<p>Studies of protein and peptide expression are vital in order to understand complex biological systems. As demonstrated in this thesis, on-line packed capillary liquid chromatography-Fourier transform ion cyclotron resonance mass spectrometry (LC-FTICR MS) is a useful analytical tool for such studies.</p><p>A proteomics method, based on global tryptic digestion and subsequent separation and detection of the peptides by LC-FTICR MS, was developed for qualitative analysis of body fluids. Initial experiments on cerebrospinal fluid (CSF) provided results that were comparable or superior to those achieved by more time- and sample-consuming techniques. The method was also successfully applied on plasma and amniotic fluid. One of the major challenges in proteomics is the broad dynamic range of proteins in biological matrices. The advantages of removing high-abundant components from CSF and plasma prior to MS were demonstrated.</p><p>In order to search for potential biomarkers, mass chromatograms of CSF from patients suffering from amyotrophic lateral sclerosis (ALS) and controls were compared using an in-house constructed pattern recognition program. ALS-specific patterns were observed, and four out of five unknown samples were correctly assigned. Alternative strategies to quantitatively compare two pools of samples rely on differential chemical labeling. The performance of one such method, quantification-using-enhanced-signal-tags, was investigated in complex sample analysis. The experimental intensity ratios were proven to be consistent with the prepared concentration ratios of abundant proteins in CSF.</p><p>Finally, the thesis reports on the first experiments where electron capture dissociation (ECD) was successfully incorporated in on-line LC-MS experiments. ECD and nozzle-skimmer fragmentation were applied to a sample of endocrine peptides extracted from mouse pancreatic islets. The two fragmentation methods provided complementary information. However, the method needs further optimization before it can be applied in the analysis of more complex samples, such as body fluids.</p>

In this thesis, methods for studying different aspects of proteomics were developed with Fourier Transform Ion Cyclotron Resonance, (FTICR), mass spectrometry. The FTICR technique provides ultra-high mass resolving power, mass accuracy at sub ppm level and sensitivity in the attomole region. Methods for quantifying biomarkers in body fluids such as cerebrospinal fluid, (CSF), and plasma were developed. Two sets of global markers with different properties were used for quantitative analysis; S-Methyl Thioacetimidate, (SMTA), and S-Methyl Thiopropionimidate, (SMTP), and [H4]- and [D4]-1-Nicotinoyloxy succinimide ester. Reduced ion suppression and higher sensitivity was obtained by coupling a High Performance Liquid Chromatography, (HPLC), system to the FTICR mass spectrometer. In body fluids, proteins and peptides are present in a broad dynamic concentration range. Therefore, depleting abundant proteins prior to analysis results in decreased ion suppression and increased sensitivity. Two commercial depletion kits were evaluated with the SMTA- and SMTP-markers. For both types of global markers, the experimental error for quantitative analysis of abundant proteins was less than 30%. This provides a lower limit for the protein up- and down regulations in complex solutions that can be monitored with HPLC-FTICR mass spectrometry. Together with the identity and quantity of selected proteins the structure, dynamics and interactions with other molecules are of great importance. The later can be elucidated with Hydrogen/Deuterium Exchange, (HDX), mass spectrometry. Structural information at high resolution can be obtained with Collision-Induced Dissociation, (CID), HDX mass spectrometry. In this thesis, exchange rates of amide hydrogens in peptides were in excellent agreement with NMR results. In some cases, the CID-fragments have different gas-phase exchange properties and as a consequence the solution phase exchange process can not be monitored. By applying Electron Capture Dissociation, (ECD), at ultra-high vacuum, the exchange process at a specific residue could be monitored.

