers setup. The laser beam is expanded by a telescope comprising lenses L1 and L2, then reflected off the SLM. The SLM plane is imaged onto the back focal plane of the microscope objective by a second telescope (L3 and L4). The desired trapping pattern is formed in or close to the image plane, which is imaged onto an EM-CCD camera. The position of the dichroic mirror (reflecting the laser up through the microscope objective) above the fluorescence filter cassette allows for independent multicolor imaging without affecting the laser trapping.

Fig. 3.
Fig. 3.

(a) The distribution of 24 nuclei found from an axial scan using the SLM. (b) GFP image at z = 0 μm, the plane where most nuclei are in focus simultaneously. (c) Optimized GFP image captured after each trap had been individually adjusted in the axial direction, allowing all nuclei to be in focus in the same image. Note the natural cell-to-cell variation in intensity and degree of nuclear localization. Scale bar 5 μm.

Fig. 4.
Fig. 4.

Analysis of the average intensities in the nuclei of the individual cells. The optimum plane to use with a 2D array is at z = 0.0μm (red triangles). The maximum average nuclear intensity found in the stack is shown as blue plus signs. The green circles corresponds to the optimized image. The fact that the nuclear intensities in this image are not always highest can to a large extent be explained by small movements of the nuclei around the equilibrium position (error bars representing the standard deviation) as well as photobleaching (black squares).

Fig. 5.
Fig. 5.

The use of less symmetric trapping patterns gives better performance. Top: GFP images; (a) the image at the single trapping plane where most nuclei are in focus and (b) the image where the axial position of each cell has been adjusted individually, in order for all nuclei to be in focus in the same image. Bottom: brightfield images; (c) image at the best single plane, and (d) optimized image. Scale bar 5 μm.

Fig. 6.
Fig. 6.

A comparison of the photobleaching using the HOTs approach presented in this paper and axial stacking. The curves show the average nuclear intensities for 24 cells trapped in an array, as in Fig. 3, for 40 consecutive images (red solid) or stacks (blue dashed). For the curve representing the stack, the nuclear intensity for each individual cell is taken from the image in the stack giving the highest signal, at each time point. The background is subtracted before normalizing the intensities to one for the first image/stack. Photobleaching makes the signal fade over time, with a faster rate when stacks are acquired at each time point. Thus, the optimization of the individual trap positions in order to bring the nucleus into one single imaging plane, allows more images containing useful information to be acquired.

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