Study and manufacturing of biosensors based on plasmonic effects and built on silicon

Abstract: Lab-on-a-chip (or LOC) devices scale down the laboratory processes for detecting illnesses and monitoring sick patients without the need of medical laboratories. Well-known examples of LOC are pregnancy test kits or portable HIV sensors. To be useful, LOC devices must be sensitive, specific, compact, and affordable. These criteria are made possible with a transducer that can convert the biological presence of the target molecule into electrical information. Since the early 2000s, integrated photonics have offered a possible solution for a transducer compatible with LOC needs. In particular, silicon micro-ring resonators represent a compact and sensitive choice to use as a transducer in LOC devices. In agreement with the requirements of LOC devices, the objective of this project is to design and assess the performance of a compact photonic biosensor. The system will be based on integrated photonic transduction. The requirements are that it is compatible with an industrial fabrication platform and fluidic systems, with a sensitivity equal to or higher than the state-of-the-art and simple to functionalize in order to localize the target molecules in the sensitive regions of the sensor. This project details the design, fabrication, and characterization of such a biosensor. We found that ring resonators with a Hybrid Plasmonic Waveguide (HPWG) cross-section fulfill the LOC requirements and outperform the state-of-the-art biosensor. Furthermore, based on a principle called mode lift, we patented new geometry of HPWG, which will be the object of an article. We simulated the HPWG structure to understand the coupling mechanisms of the modes inside the structure (more specifically, the plasmonic and the ridge dielectric modes). The fabrication was possible thanks to the collaboration of the industrial and university cleanrooms. An advantage of industrial production is that we can reproducibly create the geometric components necessary for the LOC in a high-throughput manner, thus lowering the cost per unit cell. Once the 300 mm Si wafers were patterned, the university cleanroom fabrication process adds the metallic waveguides. The Au nanopatterning on the devices characterized in this project was created using the lift-off method. The preliminary measures define the optimal testing liquid (glucose monohydrate) and the uncertainty of the measures. The HPWG samples showed an experimental sensitivity lower than the simulations. After adjusting the fabrication parameters (mainly Au and Cr deposition rates and thicknesses), the second-generation HPWG devices suggest that the mode lift improves the sensitivity for waveguides below cutoff (the sensitivity increases from 210 nm/RIU to 320 nm/RIU when only 10% of the ring resonator has an HPWG section and the rest is a ridge waveguide). Even in the case where ridge waveguides are above the cutoff, the sensitivity increases by 40 nm/RIU when using mode lift. We also showed the compatibility of the fabricated devices’ surface with differential functionalization, by means of fluorescent nanoparticles. Due to time limitations, the presence of the nanoparticles will be measured with the fabricated devices in future experiments.Les dispositifs laboratoire sur puce (ou Lab-on-a-chip ou LOC) visent à miniaturiser les procédés de laboratoires pour la détection des maladies et la surveillance des patients malades, sans avoir besoin de laboratoires médicaux. Deux exemples bien connus de LOC sont les kits de test de grossesse ou les capteurs portables du VIH. Pour être efficaces, les appareils LOC doivent être sensibles, spécifiques à l’analyte concerné, compacts et abordables. Ces critères sont possibles grâce à un transducteur, qui peut convertir la présence biologique de la molécule cible en informations électriques. Depuis le début des années 2000, la photonique intégrée a offert une solution pour un système de transduction compatible avec les besoins du LOC. En particulier, les micro-résonateurs à anneaux en silicium représentent un transducteur compact et sensible adapté aux appareils LOC. En accord avec les exigences des dispositifs LOC, l’objectif de ce projet est de concevoir et d’évaluer les performances d’un biocapteur photonique compact. Le système sera basé sur une transduction photonique intégrée. Les exigences sont : une simple fonctionnalisation, la compatibilité avec une plateforme de fabrication industrielle et des systèmes fluidiques, avec une sensibilité égale ou supérieure à l’état de l’art. Ce projet détaille la conception, la fabrication et la caractérisation d’un tel biocapteur. Nous avons constaté que les résonateurs en anneau avec une section transversale de guide d’ondes hybrides plasmoniques (HPWG) remplissent les exigences LOC et sont compétitifs en comparaison avec l’état de l’art des biocapteurs photoniques. Par ailleurs, basée sur un principe appelé mode lift, une nouvelle géométrie de HPWG a été brevetée et fera l’objet d’un article. Nous avons simulé la structure HPWG pour comprendre les mécanismes de couplage des modes photoniques à l’intérieur de la structure (plus précisément les modes plasmoniques et les modes diélectriques du guide d’onde à ruban). La fabrication a été possible grâce à la collaboration de la salle blanche industrielle de STMicroelectronics et des salles blanches universitaires de l’université de Sherbrooke et de l’Institut de Nanotechnologies de Lyon. Un avantage de la production industrielle est que nous pouvons créer de manière reproductible la géométrie des composants nécessaires pour le LOC à haut débit, réduisant ainsi le coût par unité. Une fois que les wafers de 300 mm ont été structurés, le processus de fabrication en salle blanche universitaire permet d’ajouter le métal des guides d’ondes plasmoniques. La méthode du lift-off a été utilisée pour la nanostructuration Au sur les dispositifs caractérisés dans ce projet. Des mesures préliminaires ont permis de définir le liquide d’essai optimal (glucose monohydrate) ainsi que l’incertitude des mesures. Les échantillons HPWG ont montré une sensibilité expérimentale inférieure aux simulations. Après avoir ajusté les paramètres de fabrication (principalement les taux et les épaisseurs de dépôt d’Au et de Cr), les dispositifs HPWG de deuxième génération suggèrent que le mode lift améliore la sensibilité des guides d’ondes en dessous de la coupure (la sensibilité augmente de 210 nm/RIU à 320 nm/RIU lorsque seulement 10 % du résonateur en anneau a une section HPWG). Même par rapport aux guides d’ondes au-dessus de la coupure, la sensibilité augmente de 40 nm/RIU lors de l’utilisation du mode lift. Nous avons également montré la compatibilité de la surface des appareils fabriqués avec la fonctionnalisation différentielle en utilisant des nanoparticules fluorescentes. Pour des contraintes de temps, la présence des nanoparticules ne sera mesurée que dans des futures expériences

