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Imaging methods for elemental, chemical, molecular, and morphological analyses of single cells

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Abstract

Combining elemental, chemical, molecular, and morphological imaging information from individual cells with a lateral resolution well below 1 × 1 μm2 is the current technological challenge for investigating the smallest dimensions of living systems. In the race for such analytical performance, several techniques have been successfully developed; some use probes to determine given cellular contents whereas others use possible interactions between cellular matter with light or elements for characterization of contents. Morphological techniques providing information about cell dimensions have, when combined with other techniques, also opened the way to quantitative studies. New analytical opportunities are now being considered in cell biology, combining top-performance imaging techniques, applied to the same biosystem, with microscopy (nm–μm range) techniques providing elemental (micro-X-ray fluorescence, particle-induced X-ray emission, secondary-ion mass spectrometry), chemical (Raman, coherent anti-stokes Raman, Fourier-transform infrared, and near-field), molecular (UV–visible confocal and multiphoton), and morphological (AFM, ellipsometry, X-ray phase contrast, digital holography) information. Dedicated cell-culture methods have been proposed for multimodal imaging in vitro and/or ex vivo. This review shows that in addition to UV–fluorescent techniques, the imaging modalities able to provide interesting information about a cell, with high spatial and time resolution, have grown sufficiently to envisage quantitative analysis of chemical species inside subcellular compartments.

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Abbreviations

AFM:

Atomic-force microscopy

BAM:

Brewster-angle microscopy

CARS:

Coherent anti-stokes Raman scattering

CT:

Computed tomography

DHM:

Digital holography microscopy

ER:

Endoplasmic reticulum

FOV:

Field of view

FTIR:

Fourier-transform infrared

GFP:

Green fluorescent protein

MRI:

Magnetic resonance imaging

OM:

Optical microscopy

PET:

Positron-emission microscopy

PIXE:

Particle-induced X-ray emission

QDs:

Quantum dots

SIMS:

Secondary-ion mass spectroscopy

SNOM:

Scanning near-field optical microscopy

SPECT:

Single-photon emission computed tomography

STED:

Stimulated emission depletion

UV-CF:

Ultraviolet–visible confocal fluorescence

XR-PC:

X-ray phase contrast

XRF:

X-ray fluorescence

References

  1. Stephens DJ, Allan VJ (2003) Science 300:82–86

    Article  CAS  Google Scholar 

  2. Hell SW (2007) Science 316:1153–1158

    Article  CAS  Google Scholar 

  3. Betzig E, Trautman JK (1992) Science 257:189–195

    Article  CAS  Google Scholar 

  4. Meuli R, Hwu Y, Je JH, Margaritondo G (2004) Eur Radiol 14:1550–1560

    Article  Google Scholar 

  5. Petibois C, Cestelli Guidi M (2008) Anal Bioanal Chem 391:1599–1608

    Article  CAS  Google Scholar 

  6. Petibois C, Déléris G (2006) Trends Biotechnol 24:455–462

    Article  CAS  Google Scholar 

  7. Sample V, Newman RH, Zhang J (2009) Chem Soc Rev 38:2852–2864

    Article  CAS  Google Scholar 

  8. White JG, Amos WB, Fordham M (1987) J Cell Biol 105:41–48

    Article  CAS  Google Scholar 

  9. Jaiswal JK, Goldman ER, Mattoussi H, Simon SM (2004) Nat Methods 1:73–78

    Article  Google Scholar 

  10. Prasher DC (1995) Trends Genet 11:320–323

    Article  CAS  Google Scholar 

  11. Heim R, Cubitt AB, Tsien RY (1995) Nature 373:663–664

    Article  CAS  Google Scholar 

  12. Willig KI, Kellner RR, Medda R, Hein B, Jakobs S, Hell SW (2006) Nat Methods 3:721–723

    Article  CAS  Google Scholar 

  13. Helmchen F, Denk W (2005) Nat Methods 2:932–940

    Article  CAS  Google Scholar 

  14. Flusberg BA, Cocker ED, Piyawattanametha W, Jung JC, Cheung EL, Schnitzer MJ (2005) Nat Methods 2:941–950

    Article  CAS  Google Scholar 

  15. Weon BM, Je JH, Hwu Y, Margaritondo G (2006) Int J Nanotechnol 3:280–297

    CAS  Google Scholar 

  16. Son SW, Park SY, Park GM, Ha SH, Lee GW, Lee OS, Hwu Y, Kim AR, Je JH, Oh CH (2008) Skin Res Technol 14:13–17

    Article  Google Scholar 

  17. Chaudhuri O, Parekh SH, Lam WA, Fletcher DA (2009) Nat Methods 6:383–387

    Article  CAS  Google Scholar 

  18. Novak P, Li C, Shevchuk AI, Stepanyan R, Caldwell M, Hughes S, Smart TG, Gorelik J, Ostanin VP, Lab MJ, Moss GW, Frolenkov GI, Klenerman D, Korchev YE (2009) Nat Methods 6:279–281