New biomarkers are needed to improve knowledge about pathophysiology, in order to provide earlier correct diagnosis and to follow disease progression of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD). The aim of this thesis was to find new biomarkers for these diseases. First, increased serum levels and unchanged levels in postmortal spinal cord of vascular endothelial growth factor (VEGF) were demonstrated. VEGF was not detected in cerebrospinal fluid (CSF) in ALS. Second, increased levels of fibroblast growth factor 2 were found in the CSF and serum of ALS patients. Both studies used enzyme-linked immunoassays. Third, a proteomics method for CSF analysis was explored, based on tryptic digestion and subsequent separation and detection of the peptides by on-line liquid chromatography-Fourier transform ion cyclotron resonance mass spectrometry. ALS-specific patterns were observed. Four out of five samples were correctly assigned, but no single protein biomarker could be identified. Fourth, [11C](L)-deprenyl-D2 (DED) positron emission tomography (PET) demonstrated increased retention in the pons and white matter in ALS. DED binds to monoamino oxidase B, which in the brain is primarily located in astrocytes. Thus evidence was provided that astrocytosis may be detected in vivo in ALS. Fifth, normal [11C]-PIB binding in five nondemented patients with PD was reported, in contrast to previous findings of increased retention in Alzheimer's disease reflecting amyloid aggregation. Finally, the combined use of fluorodeoxyglucose and L-[β 11C]-DOPA PET for the differential diagnosis of parkinsonian syndromes was evaluated. PET provided support for the clinical diagnosis in 62 out of 75 patients, and served to exclude suspected diagnoses in another five patients.

This thesis concerns heating and current drive in tokamak plasmas using the fast magnetosonic wave in the ion cyclotron range of frequencies. Fast wave heating is a versatile heating method for thermonuclear fusion plasmas and can provide both ion and electron heating and non-inductive current drive. Predicting and interpreting realistic heating scenarios is however difficult due to the coupled evolution of the cyclotron resonant ion velocity distributions and the wave field. The SELFO code, which solves the coupled wave equation and Fokker-Planck equation for cyclotron resonant ion species in a self-consistent manner, has been upgraded to allow the study of more advanced fast wave heating and current drive scenarios in present day experiments and in preparation for the ITER tokamak. Theoretical and experimental studies related to fast wave heating and current drive with emphasis on fast ion effects are presented. Analysis of minority ion cyclotron current drive in ITER indicates that the use of a hydrogen minority rather than the proposed helium-3 minority results in substantially more efficient current drive. The parasitic losses of power to fusion born alpha particles and beam injected ions are concluded to be acceptably low. Experiments performed at the JET tokamak on polychromatic ion cyclotron resonance heating and on fast wave electron current drive are presented and analysed. Polychromatic heating is demonstrated to increase the bulk plasma ion to electron heating ratio, in line with theoretical expectations, but the fast wave electron current drive is found to be severely degraded by parasitic power losses outside of the plasma. A theoretical analysis of parasitic power losses at radio frequency antennas indicates that the losses can be significantly increased in scenarios with low wave damping and with narrow antenna spectra, such as in electron current drive scenarios. / QC 20100506

Studies of protein and peptide expression are vital in order to understand complex biological systems. As demonstrated in this thesis, on-line packed capillary liquid chromatography-Fourier transform ion cyclotron resonance mass spectrometry (LC-FTICR MS) is a useful analytical tool for such studies. A proteomics method, based on global tryptic digestion and subsequent separation and detection of the peptides by LC-FTICR MS, was developed for qualitative analysis of body fluids. Initial experiments on cerebrospinal fluid (CSF) provided results that were comparable or superior to those achieved by more time- and sample-consuming techniques. The method was also successfully applied on plasma and amniotic fluid. One of the major challenges in proteomics is the broad dynamic range of proteins in biological matrices. The advantages of removing high-abundant components from CSF and plasma prior to MS were demonstrated. In order to search for potential biomarkers, mass chromatograms of CSF from patients suffering from amyotrophic lateral sclerosis (ALS) and controls were compared using an in-house constructed pattern recognition program. ALS-specific patterns were observed, and four out of five unknown samples were correctly assigned. Alternative strategies to quantitatively compare two pools of samples rely on differential chemical labeling. The performance of one such method, quantification-using-enhanced-signal-tags, was investigated in complex sample analysis. The experimental intensity ratios were proven to be consistent with the prepared concentration ratios of abundant proteins in CSF. Finally, the thesis reports on the first experiments where electron capture dissociation (ECD) was successfully incorporated in on-line LC-MS experiments. ECD and nozzle-skimmer fragmentation were applied to a sample of endocrine peptides extracted from mouse pancreatic islets. The two fragmentation methods provided complementary information. However, the method needs further optimization before it can be applied in the analysis of more complex samples, such as body fluids.

