6 research outputs found
Accurate and High-Resolution Particle Mass Measurement Using a Peak Filtering Algorithm
Charge
detection quadrupole ion trap mass spectrometry (CD-QIT
MS) is an effective way of achieving the mass analysis of microparticles
with ultrahigh mass. However, its mass accuracy and resolution are
still poor. To enhance the performance of CD-QIT MS, the resolution Rpeak of each peak in the mass spectra resulting
from an individual particle was assessed, and a peak filtering algorithm
that can filter out particle adducts and clusters with a lower Rpeak was proposed. By using this strategy, more
accurate mass information about the analyzed particles could be obtained,
and the mass resolution of CD-QIT MS was improved by nearly 2-fold,
which was demonstrated by using the polystyrene (PS) particle size
standards and red blood cells (RBCs). Benefiting from these advantages
of the peak filtering algorithm, the baseline separation and relative
quantification of 3 and 4 ÎĽm PS particles were achieved. To
prove the application value of this algorithm in a biological system,
the mass of yeast cells harvested at different times was measured,
and it was found that the mixed unbudded and budded yeast cells, which
otherwise would not be differentiable, were distinguished and quantified
with the algorithm
<i>N</i>‑Phenyl-2-naphthylamine as a Novel MALDI Matrix for Analysis and in Situ Imaging of Small Molecules
Due
to its strong ultraviolet absorption, low background interference
in the small molecular range, and salt tolerance capacity, <i>N</i>-phenyl-2-naphthylamine (PNA) was developed as a novel
matrix in the present study for analysis and imaging of small molecules
by matrix-assisted laser desorption/ionization mass spectrometry time-of-fight
(MALDI-TOF MS). The newly developed matrix displayed good performance
in analysis of a wide range of small-molecule metabolites including
free fatty acids, amino acids, peptides, antioxidants, and phospholipids.
In addition, PNA-assisted LDI MS imaging of small molecules in brain
tissue of rats subjected to middle cerebral artery occlusion (MCAO)
revealed unique distributions and changes of 89 small-molecule metabolites
including amino acids, antioxidants, free fatty acids, phospholipids,
and sphingolipids in brain tissue 24 h postsurgery. Fifty-nine of
the altered metabolites were identified, and all the changed metabolites
were subject to relative quantitation and statistical analysis. The
newly developed matrix has great potential application in the field
of biomedical research
MALDI-TOF MS Imaging of Metabolites with a <i>N</i>‑(1-Naphthyl) Ethylenediamine Dihydrochloride Matrix and Its Application to Colorectal Cancer Liver Metastasis
Matrix-assisted
laser desorption/ionization mass spectrometry imaging (MALDI MSI)
is a label-free technique for identifying multiplex metabolites and
determining both their distribution and relative abundance in situ.
Our previous study showed that <i>N</i>-(1-naphthyl) ethylenediamine
dihydrochloride (NEDC) could act as a matrix for laser desorption/ionization
time-of-flight mass spectrometry (LDI-TOF MS) detection of oligosaccharides
in solution. In the present study, NEDC-assisted LDI-TOF MSI yielded
many more endogenous compound peaks between <i>m</i>/<i>z</i> 60 and <i>m</i>/<i>z</i> 1600 than
9-aminoacridine (9-AA). Our results show that NEDC-assisted LDI-TOF
MSI is especially well-suited for examining distributions of glycerophospholipids
(GPs) in addition to low molecular weight metabolites below <i>m</i>/<i>z</i> 400. Particularly, NEDC matrix allowed
the LDI-TOF MSI of glucose in animal tissue. Furthermore, NEDC-assisted
LDI-TOF MSI was applied to a mouse model of colorectal cancer liver
metastasis. We revealed the distinct spatio-molecular signatures of
many detected compounds in tumor or tumor-bearing liver, and we found
that taurine, glucose, and some GPs decreased in tumor-bearing liver
as the tumor developed in liver. Importantly, we also found a glucose
gradient in metastatic tumor foci for the first time, which further
confirms the energy competition between tumors and liver remnant due
to the Warburg effect. Our results suggest that NEDC-assisted LDI
MSI provides an in situ label-free analysis of multiple glycerophospholipids
and low molecular weight metabolites (including glucose) with abundant
peaks and high spatial resolution. This will allow future application
to in situ definition of biomarkers, signaling pathways, and disease
mechanisms
2,3,4,5-Tetrakis(3′,4′-dihydroxylphenyl)thiophene: A New Matrix for the Selective Analysis of Low Molecular Weight Amines and Direct Determination of Creatinine in Urine by MALDI-TOF MS
