J. Mass Spectrom. Soc. Jpn., 53, 125-132

J. Mass Spectrom. Soc. Jpn.
Vol. 53, No. 3, 2005
COMMENTARY
Mass Microprobe Aimed at Biological Samples
῎
Yasuhide N6>ID
(Received December 9, 2004; Accepted February 26, 2005)
Mass microprobe acquires mass-to-charge ratios of ions which are generated at an extremely small area on
the sample surface. A raster achieved by moving the area of ionization over the sample surface allows to map a
wide variety of compounds existing on the surface with a lateral resolution of 1῍100 mm. The technology to
visualize a local distribution of compounds in the sample is called imaging mass spectrometry and is recognized
as an emerging field of mass spectrometry in recent years. Mass microprobe can now be applied to biological
samples, such as thin tissue sections, after significant progress of sample preparation techniques. SIMS, LDI, and
MALDI are ionization methods utilized in mass microprobe. Molecular images of light compounds, such as lipids
or metabolites, are suited to be recorded by SIMS or LDI, whereas peptides and proteins are targeted by MALDI.
Although the sensitivity is the most important issue still to be overcome, mass microprobe is superior to optical
observations for providing chemical information on biological samples, and is highly promising as a practical
tool of biological researches in very near future.
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E-mail: [email protected]
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Fig. 1.
Principle of imaging mass spectrometry with mass microprobe. A thin flat sample, such as a tissue section, is
subjected to SIMS, LDI, or MALDI source. The area of ionization on the sample surface is clearly identified by the
small exposure spot of primary ion beam (SIMS) or pulsed laser beam (LDI or MALDI). Thus a mass spectrum
corresponding to a particular location (pixel) on the sample surface is recorded. Imaging is achieved by scanning
pixels over the sample surface. After the whole mass spectra being recorded, peak intensities at each m/z are
converted to gray scale tones of image pixels, i.e., a darker represents a higher intensity, to create raster images.
Each m/z gives a raster image, which is the molecular image of that m/z over the sample surface.
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Mass Microprobe Aimed at Biological Samples
Table 1.
Institute
Current Researches for MALDI Mass Microprobe
Leader
Main research activities
Vanderbilt Univ., U.S.A.
R. M. Caprioli
Univ. Illinois, U.S.A.
Novartis Pharma AG, Switzerland
J. V. Sweedler
M. Stoeckli
Univ. Giessen, Germany
FOM-AMOLF, The Netherlands
She$eld Hallam Univ., U.K.
B. Spengler
R. M. A. Heeren
M. Clench
Penn. State Univ., U.S.A.
N. Winograd
ICSN-CNRS, France
O. Laprevote
Iowa State Univ., U.S.A.
E. S. Yeung
Univ. Metz, France
J.-F. Muller
EMSL-PNNL, U.S.A.
Univ. Manitoba, Canada
Texas A&M Univ., U.S.A.
Applied Biosystems/MDS Sciex, Canada
K. M. Beck
W. Ens
D. H. Russell
J. Y. Zhao
a)
b)
c)
d)
e)
f)
g)
Instrumentation, Method development, Molecular imaging
of proteins in tissue and cell
Method development, Molecular imaging of peptides in cell
Instrumentation, Method development, Molecular imaging
of peptides in tissue
Instrumentation (built in-house), Method development
Instrumentation (stigmatic mode), Method development
Method development
Molecular imaging of light compounds in epidermis
Instrumentation, Method development
(LDI from frozen aqueous matrix)
Instrumentation (MALDI and Cluster-SIMS),
Method developmenta)
Method development (colloidal metal additive LDI),
Molecular imaging of light compoundsb)
Instrumentation
Method developmentc)
Instrumentationd)
Instrumentation (orthogonal-configuration)e)
Instrumentation (DMAf) optics, ion-mobility device)g)
Instrumentation, Method development, Molecular imaging
of light compounds in tissue
A. Brunelle, et al., Proceedings of the 52nd ASMS Conference on Mass Spectrometry and Allied Topics, Nashville, TN, May
23῍27, 2004, WOBpm04 : 00
C. Sluszny and E. S. Yeung, Proceedings of the 52nd ASMS Conference on Mass Spectrometry and Allied Topics,
Nashville, TN, May 23῍27, 2004, TPL208
J.-F. Muller, et al., Proceedings of the 51st ASMS Conference on Mass Spectrometry and Allied Topics, Montreal, Canada,
June 8῍12, 2003, MPY497
D. S. Wunschel and K. M. Beck, Proceedings of the 51st ASMS Conference on Mass Spectrometry and Allied Topics,
Montréal, Canada, June 8῍12, 2003, MPY499
G. Piyadasa, et al., Proceedings of the 52nd ASMS Conference on Mass Spectrometry and Allied Topics, Nashville, TN,
May 23῍27, 2004, TPL207
Digital mirror array
S. D. Sherrod, et al., Proceedings of the 52nd ASMS Conference on Mass Spectrometry and Allied Topics, Nashville, TN,
May 23῍27, 2004, TPL209
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Fig. 2.
An example of MALDI mass microprobe data obtained from single cultured cerebral ganglion neuron of Aplysia
californica. (A) Raster image showing the spatial distribution of peptide with m/z 4617. (B) Mass spectra which
were taken from spots located on a line with their centers separated by 50 mm. Peaks are detected that correspond
to physiological active neuropeptides: AP, acidic peptide; ELH, egg laying hormone. MALDI matrix: a-cyano-4hydroxycinnamic acid (A) or sinapinic acid (B); 50 mg of each matrix was dissolved in 1 mL of acetone. (Figure
supplied courtesy of J. V. Sweedler and reprinted with permission from ref. 22. Copyright 2003 American
Chemical Society.)
