The characterization of biomolecules and biomolecular complexes represents an area of significant research activity because of the link between structure and function. Drug development relies on structural information in order to target certain domains. Many traditional biochemical techniques, however, are limited by their ability to characterize only certain stable forms of a molecule. As a result, multidimensional approaches, such as ion mobility mass spectrometry coupled to mass spectrometry (IMS-MS), are becoming very attractive tools as they provide fast separation, detection and identification of molecules, in addition to providing three-dimensional shape for structural elucidation. The present work expands the use and application of trapped ion mobility spectrometry-coupled to mass spectrometry (TIMS-MS) by analyzing a range of biomolecules (including proteoforms, intrinsically disordered peptides, DNA and molecular complexes). The aim is to i) evaluate the TIMS platform measuring sensitivity, selectivity, and separation of targeted compounds, ii) pioneer new applications of TIMS for a more efficient and higher throughput methodologies for identification and characterization of biomolecular ions, and iii) characterize the dynamics of selected biomolecules for insight into the folding pathways and the intra-or intermolecular interactions that define their conformational space.

Neste dissertação apresentamos um protocolo para simular, no contexto das armadilhas iônicas, o Zitterbewegung não usual, que é o análogo, na física do semicondutores, ao movimento de tremulação de uma partícula relativística. O Zitterbewegung não usual permite trajetórias cicloidais na ausência dos campos magnéticos. Além do Zitterbewegung, mostramos como gerar figuras de Lissajou para o movimento vibracional bidimensional do íon armadilhado. Ademais, o protocolo proposto nesta tese, permite gerar interações spin-órbita dos tipos Rashba e Dresselhaus, abrindo a possibilidade de simular, no âmbito dos íons armadilhados, os acoplamentos spin-órbita dos tipos Rashba e Dresselhaus, Zitterbewegung não usual e as curvas de Lissajou. Além disso, nesta tese apresentamos protocolo para produzir engenharia de interações confinadas aos subespaços do espaço de Fock. Mostramos como engenheirar os hamitonianos dos tipos Jaynes-Cumming e anti-Jaynes-Cumming confinadados aos subespaços de Fock delimitados superiormente ou inferiormente e também as interações Jaynes-Cumming e anti-Jaynes-Cumming confinados a uma fatia do espaço Fock. Esses hamitonias delimitados superiormente (inferiormente) atuam sobre os subespaço de Fock de |0&rang; a |M&rang; (|N&rang; &alpha;&infin;), enquanto aqueles confinados a uma fatia do espaço de Fock atuam sobre os subespaço de Fock de |M&rang; a |N&rang; com M < N. Enquanto que, as interações dos tipo Jaynes-Cumming ou anti-Jaynes-Cumming demilitadas superiormente conduzem qualquer estado inicial para o estado de Fock de quase-equilíbrio |N&rang; e as interações confinadas a uma fatia do espaço de Fock conduz qualquer estado inicial a superporsição de estados de Fock de equilíbrio, que estão confinados no subespaço {|N&rang; , |N + 1&rang;}. / In this dissertation we present a protocol to simulate, with a single two-leve trapped ion, the unusual zitterbewegung: the semiconductor analog of the relativistic trembling motion of eletron, allowing cycloidal trajectories in the absence of magnetic fields. Beyon zitterbewegung, we show how to generate Lissajou curves from the vibrational motion of an ion in two dimensional trap. Morever our protocol enables us to engineerthe Rashbaand the Dresselhaus-type spin-orbit interatiction, opening the possibility to simulate with a trapped ion, spin-orbit effects other than the unusual zitterbewegung and Lissajou curves. Moreover, in this work we present a protocol to engineer interactions confined to subspaces of the Fock space: we show how to engineer upper-, lower-bounded and sliced Jaynes-Cummings (JC) and anti-Jaynes-Cummings (AJC) Hamiltonians. The upperbounded (lower-bounded) interaction acting upon Fock subspaces ranging from |0&rang; to |M&rang; (|N&rang; to &infin;), and the sliced one confined to Fock subspace ranging from |M&rang; to |N&rang;, whatever M < N. Whereas the upper-bounded JC or AJC interactions is shown to drive any initial state to an equilibrium Fock states |N&rang;, the sliced one is shown to produce equilibrium superpositions of Fock states confined to the sliced subspaces {|N&rang; , |N + 1&rang;}.

