{"id":133,"date":"2017-02-09T18:35:26","date_gmt":"2017-02-09T18:35:26","guid":{"rendered":"http:\/\/nidusbiosciences.com\/?page_id=133"},"modified":"2017-02-09T18:35:26","modified_gmt":"2017-02-09T18:35:26","slug":"microbubble-arrays-pioneering-manufacture-properties-value","status":"publish","type":"page","link":"https:\/\/www.nidusmbt.com\/index.php\/microbubble-arrays-pioneering-manufacture-properties-value\/","title":{"rendered":"MicroBubble Arrays &#8212; Pioneering Manufacture, Properties &#038; Value"},"content":{"rendered":"<p>We manufacture our MBA\u2122s using our GEM\u2122 technology; both our arrays and method of manufacture are protected by a number of issued patents (<a href=\"https:\/\/www.google.com\/patents\/US8753880\" target=\"_blank\" rel=\"noopener noreferrer\">US8,753,880<\/a>,\u00a0<a href=\"https:\/\/www.google.com\/patents\/US9346197?dq=9346197&amp;hl=en&amp;sa=X&amp;ved=0ahUKEwjCj5u9yOzRAhVGRyYKHRElAvUQ6AEIHDAA\" target=\"_blank\" rel=\"noopener noreferrer\">US9,346,197<\/a>, and\u00a0<a href=\"https:\/\/www.google.com\/patents\/US9457497?dq=9457497&amp;hl=en&amp;sa=X&amp;ved=0ahUKEwjEic_XyOzRAhVQ3yYKHaqiASEQ6AEIHDAA\" target=\"_blank\" rel=\"noopener noreferrer\">US9,457,497<\/a>) as well as an expanding set of ongoing applications. \u00a0We currently make post-prototype GEN1 \u00a0MBA\u2122s at a modest production scale.<\/p>\n<h3>GEM\u2122\u00a0Manufacture<\/h3>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignleft size-medium wp-image-168\" src=\"http:\/\/nidusbiosciences.com\/wp-content\/uploads\/2017\/02\/gem_molding-272x300.png\" alt=\"\" width=\"272\" height=\"300\" \/>To briefly summarize our GEM\u2122 manufacturing process we use a patterned mold (A) as a template which we overlay with a polymer (PDMS) layer (B); we then heat this stack in an oven to let air bubbles rise into the polymer layer from the pits in the template to form the array of microbubbles (C). \u00a0After curing we remove the MBA\u2122 so-formed for further processing or immediate use, depending on the application.<\/p>\n<p>We have considerable control over the GEM\u2122 process, which allows us to produce microbubbles of different sizes (biggest diameter and mouth diameter), mouth shapes (which may be varied by changing the shape of the mouth of the pit) and array size and microbubble spacing across the array. \u00a0See, e.g.,\u00a0Giang UB, Lee D, King MR, DeLouise LA.\u00a0<a class=\"link-external\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/18030383\" target=\"_blank\" rel=\"noopener noreferrer\">\u201cMicrofabrication of cavities in polydimethylsiloxane using DRIE silicon molds.\u201d<\/a>\u00a0Lab on a chip. 2007 Dec; 7(12):1660-2. Epub 2007 Oct 12.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"size-full wp-image-276 alignright\" src=\"http:\/\/nidusbiosciences.com\/wp-content\/uploads\/2017\/02\/microbubbleArray_bubbleInset.png\" alt=\"\" width=\"253\" height=\"350\" \/><br \/>\nAlthough we make microbubbles in a variety of sizes and mouth configurations, for typical applications we fabricate\u00a0microbubbles with a 60 uM mouth diameter and a largest internal diameter of 160 uM. \u00a0These dimensions result in a bubble volume of about 1 nL, which is an appropriate size for cell growth and other applications of our technology. \u00a0Note that we produce MBA\u2122s with different microbubble densities; in our typical fabrication an array the size of a microscope slide has about 70,000 microbubbles.<\/p>\n<h3>MBA\u2122 Fluid Circulation &amp; Material Retention Properties<\/h3>\n<p>Our\u00a0GEM\u2122 manufacturing process is an elegant and efficient way of producing large arrays of microbubbles for, e.g., repetitive reaction chambers\u00a0or other repetitive well applications. \u00a0However bubble-shaped wells have unique properties of fluid flow as compared to traditional cylindrical wells, and Nidus explicitly leverages these properties to obtain superior performance in multiple application areas.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignleft size-full wp-image-155\" src=\"http:\/\/nidusbiosciences.com\/wp-content\/uploads\/2017\/02\/microbubble_fluid_flow_small.png\" alt=\"\" width=\"500\" height=\"299\" \/>The figure is reproduced from a recent publication by our co-founder Lisa DeLouise with her collaborator Dr. Michael King that shows fluid flow within and over a microbubble (Agastin S, Giang UB, Geng Y, Delouise LA, King MR.