Preterm birth (PTB) results in over 15 million early births annually and is the leading cause of neonatal deaths. There are no clinical methods currently available to evaluate risk of PTB at early stages in pregnancy; thus, a rapid diagnostic to analyze PTB risk would be beneficial. Microfluidic immunoaffinity extraction is a promising platform for preparing complex samples, such as maternal serum with PTB risk biomarkers. 3D printed microfluidic devices have advantages over conventional microfluidic systems including simple fabrication and potential for iterative optimization to improve designs. In this work, I developed immunoaffinity monoliths in 3D printed microfluidic devices modified with antibodies to enrich PTB biomarkers from human blood serum. I retained and eluted a peptide PTB biomarker in both buffer and blood serum using an immunoaffinity column. An additional three PTB biomarkers were also successfully extracted either from buffer or blood serum on single-antibody columns. Both polyclonal and monoclonal antibodies to PTB biomarkers were characterized by dot blots, biolayer interferometry, and surface plasmon resonance to determine their specificity and dissociation constants. I created multiplexed immunoaffinity columns to simultaneously enrich three PTB biomarkers from depleted human blood serum in a single extraction. This is the first demonstration of multiplexed immunoaffinity columns for PTB biomarkers in a 3D printed microfluidic device. My work is a key step towards the future development of 3D printed microfluidic devices for rapid PTB testing.

Wavelength division multiplexed (WDM) optical networks are rapidly becoming the technology of choice in network infrastructure and next-generation Internet architectures. WDM networks have the potential to provide unprecedented bandwidth, reduce processing cost, achieve protocol transparency, and enable efficient failure handling. This dissertation addresses the important issues of improving the performance and enhancing the reliability of WDM networks as well as modeling and evaluating the performance of these networks. Optical wavelength conversion is one of the emerging WDM enabling technologies that can significantly improve bandwidth utilization in optical networks. A new approach for the sparse placement of full wavelength converters based on the concept of the k-Dominating Set (k-DS) of a graph is presented. The k-DS approach is also extended to the case of limited conversion capability using three scalable and cost-effective switch designs: flexible node-sharing, strict node-sharing and static mapping. Compared to full search algorithms previously proposed in the literature, the K-DS approach has better blocking performance, has better time complexity and avoids the local minimum problem. The performance benefit of the K-DS approach is demonstrated by extensive simulation. Fiber delay line (FDL) is another emerging WDM technology that can be used to obtain limited optical buffering capability. A placement algorithm, k-WDS, for the sparse placement of FDLs at a set of selected nodes in Optical Burst Switching (OBS) networks is proposed. The algorithm can handle both uniform and non-uniform traffic patterns. Extensive performance tests have shown that k-WDS provides more efficient placement of optical fiber delay lines than the well-known approach of placing the resources at nodes with the highest experienced burst loss. Performance results that compare the benefit of using FDLs versus using optical wavelength converters (OWCs) are presented. A new algorithm, A-WDS, for the placement of an arbitrary numbers of FDLs and OWCs is introduced and is evaluated under different non-uniform traffic loads. This dissertation also introduces a new cost-effective optical switch design using FDL and a QoS-enhanced JET (just enough time) protocol suitable for optical burst switched WDM networks. The enhanced JET protocol allows classes of traffic to benefit from FDLs and OWCs while minimizing the end-to-end delay for high priority bursts. Performance evaluation models of WDM networks represent an important research area that has received increased attention. A new analytical model that captures link dependencies in all-optical WDM networks under uniform traffic is presented. The model enables the estimation of connection blocking probabilities more accurately than previously possible. The basic formula of the dependency between two links in this model reflects their degree of adjacency, the degree of connectivity of the nodes composing them and their carried traffic. The usefulness of the model is illustrated by applying it to the sparse wavelength converters placement problem in WDM networks. A lightpath containing converters is divided into smaller sub-paths such that each sub-path is a wavelength continuous path and the nodes shared between these sub-paths are full wavelength conversion capable. The blocking probability of the entire path is obtained by computing the blocking probabilities of the individual sub-paths. The analytical-based sparse placement algorithm is validated by comparing it with its simulation-based counterpart using a number of network topologies. Rapid recovery from failure and high levels of reliability are extremely important in WDM networks. A new Fault Tolerant Path Protection scheme, FTPP, for WDM mesh networks based on the alarming state of network nodes and links is introduced. The results of extensive simulation tests show that FTPP outperforms known path protection schemes in terms of loss of service ratio and network throughput. The simulation tests used a wide range of values for the load intensity, the failure arrival rate and the failure holding time. The FTPP scheme is next extended to the differentiated services model and its connection blocking performance is evaluated. Finally, a QoS-enhanced FTPP (QEFTPP) routing and path protection scheme in WDM networks is presented. QEFTPP uses preemption to minimize the connection blocking percentage for high priority traffic. Extensive simulation results have shown that QEFTPP achieves a clear QoS differentiation among the traffic classes and provides a good overall network performance.