Colombia, la misión Currie y la infancia del Banco Mundial

Durante más de medio siglo, el Banco Internacional de Reconstrucción y Fo-mento, más conocido como el Banco Mundial, ha sido una de las instituciones preeminentes en el ámbito internacional. Fundado a raíz de los Acuerdos de Bretton Woods, al finalizar la Segunda Guerra Mundial, el BM tiene hoy 188 países miembros y desembolsa créditos de fomento al desarrollo por más de us{dollar}30 mil millones anuales para sectores como salud y educación, agricultura, comercio exterior, minería y generación de energía. Colombia ha sido uno de los mayores beneficiarios de los recursos del Banco, habiendo recibido, desde que se fundó la institución, unos us{dollar}17 mil millones para una gran variedad de proyectosincluye referencias bibliográficas (páginas 253- 254)

Perceived affordances of a collaborative virtual teacher education course on CLIL and technologies during remote teaching

The objective of this paper is both to describe the course syllabus and the activities implemented in a course on CLIL and technologies for pre-service and in-service teachers from three public universities in Paraná, and also examine the perceived affordances of the initiative. The theoretical framework of affordances guided the analysis and results indicate that the interactions provided by the online course allowed teachers to learn about CLIL, have opportunities to practice their language skills, articulate the use of technological resources and also reflect about pedagogical issues specific to the English language. For the professors in charge of the initiative, it allowed them to collaborate through the course planning as well as through researching/learning together in an international online experience. The affordances for our institutions include the incorporation of new perspectives into their curriculum as well as the development of internationalization at home practices. The proposal also allowed some room for identifying some limitations such as lack of time, no interactions among peers from different regions; no involvement with proposed ethnographic case study activities, aspects which impaired community building

Monitoring Tacrolimus Concentrations in Whole Blood and Peripheral Blood Mononuclear Cells: Inter- and Intra-Patient Variability in a Cohort of Pediatric Patients

