Propõe-se método novo e completo para análise de acetona em ar exalado envolvendo coleta com pré-concentração em água, derivatização química e determinação eletroquímica assistida por novo algoritmo de processamento de sinais. Na literatura recente a acetona expirada vem sendo avaliada como biomarcador para monitoramento não invasivo de quadros clínicos como diabetes e insuficiência cardíaca, daí a importância da proposta. Entre as aminas que reagem com acetona para formar iminas eletroativas, estudadas por polarografia em meados do século passado, a glicina apresentou melhor conjunto de características para a definição do método de determinação por voltametria de onda quadrada sem a necessidade de remoção de oxigênio (25 Hz, amplitude de 20 mV, incremento de 5 mV, eletrodo de gota de mercúrio). O meio reacional, composto de glicina (2 mol·L-1) em meio NaOH (1 mol·L-1), serviu também de eletrólito e o pico de redução da imina em -1,57 V vs. Ag|AgCl constituiu o sinal analítico. Para tratamento dos sinais, foi desenvolvido e avaliado um algoritmo inovador baseado em interpolação de linha base por ajuste de curvas de Bézier e ajuste de gaussiana ao pico. Essa combinação permitiu reconhecimento e quantificação de picos relativamente baixos e largos sobre linha com curvatura acentuada e ruído, situação em que métodos convencionais falham e curvas do tipo spline se mostraram menos apropriadas. A implementação do algoritmo (disponível em http://github.com/batistagl/chemapps) foi realizada utilizando programa open source de álgebra matricial integrado diretamente com software de controle do potenciostato. Para demonstrar a generalidade da extensão dos recursos nativos do equipamento mediante integração com programação externa em linguagem Octave (open source), implementou-se a técnica da cronocoulometria tridimensional, com visualização de resultados já tratados em projeções de malha de perspectiva 3D sob qualquer ângulo. A determinação eletroquímica de acetona em fase aquosa, assistida pelo algoritmo baseado em curvas de Bézier, é rápida e automática, tem limite de detecção de 3,5·10-6 mol·L-1 (0,2 mg·L-1) e faixa linear que atende aos requisitos da análise em ar exalado. O acetaldeído, comumente presente em ar exalado, em especial, após consumo de bebidas alcoólicas, dá origem a pico voltamétrico em -1,40 V, contornando interferência que prejudica vários outros métodos publicados na literatura e abrindo possibilidade de determinação simultânea. Resultados obtidos com amostras reais são concordantes com os obtidos por método espectrofotométrico, em uso rotineiro desde o seu aperfeiçoamento na dissertação de mestrado do autor desta tese. Em relação à dissertação, também se otimizou a geometria do dispositivo de coleta, de modo a concentrar a acetona num volume menor de água gelada e prover maior conforto ao paciente. O método completo apresentado, englobando o dispositivo de amostragem aperfeiçoado e o novo e efetivo algoritmo para tratamento automático de sinais voltamétricos, está pronto para ser aplicado. Evolução para um analisador portátil depende de melhorias no limite de detecção e facilidade de obtenção eletrodos sólidos (impressos) com filme de mercúrio, vez que eletrodos de bismuto ou diamante dopado com boro, entre outros, não apresentaram resposta. / A new and complete method for analyzing acetone in exhaled breath is proposed, involving sample collection by preconcentration in water, chemical derivatization and electrochemical determination assisted by a new signal processing algorithm. Breath acetone is under investigation in the medical literature as a biomarker for noninvasive monitoring of clinical conditions such as diabetes and heart failure and better analyzers are demanded. Some amines that react with acetone to form electroactive imines, already studied by polarography in the middle of the last century, were evaluated here as derivatizing agents and glycine presented the best compromise for the definition of a determination method by square wave voltammetry without purging of dissolved oxygen (20 mV pulses at 25 Hz with 5 mV scanning steps, mercury drop electrode). The derivatization medium of glycine (2 mol·L-1) and NaOH (1 mol·L-1) also serves as electrolyte and the imine reduction peak at -1.57 V vs. Ag|AgCl constitutes the analytical signal. For signal processing a novel algorithm based on baseline automatic prediction using Bézier curves was developed in combination with Gaussian peak fitting. This innovative combination enables the recognition and quantification of relatively low and broad peaks on a curved and noisy baseline while standard procedures fail and fitting of splines is less appropriate. The algorithm (available at http://github.com/batistagl/chemapps) was implemented using open source matrix algebra software directly integrated with the potentiostat control software. The generality of this approach to extend the native resources of commercial equipment was evidenced by proceeding the implementation of 3D chronocoulometry with help of the open source Octave language. The processed charge vs. potential vs. time function 3-D surfaces for the forward and backward steps can be observed from any angle on the screen. The fast automatic electrochemical determination of acetone assisted by the Bézier based curve fitting algorithm, with an acetone detection limit of 3.5·10-6 mol·L-1 (0.2 mg·L-1) and a wide linear range is entirely satisfactory for breath analysis. Acetaldehyde, an expected component of breath, especially after ingestion of alcohol, and a common interferent for some other analytical methods, generates a peak at -1.40 V that does not interfere with the acetone determination and that is possibly suitable for simultaneous determination of this analyte. Results obtained with real samples are in agreement with spectrophotometric determinations routinely applied to breath analysis, formerly developed in the master dissertation of the author of this thesis. The geometry of the impinger sampling device was also improved (in comparison with the dissertation) in order to collect the acetone in a smaller volume of cooled water and to allow the patient to breath more freely. The complete method at its current state of development, encompassing the improved sampler and the new effective signal processing algorithm for voltammetric signals is ready for use. Evolution to a portable analyzer can be envisioned if the shortcomings of detection limits of solid (screen-printed) electrode preparation with a mercury film are overcome, once the imine signal was not observed on solid electrodes like bismuth and boron doped diamond.

The work presented in this thesis is concerned with development of spectroscopic detection methods based on absorption spectroscopy using semiconductor lasers, with particular ref- erence to the field of medical diagnostics through breath analysis. The first part of this thesis deals with the design and testing of a prototype analyser for simultaneous monitoring of the exchange gases O₂ , CO₂ and H₂O in breath. The aim of this analyser is to provide information required to monitor respiration, with potential use in intensive care monitoring or during anaesthesia. The relatively high concentrations of these gases in breath and read- ily available diode laser sources make detection in the near-infrared (NIR) ideal. However, the relatively weakly absorbing A-band O₂ transitions at 760 nm require the application of a sensitive spectroscopic method, cavity enhanced absorption spectroscopy (CEAS). In contrast, CO₂ and H₂O are monitored using direct single pass absorption spectroscopy, with transitions arising from the 2ν₁ + ν₃ band at 2 μm and ν₁ + ν₃ band at 1.3 μm, respectively. It has been demonstrated that these gases can be detected simultaneously over a short pathlength (2.74 - 4 cm) in the respiratory flow by combining various spectroscopic methodologies and real-time data analysis. This analyser is shown to offer a viable alter- native for monitoring respiration, exhibiting absolute detection limits of changes of 0.26 % O₂ , 0.02 % CO₂ and 0.003 % H₂O with a 10 ms time resolution, which are comparable to current mass spectrometry based methods, but without their inherent delays. Following this, investigations into the detection of the main gas constituents in breath in the NIR employing noise-reduction modulation based spectroscopic techniques, namely wavelength and frequency modulation (WMS and FMS respectively) are also reported. The described WMS studies on water at 1.37 μm provide a demonstration of conventional WMS detection, as well as a “proof-of-principle” example of a relatively new approach to calibrating the non-absolute information obtained from a WMS absorption signal. Typically WMS spectra are calibrated using mixtures of known gas concentrations or an absolute direct absorption spectrum where possible. In this work however, a self-calibrating method, the phasor decomposition method (PDM), is employed and the returned concentration from this calibration is compared to direct absorption measurement. From this, the calculated concentration using the PDM is found to differ by 9 % from the concentration value obtained by direct absorption, providing an alternative method of calibration for when direct absorption measurements are not possible. The use of FMS in the NIR is also demonstrated as a potential alternative to CEAS for monitoring O₂ at 760 nm. FMS detection is performed on atmospherically broadened O₂ and a time-normalised α_min(t) of 2.45 ×10⁻⁶ cm⁻¹ s^1/2 is obtained, which is two orders of