{"id":60967,"date":"2023-11-29T11:49:02","date_gmt":"2023-11-29T09:49:02","guid":{"rendered":"https:\/\/www.iemn.fr\/?p=60967"},"modified":"2023-11-29T17:55:55","modified_gmt":"2023-11-29T15:55:55","slug":"these-paul-moustiez-fabrication-de-nanoaiguilles-en-silicium-en-vue-dune-detection-intracellulaire-de-biomarqueurs-de-maladies-neurodegeneratives","status":"publish","type":"post","link":"https:\/\/www.iemn.fr\/en\/agenda\/these-paul-moustiez-fabrication-de-nanoaiguilles-en-silicium-en-vue-dune-detection-intracellulaire-de-biomarqueurs-de-maladies-neurodegeneratives.html","title":{"rendered":"THESE Paul MOUSTIEZ : \u00ab\u00a0Fabrication de nanoaiguilles en silicium en vue d\u2019une d\u00e9tection intracellulaire de biomarqueurs de maladies neurod\u00e9g\u00e9n\u00e9ratives \u00bb"},"content":{"rendered":"<div id='layer_slider_1'  class='avia-layerslider main_color avia-shadow  avia-builder-el-0  el_before_av_heading  avia-builder-el-first  container_wrap sidebar_right'  style='height: 261px;'  ><div id=\"layerslider_58_l2z4zx6zmuq7\" data-ls-slug=\"homepageslider\" class=\"ls-wp-container fitvidsignore ls-selectable\" style=\"width:1140px;height:260px;margin:0 auto;margin-bottom: 0px;\"><div class=\"ls-slide\" data-ls=\"duration:6000;transition2d:5;\"><img loading=\"lazy\" decoding=\"async\" width=\"2600\" height=\"270\" src=\"https:\/\/www.iemn.fr\/wp-content\/uploads\/2019\/01\/sliders_news1.jpg\" class=\"ls-bg\" alt=\"\" srcset=\"https:\/\/www.iemn.fr\/wp-content\/uploads\/2019\/01\/sliders_news1.jpg 2600w, https:\/\/www.iemn.fr\/wp-content\/uploads\/2019\/01\/sliders_news1-300x31.jpg 300w, https:\/\/www.iemn.fr\/wp-content\/uploads\/2019\/01\/sliders_news1-768x80.jpg 768w, https:\/\/www.iemn.fr\/wp-content\/uploads\/2019\/01\/sliders_news1-1030x107.jpg 1030w, https:\/\/www.iemn.fr\/wp-content\/uploads\/2019\/01\/sliders_news1-1500x156.jpg 1500w, https:\/\/www.iemn.fr\/wp-content\/uploads\/2019\/01\/sliders_news1-705x73.jpg 705w\" sizes=\"auto, (max-width: 2600px) 100vw, 2600px\" \/><ls-layer style=\"font-size:14px;text-align:left;font-style:normal;text-decoration:none;text-transform:none;font-weight:700;letter-spacing:0px;border-style:solid;border-color:#000;background-position:0% 0%;background-repeat:no-repeat;width:180px;height:30px;left:0px;top:231px;line-height:32px;color:#ffffff;border-radius:6px 6px 6px 6px;padding-left:50px;background-color:rgba(0, 0, 0, 0.57);\" class=\"ls-l ls-ib-icon ls-text-layer\" data-ls=\"minfontsize:0;minmobilefontsize:0;\"><i class=\"fa fa-quote-right\" style=\"color:#ffffff;margin-right:0.8em;font-size:1em;transform:translateY( -0.125em );\"><\/i>ACTUALITES<\/ls-layer><\/div><\/div><\/div><div id='after_layer_slider_1'  class='main_color av_default_container_wrap container_wrap sidebar_right'  ><div class='container av-section-cont-open' ><div class='template-page content  av-content-small alpha units'><div class='post-entry post-entry-type-page post-entry-60967'><div class='entry-content-wrapper clearfix'>\n\n<style type=\"text\/css\" data-created_by=\"avia_inline_auto\" id=\"style-css-av-lpjy86z4-16784e60d09799894e47789b11c7cef9\">\n#top .av-special-heading.av-lpjy86z4-16784e60d09799894e47789b11c7cef9{\nmargin:0 0 10px 0;\npadding-bottom:4px;\n}\nbody .av-special-heading.av-lpjy86z4-16784e60d09799894e47789b11c7cef9 .av-special-heading-tag .heading-char{\nfont-size:25px;\n}\n.av-special-heading.av-lpjy86z4-16784e60d09799894e47789b11c7cef9 .av-subheading{\nfont-size:15px;\n}\n<\/style>\n<div  class='av-special-heading av-lpjy86z4-16784e60d09799894e47789b11c7cef9 av-special-heading-h2  avia-builder-el-1  el_after_av_layerslider  el_before_av_hr  avia-builder-el-first'><h2 class='av-special-heading-tag'  itemprop=\"headline\"  >THESE Paul MOUSTIEZ : \u00ab\u00a0Fabrication de nanoaiguilles en silicium en vue d\u2019une d\u00e9tection intracellulaire de biomarqueurs de maladies neurod\u00e9g\u00e9n\u00e9ratives \u00bb<\/h2><div class=\"special-heading-border\"><div class=\"special-heading-inner-border\"><\/div><\/div><\/div>\n\n<style type=\"text\/css\" data-created_by=\"avia_inline_auto\" id=\"style-css-av-18u73nj-dad6a947580930e400fc42ba200e80f1\">\n#top .hr.av-18u73nj-dad6a947580930e400fc42ba200e80f1{\nmargin-top:5px;\nmargin-bottom:5px;\n}\n.hr.av-18u73nj-dad6a947580930e400fc42ba200e80f1 .hr-inner{\nwidth:100%;\n}\n<\/style>\n<div  class='hr av-18u73nj-dad6a947580930e400fc42ba200e80f1 hr-custom  avia-builder-el-2  el_after_av_heading  el_before_av_textblock  hr-left hr-icon-no'><span class='hr-inner inner-border-av-border-thin'><span class=\"hr-inner-style\"><\/span><\/span><\/div>\n<section  class='av_textblock_section av-jriy64i8-2f4600354c0449b610997916bbd9b6bc'   itemscope=\"itemscope\" itemtype=\"https:\/\/schema.org\/BlogPosting\" itemprop=\"blogPost\" ><div class='avia_textblock'  itemprop=\"text\" >\n<style type=\"text\/css\" data-created_by=\"avia_inline_auto\" id=\"style-css-av-13ewzjw-68e036126b913e5028f77311dc66b825\">\n.av_font_icon.av-13ewzjw-68e036126b913e5028f77311dc66b825{\ncolor:#bfbfbf;\nborder-color:#bfbfbf;\n}\n.av_font_icon.av-13ewzjw-68e036126b913e5028f77311dc66b825 .av-icon-char{\nfont-size:60px;\nline-height:60px;\n}\n<\/style>\n<span  class='av_font_icon av-13ewzjw-68e036126b913e5028f77311dc66b825 avia_animate_when_visible av-icon-style- avia-icon-pos-left avia-icon-animate'><span class='av-icon-char' aria-hidden='true' data-av_icon='\ue8c9' data-av_iconfont='entypo-fontello' ><\/span><\/span>\n<p><strong>Paul Moustiez<br \/>\n<\/strong><\/p>\n<p>Soutenance : 19 d\u00e9cembre \u00e0 14H<strong><br \/>\n<\/strong>IEMN Amphitheatre - Central Laboratory - Villeneuve d'Ascq<\/p>\n<\/div><\/section>\n<section  class='av_textblock_section av-jtefqx33-628129dba2299b2ecd65ebfc92eac29d'   itemscope=\"itemscope\" itemtype=\"https:\/\/schema.org\/BlogPosting\" itemprop=\"blogPost\" ><div class='avia_textblock'  itemprop=\"text\" ><div  class='hr av-kjh3zw-4dff888f744b728a1aca9b3a0971493a hr-default  avia-builder-el-6  avia-builder-el-no-sibling'><span class='hr-inner'><span class=\"hr-inner-style\"><\/span><\/span><\/div>\n<h5><strong><span style=\"color: #800000;\">Jury :<\/span><\/strong><\/h5>\n<ul>\n<li>Fr\u00e9d\u00e9rique CUNIN &#8211; <i>Directrice de Recherche, CNRS, rapporteure\u00a0\u00a0\u00a0 .<br \/>\n<\/i>Guilhem LARRIEU <i>&#8211; Directeur de Recherche, CNRS, rapporteur.<br \/>\n<\/i>Christine ENJALBAL &#8211; <i>Professeure des universit\u00e9s, Universit\u00e9 de Montpellier, examinatrice.<br \/>\n<\/i>Marie-Aline MATTELIN &#8211; <i>Docteure, Puxano, examinatrice.<br \/>\n<\/i>Vincent THOMY &#8211; <i>Professeur des universit\u00e9s, Universit\u00e9 de Lille, examinateur.<br \/>\n<\/i>Sophie HALLIEZ &#8211; <i>Ma\u00eetresse de conf\u00e9rences, Universit\u00e9 de Lille, invit\u00e9e.<br \/>\n<\/i>Yannick COFFINIER &#8211; <i>Directeur de Recherche, CNRS<\/i>, directeur de th\u00e8se.<\/li>\n<\/ul>\n<h5>Summary:<\/h5>\n<p>Les maladies neurod\u00e9g\u00e9n\u00e9ratives sont des maladies chroniques progressives touchant le syst\u00e8me nerveux central. Tandis que ces maladies ont des origines multifactorielles, leur fr\u00e9quence augmente avec l\u2019\u00e2ge. En raison du vieillissement progressif de la population, et de l\u2019absence de traitement, elles deviennent un enjeu majeur de sant\u00e9 publique. Pour exemple, la maladie d\u2019Alzheimer pourrait toucher 1 personne dans le monde sur 85 d\u2019ici 2050. C\u2019est dans ce contexte que les chercheurs \u00e9tudient diff\u00e9rentes pistes pour