Tacrolimus (TAC) is a first-choice immunosuppressant for solid organ transplantation, characterized by high potential for drug-drug interactions, significant inter- and intra-patient variability, and narrow therapeutic index. Therapeutic drug monitoring (TDM) of TAC concentrations in whole blood (WB) is capable of reducing the incidence of adverse events. Since TAC acts within lymphocytes, its monitoring in peripheral blood mononuclear cells (PBMC) may represent a valid future alternative for TDM. Nevertheless, TAC intracellular concentrations and their variability are poorly described, particularly in the pediatric context. Therefore, our aim was describing TAC concentrations in WB and PBMC and their variability in a cohort of pediatric patients undergoing constant immunosuppressive maintenance therapy, after liver transplantation. TAC intra-PBMCs quantification was performed through a validated UHPLC–MS/MS assay over a period of 2–3 months. There were 27 patients included in this study. No significant TAC changes in intracellular concentrations were observed (p = 0.710), with a median percent change of −0.1% (IQR −22.4%–+46.9%) between timings: this intra-individual variability was similar to the one in WB, −2.9% (IQR −29.4–+42.1; p = 0.902). Among different patients, TAC weight-adjusted dose and age appeared to be significant predictors of TAC concentrations in WB and PBMC. Intra-individual seasonal variation of TAC concentrations in WB, but not in PBMC, have been observed. These data show that the intra-individual variability in TAC intracellular exposure is comparable to the one observed in WB. This opens the way for further studies aiming at the identification of therapeutic ranges for TAC intra-PBMC concentrations

Kondo Conductance in an Atomic Nanocontact from First Principles

The electrical conductance of atomic metal contacts represents a powerful tool to detect nanomagnetism. Conductance reflects magnetism through anomalies at zero bias -- generally with Fano lineshapes -- due to the Kondo screening of the magnetic impurity bridging the contact. A full atomic-level understanding of this nutshell many-body system is of the greatest importance, especially in view of our increasing need to control nanocurrents by means of magnetism. Disappointingly, zero bias conductance anomalies are not presently calculable from atomistic scratch. In this Letter we demonstrate a working route connecting approximately but quantitatively density functional theory (DFT) and numerical renormalization group (NRG) approaches and leading to a first-principles conductance calculation for a nanocontact, exemplified by a Ni impurity in a Au nanowire. A Fano-like conductance lineshape is obtained microscopically, and shown to be controlled by the impurity s-level position. We also find a relationship between conductance anomaly and geometry, and uncover the possibility of opposite antiferromagnetic and ferromagnetic Kondo screening -- the latter exhibiting a totally different and unexplored zero bias anomaly. The present matching method between DFT and NRG should permit the quantitative understanding and exploration of this larger variety of Kondo phenomena at more general magnetic nanocontacts.Comment: 11 pages, 3 figures. Supplementary materials under request at [email protected]

MicroRNA-200 Family Modulation in Distinct Breast Cancer Phenotypes

The epithelial to mesenchymal transition (EMT) contributes to tumor invasion and metastasis in a variety of cancer types. In human breast cancer, gene expression studies have determined that basal-B/claudin-low and metaplastic cancers exhibit EMT-related characteristics, but the molecular mechanisms underlying this observation are unknown. As the family of miR-200 microRNAs has been shown to regulate EMT in normal tissues and cancer, here we evaluated whether the expression of the miR-200 family (miR-200f) and their epigenetic state correlate with EMT features in human breast carcinomas. We analyzed by qRT-PCR the expression of miR-200f members and various EMT-transcriptional inducers in a series of 70 breast cancers comprising an array of phenotypic subtypes: estrogen receptor positive (ER+), HER2 positive (HER2+), and triple negative (TN), including a subset of metaplastic breast carcinomas (MBCs) with sarcomatous (homologous or heterologous) differentiation. No MBCs with squamous differentiation were included. The DNA methylation status of miR-200f loci in tumor samples were inspected using Sequenom MassArray® MALDI-TOF platform. We also used two non-tumorigenic breast basal cell lines that spontaneously undergo EMT to study the modulation of miR-200f expression during EMT in vitro. We demonstrate that miR-200f is strongly decreased in MBCs compared with other cancer types. TN and HER2+ breast cancers also exhibited lower miR-200f expression than ER+ tumors. Significantly, the decreased miR-200f expression found in MBCs is accompanied by an increase in the expression levels of EMT-transcriptional inducers, and hypermethylation of the miR-200c-141 locus. Similar to tumor samples, we demonstrated that downregulation of miR-200f and hypermethylation of the miR-200c-141 locus, together with upregulation of EMT-transcriptional inducers also occur in an in vitro cellular model of spontaneous EMT. Thus, the expression and methylation status of miR-200f could be used as hypothetical biomarkers to assess the occurrence of EMT in breast cancer. © 2012 Castilla et al.This work was supported by grants from: the Instituto de Salud Carlos III (ISCIII; Grant Nos PI07/90324 and PI080971) and the Ministerio de Ciencia e Innovación (MCINN), co-financed by the European Development Regional Fund, “A way to achieve Europe” EDRF (Grant No. RD06/0020/0013); the Junta de Andalucía (Consejería de Salud, Grant No.PI-0384/2007, PI0581/2009); the Consejería de Innovación (Proyecto de Excelencia, Grant No. P07-CVI-03100); and Sandra Ibarra Foundation (Grant No. 2011/088) to JP. MAC and JDM are PhD researchers funded by the ISCIII (Grant No. RD06/0020/0013) and the Consejería de Salud, Junta de Andalucía (PI0581/2009), respectively. DS was funded by an EU Marie Curie Intra-European Fellowship (PIEF-GA-2008-221083) and by Breakthrough Breast Cancer. LRP is a PhD student recipient of a PFIS fellowship (Grant No. F109/00193). MB is a researcher funded by the ISCIII-Red de Biobancos RD09/0076/00085. SR works as a lab technician supported by the ISCIII (PI080971). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer Reviewe