magnitude less sensitive than the value of α_min(t) = 2.35 ×10⁻⁸ cm⁻¹ s^1/2 obtained with CEAS. This combined with the experimental requirements of an FMS system, make its use for detection of O₂ a less practicable option compared to CEAS for real-time breath analysis. The latter work in this thesis involves a change in focus to detection of trace gases in breath in the mid-infrared (MIR). The move of spectroscopic detection to the MIR exploits the larger absorption cross-sections available in this region, and to achieve this, a relatively new form of semiconductor laser, the quantum cascade laser (QCL) is used. The design of a continuous wave QCL spectrometer at 8 μm and its operating characteristics are demon- strated and improvements in its performances are also discussed. This QCL system is then utilised to demonstrate the potential of monitoring species in breath, namely the narrow- band absorber methane and the broadband absorber acetone, taking into consideration the potential interference from other absorbing species in breath and the different spectroscopic characteristics exhibited by these molecules. Finally, the potential to further improve the sensitive detection of trace gases in breath in the MIR is also investigated with studies on the use of CEAS and multipass cells. In this work, the molecule of interest is the biomarker OCS, using transitions of the 2ν₂ band at 1031 cm⁻¹ , that are probed using a 10 μm QCL. The application of CEAS in the MIR is not as well developed as in the NIR, and the experimental consequences of using optical cavities at these wavelengths, where equipment tends to be more limited, are investigated and sensitivities discussed in the context of other literature. The experimental procedure of optimising a cavity for CEAS using the off-axis alignment method is also studied in detail, as well as the addition of WMS to further improve the signal quality. An effective absorption pathlength of ∼ 100 m was achieved in the cavity, with a bandwidth reduced α_min(BW) of 1.7 ×10⁻⁷ cm⁻¹ Hz^−1/2 using WMS CEAS achieved. With the poorer quality optics and limitations in equipment in the MIR for CEAS experiments, the use of a multipass cell, a 238 m Herriott cell, is also investigated as an alternative to the use of an optical cavity at 10 μm. Detection of OCS using direct absorption and WMS is demonstrated in the Herriott cell, achieving α_min(BW) = 2.03×10⁻⁸ cm⁻¹ Hz^−1/2 using WMS. This shows an improvement in sensitivity compared to WMS CEAS, and also shows the potential for future work on biomarker detection, as it approaches the ∼ ppb levels required for breath analysis.

A dissertação se situa no campo de pesquisa de métodos não invasivos de análise clínica, mais especificamente, de prognóstico da gravidade de insuficiência cardíaca, IC, com base em bioindicador presente no ar exalado por pacientes, em estudo no IncorHCFMUSP. O bioindicador mais relevante encontrado por GC-MS foi a acetona (propanona). Para a coleta do ar exalado desenvolveu-se dispositivo que compreende frasco borbulhador (impinger) com difusor, contendo 5 mL de água, imerso em banho de gelo e acoplado a saco plástico para definição de volume amostrado (7,6 L). A preservação de amostras deu-se por congelamento a -80ºC. Para a determinação do analito, escolheu-se método espectrofotométrico (474 nm) baseado na reação da acetona com salicilaldeído em meio básico, apresentando limite de detecção de 0,3 mg/L em fase líquida e 0,3 µg/L em ar exalado. Foram realizados estudos de eficiência de coleta por geração de atmosfera controlada. Resultados iniciais obtidos com amostras coletadas de pacientes portadores de IC pelos colaboradores do Incor indicam a potencialidade do bioindicador e dos equipamentos e métodos desenvolvidos para acetona nesta dissertação. / The dissertation fits in the research field of noninvasive clinical analysis, more specifically, the prognosis of the severity of heart failure, HF, based on a biomarker found in the air exhaled by patients, in a study at InCor-HCFMUSP. The most relevant biomarker found by GC-MS was acetone (propanone). For the breath collection a device was developed which comprises a scrubber flask (impinger) with diffuser, containing 5 mL of water, immersed in an ice bath and attached to a plastic bag for delimitation of the sample volume (7,6 L). For the determination of acetone a spectrometric method (474 nm) was chosen based on a reaction of acetone with salicylaldehyde in alkaline medium, with detection limits of 0,3 mg/L in liquid phase and 0,3 µg/L in breath. Preliminary studies made with samples collected from HF patients by the co-workers from InCor indicate the potential of the identified biomarker and the suitability of the equipment and methods developed in this dissertation for its analysis.