Neste dissertação apresentamos um protocolo para simular, no contexto das armadilhas iônicas, o Zitterbewegung não usual, que é o análogo, na física do semicondutores, ao movimento de tremulação de uma partícula relativística. O Zitterbewegung não usual permite trajetórias cicloidais na ausência dos campos magnéticos. Além do Zitterbewegung, mostramos como gerar figuras de Lissajou para o movimento vibracional bidimensional do íon armadilhado. Ademais, o protocolo proposto nesta tese, permite gerar interações spin-órbita dos tipos Rashba e Dresselhaus, abrindo a possibilidade de simular, no âmbito dos íons armadilhados, os acoplamentos spin-órbita dos tipos Rashba e Dresselhaus, Zitterbewegung não usual e as curvas de Lissajou. Além disso, nesta tese apresentamos protocolo para produzir engenharia de interações confinadas aos subespaços do espaço de Fock. Mostramos como engenheirar os hamitonianos dos tipos Jaynes-Cumming e anti-Jaynes-Cumming confinadados aos subespaços de Fock delimitados superiormente ou inferiormente e também as interações Jaynes-Cumming e anti-Jaynes-Cumming confinados a uma fatia do espaço Fock. Esses hamitonias delimitados superiormente (inferiormente) atuam sobre os subespaço de Fock de |0&rang; a |M&rang; (|N&rang; &alpha;&infin;), enquanto aqueles confinados a uma fatia do espaço de Fock atuam sobre os subespaço de Fock de |M&rang; a |N&rang; com M < N. Enquanto que, as interações dos tipo Jaynes-Cumming ou anti-Jaynes-Cumming demilitadas superiormente conduzem qualquer estado inicial para o estado de Fock de quase-equilíbrio |N&rang; e as interações confinadas a uma fatia do espaço de Fock conduz qualquer estado inicial a superporsição de estados de Fock de equilíbrio, que estão confinados no subespaço {|N&rang; , |N + 1&rang;}. / In this dissertation we present a protocol to simulate, with a single two-leve trapped ion, the unusual zitterbewegung: the semiconductor analog of the relativistic trembling motion of eletron, allowing cycloidal trajectories in the absence of magnetic fields. Beyon zitterbewegung, we show how to generate Lissajou curves from the vibrational motion of an ion in two dimensional trap. Morever our protocol enables us to engineerthe Rashbaand the Dresselhaus-type spin-orbit interatiction, opening the possibility to simulate with a trapped ion, spin-orbit effects other than the unusual zitterbewegung and Lissajou curves. Moreover, in this work we present a protocol to engineer interactions confined to subspaces of the Fock space: we show how to engineer upper-, lower-bounded and sliced Jaynes-Cummings (JC) and anti-Jaynes-Cummings (AJC) Hamiltonians. The upperbounded (lower-bounded) interaction acting upon Fock subspaces ranging from |0&rang; to |M&rang; (|N&rang; to &infin;), and the sliced one confined to Fock subspace ranging from |M&rang; to |N&rang;, whatever M < N. Whereas the upper-bounded JC or AJC interactions is shown to drive any initial state to an equilibrium Fock states |N&rang;, the sliced one is shown to produce equilibrium superpositions of Fock states confined to the sliced subspaces {|N&rang; , |N + 1&rang;}.

The complexity of biological matrices makes the detection and quantification of compounds of interest challenging. For successful targeted or untargeted identification of compounds within a biological environment, the use of complementary separation techniques is routinely required; in many situations, a single analytical technique is not sufficient. In the present dissertation, a multidimensional analytical technique was developed and evaluated, a combination of new sample preparation/extraction protocols, liquid chromatography, trapped ion mobility and mass spectrometry (e.g., LC-TIMS-MS and LC-TIMS-MS/MS). The performance of these techniques was evaluated for the detection of polybrominated diphenyl ethers metabolites, polychlorinated biphenyls metabolites in human plasma, opioid metabolites in human urine, and lipids in Dictyostelium discoideum cells. The new workflows and methods described in the body of this dissertation allows for rapid, selective, sensitive and high-resolution detection of biomarkers in biological matrices with increased confidence, sensitivity and shorter sample preparation and analysis time.