Lungcancer är en heterogen sjukdom som kräver många histopatologiska analyser för att diagnostisera och behandla effektivt. Dessa analyser utförs för närvarande med singelplex immunohistokemi (IHC) vilket kräver mycket vävnadsprovmaterial om flera markörer behöver färgas för. I den här studien testades två tillvägagångssätt för multiplex immunfluorescens (IF) (indirekt sekventiell IF och multiplex tyramide signal amplification med spektral avblandning) för att se om en panel av 7 markörer, som rutinmässigt används kliniskt, kunde färgas i ett enda experiment på samma vävnadsprov. För att göra detta användes COMET- och LabSat-instrumenten från Lunaphore och de utvärderades utifrån kvalité och användarvänlighet. På COMETen kunde alla sju markörer inkluderas i panelen medan tillvägagångssättet med TSA på LabSat var begränsat till sex markörer på grund av protokollet för spektral separation. Panelen optimerades på COMET och sedan gjordes multiplexa färgningar med båda instrumenten. Färgningarna från LabSat avbildades med mikroskopet på PhenoImager Fusion-instrumentet. Alla färgningar på COMET var av god kvalité medan LabSat hade behövt vidare optimering för att prestera på samma nivå. COMETen fanns också vara det mer användarvänliga instrumentet pga det integrerade mikroskopet och mindre behov av användarintervention. Denna studie visade att det är möjligt att översätta singelplexa IHC-analyser till multiplex IF med vissa optimeringar och byte av några antikroppskloner. / Lung cancer is a heterogeneous group of malignancies that requires many histopathological analyses to diagnose and treat efficiently. These analyses are currently performed with singleplex immunohistochemistry (IHC) which needs a lot of tissue sample material if multiple markers have to be stained for. In this study, two different multiplexed immunofluorescence (IF) approaches (indirect sequential IF and multiplexed tyramide signal amplification with spectral unmixing) were tested to see if a panel of 7 markers routinely used in clinic to could be stained in a single experiment on the same tissue sample. To do this, the COMET and LabSat instruments from Lunaphore were used and evaluated in regards to quality and ease of use. With the COMET all seven markers could be included in the panel while the TSA approach on LabSat was limited to six markers due to the spectral unmixing protocol. The panel was optimized on COMET and then multiplexed stainings were performed on both instruments. The LabSat staining was imaged on the PhenoImager Fusion microscope. All the stainings were of good quality on the COMET while the LabSat would have needed further optimization to perform at the same level. The COMET was also found to be the more user-friendly instrument due to its integrated microscope and lesser need for user intervention. This study showed that it is possible to translate singleplex IHC analyses into multiplexed IF with some optimizations and change of a few antibody clones.