Small organic matrixes are still the most commonly used
ones in
matrix-assisted laser desorption/ionization mass spectrometry (MALDI
MS) because of their advantages of high sensitivity, convenience,
and cost-effectiveness. However, due to the matrix interference in
the low mass region, the direct analysis of low molecular weight amines
in complex surroundings with conventional organic matrixes remains
a challenge. Here, a new Brønsted–Lowry acid compound
2,3,4,5-tetrakisÂ(3′,4′-dihydroxylphenyl)Âthiophene (DHPT)
was designed, synthesized, and applied as a matrix for analysis of
low molecular weight amines by MALDI-TOF MS. DHPT displays good selectivity
in the analysis of amines without matrix-related interference and
the low picomole/femtomole limit-of-detection was obtained in positive
ion mode. With DHPT, the metabolites including creatinine, glycine,
alloxan, allantoin, and 3-hydroxyhippuric acid in human urine were
directly analyzed by MALDI-TOF MS. The identity of these metabolites
was confirmed by tandem mass spectrometry. Furthermore, the urine
creatinine was quantitatively determined using isotope-labeled internal
standard. This DHPT-assisted LDI MS method provides a general approach
for both qualitative and quantitative analysis of low molecular weight
amines
Quantitative Assessment of Protein Adsorption on Microparticles with Particle Mass Spectrometry
In
this paper, particle mass spectrometry (PMS), which consists
of an aerodynamic desorption/ionization (AD) source, a quadrupole
ion trap (QIT) mass analyzer, and a charge detector, was exploited
to characterize the protein adsorption on microparticles based on
the mass variations of microparticles before and after protein adsorption.
This method is simple and has low sample cost. Importantly, its mass
resolution is good enough to distinguish the microparticles with and
without protein. For the adsorption of bovine serum albumin (BSA)
on 3 ÎĽm porous poly styrene-divinylbenzene (poly S-DVB), the
minimum mass increase that can be resolved by PMS corresponds to 128
fg (1.8 ng/cm<sup>2</sup>) or 1.17 Ă— 10<sup>6</sup> BSA molecules
on each poly S-DVB particle. With PMS, the adsorption process of BSA
on poly S-DVB spheres was successfully characterized, and the obtained
maximum adsorption capacity <i>q</i><sub>m</sub> and dissociation
constant <i>K</i><sub>d</sub> were consistent with that
determined by the conventional depletion method. In addition, the
influence of surface modification of silica particles on the enzyme
immobilization was evaluated. Compared with C<sub>4</sub> (propyldimethylsilane),
C<sub>8</sub> (octyldimethylsilane), and Ph (phenyldimethylchlorosilane),
the CN (cyanoethyldimethylchlorosilane) functionalized silica particles
were screened to be most beneficial for the immobilization of both
lysozyme and trypsin
1,5-Diaminonaphthalene Hydrochloride Assisted Laser Desorption/Ionization Mass Spectrometry Imaging of Small Molecules in Tissues Following Focal Cerebral Ischemia
A sensitive
analytical technique for visualizing small endogenous
molecules simultaneously is of great significance for clearly elucidating
metabolic mechanisms during pathological progression. In the present
study, 1,5-naphthalenediamine (1,5-DAN) hydrochloride was prepared
for matrix-assisted laser desorption/ionization (MALDI) mass spectrometry
imaging (MSI) of small molecules in liver, brain, and kidneys from
mice. Furthermore, 1,5-DAN hydrochloride assisted LDI MSI of small
molecules in brain tissue of rats subjected to middle cerebral artery
occlusion (MCAO) was carried out to investigate the altered metabolic
pathways and mechanisms underlying the development of ischemic brain
damage. Our results suggested that the newly prepared matrix possessed
brilliant features including low cost, strong ultraviolet absorption,
high salt tolerance capacity, and fewer background signals especially
in the low mass range (typically <i>m</i>/<i>z</i> < 500), which permitted us to visualize the spatial distribution
of a broad range of small molecule metabolites including metal ions,
amino acids, carboxylic acids, nucleotide derivatives, peptide, and
lipids simultaneously. Nineteen endogenous metabolites involved in
metabolic networks such as ATP metabolism, tricarboxylic acid (TCA)
cycle, glutamate-glutamine cycle, and malate-aspartate shuttle, together
with metal ions and phospholipids as well as antioxidants underwent
relatively obvious changes after 24 h of MCAO. The results were highly
consistent with the data obtained by MRM MS analysis. These findings
highlighted the promising potential of the organic salt matrix for
application in the field of biomedical research