This thesis reports high-fidelity near-field spatial microwave addressing of long-lived ⁴³Ca⁺ "atomic clock" qubits performed in a two-zone single-layer surface-electrode ion trap. Addressing is implemented by using two of the trap's integrated microwave electrodes, one in each zone, to drive single-qubit rotations in the zone we choose to address whilst interferometrically cancelling the microwave field at the neighbour (non-addressed) zone. Using this field-nulling scheme, we measure a Rabi frequency ratio between addressed and non-addressed zones of up to 1400, from which we calculate an addressing error (or a spin-flip probability on the qubit transition) of 1e-6. Off-resonant excitation out of the qubit state is a more significant source of error in this experiment, but we also demonstrate polarisation control of the microwave field at an error level of 2e-5, which, if combined with individual-ion addressing, would be sufficient to suppress off-resonant excitation errors to the 1e-9 level. Further, this thesis presents preliminary results obtained with a micron-scale coupled-microstrip differential antenna probe that can be scanned over an ion-trap chip to map microwave magnetic near fields. The probe is designed to enable the measurement of fields at tens of microns above electrode surfaces and to act as an effective characterisation tool, speeding up design-fabrication-characterisation cycles in the production of new prototype microwave ion-trap chips. Finally, a new multi-layer design for an ion-trap chip which displays, in simulations, a 100-fold improvement in addressing performance, is presented. The chip electrode structure is designed to use the cancelling effect of microwave return currents to produce Rabi frequency ratios of order 1000 between trap zones using a single microwave electrode (i.e. without the need for nulling fields). If realised, this chip could be used to drive individually addressed single-qubit operations on arrays of memory qubits in parallel and with high fidelity.

This dissertation focuses on the development of analytical methods based on Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) and their applications for separation and structural characterization of oligosaccharides. Porous graphitized carbon liquid chromatography (PGC-LC), gated-trapped ion mobility spectrometry (Gated-TIMS), and electronic excitation dissociation tandem mass spectrometry (EED MS/MS) are three essential techniques employed here. First, the EED method was optimized to generate more informative glycan tandem mass spectra for accurate structural analysis. Glycans were reduced and permethylated or labeled with a reducing-end fixed charge to increase sensitivity, avoid gas-phase structural rearrangement, and facilitate spectral interpretation. EED of glycans produced nearly complete series of Z-, Y- and 1,5X-ions, that appear in the spectra as triplets with characteristic spacing, thus facilitating accurate determination of the glycan topology. Additional radical-driven dissociation pathways were identified, from which different types of linkage-diagnostic ions (cross-ring, secondary, or internal fragments) were generated. The results demonstrated that linkage analysis can be accomplished by utilizing one or a combination of several linkage-diagnostic fragments. EED MS/MS was then implemented, in conjunction with PGC-LC or Gated-TIMS, for on-line separation and characterization of complex mixtures of glycans. These two methods were successfully applied for high-throughput and detailed structural analysis of N-glycans released from human serum, O-glycans released from bovine submaxillary mucin and free oligosaccharides. The performance of these methods was tested and improved through analysis of different types of glycans from a variety of biological sources. Finally, in collaboration with bioinformaticians, a spectral interpretation algorithm, GlycoDeNovo, has been developed for automated and de novo glycan topology reconstruction from their tandem mass spectra. A large number of EED tandem spectra of glycan standards generated in house were used as the training dataset to establish appropriate IonClassifiers for candidate ranking. GlycoDeNovo is capable of identifying correct topologies from MS/MS spectra of glycans in different derivatized forms. Several aspects of this collaborative project were covered in this thesis, including glycan derivatization, data acquisition and manual spectral interpretation to guide the development and evaluate the performance of the automated approach. In this thesis research, integrated approaches utilizing PGC-LC–EED-MS/MS and Gated-TIMS–EED-MS/MS, and the appropriate bioinformatics software, have been established for structural analysis of glycan mixtures. They hold great potential for comprehensive, automated, and de novo glycome characterization.