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第22448号 / 工博第4709号 / 新制||工||1735(附属図書館) / 京都大学大学院工学研究科電子工学専攻 / (主査)教授 竹内 繁樹, 教授 白石 誠司, 准教授 浅野 卓 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

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O problema estudado relaciona-se ao planejamento de redes ópticas de acesso TWDM (Time and Wavelength Division Multiplexing), tendo como meta prover meios para atender ao consumo crescente de banda e, ao mesmo tempo, associar o mesmo ao menor consumo de energia possível e disponibilizar serviços de qualidade aos usuários da rede. Neste contexto, após a apresentação de uma revisão bibliográfica, alguns trabalhos foram selecionados como referências base para o estudo. Neste, foram analisadas técnicas de gerenciamento do comprimento de onda numa possível migração tecnológica dos equipamentos de acesso à rede pelo lado do usuário, as unidades de rede óptica (ONUs), considerando ser possível aproveitar de forma eficiente a distribuição de ONUs em cada par de comprimentos de onda, e como resultado, desligar interfaces de gerenciamento para economia de energia. Em paralelo a este objetivo, foram agregados métodos de \"registro adaptativo\" para melhorar o desempenho das ONUs que estão migrando e/ou entrando na rede, evitando colisões entre seus sinais e aumentando as chances de registro no terminal de linha óptico (OLT). Além do mais, o trabalho aborda o cumprimento do contrato de serviços (SLA) por parte das operadoras de telecomunicações, bem como oferece meios de estruturar uma rede óptica passiva (PON) para oferecer serviços com garantia de métricas de qualidade (QoS). Diferentes cenários foram tratados ao variar a porcentagem de usuários ativos na rede, e percebeu-se que, quando a PON opera com baixo índice de atividade (média 10% de ONUs ativas), foi possível economizar mais de 80% de energia em interfaces de gerenciamento. Por outro lado, ao envolver cenários mais realistas em redes ópticas (média de 50% de ONUs ativas), o TWDM-PON economizou quase 50% de energia nestas interfaces ao ser configurado com baixo período de migração (5 minutos). Além disso, alcançou um SLA de aproximadamente 100%, um valor considerado acima do usual quando se trata de cumprimento de serviços. Como uma tecnologia emergente, o TWDM-PON destaca-se num cenário que deve ser planejado para ser compatível com tecnologias implantadas, e além de disso, superar o legado de redes PON na economia de energia e qualidade de serviços oferecidos. / The problem studied is related to the planning of optical access networks TWDM (Time and Wavelength Division Multiplexing), aiming to provide means to meet the increasing bandwidth consumption and, at the same time, associating it to the lowest possible power consumption and providing quality services to the network users. In this context, following the presentation of a literature review, some studies were selected as a reference basis for the study. In this, some wavelength management techniques were analyzed aiming a possible technological migration of the network access equipment at the user side, the optical network units (ONU), whereas it is possible to use efficiently the ONUs distribution in each pair of wavelength. As a result, it becomes possible to switch off some management interfaces thus assuring a degree of power consumption save. In parallel, methods for providing an \"adaptive record\" of ONUs have been aggregated to improve the performance of those ONUs that are migrating and/or entering the network, avoiding collisions between their signals and increasing the chance of their registration in the optical line terminal (OLT). Furthermore, this work deals with the fulfillment of the service agreement (SLA) signed by telecommunications operators and proposes ways to design a passive optical network (PON) in order to offer services with quality metrics assurance (QoS). Different scenarios were treated to vary the percentage of active users on the network, and it was noticed that when the PON operates with low rate of activity (average 10% of active ONUs), it was possible to save over 80% energy in the management interfaces. Moreover, by involving more realistic scenarios in optical networks (50%, in average, of active ONUs), the TWDM-PON saved almost 50% of energy at the interfaces to be configured with low migration period (5 minutes). Additionally, it reached an SLA of approximately 100%, a value considered above the usual when it comes to compliance services. As an emerging technology, TWDM-PON stands out in a scenario that should be designed to be compatible with deployed technologies, and beyond that, to overcome the legacy of PON networks in energy saving and quality of services offered.