permettre une meilleure compr\u00e9hension de cette maladie et de ses m\u00e9canismes pathophysiologies. Ils savent aujourd\u2019hui qu\u2019une hyperphosphorylation de la prot\u00e9ine Tau et la production de formes toxiques de peptides beta-amylo\u00efdes s\u2019agglom\u00e9rant en plaques s\u00e9niles en sont les principales causes. L\u2019origine de ces dysfonctionnements est quant \u00e0 elle encore mal connue mais pourrait \u00eatre \u00e9lucid\u00e9e par l\u2019\u00e9tude des m\u00e9canismes biochimiques intracellulaire. Dans ce contexte, nous avons imagin\u00e9 un dispositif in vitro reposant sur l\u2019utilisation de nanoaiguilles en silicium ayant la facult\u00e9 de sonder le cytoplasme cellulaire de neurones pour y d\u00e9tecter les biomarqueurs de l\u2019Alzheimer et en suivre l\u2019\u00e9volution. Notre travail a repos\u00e9 sur l\u2019\u00e9laboration de ce capteur qui s\u2019est divis\u00e9e en 3 points. Le premier \u00e9tait la fabrication des nanoaiguilles par d\u00e9veloppement de techniques peu on\u00e9reuses comme la lithographie de nanosph\u00e8re suivit de m\u00e9thodes de gravure humide ou s\u00e8ches. Le second point \u00e9tait l\u2019optimisation de ces aiguilles pour l\u2019identification bimodale de mol\u00e9cules par spectrom\u00e9trie de masse (SALDI-MS) et par spectrom\u00e9trie Raman exalt\u00e9e de surface (SERS). Le troisi\u00e8me point portait sur l\u2019\u00e9tude de l\u2019interaction entre nos aiguilles et les neurones avec \u00e0 l\u2019esprit la volont\u00e9 de capture de biomarqueurs et la pr\u00e9servation de l\u2019int\u00e9grit\u00e9 cellulaire. La lithographie de nanosph\u00e8res a pu \u00eatre d\u00e9velopp\u00e9e, et les aiguilles ont \u00e9t\u00e9 fabriqu\u00e9es selon 2 voies que sont la gravure humide assist\u00e9e par m\u00e9tal (MACE) et la gravure s\u00e8che par gravure plasma continue. De la rhodamine 6G, des peptides standards ainsi que des peptides beta-amylo\u00efdes ont pu \u00eatre d\u00e9tect\u00e9s par SALDI-MS et SERS sur nos r\u00e9seaux d\u2019aiguilles. Enfin nous avons constat\u00e9 la biocompatibilit\u00e9 de nos aiguilles avec le milieu cellulaire et caract\u00e9ris\u00e9 leur interaction.<\/p>\n<h5>Abstract:<\/h5>\n<p>Neurodegenerative diseases are chronic progressive disorders of the central nervous system. While these diseases have multifactorial origins, their frequency increases with age. With a progressively ageing population, and no treatment available, they are becoming a major public health issue. For example, Alzheimer&rsquo;s disease could affect 1 in 85 people worldwide by 2050. It is against this backdrop that researchers are exploring various avenues to gain a better understanding of this disease and its pathophysiological mechanisms. They now know that hyperphosphorylation of the Tau protein and the production of toxic forms of beta-amyloid peptides, which agglomerate to form senile plaques, are the main causes. The origins of these dysfunctions are still poorly understood, but could be elucidated by studying intracellular biochemical mechanisms. In this context, we have devised an in vitro device based on the use of silicon nanoneedles capable of probing the cell cytoplasm of neurons to detect biomarkers of Alzheimer&rsquo;s disease and monitor their evolution. Our work was based on the development of this sensor, which was divided into 3 stages. The first was the fabrication of the nanoneedles by developing low-cost techniques such as nanosphere lithography followed by wet and dry etching methods. The second was the optimization of these needles for bimodal molecule identification by mass spectrometry (SALDI-MS) and surface enhanced Raman spectrometry (SERS). The third point concerned the study of the interaction between our needles and neurons, with a view to capturing biomarkers and preserving cellular integrity. Nanosphere lithography was developed, and the needles were fabricated in 2 ways: metal-assisted wet etching (MACE) and continuous plasma dry etching. Rhodamine 6G, standard peptides and beta-amyloid peptides were detected by SALDI-MS and SERS on our needle arrays. Finally, we assessed the biocompatibility of our needles with the cellular environment and characterized their interaction.