{"id":5177,"date":"2018-09-04T15:12:44","date_gmt":"2018-09-04T15:12:44","guid":{"rendered":"http:\/\/41j.com\/blog\/?p=5177"},"modified":"2018-09-04T15:12:44","modified_gmt":"2018-09-04T15:12:44","slug":"insilixa","status":"publish","type":"post","link":"https:\/\/41j.com\/blog\/2018\/09\/insilixa\/","title":{"rendered":"InSilixa"},"content":{"rendered":"<p>This post reviews inSilixa, it&#8217;s a follow on from <a href=\"http:\/\/41j.com\/blog\/2018\/07\/dna-sequencing-companies-july-2018\/\">my list of sequencing companies<\/a>. As we&#8217;ll see inSilixa isn&#8217;t really focused on sequencing, but it&#8217;s an interesting company anyway.<\/p>\n<h2>Business<\/h2>\n<p>inSilixa was founded in 2012, according to Crunchbase they&#8217;ve raised 13MUSD from PointGuard Ventures and Morningside Group. They appear to have received 2 SBIR grants totalling ~2MUSD. The company is based in Sunnyvale.<\/p>\n<h2>Technology<\/h2>\n<p>inSilixa appear to have a number of devices under develop, however their main focus seems to be a 1008 probe, hybridisation probe chip (other applications have been suggested, including sequencing by synthesis). The best source for most of this is a 2014 Hotchips presentation [4].<\/p>\n<p>This presentation discusses a Hydra-1K chip, this is a 1008 sensor optical detection chip:<\/p>\n<p><a href=\"http:\/\/41j.com\/blog\/2018\/09\/insilixa\/insilixaa1\/\" rel=\"attachment wp-att-5192\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter  wp-image-5192\" src=\"http:\/\/41j.com\/blog\/wp-content\/uploads\/2018\/09\/insilixaA1.png\" alt=\"\" width=\"462\" height=\"327\" \/><\/a><\/p>\n<p>Probes are printed directly on top of sensors (printed, much like other array chips). Each sensor (photodiode) has a heater along side. This allows them to heat probes and melt them. As far as I can tell, this isn&#8217;t a TEC (Peltier) so there&#8217;s no ability to cool things back down. This seems somewhat limiting, in that the chips will start at room temperature, which may not be very well controlled.<\/p>\n<p>The utility of embedding the heater on the chip isn&#8217;t so clear to me (as opposed to having a TEC attached to a jig which would mate onto the flow cell). Overall, I&#8217;m not clear that a similar device couldn&#8217;t be created by functionalizing a standard CMOS sensor&#8230; perhaps it&#8217;s related to the dynamic range required in the photodiodes.<\/p>\n<p><a href=\"http:\/\/41j.com\/blog\/2018\/09\/insilixa\/insilixaa3\/\" rel=\"attachment wp-att-5190\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter  wp-image-5190\" src=\"http:\/\/41j.com\/blog\/wp-content\/uploads\/2018\/09\/insilixaA3.png\" alt=\"\" width=\"478\" height=\"341\" \/><\/a><\/p>\n<p>One of the problems with hybridisation is that it&#8217;s not very specific. To get more information out of process inSilixa monitor the melting process in real-time (much like real time\/qPCR). They ramp the \u00a0temperature while monitoring the amount of fluorescence registered on the photodiode. This gives them a measurement of how much the DNA has melted, and allow them to generate a melting curve for each spot:<\/p>\n<p><a href=\"http:\/\/41j.com\/blog\/2018\/09\/insilixa\/insilixaa6\/\" rel=\"attachment wp-att-5188\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter  wp-image-5188\" src=\"http:\/\/41j.com\/blog\/wp-content\/uploads\/2018\/09\/insilixaA6.png\" alt=\"\" width=\"561\" height=\"418\" \/><\/a><\/p>\n<p>In most cases, I&#8217;d guess a mismatch should melt at a lower temperature and this should be visible on the curves.