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Mass Microprobe Aimed at Biological Samples
Fig. 3.
Schematic diagram of a stigmatic mode (mass microscope). Relative positions of analytes within the exposure spot
of pulsed primary ion beam (SIMS) or pulsed laser beam (LDI or MALDI) are conserved through flying in the
mass analyzer region, which consists of stigmatic achromatic ion transfer optics. Each bunch of ions separated
according to the flight time (m/z) is subjected to magnification with electrostatic lenses followed by a position
sensitive detector to create the enlarged molecular image directly.
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P. J. Todd, T. G. Schaa#, P. Chaurand, and R. M. Caprioli,
J. Mass Spectrom., 36, 355 (2001).
P. Chaurand, S. A. Schwartz, and R. M. Caprioli, Anal.
Chem., 76, 86A (2004).
M. L. Pacholski and N. Winograd, Chem. Rev., 99, 2977
(1999).
P. J. Todd, J. M. McMahon, R. T. Short, and C. A. McCandlish, Anal. Chem., 69, 529A (1997).
P. Chaurand and R. M. Caprioli, Electrophoresis, 23, 3125
(2002).
M. Stoeckli, P. Chaurand, D. E. Hallahan, and R. M.
Caprioli, Nat. Med., 7, 493 (2001).
A. Benninghoven, B. Hagenho#, and E. Niehuis, Anal.
Y. Naito
8)
9)
10)
11)
12)
13)
14)
15)
16)
17)
18)
19)
20)
21)
22)
Chem., 65, 630A (1993).
A. Benninghoven and W. K. Sichtermann, Anal. Chem.,
50, 1180 (1978).
J. M. McMahon, N. N. Dookeran, and P. J. Todd, J. Am.
Soc. Mass Spectrom., 6, 1047 (1995).
A. Delcorte, N. Medard, and P. Bertrand, Anal. Chem., 74,
4955 (2002).
C. C. Grimm, R. T. Short, and P. J. Todd, J. Am. Soc. Mass
Spectrom., 2, 362 (1991).
B. Spengler and M. Hubert, J. Am. Soc. Mass Spectrom.,
13, 735 (2002).
P. Chaurand, G. Hayn, U. Matter, and R. M. Caprioli,
Proceedings of the 52nd ASMS Conference on Mass
Spectrometry and Allied Topics, Nashville, TN, May
23῍27, 2004, TPL210.
M. Stoeckli, T. B. Farmer, and R. M. Caprioli, J. Am. Soc.
Mass Spectrom., 10, 67 (1999).
http://rsb.info.nih.gov
B. J. Xu, R. M. Caprioli, M. E. Sanders, and R. A. Jensen,
J. Am. Soc. Mass Spectrom., 13, 1292 (2002).
T. L. Colliver, C. L. Brummel, M. L. Pacholski, F. D.
Swanek, A. G. Ewing, and N. Winograd, Anal. Chem., 69,
2225 (1997).
J. M. McMahon, R. T. Short, C. A. McCandlish, J. T.
Brenna, and P. J. Todd, Rapid Commun. Mass Spectrom.,
10, 335 (1996).
L. Van Vaeck, K. Poels, S. De Nollin, A. Hachimi, and R.
Gijbels, Cell Biol. Int., 21, 635 (1997).
L. Van Vaeck, H. Struyf, W. Van Roy, and F. Adams,
Mass Spectrom. Rev., 13, 209 (1994).
M. Stoeckli, D. Staab, M. Staufenbiel, K.-H. Wiederhold,
and L. Signor, Anal. Biochem., 311, 33 (2002).
S. S. Rubakhin, W. T. Greenough, and J. V. Sweedler,
23)
24)
25)
26)
27)
28)
29)
30)
31)
32)
33)
Anal. Chem., 75, 5374 (2003).
M. L. Reyzer, Y. Hsieh, K. Ng, W. A. Korfmacher, and R.
M. Caprioli, J. Mass Spectrom., 38, 1081 (2003).
J. Bunch, M. R. Clench, and D. S. Richards, Proceedings
of the 52nd ASMS Conference on Mass Spectrometry
and Allied Topics, Nashville, TN, May 23῍27, 2004, TPL
216.
R. Holm and D. Holtkamp, “Microbeam Analysisῌ
1989,” ed. by P. E. Russell, San Francisco Press Inc., San
Francisco (1989), pp. 325῍329.
J. Wei, J. M. Buriak, and G. Siuzdak, Nature, 399, 243
(1999).
S. Berkenkamp, M. Karas, and F. Hillenkamp, Proc. Natl.
Acad. Sci. U.S.A., 93, 7003 (1996).
J. I. Berry, S. Sun, Y. Dou, A. Wucher, and N. Winograd,
Anal. Chem., 75, 5146 (2003).
J. Y. Zhao, A. Dindyal-Popescu, G. Scott, M. Yang, and J.
E. Wingate, Proceedings of the 52nd ASMS Conference
on Mass Spectrometry and Allied Topics, Nashville, TN,
May 23῍27, 2004, TPL215.
B. W. Schueler, Microsc. Microanal. Microstruct., 3, 119
(1992).
R & D 34 (2), 11
(1999).
S. L. Luxembourg, T. H. Mize, L. A. McDonnell, and R. M.
A. Heeren, Anal. Chem., 76, 5339 (2004).
T. Matsuo, M. Toyoda, T. Sakurai, and M. Ishihara, J.
Mass Spectrom., 32, 1179 (1997).
Keywords: Mass microprobe, Imaging mass spectrometry,
Molecular imaging, Secondary ion mass spectrometry (SIMS),
Laser microprobe mass spectrometry (LMMS), Matrix-assisted
laser desorption/ionization (MALDI)
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