A dissertação se situa no campo de pesquisa de métodos não invasivos de análise clínica, mais especificamente, de prognóstico da gravidade de insuficiência cardíaca, IC, com base em bioindicador presente no ar exalado por pacientes, em estudo no IncorHCFMUSP. O bioindicador mais relevante encontrado por GC-MS foi a acetona (propanona). Para a coleta do ar exalado desenvolveu-se dispositivo que compreende frasco borbulhador (impinger) com difusor, contendo 5 mL de água, imerso em banho de gelo e acoplado a saco plástico para definição de volume amostrado (7,6 L). A preservação de amostras deu-se por congelamento a -80ºC. Para a determinação do analito, escolheu-se método espectrofotométrico (474 nm) baseado na reação da acetona com salicilaldeído em meio básico, apresentando limite de detecção de 0,3 mg/L em fase líquida e 0,3 µg/L em ar exalado. Foram realizados estudos de eficiência de coleta por geração de atmosfera controlada. Resultados iniciais obtidos com amostras coletadas de pacientes portadores de IC pelos colaboradores do Incor indicam a potencialidade do bioindicador e dos equipamentos e métodos desenvolvidos para acetona nesta dissertação. / The dissertation fits in the research field of noninvasive clinical analysis, more specifically, the prognosis of the severity of heart failure, HF, based on a biomarker found in the air exhaled by patients, in a study at InCor-HCFMUSP. The most relevant biomarker found by GC-MS was acetone (propanone). For the breath collection a device was developed which comprises a scrubber flask (impinger) with diffuser, containing 5 mL of water, immersed in an ice bath and attached to a plastic bag for delimitation of the sample volume (7,6 L). For the determination of acetone a spectrometric method (474 nm) was chosen based on a reaction of acetone with salicylaldehyde in alkaline medium, with detection limits of 0,3 mg/L in liquid phase and 0,3 µg/L in breath. Preliminary studies made with samples collected from HF patients by the co-workers from InCor indicate the potential of the identified biomarker and the suitability of the equipment and methods developed in this dissertation for its analysis.

Ce travail de thèse a permis le développement et la caractérisation d'instruments basés sur la technique "OF-CEAS" dans le moyen infrarouge pour la détection de traces dans différents mélanges en phase gazeuse. Le Laser à Cascades Inter-bandes (ICL) est la dernière innovation des lasers à semi-conducteurs dans cette zone spectrale. La compatibilité des ICL avec l'OF-CEAS ouvre la voie vers de nouvelles applications pour la réalisation d'instruments compacts et robustes avec un temps de réponse rapide tout en présentant une très bonne limite de détection.Une démonstration de la bonne sensibilité et stabilité des instruments OF-CEAS aété réalisé avec la mesure de continua d'absorption (de la vapeur d'eau et de l'azote). Mais également avec la détection d'une raie quadrupolaire de l'azote de très faible intensité (3x10-29 cm-1/(moléc cm-2). L'objectif principale de ces travaux consistait au développement d'un instrument dédié à la détection de monoxyde d'azote pour l'analyse du gaz exhalé. L'analyseur ainsi réalisé présente une sensibilité de 6x10-10 cm-1 en une acquisition de 180 ms. Sa limite de détection sur le NO est à l'état de l'art, avec à court terme (180 ms) un minimum de 50 ppt est atteint. Celui-ci parvient à un niveau sub-ppt (0.9 ppt) en 12 min d'intégration. / This work of these has made it possible to develop and characterize the use of instruments on the "OF-CEAS" technique in the mid-infrared for traces' detection in different mixtures in the gas phase. Inter-band Cascade Laser (ICL) is the latest innovation in semiconductor lasers in this spectral region. Compatibility of ICL with OF-CEAS offers new applications for compact and robust instruments with fast response time and a low detection limit. A demonstration of the good sensitivity and stability of the OF-CEAS instruments was performed with continua absorption measurements (water vapor and nitrogen). But also with the detection of a very low intensity quadrupole line of nitrogen (3x10-29 cm-1/(moléc cm-2). The main objective of this work was to develop an instrument dedicated to nitrogen oxide detection for the analysis of exhaled breath. The analyzer is presented at the sensitivity of 6x10-10 cm-1 in an acquisition of 180 ms. Its limit of detection on NO is at the state of the art, with short term (180 ms) limit of 50 ppt. It reaches the sub-ppt level (0.9 ppt) with 12 min of integration.

No description available.

