Ultra-sensitive native fluorescence detection of proteins with miniaturized one- and two-dimensional polyacrylamide gel electrophoresis was achieved with laser side-entry excitation, which provides both high excitation power and low background level. The detection limit for R-phycoerythrin protein spots in 1-D SDS-PAGE was as low as 15 fg, which corresponds to 40 thousand molecules only. The average detection limit of six standard native proteins was 5 pg per band and the dynamic range spanned more than 3 orders of magnitude. Approximately 150 protein spots from 30 ng of total Escherichia coli extraction were detected on a 0.8 cm x 1 cm gel in two-dimensional separation.;Estrogen-DNA adducts as 4-OHE1(E2)-1-N3Ade and 4-OHE1(E2)-2-NacCys were hypothesized as early risk assessment of prostate and breast cancers. Capillary electrophoresis, luminescence/absorption spectroscopy and LC-MS were used to characterize and detect these adducts. Monoclonal antibodies against each individual adduct were developed and used to enrich such compounds from urine samples of prostate and breast cancer patients as well as healthy people. Adduct 4-OHE1-1-N3Ade was detected at much higher level in urine from subjects with prostate cancer patients compared to healthy males. The same adduct and 4- OHE1-2-NacCys were also detected at a much higher level in urine from a woman with breast carcinoma than samples from healthy controls. These two DNA adducts may serve as novel biomarkers for early diagnostic of cancers.;The adsorption properties of R-phycoerythrin (RPE), on the fused-silica surface were studied using capillary electrophoresis (CE) and single molecule spectroscopy. The band shapes and migration times were measured in CE. Adsorption and desorption events were recorded at the single-molecule level by imaging of the evanescent-field layer using total internal reflection. The adsorbed RPE molecules on the fused-silica prism surface were counted with confidence based on ImageJ software. The capacity factor and desorption rate were estimated from the counting results. The mobility-based adsorption isotherms were constructed from both computer simulations and experiments to determine the capacity factor.;Colloidal graphite was investigated as an alternative matrix for laser desorption/ionization and imaging mass spectrometry (MS). Conventional matrix assisted desorption/ionization (MALDI) MS has strong interference peaks in low mass region (<500 Da) and this greatly limits the application of MALDI MS for analysis of small molecules. Graphite assisted laser desorption/ionization (GALDI) provides good sensitivity in the detection of small molecules such as organic acids, flavonoids and oligosaccharides. The detection limit of fatty acids and flavonoids in negative ion mode are in low femtomoles range. Another advantage of graphite over conventional MALDI matrix is that graphite sprayed surfaces are very homogeneous, which is required for IMS purposes. Fruits were chosen to evaluate the practical utility of GALDI since many types of small molecules are present in them. Distribution of these small molecules in fruit slices was investigated by using IMS and IMS/MS.;The possibility of discriminating isomeric disaccharides with different linkage types and different monosaccharide residues (glucose, galactose, and mannose at the non-reducing end) was investigated with tandem mass spectrometry (MS) and linear discriminant analysis (LDA). Acidic fullerene matrix is very suitable for the analysis of disaccharides as it has very clean background in the low mass region. Disaccharides with different linkage types give different tandem mass profiles from various cross-ring fragmentation pathways. Disaccharide isomers with the same linkage type but different monosaccharide residues bear the same fragmentation profiles, but the relative ratios of the fragment ion intensities were distinctively different. Statistical tool as linear discriminant analysis was used to analyze the tandem mass spectra. Disaccharide isomers with both different linkages and different monosaccharide residues were successfully discriminated.