The subject of this thesis is high-precision mass-measurements performed with Penning trap mass spectrometers (PTMS). In particular it describes the SMILETRAP I PTMS and the final results obtained with it, the masses of 40Ca and that of the proton. The mass of 40Ca is an indispensible input in the evaluation of measurements of the bound electron g-factor, used to test quantum electrodynamical calculations in strong fields. The value obtained agrees with available literature values but has a ten times higher precision. The measurement of the proton mass, considered a fundamental physical constant, was performed with the aim of validating other Penning trap results and to test the limit of SMILETRAP I. It was also anticipated that a measurement at a relative precision close to 10-10 would give insight in how to treat certain systematic uncertainties. The result is a value of the proton mass in agreement with earlier measurements and with an unprecedented precision of 1.8×10-10. Vital for the achieved precision of the proton mass measurement was the use of the Ramsey excitation technique. This technique, how it was implemented at SMILETRAP I and the benefits from it is discussed in the thesis and in one of the included papers. The second part of the thesis describes the improved SMILETRAP II setup at the S-EBIT laboratory, AlbaNova. All major changes and upgrades compared to SMILETRAP I are discussed. This includes, apart from the Ramsey excitation technique, higher ionic charge states, improved temperature stabilization, longer run times, different reference ions, stronger and more stable magnetic field and a more efficient ion detection. Altogether these changes should reduce the uncertainty in future mass determinations by an order of magnitude, possibly down to 10-11. / At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 9: Accepted.

Nós calculamos o efeito da interação elétron-fonons longitudinais óticos (LO) sobre a energia de transição ls &#8594 2p+ entre os níveis de uma impureza doadora, localizada em um poço quântico de GaAs-AlxGa1-xAs. Nossos resultados para a energia de transição em função do campo magnético aplicado mostram claramente, que a saturação da energia de transição (efeito pinning) ocorre na energia dos fônons LO, em boa concordância com recentes dados experimentais. Obtemos também a massa de cíclotron de polarons confinados em fios quânticos quase-unidimensionais, com potencial de confinamento parabólico. Observamos que o comportamento da massa é diferente daquele para sistemas bi-dimensionais e que esta diferença é maior quanto maior o potencial de confinamento. Para a heterojunção de GaAs-AlGaAs e GaAs-GaSb, investigamos a importância da interação elétron-fonons interfaciais sobre a massa de cíclotron. Verificamos que a contribuição dos fonons interfaciais é fundamental nas regiões próximas às resonâncias, onde domina o espectro. Finalmente, calculamos a energia de ligação de uma impureza hidrogenóide, localizada no centro de um ponto quântico circular de GaAs-AlGaAs. Na ausência de campo magnético aplicado, obtivemos uma expressão analítica para a função de onda do elétron ligado. Notamos, que a influência do campo magnético sobre a energia de ligação é fraca nas regiões de pequenos raios, devido ao forte potencial de confinamento. / We calculate the effects of the electron-longitudinal optical (LO) phonons interaction on the intra donor ls &#8594 2p+ transition energy in GaAs-AlGaAs quantum wells structures. Our results to the transition energy as a function of the magnetic Field strength, show that the pinning effect occur in the phonon LO energy in good agreement with recent experimental data. The cyclotron mass of polarons confined in quasi.one.dimensional quantum-well wires with parabolic confinement potential, is also obtained. The behavior of electrons effective mass with magnetic field is different, of the two-dimensional systems, and the difference increase when the confinement potential increase. To heterojunctions of GaAs-AlAs and GaAs-GaSb, we investigate the electroninterfacials optical (IO) phonons interactions on the effective cyclotron mass. We find that the electron-IO-phonons interaction is fundamental near the resonances, where they dominate the spectra. Finally, the ground state binding energy of donor impurity, placed in the center of a circular quantum dot is calculated. Without magnetic field, we obtained the analytic expression to the bound electron wave function. The influence of the magnetic field on the donor binding energy is weaker, when the radius of the quantum dot became smaller.