\u00a0<a class=\"link-external\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/21716809\" target=\"_blank\" rel=\"noopener noreferrer\">&#8220;Continuously perfused microbubble array for 3D tumor spheroid model.&#8221;<\/a>\u00a0Biomicrofluidics. 2011 Jun; 5(2):24110. Epub 2011 Jun 03). \u00a0Panels (a) and (b) show fluid flow in a circular path within a microbubble, i.e., a flow which allows bubble contents to circulate largely without being lost to the surround. \u00a0Panels (c) and (d) show flow velocity above and within a bubble, with red a high flow and blue a low flow. \u00a0These panels further demonstrate how bubble contents are largely retained in our\u00a0MBA\u2122 products.<\/p>\n<h3>Example Application &#8212; Tumor Spheroid Formation in MBA\u2122s<\/h3>\n<p>As we discuss elsewhere there are a large number of applications that Nidus targets that benefit from this unique fluid-flow property and microbubble content retention. \u00a0One example from the same publication is shown below, specifically, the formation by a colon cancer cell line (Colo205) of tumor spheroids in the microbubble environment:<\/p>\n<div id=\"f3\" class=\"fig whole_rhythm\"><\/div>\n<div class=\"page\" title=\"Page 5\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-161\" src=\"http:\/\/nidusbiosciences.com\/wp-content\/uploads\/2017\/02\/tumor_spheroids.png\" alt=\"\" width=\"863\" height=\"300\" \/><\/div>\n<p>These multi-cellular tumor spheroids have been established by multiple researchers as a relevant tumor model for drug testing in cancer research; our \u00a0MBA\u2122 system provides a particularly simple and effective system for growing and manipulating such tumor spheroids and, as a result, has high potential for cancer research and commercial cancer cell testing and analysis. \u00a0For more information, see, e.g., Chandrasekaran S, King MR (2012), &#8220;<a href=\"http:\/\/dx.doi.org\/10.4172\/2155-9538.1000e109\" target=\"_blank\" rel=\"noopener noreferrer\">Gather Round: In Vitro Tumor Spheroids as Improved Models of In Vivo Tumors,<\/a>&#8221; J Bioengineer &amp; Biomedical Sci 2:e109.<\/p>\n<hr \/>\n<p>Nidus wishes to thank Dr. Michael King for his permission to reproduce two figures from \u00a0Agastin S, Giang UB, Geng Y, Delouise LA, King MR.\u00a0<a class=\"link-external\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/21716809\" target=\"_blank\" rel=\"noopener noreferrer\">&#8220;Continuously perfused microbubble array for 3D tumor spheroid model.&#8221;<\/a>\u00a0Biomicrofluidics. 2011 Jun; 5(2):24110. Epub 2011 Jun 03. \u00a0All other figures reproduced by permission.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>We manufacture our MBA\u2122s using our GEM\u2122 technology; both our arrays and method of manufacture are protected by a number of issued patents (US8,753,880,\u00a0US9,346,197, and\u00a0US9,457,497) as well as an expanding set of ongoing applications. \u00a0We currently make post-prototype GEN1 \u00a0MBA\u2122s at a modest production scale. GEM\u2122\u00a0Manufacture To briefly summarize our GEM\u2122 manufacturing process we use &hellip; <a href=\"https:\/\/www.nidusmbt.com\/index.php\/microbubble-arrays-pioneering-manufacture-properties-value\/\" class=\"more-link\">Continue reading<span class=\"screen-reader-text\"> &#8220;MicroBubble Arrays &#8212; Pioneering Manufacture, Properties &#038; Value&#8221;<\/span><\/a><\/p>\n","protected":false},"author":2,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"om_disable_all_campaigns":false,"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"footnotes":""},"class_list":["post-133","page","type-page","status-publish","hentry"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.4 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>MicroBubble Arrays - Pioneering Manufacture, Properties &amp; Value - Nidus MB Technologies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.nidusmbt.com\/index.php\/microbubble-arrays-pioneering-manufacture-properties-value\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"MicroBubble Arrays - Pioneering Manufacture, Properties &amp; Value - Nidus MB Technologies\" \/>\n<meta property=\"og:description\" content=\"We manufacture our MBA\u2122s using our GEM\u2122 technology; both our arrays and method of manufacture are protected by a number of issued patents (US8,753,880,\u00a0US9,346,197, and\u00a0US9,457,497) as well as an expanding set of ongoing applications. \u00a0We currently make post-prototype GEN1 \u00a0MBA\u2122s at a modest production scale. 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