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 awide variety of compounds existing on the surface with a lateral resolution of 1῍100 mm. The technology tovisualize 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 biologicalsamples, 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 opticalobservations 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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Institute of Free Electron Laser, Graduate School of Engineering, Osaka University (2῍9῍5 Tsuda-Yamate, Hirakata
573῍0128, Japan)
E-mail: naito@fel.eng.osaka-u.ac.jp
w;<x eyz=3Fl3F tῌ431῍1202 >{V|{?
1955῍1v
The Graduate School for the Creation of New Protonics Industries (1955῍1 Kurematsu-cho, Hamamatsu 431῍1202, Japan)
E-mail: naito@gpi.ac.jp

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Y. Naito

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 thesmall 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 scanningpixels 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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MALDI) ;5nu,Gn()*+, $%&'-./01234
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ῌ 126 ῌ

Mass Microprobe Aimed at Biological Samples 

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Mass Microprobe Aimed at Biological Samples

Table 1.

Current Researches for MALDI Mass Microprobe

Institute

LeaderMain 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. EnsD. H. Russell
J. Y. Zhao

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 imagingof light compounds in tissuea)A. Brunelle, et al., Proceedings of the 52nd ASMS Conference on Mass Spectrometry and Allied Topics, Nashville, TN, May23῍27, 2004, WOBpm04 : 00
b)
C. Sluszny and E. S. Yeung, Proceedings of the 52nd ASMS Conference on Mass Spectrometry and Allied Topics,
Nashville, TN, May 23῍27, 2004, TPL208c)
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)
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May 23῍27, 2004, TPL209 

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Y. Naito

Fig. 2.

An example of MALDI mass microprobe data obtained from single cultured cerebral ganglion neuron of Aplysia
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Schematic diagram of a stigmatic mode (mass microscope). Relative positions of analytes within the exposure spotof pulsed primary ion beam (SIMS) or pulsed laser beam (LDI or MALDI) are conserved through ﬂying in themass analyzer region, which consists of stigmatic achromatic ion transfer optics. Each bunch of ions separated
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Keywords: Mass microprobe, Imaging mass spectrometry,
Molecular imaging, Secondary ion mass spectrometry (SIMS),
Laser microprobe mass spectrometry (LMMS), Matrix-assisted
laser desorption/ionization (MALDI)

ῌ 132 ῌ