Biomedical Engineering Reference
In-Depth Information
TFA
Tri fl uoroacetatic acid
TLC
Thin layer chromatography
UPLC
Ultraperformance liquid chromatography
1
Introduction
Mass spectrometry has provided a wealth of information on chemical structural
determination, identification, and a trace level chemical analysis. It has many appli-
cations in the biochemistry, pharmaceutical, and clinical diagnostic research field.
Electrospray ionization (ESI), a very powerful MS ionization mode, has been
coupled with liquid chromatography becoming a popular tool in biomolecular anal-
ysis and drug analysis applications [
1
]. Use of HPLC or ultra performance liquid
chromatography (UPLC) combined with a mass spectrometry through the inter-
faceāESI has become a powerful and routinely used analytical tool for many fields
in scientific research, pharma industry, healthcare, and clinical diagnostic
applications.
A fast-growing application of the MALDI technique is use in combination with
Time-of-Flight mass spectrometry (MALDI-TOF-MS) and has been applied to the
determination of molecular weight for biological macromolecules [
2-
4
] . Currently,
analytes that have molecular weights of <1,000 Da can be analyzed by MALDI-
TOF-MS [
5-
7
] .
A direct molecular imaging detection method that does not require the use of
specific labels for visualization of the biodistribution of target biomolecules in tis-
sues is based on MALDI-TOF-MS. The MALDI-TOF-Imaging mass spectrometry
(IMS) is rapidly developing into a powerful technique that enables us to identify and
localize biological compounds directly on tissue sections within a user-defined area
and without the need for radioactive, fluorescence labels, or immunochemical
reagents [
8-
14
]. It has enjoyed broad use for studying macromolecular entities such
as proteins and peptides [
15-
26
] , lipids [
27-
37
] , carbohydrates [
38
] , oligosaccha-
rides and oligonucleotides [
39,
40
] , biomarkers [
41-
48
] , and small pharmaceutical
compounds and their metabolites [
49-
58
] as well as others. More recently MALDI-
TOF-MS imaging has been developed to directly determine the distribution of drugs
and drug metabolites in tissue sections benefiting the drug development process.
MALDI-TOF-IMS direct analysis and imaging of tissue section show continuously
increased performances in term of detected molecules, sensitivity, and applications.
MALDI-TOF-IMS analysis of protein and peptides in three-dimensional (3D) volume
reconstruction explores the proteome of complex tissue such as the brain [
59
] .
The MALDI-Fourier Transform Ion Cyclotron Resonance Mass Spectrometry
(MALDI-FT-ICR-MS) and MALDI-Quadrupole-Ion-trap-TOF Mass Spectrometry
(MALDI-QIT-TOF-MS) can be used on IMS. The FT-ICR-MS could provide the
high resolution, expansive mass range and high sensitivity imaging MS data and
good for determining the elemental composition of small molecules [
60
] .