<\/p>\n<\/div><\/section>\n<\/div><\/div><\/div><!-- close content main div --><\/div><\/div><div id='layer_slider_2'  class='avia-layerslider main_color avia-shadow  avia-builder-el-7  el_after_av_textblock  avia-builder-el-last  slider-not-first container_wrap sidebar_right'  style='height: 261px;'  ><div id=\"layerslider_58_1ruzhuv88r5nm\" data-ls-slug=\"homepageslider\" class=\"ls-wp-container fitvidsignore ls-selectable\" style=\"width:1140px;height:260px;margin:0 auto;margin-bottom: 0px;\"><div class=\"ls-slide\" data-ls=\"duration:6000;transition2d:5;\"><img loading=\"lazy\" decoding=\"async\" width=\"2600\" height=\"270\" src=\"https:\/\/www.iemn.fr\/wp-content\/uploads\/2019\/01\/sliders_news1.jpg\" class=\"ls-bg\" alt=\"\" srcset=\"https:\/\/www.iemn.fr\/wp-content\/uploads\/2019\/01\/sliders_news1.jpg 2600w, https:\/\/www.iemn.fr\/wp-content\/uploads\/2019\/01\/sliders_news1-300x31.jpg 300w, https:\/\/www.iemn.fr\/wp-content\/uploads\/2019\/01\/sliders_news1-768x80.jpg 768w, https:\/\/www.iemn.fr\/wp-content\/uploads\/2019\/01\/sliders_news1-1030x107.jpg 1030w, https:\/\/www.iemn.fr\/wp-content\/uploads\/2019\/01\/sliders_news1-1500x156.jpg 1500w, https:\/\/www.iemn.fr\/wp-content\/uploads\/2019\/01\/sliders_news1-705x73.jpg 705w\" sizes=\"auto, (max-width: 2600px) 100vw, 2600px\" \/><ls-layer style=\"font-size:14px;text-align:left;font-style:normal;text-decoration:none;text-transform:none;font-weight:700;letter-spacing:0px;border-style:solid;border-color:#000;background-position:0% 0%;background-repeat:no-repeat;width:180px;height:30px;left:0px;top:231px;line-height:32px;color:#ffffff;border-radius:6px 6px 6px 6px;padding-left:50px;background-color:rgba(0, 0, 0, 0.57);\" class=\"ls-l ls-ib-icon ls-text-layer\" data-ls=\"minfontsize:0;minmobilefontsize:0;\"><i class=\"fa fa-quote-right\" style=\"color:#ffffff;margin-right:0.8em;font-size:1em;transform:translateY( -0.125em );\"><\/i>ACTUALITES<\/ls-layer><\/div><\/div><\/div>","protected":false},"excerpt":{"rendered":"","protected":false},"author":20,"featured_media":60977,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[87,65,84,187],"tags":[],"class_list":["post-60967","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-agenda-en","category-agenda","category-agenda-en-en","category-annonces-these"],"_links":{"self":[{"href":"https:\/\/www.iemn.fr\/en\/wp-json\/wp\/v2\/posts\/60967","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.iemn.fr\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.iemn.fr\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.iemn.fr\/en\/wp-json\/wp\/v2\/users\/20"}],"replies":[{"embeddable":true,"href":"https:\/\/www.iemn.fr\/en\/wp-json\/wp\/v2\/comments?post=60967"}],"version-history":[{"count":0,"href":"https:\/\/www.iemn.fr\/en\/wp-json\/wp\/v2\/posts\/60967\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.iemn.fr\/en\/wp-json\/wp\/v2\/media\/60977"}],"wp:attachment":[{"href":"https:\/\/www.iemn.fr\/en\/wp-json\/wp\/v2\/media?parent=60967"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.iemn.fr\/en\/wp-json\/wp\/v2\/categories?post=60967"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.iemn.fr\/en\/wp-json\/wp\/v2\/tags?post=60967"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}