Dans le domaine de la santé, l’analyse de l'haleine expirée offre un outil simple et non invasif pour le diagnostic précoce des maladies. Les capteurs de gaz à base de SnO2 modifies semblent être des dispositifs prometteurs pour détecter les gaz polaires tels que l'ammoniac. Dans cette étude, la fonctionnalisation de la surface de SnO2 a été réalisée afin d'obtenir un capteur de gaz sensible et sélectif à l'ammoniac, qui fonctionne à température ambiante. La première étape de la fonctionnalisation est la fixation covalente d’un film de 3-aminopropyltrethoxysalane (APTES) sur SnO2 en phase vapeur ou liquide. Les caractérisations effectuées par Spectroscopie Infrarouge et Spectrométrie photoélectronique X montrent qu’une quantité plus importante d'APTES a été greffée en phase liquide hydratée. La deuxième étape consiste à fonctionnaliser le SnO2-APTES avec des molécules contenant du chlorure d'acyle avec différents groupes tel que des groupes alkyle, acide et ester. Les capteurs modifiés par des acides et des esters sont sensibles à l’ammoniac entre 0,2 et 10 ppm à température ambiante. Cependant, le SnO2 APTES modifié par l’ester s'est révélé être plus sélectif que le capteur modifié par l'acide pour l’ethanol et le mondxyde de carbone. Ces résultats impliquent que la réponse est générée par les groupes fonctionnels acide et ester, NH3 modifie le moment dipolaire de la couche moléculaire greffée, ce qui entraine une modification de la conductance de SnO2. Le fonctionnement à température ambiante est l'un des avantages de ces capteurs, tout comme leur sélectivité à l'ammoniac en regard d'autres gaz tels que l'éthanol, le monoxyde de carbone et l'acétone. / One of the major challenges in the modern era is how we can detect the disease when we are still feeling healthy via noninvasive methods. Exhaled breath analysis is offering a simple and noninvasive tool for early diagnosis of diseases. Molecularly modified SnO2 sensors seem to be promising devices for sensing polar gases such as ammonia. SnO2 surface functionalization was performed in order to obtain sensitive and selective ammonia gas sensor that operates at room temperature. The first step of functionalization is the covalently attachment of 3-aminopropyltriethoxysilane (APTES) film on SnO2 in vapor or liquid phases. The characterization performed by the Infrared Spectroscopy and X-ray Photoelectron Spectroscopy, show that more APTES were grafted by hydrous liquid phase silanization. The second step was the functionalization of APTES modified SnO2 with molecules having acyl chloride of end functional groups molecules such as alkyl, acid and ester groups. Pure SnO2 and APTES modified SnO2 sensors did not show any significant sensitivity to ammonia (0.2-100 ppm) at 25 °C. On the contrary, acid and ester modified sensors are sensitive to ammonia between 0.2 and 10 ppm at room temperature. However, ester modified SnO2 was more selective than acid modified sensor regarding the ethanol and carbon monoxide gases. Ammonia variates the attached molecular layer’s dipole moment which leads to change in SnO2 conductance. Working at ambient temperature is also one of the advantages of these sensors in addition to the selectivity to ammonia regarding other gases such as ethanol, carbon monoxide and acetone.

Ein nicht-invasiver Atemtest zur Lungenkrebsdetektion setzt Kenntnis über lungenkrebsspezifische Substanzen voraus. Die Identifizierung von Lungenkrebsbiomarkern in der Atemluft war das Ziel dieser Arbeit. Leichtflüchtige organische Substanzen (VOC) wurden als Zielkomponenten ausgewählt. Für die VOC-Analytik wurde eine SPME-GC-MS-Methode entwickelt und sowohl auf Modellsysteme als auch auf Realproben angewendet. Drei Lungenadenokarzinomzelllinien wurden in-vitro untersucht. Die VOC-Analyse wurde mit drei verschiedenen Probenahmestrategien durchgeführt und es war ein deutlicher Hintergrundeinfluss der eingesetzten Einwegzellkulturflaschen auf das analysierte VOC-Profil feststellbar. Trotzdem konnten signifikante Unterschiede zwischen Tumorzellen und zellfreien Nährmedien beobachtet werden: 1-Propanol wurde von den Zellen produziert, während der Gehalt einiger Aldehyde sank. Die eingeschränkte Ähnlichkeit des gewählten Zellkulturmodells mit realen Atemluftproben bedingt eine geringe Eignung dieser Ergebnisse für die Biomarkerableitung. Ein Gasmodell auf Basis angefeuchteter, synthetischer Luft wurde als Grundlage für die qualitätsgesicherte, quantitative VOC-Analyse der realen Atemluftproben konzipiert. Diese Modellluft wurde mit 24 Zielsubstanzen (Alkane, Aromaten, sauerstoffhaltige Spezies) sowie 3 Matrix-VOC mit starker Dominanz in den Atemluftproben (Isopren, Aceton, 2-Propanol) angereichert. In Kooperation mit zwei Berliner Kliniken wurden 37 Atemluftproben von Lungenkrebspatienten und 23 Proben von Gesunden gesammelt. Die Anwendung von 1-Butanol als univariater Marker erlaubt eine Erkennung von Lungenkrebs mit einer Sensitivität von 92% und Spezifität von 78%. Durch lineare Diskriminanzanalyse