CMOS and MEMS Based Microsystems for Manipulation and Detection of Magnetic Beads for Biomedical Applications

RÉSUMÉ Les micro et nano billes magnétiques dédiées à l'étiquetage des bio-particules attirent de plus en plus d'intérêt dans de nombreuses applications environnementales et sanitaires, tels que l'analyse de gènes, le transport des médicaments, la purification et l'immunologie. Les dimensions réduites et la haute sensibilité des billes magnétiques rendent leurs manipulations à haute précision possibles. Leur simplicité de suivi dans le milieu biologique et leur biocompatibilité permettent d’effectuer des détections rapides et à haute sensibilité pour des applications in vivo et in vitro. L'utilisation traditionnelle des billes magnétiques prend place dans un laboratoire se servant du matériel encombrant et dispendieux. Avec le développement de la technologie de microfabrication, des billes magnétiques peuvent être traitées dans un microsystème, plus précisément, dans une structure laboratoire sur puce (LoC). La combinaison microfluidique et microélectronique offre des possibilités d’autoévaluation, ce qui peut augmenter l'efficacité du travail. Cette thèse est orientée vers de nouvelles approches pour la manipulation et la détection de bio-particules se servant de la technologie de microsystèmes basées sur des structures microelectroniques et microfluidiques et en utilisant des marqueurs de billes magnétiques. Basé sur un réseau de microbobines à la fois comme une source de champ magnétique et un capteur inductif, le microsystème proposé est réalisé grâce à l'efficacité de fabrication de structures CMOS-MEMS, ainsi que des circuits intégrés dédiés CMOS de haute performance afin d'obtenir un rendement élevé de manipulation et de détection de billes magnétiques. Plusieurs défis ont été analysés dans la mise en œuvre de ces microsystèmes et des solutions correspondantes fournies. Plus précisément, la conception et la mise en œuvre d'une plate-forme contrôlée en température en format portable sont d'abord présentées, dans un effort réalisé pour résoudre la question de la chaleur par effet Joule lors de l'application du réseau de microbobines comme une source de champ magnétique dédié à la manipulation de billes magnétiques. Une plateforme similaire à cette dernière a été améliorée pour effectuer une analyse magnétique immunologique, en ajoutant des circuits de détection par des billes magnétiques. De plus, des IgG et anti-IgG de souris ont été utilisés dans des expériences pour vérifier les performances de détection de la plateforme de microsystème proposé.----------ABSTRACT Magnetic micro/nano beads as labels of bio-particles have been attracting more and more interest in many environmental and health applications, such as gene and drug delivery, purification, and immunoassay. The miniature size and high sensitivity of magnetic bead allow accurate manipulation, whereas its high distinguishability from biological background and biocompatibility make fast and high sensitivity detection possible for in vitro and in vivo applications. Traditional employment of magnetic beads is done in laboratory environment with the assist of bulky and expensive equipment. Thanks to the development of microfabrication technology, magnetic beads therefore can be handled on a microsystem, more specifically, a Lab-on-Chip (LoC). The combination of microfluidics with microelectronics offers the possibility of automatic analyses, which can liberate the labor and increase the efficiency.This thesis focuses on new approaches for bio-particles manipulation and detection on microelectronic/microfluidic hybrid microsystems using magnetic beads as labels. Based on planar microcoil array as both magnetic field source and the front-end inductive sensor, the proposed microsystems can take advantage of the massive producible CMOS/MEMS fabrication process, as well as the customized high performance CMOS circuits, to achieve a high efficient magnetic beads manipulation and a quantitative detection. Several challenges in implementing such microsystems are analyzed and corresponding solutions are provided. Specifically, the design and implementation of a temperature controllable LoC platform in portable format is firstly presented, for the sake of resolving the Joule heat issue when applying microcoil array as magnetic field source in magnetic beads manipulation. The similar platform is then improved to be used for magnetic immunoassay, by adding magnetic beads sensing circuits. Mouse IgG and anti-mouse IgG are employed in experiments to verify the detection performance of the proposed microsystem platform. Additionally, a fully integrated silicon substrate MEMS chip which integrates both microfluidic channel and microcoil array on a single chip is designed and fabricated following the Finite Element Analysis (FEA) simulation results and tested using bio-particles attached magnetic beads. This monolithic chip has the potential to be applied for in vivo applications

