EDITORIAL pubs.acs.org/ac
Novel Optical Probes for Advanced Chemical Imaging
I
n 2006, the National Research Council (NRC) published an extensive report titled Visualizing Chemistry: The Progress and Promise of Advanced Chemical Imaging.1 Its primary objectives were to (i) provide a summary of the state-of-the-art in chemical imaging technology, (ii) identify existing challenges in chemical imaging, and (iii) outline promising routes to possible breakthroughs in meeting these challenges. The variety of topics covered reflects the broad range of methods that fall within the realm of chemical imaging. Included are optical and spectroscopic imaging; optical, electron, electrochemical, and topographic proximal probe methods; magnetic resonance imaging; and X-ray, ion, electron, and neutron microscopies. The variety of experiments in which these methods are applied is equally diverse, spanning compositional, structural and dynamics studies of systems ranging from relatively simple few-component selfassembled materials to complex biological organisms. This Virtual Issue of Analytical Chemistry provides an update on the optical imaging science described in the NRC report, emphasizing work published in the journal over the previous ∼5 years. The articles included serve as representative examples of some of the most exciting advances now being made. This issue begins with recent reports describing subdiffraction-limited optical imaging by both near-field optical2,3 and single molecule methods. A recent Perspective published by the Moerner group provides a detailed overview of single molecule methods and their applications to live-cell imaging.4 Some of the most exciting studies in this area employ superlocalization methods to achieve subdiffraction-limited spatial resolution (down to ∼1 nm) in imaging experiments.4,5 Other reports describe the continued development of methods for three-dimensional tracking of single particles under high background conditions,6 such as may be found in samples ranging from gels to live cells. Tracking methods provide valuable data on diffusion mechanisms and on probe-target binding. Molecular orientation and orientation dynamics are also being widely explored, and new methods for rapidly acquiring such data continue to be developed.7 Some of the most important single molecule experiments now being performed seek a better understanding of (bio)molecule conformation, binding dynamics,8 and reaction kinetics.9 It is seldom possible to synchronize the dynamics in such systems, preventing their study by ensemble methods.4 The coupling of fluorescence lifetime imaging with single molecule detection affords a unique route to probing dynamics on a wide range of time scales.10 Advances continue to be made in the development of new nanoparticles and quantum dots for use as labels and probes in optical imaging experiments. These probes have helped overcome problems associated with photobleaching of organic dyes. Recent reports describe the use of luminescent quantum dots for detection of rare cell types in complex samples.11 A number of research groups are also working on methods for detection of nonluminescent nanoparticles at the single particle level. Such studies include the implementation of plasmon enhanced Rayleigh scattering from silver-nanoparticle based biosensors for the r 2011 American Chemical Society
imaging of receptor site locations on cells.12 Important alternative contrast mechanisms for single nanoparticle detection and imaging include wavelength-dependent differential interference contrast13 and photothermal interference methods.14 While semiconductor quantum dots and noble metal nanoparticles are most commonly employed in imaging studies, the use of aluminum nanoparticles has been proposed as a route to enhancing native biomolecule luminescence for label-free imaging.15 In addition to nanoparticle-based methods, the high-resolution imaging of patterned films on planar metal substrates has been demonstrated by angle-resolved through-objective surface plasmon resonance microscopy.16 Nonlinear optical methods continue to be developed and employed for imaging a wide variety of samples. Multiphotonexcited fluorescence methods provide direct access to improved spatial resolution (in all three-dimensions) through the nonlinear dependence of fluorescence excitation on incident laser intensity. Fluorescence excitation using pulses of near-IR light from a mode-locked laser source affords additional advantages for imaging within biological tissues as these exhibit enhanced transparency in this spectral region.17 Other exciting demonstrations in nonlinear optical imaging include the visualization of collagen fibers in cancerous tissue,18 and of noncentrosymmetric crystalline domains in organic samples19 by second harmonic generation microscopy. Reports describing the continued development of coherent antistokes Raman spectroscopy (CARS) imaging demonstrate the capabilities of this method for high-resolution imaging of chemical composition in polymer blends20 and lipid films21 and for following dynamical processes in living cells.22 CARS imaging affords distinct advantages over spontaneous Raman methods through the coherent and strongly enhanced signals it provides. CARS microscopy experiments, which seek to distinguish resonant signals from the ever-present nonresonant background,20,21,23 are being reported and employed to obtain quantitative chemical information on sample composition.20 Surface enhanced Raman spectroscopy (SERS) imaging methods, which employ plasmonic nanoparticles for signal enhancement, are being used to image a variety of samples from patterned films to cells.24 When coupled with near-field optical probes,2 SERS imaging offers the possibility of dramatically improved spatial resolution, higher signal levels, and greater imaging speeds, as compared to unenhanced Raman methods. Laser-desorption imaging mass spectrometry represents another unique tool for chemical imaging. While spatial resolution is limited in most studies, improvements continue to be made. Resolution can be enhanced by incorporation of metal colloids in the sample25 for localized deposition of laser energy, while the combination of laser ablation by near-field optical illumination and mass spectrometric detection provides a possible route to
Published: October 17, 2011 8048
dx.doi.org/10.1021/ac2026749 | Anal. Chem. 2011, 83, 8048–8049
Analytical Chemistry subdiffraction-limited spatial resolution.3 Although often performed under vacuum, laser-desorption imaging has also been demonstrated under atmospheric pressure.3,26 The range of samples that can be studied by laser desorption imaging mass spectrometry now includes very complex materials, such as whole-body animal tissue sections.27 The representative articles within this Virtual Issue clearly depict the significant progress that continues to be made in the development of new optical imaging methods and in their application to the chemical imaging of diverse and complex samples. However, much progress remains to be made, with likely advances coming in the development of improved spatial and temporal resolution, quantitation, signal enhancement, and noise and background reduction and in the acquisition of detailed chemical information on the structure and function of complex biological samples.