    Article  CAS  Google Scholar 

  19. Lapshin RV (2004) Nanotechnology 15:1135–1151

    Article  CAS  Google Scholar 

  20. Malmsten M, Siegel G, Becker A (2001) J Colloid Interface Sci 240:372–374

    Article  CAS  Google Scholar 

  21. Colomb T, Kuhn J, Charriere F, Depeursinge C, Marquet P, Aspert N (2006) Opt Express 14:4300–4306

    Article  Google Scholar 

  22. Rappaz B, Marquet P, Cuche E, Emery Y, Depeursinge C, Magistretti P (2005) Opt Express 13:9361–9373

    Article  Google Scholar 

  23. Emery Y, Cuche E, Colomb T, Depeursinge C, Rappaz B, Marquet P, Magistretti P (2007) J Phys Conf Ser 61:1317–1321

    Article  Google Scholar 

  24. Paunesku T, Vogt S, Maser J, Lai B, Woloschak G (2006) J Cell Biochem 99:1489–1502

    Article  CAS  Google Scholar 

  25. Finney L, Mandava S, Ursos L, Zhang W, Rodi D, Vogt S, Legnini D, Maser J, Ikpatt F, Olopade OI, Glesne D (2007) Proc Natl Acad Sci USA 104:2247–2252

    Article  CAS  Google Scholar 

  26. Yang L, McRae R, Henary MM, Patel R, Lai B, Vogt S, Fahrni CJ (2005) Proc Natl Acad Sci USA 102:11179–11184

    Article  CAS  Google Scholar 

  27. Corezzi S, Urbanelli L, Cloetens P, Emiliani C, Helfen L, Bohic S, Elisei F, Fioretto D (2009) Anal Biochem 388:33–39

    Article  CAS  Google Scholar 

  28. Fahrni CJ (2007) Curr Opin Chem Biol 11:121–127

    Article  CAS  Google Scholar 

  29. Rokita E, Mutsaers PHA, Quaedackers JA, Taton G, de Voigt MJA (1998) Nucl Instrum Methods Phys B 319:180–185

    Article  Google Scholar 

  30. Kemner KM, Kelly SD, Lai B, Maser J, O’Loughlin EJ, Sholto-Douglas D, Cai Z, Schneegurt MA, Kulpa CF Jr, Nealson KH (2004) Science 306:686–687

    Article  CAS  Google Scholar 

  31. Chandra S (2004) Appl Surf Sci 231–2:467–469

    Article  Google Scholar 

  32. Arlinghaus HF, Kriegeskotte C, Fartmann M, Wittig A, Sauerwein W, Lipinsky D (2006) Appl Surf Sci 252:6941–6948

    Article  CAS  Google Scholar 

  33. Petibois C, Piccinini M, Cestelli-Guidi M, Marcelli A (2010) J Synchrotron Radiat 17:1–11

    Article  CAS  Google Scholar 

  34. Petibois C, Deleris G, Piccinini M, Cestelli Guidi M, Marcelli A (2009) Nat Photonics 3:179

  35. Kuimova MK, Chan KL, Kazarian SG (2009) Appl Spectrosc 63:164–171

    Article  CAS  Google Scholar 

  36. Freudiger CW, Min W, Saar BG, Lu S, Holtom GR, He C, Tsai JC, Kang JX, Xie XS (2008) Science 322:1857–1861

    Article  CAS  Google Scholar 

  37. Fu Y, Huff TB, Wang HW, Wang H, Cheng JX (2008) Opt Express 16:19396–19409

    Article  CAS  Google Scholar 

  38. Wang K, Mittleman DM (2004) Nature 432:376–379

    Article  CAS  Google Scholar 

  39. Vobornik D, Margaritondo G, Sanghera JS, Thielen P, Aggarwal ID, Ivanovc B, Tolk NH, Mannid V, Grimaldi S, Lisi A, Rieti S, Piston DW, Generosi R, Luce M, Perfetti P, Cricenti A (2005) J Alloys Compounds 401:80–85

    Article  CAS  Google Scholar 

  40. Phelps ME (2000) Proc Natl Acad Sci USA 97:9226–9233

    Article  CAS  Google Scholar 

  41. Miller JC, Thrall JH (2004) J Am Coll Radiol 1:4–23

    Article  Google Scholar 

  42. Higgins CM, Jung C, Xu Z (2003) BMC Neurosci 4:16

    Article  Google Scholar 

  43. Lin HH, Lai JS, Chin AL, Chen YC, Chiang AS (2007) Cell 128:1205–1217

    Article  CAS  Google Scholar 

  44. Kazarian SG, Chan KL (2006) Biochim Biophys Acta 1758:858–867

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The author is indebted to “Ligue Contre le Cancer”, “Association Françasie contre les Myopathies”, and the “Agence Nationale pour la Recherche – ANR” for financial support.

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Correspondence to Cyril Petibois.

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Petibois, C. Imaging methods for elemental, chemical, molecular, and morphological analyses of single cells. Anal Bioanal Chem 397, 2051–2065 (2010). https://doi.org/10.1007/s00216-010-3618-7

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  • DOI: https://doi.org/10.1007/s00216-010-3618-7

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