An Investigation of Social Support Exchange and Communication Patterns among Chinese on Online Discussion Forum

Online Health Communities (OHCs), frequently adopted as online discussion forums for online users to communicate on health issues, have been used worldwide. By analyzing a representative breast-cancer-related OHC from mainland China—Baidu Discussion Forum, this study attempts to investigate social support exchange and communication patterns through user-generated content by data mining approaches. According to the outcomes, emotional support seeking and providing presents itself to be a more critical theme among Chinese users than other types of social support. In addition, almost half of the users on Baidu Discussion Forum have simple patterns of involvement, and a fairly small proportion of highly active Chinese users are quite influential in shaping the connections of the social support network. Meanwhile, the off-topic discussions which are not directly on health concerns are not frequently touched by Chinese people. This may impact the longevity of both users and threads, and undermine the foundation of OHCs in the long term. The findings have practical implications for researchers and health practitioners targeting on the Chinese population

Transcriptome profiling reveals the crucial biological pathways involved in cold response in Moso bamboo (Phyllostachys edulis).

Most bamboo species including Moso bamboo (Phyllostachys edulis) are tropical or subtropical plants that greatly contribute to human well-being. Low temperature is one of the main environmental factors restricting bamboo growth and geographic distribution. Our knowledge of the molecular changes during bamboo adaption to cold stress remains limited. Here, we provided a general overview of the cold-responsive transcriptional profiles in Moso bamboo by systematically analyzing its transcriptomic response under cold stress. Our results showed that low temperature induced strong morphological and biochemical alternations in Moso bamboo. To examine the global gene expression changes in response to cold, 12 libraries (non-treated, cold-treated 0.5, 1 and 24 h at -2 °C) were sequenced using an Illumina sequencing platform. Only a few differentially expressed genes (DEGs) were identified at early stage, while a large number of DEGs were identified at late stage in this study, suggesting that the majority of cold response genes in bamboo are late-responsive genes. A total of 222 transcription factors from 24 different families were differentially expressed during 24-h cold treatment, and the expressions of several well-known C-repeat/dehydration responsive element-binding factor negative regulators were significantly upregulated in response to cold, indicating the existence of special cold response networks. Our data also revealed that the expression of genes related to cell wall and the biosynthesis of fatty acids were altered in response to cold stress, indicating their potential roles in the acquisition of bamboo cold tolerance. In summary, our studies showed that both plant kingdom-conserved and species-specific cold response pathways exist in Moso bamboo, which lays the foundation for studying the regulatory mechanisms underlying bamboo cold stress response and provides useful gene resources for the construction of cold-tolerant bamboo through genetic engineering in the future

Response of the root morphological structure of Fokienia hodginsii seedlings to competition from neighboring plants in a heterogeneous nutrient environment