Ce manuscrit présente l'étude de la fabrication de couches minces de silicium basée sur des différents types de dépôt chimique en phase vapeur assisté par plasma (PECVD) pour des applications dans le photovoltaïque. Tout d'abord, nous avons combiné une chimie du plasma halogéné en utilisant un mélange de SiF4/H2 et la technique plasmas distributés matriciellement à résonance cyclotronique électronique (MDECR) PECVD pour le dépôt de μc-Si:H à grande vitesse. Nous trouvons que les conditions d'énergie ionique modérée sont bénéfiques pour obtenir une diminution significative de la densité des nano-vides, et ainis nous pouvons obtenir un matériaux de meilleure qualité avec une meilleure stabilité. Une méthode de dépôt en deux étapes a été introduite comme moyen alternatif d'éliminer la formation d'une couche d'incubation amorphe pendant la croissance du film. Ensuite, nous avons exploré la technique d'excitation Tailored Voltage Waveform (TVW) pour les processus plasma radiofréquence capacitivement couplé (RF-CCP). Grâce à l'utilisation de TVW, il est possible d'étudier indépendamment l'influence de l'énergie ionique sur le dépôt de matériaux à une pression de processus relativement élevée. Basé sur ce point, nous avons étudié le dépôt de μc-Si:H et a-Si:H à partir des plasma de SiF4/H2/Ar et de SiH4/H2, respectivement. A partir d'une analyse des propriétés structurelles et électroniques, nous constatons que la variation de l'énergie ionique peut directement traduite dans la qualité du matériaux. Les résultats se sont appliqués aux dispositifs photovoltaïques et ont établi des liens complets entre les paramètres de plasma contrôlables par TVW et les propriétés de matériaux déposé, et finalement, les performances du dispositif photovoltaïque correspondant. Enfin, nous avons trouvé que dans le cas du dépôt de couches minces de silicium à partir du plasma de SiF4/H2/Ar à l'aide de sawtooth TVW, on peut réaliser un processus de dépôt sur une électrode, sans aucun dépôt ou gravure. contre-électrode. Ceci est dû à deux effets: la nature multi-précurseur du processus de surface résultant et la réponse de plasma spatiale asymétrique par l'effet d'asymétrie de pente de la sawtooth TVW. La découverte de tels procédés “electrode-selective” encourage la perspective que l'on puisse choisir un ensemble de conditions de traitement pour obtenir une grande variété de dépôts désirés sur une électrode, tout en laissant l'autre vierge. / This thesis describes the study of silicon thin film materials deposition and the resulting photovoltaic devices fabrication using different types of plasma-enhanced chemical vapour deposition (PECVD) techniques.In the first part, we combine a SiF4/H2 plasma chemistry with the matrix-distributed electron cyclotron resonance (MDECR) PECVD to obtain high growth rate microcrystalline silicon (µc-Si:H). Due to the special design of MDECR system, careful investigation of the impact energy of impinging ions to material deposition can be accessible. We find that moderate ion energy conditions is beneficial to achieve a significant drop in the density of nano-voids, thus a higher quality material with better stability can be obtained. A two-step deposition method is introduced as an alternative way to eliminate the existence of amorphous incubation layer during film growth.The second part of work is dedicate to the exploration of the Tailored Voltage Waveforms (TVWs) excitation technique for capacitively coupled plasmas (CCP) processes. As an advantage over the conventional sinusoidal excitations, TVWs technique provide an elegant solution for the ion flux-energy decoupling in CCP discharges through the electrical asymmetry effect, which makes the independent study of the impact of ion energy for material deposition at relatively high process pressure possible. Based on this insight, we have studied the deposition of µc-Si:H and amorphous silicon (a-Si:H) from the SiF4/H2/Ar and SiH4/H2 plasma chemistry, respectively. From the structural and electronic properties analysis, we find that the variation of ion energy can be directly translated into the material quality. We have further applied these results to photovoltaic applications and established bottom-up links from the controllable plasma parameters via TVWs to the deposited material properties, and eventually to the resulting device quality.In the last part, as a further application of TVWs, an “electrode-selective” effect has been discovered in the CCP processes. In the case of silicon thin film deposition from the SiF4/H2/Ar plasma chemistry, one can achieve a deposition process on one electrode, while at the same time either no deposition or an etching process on the counter electrode. This is due to two effects: the multi-precursor nature of the resulting surface process and the asymmetric plasma response through the utilization of TVWs. Moreover, such deposition/etching balance can be directly controlled through H2 flow rate. From a temporal asymmetry point of view, we have further studied the impact of process pressure and reactor geometry to the asymmetric plasma response for both the single-gas and multi-gas plasmas using the sawtooth waveforms. The product of pressure and inter-electrode distance P·di is deduced to be a crucial parameter in determine the plasma heating mode, so that a more flexible control over the discharge asymmetry as well as the relating “electrode-selective” surface process can be expected.