konnte ein Set aus 4 VOC (1-Butanol, 2-Butanon, 2-Pentanon, n-Hexanal) ermittelt werden, welches ebenfalls eine Sensitivität von 92% und mit 87% eine höhere Spezifität aufwies. Gegebenenfalls handelt es sich bei diesen Substanzen jedoch nur um allgemeine Krankheitsmarker. / A non-invasive breath test for lung cancer detection would be favorable but knowledge on lung cancer specific substances is required. This work aims at the identification of potential lung cancer biomarkers in breath. Volatile organic compounds (VOC) were chosen as targets and a SPME-GC-MS method was developed to analyze the VOC profiles of model systems and real samples. Three lung adenocarcinoma cell lines were investigated in-vitro. The VOC analysis, carried out with 3 different sampling strategies, was influenced by the VOC background of the used disposable culture vessels. Changes in the VOC profiles of cell lines compared to cell-free culture media were obvious: 1-propanol was released by the tumor cells whereas the content of some aldehydes was diminished. The similarity of this model system with real breath samples of lung cancer patients was seen to be insignificant. Consequently, these cell cultures were not suitable for biomarker identification. A gaseous model consisting of humidified synthetic air was developed. It was fortified with 24 target VOC (alkanes, aromatics and oxygenated species) as well as 3 matrix compounds (isoprene, acetone and 2-propanol) dominating patients’ VOC profiles in breath. This model was used for the quality assured quantitative VOC analysis in real breath samples. In cooperation with two hospitals 37 single mixed expiratory breath samples from lung cancer patients and 23 from healthy controls were collected. Applying 1-butanol as an univariate biomarker patients and controls were discriminated with a sensitivity of 92% and a specificity of 78%. Linear discriminant analysis displayed a set of 4 VOC (1-butanol, 2-butanone, 2-pentanone, n-hexanal) with similar sensitivity but higher specificity of 87%. However, these potential biomarkers might rather be a consequence of illness in general.

Today, the growing and aging population, and the rise of new global threats on human health puts an increasing demand on the healthcare system and calls for preventive actions. To make existing medical treatments more efficient and widely accessible and to prevent the emergence of new threats such as drug-resistant bacteria, improved diagnostic technologies are needed. Potential solutions to address these medical challenges could come from the development of novel lab-on-chip (LoC) for point-of-care (PoC) diagnostics. At the same time, the increasing demand for sustainable energy calls for the development of novel approaches for energy conversion and storage systems (ECS), to which micro- and nanotechnologies could also contribute. This thesis has for objective to contribute to these developments and presents the results of interdisciplinary research at the crossing of three disciplines of physics and engineering: electrokinetic transport in fluids, manufacturing of micro- and nanofluidic systems, and surface control and modification. By combining knowledge from each of these disciplines, novel solutions and functionalities were developed at the macro-, micro- and nanoscale, towards applications in PoC diagnostics and ECS systems. At the macroscale, electrokinetic transport was applied to the development of a novel PoC sampler for the efficient capture of exhaled breath aerosol onto a microfluidic platform. At the microscale, several methods for polymer micromanufacturing and surface modification were developed. Using direct photolithography in off-stoichiometry thiol-ene (OSTE) polymers, a novel manufacturing method for mold-free rapid prototyping of microfluidic devices was developed. An investigation of the photolithography of OSTE polymers revealed that a novel photopatterning mechanism arises from the off-stoichiometric polymer formulation. Using photografting on OSTE surfaces, a novel surface modification method was developed for the photopatterning of the surface energy. Finally, a novel method was developed for single-step microstructuring and micropatterning of surface energy, using a molecular self-alignment process resulting in spontaneous mimicking, in the replica, of the surface energy of the mold. At the nanoscale, several solutions for the study of electrokinetic transport toward selective biofiltration and energy conversion were developed. A novel, comprehensive model was developed for electrostatic gating of the electrokinetic transport in nanofluidics. A novel method for the manufacturing of electrostatically-gated nanofluidic membranes was developed, using atomic layer deposition (ALD) in deep anodic alumina oxide (AAO) nanopores. Finally, a preliminary investigation of the nanopatterning of OSTE polymers was performed for the manufacturing of polymer nanofluidic devices. / <p>QC 20140509</p> / Rappid / NanoGate / Norosensor