O problema estudado relaciona-se ao planejamento de redes ópticas de acesso TWDM (Time and Wavelength Division Multiplexing), tendo como meta prover meios para atender ao consumo crescente de banda e, ao mesmo tempo, associar o mesmo ao menor consumo de energia possível e disponibilizar serviços de qualidade aos usuários da rede. Neste contexto, após a apresentação de uma revisão bibliográfica, alguns trabalhos foram selecionados como referências base para o estudo. Neste, foram analisadas técnicas de gerenciamento do comprimento de onda numa possível migração tecnológica dos equipamentos de acesso à rede pelo lado do usuário, as unidades de rede óptica (ONUs), considerando ser possível aproveitar de forma eficiente a distribuição de ONUs em cada par de comprimentos de onda, e como resultado, desligar interfaces de gerenciamento para economia de energia. Em paralelo a este objetivo, foram agregados métodos de \"registro adaptativo\" para melhorar o desempenho das ONUs que estão migrando e/ou entrando na rede, evitando colisões entre seus sinais e aumentando as chances de registro no terminal de linha óptico (OLT). Além do mais, o trabalho aborda o cumprimento do contrato de serviços (SLA) por parte das operadoras de telecomunicações, bem como oferece meios de estruturar uma rede óptica passiva (PON) para oferecer serviços com garantia de métricas de qualidade (QoS). Diferentes cenários foram tratados ao variar a porcentagem de usuários ativos na rede, e percebeu-se que, quando a PON opera com baixo índice de atividade (média 10% de ONUs ativas), foi possível economizar mais de 80% de energia em interfaces de gerenciamento. Por outro lado, ao envolver cenários mais realistas em redes ópticas (média de 50% de ONUs ativas), o TWDM-PON economizou quase 50% de energia nestas interfaces ao ser configurado com baixo período de migração (5 minutos). Além disso, alcançou um SLA de aproximadamente 100%, um valor considerado acima do usual quando se trata de cumprimento de serviços. Como uma tecnologia emergente, o TWDM-PON destaca-se num cenário que deve ser planejado para ser compatível com tecnologias implantadas, e além de disso, superar o legado de redes PON na economia de energia e qualidade de serviços oferecidos. / The problem studied is related to the planning of optical access networks TWDM (Time and Wavelength Division Multiplexing), aiming to provide means to meet the increasing bandwidth consumption and, at the same time, associating it to the lowest possible power consumption and providing quality services to the network users. In this context, following the presentation of a literature review, some studies were selected as a reference basis for the study. In this, some wavelength management techniques were analyzed aiming a possible technological migration of the network access equipment at the user side, the optical network units (ONU), whereas it is possible to use efficiently the ONUs distribution in each pair of wavelength. As a result, it becomes possible to switch off some management interfaces thus assuring a degree of power consumption save. In parallel, methods for providing an \"adaptive record\" of ONUs have been aggregated to improve the performance of those ONUs that are migrating and/or entering the network, avoiding collisions between their signals and increasing the chance of their registration in the optical line terminal (OLT). Furthermore, this work deals with the fulfillment of the service agreement (SLA) signed by telecommunications operators and proposes ways to design a passive optical network (PON) in order to offer services with quality metrics assurance (QoS). Different scenarios were treated to vary the percentage of active users on the network, and it was noticed that when the PON operates with low rate of activity (average 10% of active ONUs), it was possible to save over 80% energy in the management interfaces. Moreover, by involving more realistic scenarios in optical networks (50%, in average, of active ONUs), the TWDM-PON saved almost 50% of energy at the interfaces to be configured with low migration period (5 minutes). Additionally, it reached an SLA of approximately 100%, a value considered above the usual when it comes to compliance services. As an emerging technology, TWDM-PON stands out in a scenario that should be designed to be compatible with deployed technologies, and beyond that, to overcome the legacy of PON networks in energy saving and quality of services offered.