Durante a década de 90 diversos trabalhos surgiram com o objetivo de investigar a localização de estados quânticos. No contexto da eletrodinâmica quântica de cavidades é possível localizar estados não clássicos de um dado campo externo aplicado ao sistema, uma cavidade preenchida com um material não linear inicialmente preparada no estado de vácuo. Baseado em tal cenário, propomos uma técnica de localização de estados vibracionais de um íon armadilhado. Para isso, considera-se um íon armadilhado em um potencial confinante cujos graus de liberdade vibracionais e os níveis eletrônicos do íon são acoplados por meio de um laser. Uma vez gerada a interação, faz-se uso da técnica de engenharia de reservatórios a fim de obtermos uma equação mestra na qual haja uma dinâmica emissiva e absortiva, ambas artificiais, promovidas por liouvillianos engenheirados, obtidos utilizando o sistema auxiliar (níveis internos do íon). Decorre-se disso uma dinâmica efetiva, já que a emissão espontânea é sempre presente. Sob um certo regime de parâmetros, a competição entre os liouvillianos leva o sistema de interesse para um estado vibracional estacionário caracterizando a localização. A técnica apresentada é mais geral pois mesmo partindo-se de um estado de máxima mistura, a localização é atingida com alta fidelidade em relação ao estado vibracional almejado. O papel exercido pela engenharia de interações para o sucesso da localização é o principal fator motivador deste trabalho. / In the 90s several works arose in order to investigate the localization of quantum states. In the context of quantum electrodynamics of cavities, it is possible to find non-classical states of a given external field applied to the system employing, for instance, a cavity (initially prepared in the vacuum states) filled with a non-linear material. In such scenario, we propose a trapped ion vibrational state localization technique. Consider a trapped ion confined in a potential whose vibrational and electronic degrees of freedom are coupled through two laser fields. Once such interaction is generated, we make use of the reservoir engineering technique in order to obtain a master equation in which there is an artificial dynamics of emission and absorption promoted by engineerined liouvillians obtained by using an auxiliary system (internal ion levels) within an effective dynamics, since the spontaneous emission is always present. Under a certain set of parameters, competition among liouvillians takes the system of interest to a vibrational steady-state featuring localization. The presented technique is interesting because the steady-state is achieved with high fidelity with respect to the desired vibrational state even when starting with highly mixed states. The role presented by the engineered interactions is fundamental for a successful localization and it is the primary motivation of this work.

Durante a década de 90 diversos trabalhos surgiram com o objetivo de investigar a localização de estados quânticos. No contexto da eletrodinâmica quântica de cavidades é possível localizar estados não clássicos de um dado campo externo aplicado ao sistema, uma cavidade preenchida com um material não linear inicialmente preparada no estado de vácuo. Baseado em tal cenário, propomos uma técnica de localização de estados vibracionais de um íon armadilhado. Para isso, considera-se um íon armadilhado em um potencial confinante cujos graus de liberdade vibracionais e os níveis eletrônicos do íon são acoplados por meio de um laser. Uma vez gerada a interação, faz-se uso da técnica de engenharia de reservatórios a fim de obtermos uma equação mestra na qual haja uma dinâmica emissiva e absortiva, ambas artificiais, promovidas por liouvillianos engenheirados, obtidos utilizando o sistema auxiliar (níveis internos do íon). Decorre-se disso uma dinâmica efetiva, já que a emissão espontânea é sempre presente. Sob um certo regime de parâmetros, a competição entre os liouvillianos leva o sistema de interesse para um estado vibracional estacionário caracterizando a localização. A técnica apresentada é mais geral pois mesmo partindo-se de um estado de máxima mistura, a localização é atingida com alta fidelidade em relação ao estado vibracional almejado. O papel exercido pela engenharia de interações para o sucesso da localização é o principal fator motivador deste trabalho. / In the 90s several works arose in order to investigate the localization of quantum states. In the context of quantum electrodynamics of cavities, it is possible to find non-classical states of a given external field applied to the system employing, for instance, a cavity (initially prepared in the vacuum states) filled with a non-linear material. In such scenario, we propose a trapped ion vibrational state localization technique. Consider a trapped ion confined in a potential whose vibrational and electronic degrees of freedom are coupled through two laser fields. Once such interaction is generated, we make use of the reservoir engineering technique in order to obtain a master equation in which there is an artificial dynamics of emission and absorption promoted by engineerined liouvillians obtained by using an auxiliary system (internal ion levels) within an effective dynamics, since the spontaneous emission is always present. Under a certain set of parameters, competition among liouvillians takes the system of interest to a vibrational steady-state featuring localization. The presented technique is interesting because the steady-state is achieved with high fidelity with respect to the desired vibrational state even when starting with highly mixed states. The role presented by the engineered interactions is fundamental for a successful localization and it is the primary motivation of this work.