Es wurde eine Elektron-Zyklotron-Resonanz-Ionenquelle mit einer Mikrowellenfrequenz von2,45 GHz für die Produktion intensiver Ströme einfach geladener Metallionen entwickelt. Deren Beladung mit Metalldampf erfolgt über ein integriertes zylindrisches Sputtermagnetron, welches speziell für diese Aufgabe entworfen wurde. Die entstandene MECRIS, engl. Magnetron Electron Cyclotron Resonance Ion Source, vereinigt die ECR-Ionenquellentechnologie mit der Magnetron-Sputtertechnologie auf bisher einzigartige Weise und verkörpert so ein neues Metallionen-Quellenkonzept. Unter Verwendung eines Al-Sputtertargets konnte die Funktionsfähigkeit der MECRIS an dem Beispiel der Al+-Ionenerzeugung erfolgreich demonstriert werden. Der extrahierbare Al+-Ionenstrom wurde über einen neuartigen, im Rahmen der Arbeit entwickelten, Hochstrom-Faraday-Cup gemessen. Auf Basis numerischer Berechnungen wurde das Gesamtmagnetfeld so ausgelegt, dass die Permanentmagnete des Magnetrons und die Spulen der ECR-Quelle eine Minimum-B-Struktur erzeugen, welche einen effektiven Elektroneneinschluss nach dem magnetischen Spiegelprinzip ermöglicht. Gleichzeitig wird durch eine geschlossene ECR-Fläche, mit der magnetischen Resonanzflussdichte von 87,5 mT, eine optimale Heizung der Plasmaelektronen realisiert. Die mithilfe einer Doppel-Langmuir-Sonde gemessene Elektronentemperatur steigt in Richtung Quellenmitte an und beträgt maximal 11 eV. Geheizte Elektronen erlauben die effiziente Stoßionisation der Al-Atome, welche mit einer Rate von über 1E18 Al-Atome/s eingespeist werden und eine höchstmögliche Dichte von 2E10 1/cm³ aufweisen. Die MECRIS erzeugt hauptsächlich einfach geladene Ionen des gesputterten Materials (Al+) und des Prozessgases (Ar+). Der Al+-Ionenextraktionsstrom ist über die Erhöhung der Prozessparameter Sputterleistung, Mikrowellenleistung, Spulenstrom und Extraktionsspannung um eine Größenordnung bis auf maximal 135 μA steigerbar, was einer Stromdichte von 270 μA/cm² über die Extraktionsfläche von rund 0,5 cm² entspricht. Dies steht im Einklang mit der Prozessparameterabhängigkeit der anhand der Sonde bestimmten Plasmadichte, welche einen größtmöglichen Wert von etwa 6E11 1/cm³ annimmt. Das Verhältnis von extrahiertem Al+- zu Ar+-Ionenstrom kann durch Optimierung der Prozessparameter von 0,3 auf maximal 2 angehoben werden. Sondenmessungen des entsprechenden Ionendichteverhältnisses bestätigen diesen Sachverhalt. Um möglichst große Extraktionsströme und Al+/Ar+-Verhältnisse zu generieren, muss die ECR-Fläche demnach in dem Bereich der höchsten Al-Atomdichte in der Targetebene lokalisiert sein. Gegenüber dem alleinigen Magnetronplasma (ohne Mikrowelleneinspeisung) können mit dem MECRIS-Plasma um bis zu 140 % höhere Al+-Ionenströme produziert werden. Aus Sondenuntersuchungen geht hervor, dass dies eine Folge der um etwa eine Größenordnung gesteigerten Plasmadichte und der um rund 7 eV größeren Elektronentemperatur des MECRIS-Plasmas ist. Das MECRIS-Plasma wurde außerdem mittels optischer Emissionsspektroskopie charakterisiert und durch ein globales sowie ein zweidimensionales Modell simuliert. Die gewonnenen Prozessparameterabhängigkeiten der Plasmadichte, Elektronentemperatur sowie Al+- und Ar+-Ionendichte stimmen mit den Sondenergebnissen überein. Teilweise treten jedoch Absolutwertunterschiede von bis zu zwei Größenordnungen auf. Die Erhöhung der Sputterleistung und Extraktionsspannung über die derzeitigen Grenzen von 10 kW bzw. 30 kV sowie die Optimierung der Extraktionseinheit hinsichtlich minimaler Elektrodenblindströme bietet das Potential, den Al+-Ionenstrom bis in den mA-Bereich zu steigern. / An electron cyclotron resonance ion source working at a microwave frequency of 2.45 GHz has been developed in order to generate an intense current of singly charged metal ions. It is loaded with metal vapor by an integrated cylindrical sputter magnetron, which was especially designed for this purpose. The MECRIS (Magnetron Electron Cyclotron Resonance Ion Source) merges ECR ion source technology with sputter magnetron technology in a unique manner representing a new metal ion source concept. By using an Al sputter target, the efficiency of the MECRIS was demonstrated successfully for the example of Al+ ion production. The extractable ion current was measured by a newly developed high-current Faraday cup. On the basis of numerical modeling, the total magnetic field was set in a way that the permanent magnets of the magnetron and the coils of the ECR source are forming a