EDITORIAL
(24) Lee, S.; Kim, S.; Choo, J.; Shin, S. Y.; Lee, Y. H.; Choi, H. Y.; Ha, S.; Kang, K.; Oh, C. H. Anal. Chem. 2007, 79, 916–922. (25) Jun, J. H.; Song, Z.; Liu, Z.; Nikolau, B. J.; Yeung, E. S.; Lee, Y. J. Anal. Chem. 2010, 82, 3255–3265. (26) Li, Y.; Shrestha, B.; Vertes, A. Anal. Chem. 2007, 79, 523–532. (27) Khatib-Shahidi, S.; Andersson, M.; Herman, J. L.; Gillespie, T. A.; Caprioli, R. M. Anal. Chem. 2006, 78, 6448–6456.
’ REFERENCES (1) National Research Council. Visualizing Chemistry: The Progress and Promise of Advanced Chemical Imaging; National Academies Press: Washington, DC, 2006. (2) Hankus, M. E.; Li, H.; Gibson, G. J.; Cullum, B. M. Anal. Chem. 2006, 78, 7535–7546. (3) Schmitz, T. A.; Gamez, G.; Setz, P. D.; Zhu, L.; Zenobi, R. Anal. Chem. 2008, 80, 6537–6544. (4) Lord, S. J.; Lee, H.-I. D.; Moerner, W. E. Anal. Chem. 2010, 82, 2192–2203. (5) Luo, Y.; Sun, W.; Liu, C.; Wang, G.; Fang, N. Anal. Chem. 2011, 83, 5073–5077. (6) Wells, N. P.; Lessard, G. A.; Werner, J. H. Anal. Chem. 2008, 80, 9830–9834. (7) Xiao, L.; Qiao, Y. X.; He, Y.; Yeung, E. S. Anal. Chem. 2010, 82, 5268–5274. (8) Wayment, J. R.; Harris, J. M. Anal. Chem. 2009, 81, 336–341. (9) Li, J.; Yeung, E. S. Anal. Chem. 2008, 80, 8509–8513. (10) Roth, C. M.; Heinlein, P. I.; Heilemann, M.; Herten, D.-P. Anal. Chem. 2007, 79, 7340–7345. (11) Liu, J.; Lau, S. K.; Varma, V. A.; Kairdolf, B. A.; Nie, S. Anal. Chem. 2010, 82, 6237–6243. (12) Huang, T.; Nallathamby, P. D.; Gillet, D.; Xu, X.-H. N. Anal. Chem. 2007, 79, 7708–7718. (13) Sun, W.; Wang, G.; Fang, N.; Yeung, E. S. Anal. Chem. 2009, 81, 9203–9208. (14) Cognet, L.; Berciaud, S.; Lasne, D.; Lounis, B. Anal. Chem. 2008, 80, 2288–2294. (15) Chowdhury, M. H.; Ray, K.; Gray, S. K.; Pond, J.; Lakowicz, J. R. Anal. Chem. 2009, 81, 1397–1403. (16) Huang, B.; Yu, F.; Zare, R. N. Anal. Chem. 2007, 79, 2979–2983. (17) Hwang, Y.-J.; Granelli, J.; Lyubovitsky, J. G. Anal. Chem. 2011, 83, 200–206. (18) Campagnola, P. Anal. Chem. 2011, 83, 3224–3231. (19) Wanapun, D.; Kestur, U. S.; Taylor, L. S.; Simpson, G. J. Anal. Chem. 2011, 83, 4745–4751. (20) Lee, Y. J.; Moon, D.; Migler, K. B.; Cicerone, M. T. Anal. Chem. 2011, 83, 2733–2739. (21) Chowdary, P. D.; Benalcazar, W. A.; Jiang, Z.; Marks, D. M.; Boppart, S. A.; Gruebele, M. Anal. Chem. 2010, 82, 3812–3818. (22) Kano, H.; Hamaguchi, H. Anal. Chem. 2007, 79, 8967–8973. (23) Jurna, M.; Garbacik, E. T.; Korterik, J. P.; Herek, J. L.; Otto, C.; Offerhaus, H. L. Anal. Chem. 2010, 82, 7656–7659. 8049
dx.doi.org/10.1021/ac2026749 |Anal. Chem. 2011, 83, 8048–8049