Dynamic of nitrogen and dissolved organic carbon in an alpine forested catchment: atmospheric deposition and soil solution trends

A number of studies have reported decreasing trends of acidifying and N deposition inputs to forest areas throughout Europe and the USA in recent decades. There is a need to assess the responses of the ecosystem to declining atmospheric pollution by monitoring the variations of chemical species in the various compartments of the forest ecosystem on a long temporal scale. In this study, we report on patterns and trends in throughfall deposition concentrations of inorganic N, dissolved organic N (DON) and C (DOC) over a 20-year (1995–2015) period in the LTER site -Val Masino (1190 m a.s.l.), a spruce forest, in the Central Italian Alps. The same chemical species were studied in the litter floor leachates and mineral soil solution, at three different depths (15, 40 and 70 cm), over a 10-year period (2005–2015). Inorganic N concentration was drastically reduced as throughfall and litter floor leachates percolated through the topsoil, where the measured mean values (2 µeq L-1) were much lower than the critical limits established for coniferous stands (14 µeq L-1). The seasonal temperature dependence of throughfall DOC and DON concentration suggests that the microbial community living on the needles was the main source of dissolved organic matter. Most of DOC and DON infiltrating from the litter floor were retained in the mineral soil. The rainfall amount was the only climatic factor exerting a control on DOC and N compounds in throughfall and forest floor leachates over a decadal period. Concentration of SO4 and NO3 declined by 50% and 26% respectively in throughfall deposition. Trends of NO3 and SO4 in forest floor leachates and mineral soil solution mirrored declining depositions. No trends in both DON and DOC concentration and in DOC/DON ratio in soil solutions were observed. These outcomes suggest that the declining NO3 and SO4 atmospheric inputs did not influence the dynamic of DON and DOC in the Val Masino forest. The results of this study are particularly relevant, as they are based on a comprehensive survey of all the main compartments of the forest ecosystem. Moreover, this kind of long-term research has rarely been carried out in the Alpine region

PERCEPÇÕES DE ESTUDANTES E PROFISSIONAIS CHINESES SOBRE O STATUS DO INGLÊS COMO LÍNGUA FRANCA

A expansão do uso da língua inglesa caracterizou-a como língua franca global. Em decorrência, esse status trouxe a necessidade de reconceitualizações do que seja ensinar essa língua, seus objetivos e seus modelos. Assim, neste estudo, objetivamos investigar se o ensino-aprendizagem da língua inglesa no contexto chinês despertou para a mencionada realidade, analisando o que estudantes e profissionais pensam sobre o ensino de uma língua considerada internacional. Como aportes teóricos, utilizamos Phillipson (2008), Mckay (2003), Pennycook (1994), Leffa (2002) e Gimenez (2002; prelo). O trabalho foi desenvolvido tendo por base um questionário, colhendo as opiniões de dez profissionais e estudantes chineses de diversas áreas acerca do ensino de língua inglesa como língua franca. Do que foi analisado, concluímos que a visão dos sujeitos entrevistados se aproxima da visão dos pesquisadores sobre o status dessa língua: ao considerarem relevante sua aprendizagem para propósitos específicos; ao valorizarem a cultura do próprio país e não apenas daqueles que a possuem como primeira língua; ao considerá-la útil para a comunicação com pessoas de vários lugares do mundo. Por outro lado, os chineses preferem como professor o falante nativo, divergindo, assim, da opinião dos estudiosos