minimum-B-structure, providing an effective electron trap by the magnetic mirror principle. Simultaneously, optimal electron heating is achieved by a closed ECR-surface at resonant magnetic flux density of 87.5 mT. Electron temperature increases towards the center of the source to a maximum of about 11 eV and was measured by a double Langmuir probe. Due to the heated electron population, efficient electron impact ionization of the Al atoms is accomplished. Al atoms are injected with a rate of more than 1E18 Al-atoms/s resulting in a maximum Al atom density of 2E10 1/cm³. The MECRIS produces mainly singly charged ions of the sputtered material (Al+) and the process gas (Ar+). The Al+ ion extraction current is elevated by one order of magnitude to a maximum of 135 μA by increasing the process parameters sputter magnetron power, microwave power, coil current, and acceleration voltage. Related to the extraction area of about 0.5 cm², the highest possible Al+ ion current density is 270 μA/cm². A corresponding process parameter dependency was found for the plasma density showing a peak value of about 6E11 1/cm³, which was deduced from probe measurements. The ratio of the extracted Al+ ion current to the Ar+ ion current can be enhanced from 0.3 to a maximum of 2 by optimization of the process parameters. This was confirmed by probe investigations of the appropriate ion density ratio. In conclusion, the ECR-surface needs to be located in the area of the highest Al atom density in the target plane in order to improve the extraction current and Al+/Ar+ ratio. The MECRIS plasma produces an Al+ ion current, which is up to 140 % higher compared to that of the sole sputter magnetron plasma (without microwave injection). As revealed by probe measurements, this effect is due to the higher plasma density and electron temperature of the MECRIS plasma, leading to a difference of one order of magnitude and 7 eV, respectively. Additionally, the MECRIS plasma has been characterized by optical emission spectroscopy and simulated by a global and a two-dimensional model. Retrieved process parameter dependencies of plasma density, electron temperature, Al+ ion density, and Ar+ ion density coincide with probe findings. Although a discrepancy of the absolute values of partly up to two orders of magnitude is evident. Potentially, the Al+ ion current can be enhanced to the mA-region by optimizing the ion extraction system for minimal idle electrode currents and by rising sputter magnetron power as well as acceleration voltage above the actual limits of 10 kW and 30 kV, respectively.

Mass spectrometry has in recent years been established as the standard method for protein identification and characterization in proteomics with excellent intrinsic sensitivity and specificity. Fourier transform ion cyclotron resonance is the mass spectrometric technique that provides the highest resolving power and mass accuracy, increasing the amount of information that can be obtained from complex samples. This thesis concerns how useful information on proteins of interest can be extracted from mass spectrometric data on different levels of protein structure and how to obtain this data experimentally. It was shown that it is possible to analyze complex mixtures of protein tryptic digests by direct infusion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry and identify abundant proteins by peptide mass fingerprinting. Coupling on-line methods such as liquid chromatography and capillary electrophoresis increased the number of proteins that could be identified in human body fluids. Protein identification was also improved by novel statistical methods utilizing prediction of chromatographic behavior and the non-randomness of enzymatic digestion. To identify proteins by short sequence tags, electron capture dissociation was implemented, improved and finally coupled on-line to liquid chromatography for the first time. The combined techniques can be used to sequence large proteins de novo or to localize and characterize any labile post-translational modification. New computer algorithms for the automated analysis of isotope exchange mass spectra were developed to facilitate the study of protein structural dynamics. The non-covalent interaction between HIV-inhibitory peptides and the oligomerization of amyloid β-peptides were investigated, reporting several new findings with possible relevance for development of anti-HIV drug therapies and understanding of fundamental mechanisms in Alzheimer’s disease.