IntroductionCritical changes often occur in Fokienia hodginsii seedlings during the process of growth owing to differences in the surrounding environment. The most common differences are heterogeneous nutrient environments and competition from neighboring plants.MethodsIn this study, we selected one-year-old, high-quality Fokienia hodginsii seedlings as experimental materials. Three planting patterns were established to simulate different competitive treatments, and seedlings were also exposed to three heterogeneous nutrient environments and a homogeneous nutrient environment (control) to determine their effect on the root morphology and structure of F. hodginsii seedlings.ResultsHeterogeneous nutrient environments, compared with a homogeneous environment, significantly increased the dry matter accumulation and root morphology indexes of the root system of F. hodginsii, which proliferated in nutrient-rich patches, and the P heterogeneous environment had the most significant enhancement effect, with dry matter accumulation 70.2%, 7.0%, and 27.0% higher than that in homogeneous and N and K heterogeneous environments, respectively. Homogeneous environments significantly increased the specific root length and root area of the root system; the dry matter mass and morphological structure of the root system of F. hodginsii with a heterospecific neighbor were higher than those under conspecific neighbor and single-plant treatments, and the root area of the root system under the conspecific neighbor treatment was higher than that under the heterospecific neighbor treatment, by 20% and 23%, respectively. Moreover, the root system under heterospecific neighbor treatment had high sensitivity; the heterogeneous nutrient environment increased the mean diameter of the fine roots of the seedlings of F. hodginsii and the diameter of the vascular bundle, and the effect was most significant in the P heterogeneous environment, exceeding that in the N and K heterogeneous environments. The effect was most significant in the P heterogeneous environment, which increased fine root diameter by 20.5% and 10.3%, respectively, compared with the homogeneous environment; in contrast, the fine root vascular ratio was highest in the homogeneous environment, and most of the indicators of the fine root anatomical structure in the nutrient-rich patches were of greater values than those in the nutrient-poor patches in the different heterogeneous environments; competition promoted most of the indicators of the fine root anatomical structure of F. hodginsii seedlings. According a principal component analysis (PCA), the N, Pm and K heterogeneous environments with heterospecific neighbors and the P heterogeneous environment with a conspecific neighbor had higher evaluation in the calculation of eigenvalues of the PCA.DiscussionThe root dry matter accumulation, root morphology, and anatomical structure of F. hodginsii seedlings in the heterogeneous nutrient environment were more developed than those in the homogeneous nutrient environment. The effect of the P heterogeneous environment was the most significant. The heterospecific neighbor treatment was more conducive to the expansion and development of root morphology of F. hodginsii seedlings than were the conspecific neighbor and single-plant treatments

Effects of AMF inoculation on the eco-physiological characteristics of Imperata cylindrica under differing soil nitrogen conditions

Arbuscular mycorrhizal fungi (AMF) play a key role in terrestrial ecosystems, while the ecological restoration application of AMF in mining areas has been progressively gaining attention. This study simulated a low nitrogen (N) environment in copper tailings mining soil to explore inoculative effects of four AMF species on the eco-physiological characteristics of Imperata cylindrica, and provided plant-microbial symbiote with excellent resistance to copper tailings. Results show that N, soil type, AMF species, and associated interactions significantly affected ammonium (NH4  +), nitrate nitrogen (NO3  −), and total nitrogen (TN) content and photosynthetic characteristics of I. cylindrica. Additionally, interactions between soil type and AMF species significantly affected the biomass, plant height, and tiller number of I. cylindrica. Rhizophagus irregularis and Glomus claroideun significantly increased TN and NH4  + content in the belowground components I. cylindrica in non-mineralized sand. Moreover, the inoculation of these two fungi species significantly increased belowground NH4  + content in mineralized sand. The net photosynthetic rate positively correlated to aboveground total carbon (TC) and TN content under the high N and non-mineralized sand treatment. Moreover, Glomus claroideun and Glomus etunicatum inoculation significantly increased both net photosynthetic and water utilization rates, while F. mosseae inoculation significantly increased the transpiration rate under the low N treatment. Additionally, aboveground total sulfur (TS) content positively correlated to the intercellular carbon dioxide (CO2) concentration, stomatal conductance, and the transpiration rate under the low N sand treatment. Furthermore, G. claroideun, G. etunicatum, and F. mosseae inoculation significantly increased aboveground NH4  + and belowground TC content of I. cylindrica, while G. etunicatum significantly increased belowground NH4  + content. Average membership function values of all physiological and ecological I. cylindrica indexes infected with AMF species were higher compared to the control group, while corresponding values of I. cylindrica inoculated with G. claroideun were highest overall. Finally, comprehensive evaluation coefficients were highest under both the low N and high N mineralized sand treatments. This study provides information on microbial resources and plant-microbe symbionts in a copper tailings area, while aiming to improve current nutrient-poor soil conditions and ecological restoration efficiency in copper tailings areas

Polarization of Σ

We show that Sigma(+) hyperons produced by 800 GeV/c protons on targets of Be and Cu have significant polarizations (15-20%). These polarizations persist at values of p(t)approximate to2 GeV/c and a wide range of x(F). The polarizations from the Cu target are consistently less than from Be. The average ratio of the Sigma(+) polarization from Cu to that from Be is 0.68+/-0.08