Chapter 13: Imaging of cells and tissues with mass spectrometry: adding chemical information to imaging

Abstract

Techniques that map the distribution of compounds in biological tissues can be invaluable in addressing a number of critical questions in biology and medicine. One of the newer methods, mass spectrometric imaging, has enabled investigation of spatial localization for a variety of compounds ranging from atomics to proteins. The ability of mass spectrometry to detect and differentiate a large number of unlabeled compounds makes the approach amenable to the study of complex biological tissues. This chapter focuses on recent advances in the instrumentation and sample preparation protocols that make mass spectrometric imaging of biological samples possible, including strategies for both tissue and single-cell imaging using the following mass spectrometric ionization methods: matrix-assisted laser desorption/ionization, secondary ion, electrospray, and desorption electrospray.

Figure 1

Overview of MSI. A series of complete mass spectra are taken in an ordered array across the sample. The intensity of the signal for selected compounds of interest are then plotted following data acquisition to create a series of ion images. (Reprinted with permission from reference (Rohner et al. 2005).)

Figure 2

MALDI-MS images of the peptide angiotensin I (m/z 1297) on electron microscopy calibration grids (100 μm hole-to-hole spacing), obtained using an oversampling technique at raster sizes of (a) 100 μm, (b) 50 μm, (c) 25 μm, and (d) 15 μm, illustrate the utility of oversampling to resolve small features in the sample. (Reprinted with permission from reference (Jurchen et al. 2005).)

Figure 3

Tissue processing. (a) Tissue oriented on a cryostat, prior to sectioning. (b) Sectioned tissues are then rinsed with ethanol and often (c) stained for histology (microphotograph of stained tissue is presented). (Reprinted with permission from reference (Chaurand et al. 2006).)

Figure 4

MALDI matrix applied to (A) unseeded rat liver tissue and (B) matrix seeded tissue. Greater crystal homogeneity is observed in tissues that have been previously seeded with ground matrix. (Reprinted with permission from reference (Aerni et al. 2006).)

Figure 5

Negative ion DESI MS images of (A) m/z 810 and (B) m/z 255 from a 4 μm coronal section of rat brain tissue illustrate the utility of the method to resolve morphological features in tissues. (Reprinted with permission from reference (Ifa et al. 2007).)