Biomedical Engineering Reference
In-Depth Information
15.7.1 Elemental Mass Spectrometry
Inductively coupled plasma mass spectrometry (ICP-MS) is the most advanced and
sensitive means of determining the elemental composition of materials. Classically, it
has been used for ultratrace (as low as parts per quadrillion) detection of metals and
other elements in both environmental (water, soil, and air) andclinical (blood andurine)
samples. The key component of the analysis is high-temperature plasma (approxi-
mately 7500K) that is created through the coupling of high radio frequency energy into
a flowing inert gas, such as argon. Material introduced into the plasma is completely
vaporized into its component elemental ions. The elemental ions representative of the
sample are extracted and introduced into themass analyzer, a quadrupolemass filter for
example, which can provide approximately seven orders of magnitude abundance
sensitivity (resolution between adjacent mass channels) and nine orders of dynamic
range. It is these characteristics that make elemental mass spectrometry a logical
alternative to fluorescence as a detection method in bioanalysis [28-31].
15.7.2 Mass Cytometry
Mass cytometry uses single isotopes of pure elements in the formof solublemetal ions
as tags bound to antibodies instead of fluorophores for measuring target epitopes in
single cells [28]. Notably, mass cytometry has essentially the same workflow as
conventional fluorescence cytometry. Once labeled, single cells are individually
sampled, atomized and ionized by ICP injection, and the resulting ions are mass
measured. The signal from each unique mass channel is then correlated back to a
particular isotopic element and thus to the expression of a given epitope on each cell
(Figure 15.10). This instrument was originally conceived in Scott Tanner's group at
the University of Toronto and is now available under the commercial name of CyTOF,
made byDVS Sciences. The general workflow for themass cytometer data acquisition
is as follows:
.
Labeled cells are nebulized into single-cell droplets and enter the plasma at a rate
of up to 1000 cells/s. The cells are completely destroyed and reduced to a “cloud”
FIGURE 15.10
Analysis of cellular markers with ICP-based mass cytometry. An affinity
product (e.g., antibody) tagged with a specific elemental isotope binds to the protein or
molecule of interest. The cell is introduced into the plasma source, atomized, ionized, and then
the elemental composition is mass measured. Signals corresponding to each elemental isotope
tag are quantified and correlated with the abundance of the target of interest.
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