<\/p>\n<p>So, that&#8217;s the system they appear to be focused on at the moment. However they also mention\u00a0&#8220;ion-selective SAMs in sequence-by-synthesis arrays&#8221; on their website. That sounds pretty much like an ISFET approach, but it doesn&#8217;t look like it&#8217;s being actively explored. Bio-luminesence, voltammetry, and impedance measurements are also briefly mentioned, but there are few details on these approaches.<\/p>\n<p>An interesting approach, clearly targeted at clinical diagnostics. Will be interesting to see if they make a move into sequencing in the future.<\/p>\n<p><a href=\"http:\/\/41j.com\/blog\/2018\/09\/insilixa\/insilixa2-2\/\" rel=\"attachment wp-att-5182\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter  wp-image-5182\" src=\"http:\/\/41j.com\/blog\/wp-content\/uploads\/2018\/09\/insilixa2.png\" alt=\"\" width=\"544\" height=\"644\" \/><\/a><\/p>\n<p><a href=\"http:\/\/41j.com\/blog\/2018\/09\/insilixa\/insilixaa6\/\" rel=\"attachment wp-att-5188\"><br \/>\n<\/a> <a href=\"http:\/\/41j.com\/blog\/2018\/09\/insilixa\/insilixaa5\/\" rel=\"attachment wp-att-5189\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter  wp-image-5189\" src=\"http:\/\/41j.com\/blog\/wp-content\/uploads\/2018\/09\/insilixaA5.png\" alt=\"\" width=\"595\" height=\"405\" \/><\/a> <a href=\"http:\/\/41j.com\/blog\/2018\/09\/insilixa\/insilixaa3\/\" rel=\"attachment wp-att-5190\"><br \/>\n<\/a> <a href=\"http:\/\/41j.com\/blog\/2018\/09\/insilixa\/insilixaa2\/\" rel=\"attachment wp-att-5191\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter  wp-image-5191\" src=\"http:\/\/41j.com\/blog\/wp-content\/uploads\/2018\/09\/insilixaA2.png\" alt=\"\" width=\"599\" height=\"437\" \/><\/a><\/p>\n<p><a href=\"http:\/\/41j.com\/blog\/2018\/09\/insilixa\/insilixa1\/\" rel=\"attachment wp-att-5178\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter  wp-image-5178\" src=\"http:\/\/41j.com\/blog\/wp-content\/uploads\/2018\/09\/insilixa1.jpg\" alt=\"\" width=\"549\" height=\"593\" \/><\/a><\/p>\n<p><a href=\"http:\/\/41j.com\/blog\/2018\/09\/insilixa\/insilixa2\/\" rel=\"attachment wp-att-5179\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter  wp-image-5179\" src=\"http:\/\/41j.com\/blog\/wp-content\/uploads\/2018\/09\/insilixa2.jpg\" alt=\"\" width=\"552\" height=\"462\" \/><\/a><\/p>\n<p><a href=\"http:\/\/41j.com\/blog\/2018\/09\/insilixa\/insilixa3\/\" rel=\"attachment wp-att-5180\"><img loading=\"lazy\" decoding=\"async\" class=\"aligncenter  wp-image-5180\" src=\"http:\/\/41j.com\/blog\/wp-content\/uploads\/2018\/09\/insilixa3.jpg\" alt=\"\" width=\"573\" height=\"616\" \/><\/a><\/p>\n<h2>Notes<\/h2>\n<p>[1] https:\/\/www.crunchbase.com\/organization\/insilixa &#8211; 13MUSD. (2014)<\/p>\n<p>[2] https:\/\/www.sbir.gov\/sbirsearch\/detail\/412438<\/p>\n<p>[3] http:\/\/www.freepatentsonline.com\/WO2017155858A1.pdf<\/p>\n<p>[4] https:\/\/www.hotchips.org\/wp-content\/uploads\/hc_archives\/hc26\/HC26-11-day1-epub\/HC26.11-3-Technology-epub\/HC26.11.335-BioChip-Hassibi-InSilixa_08112014_FINAL.pdf<\/p>\n<p>[5] https:\/\/www.youtube.com\/watch?v=3icgDvXu1vA<br \/>\n<span class=\"embed-youtube\" style=\"text-align:center; display: block;\"><iframe loading=\"lazy\" class=\"youtube-player\" width=\"640\" height=\"360\" src=\"https:\/\/www.youtube.com\/embed\/FyxzNVTQea4?version=3&#038;rel=1&#038;showsearch=0&#038;showinfo=1&#038;iv_load_policy=1&#038;fs=1&#038;hl=en-US&#038;autohide=2&#038;wmode=transparent\" allowfullscreen=\"true\" style=\"border:0;\" sandbox=\"allow-scripts allow-same-origin allow-popups allow-presentation allow-popups-to-escape-sandbox\"><\/iframe><\/span><\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>This post reviews inSilixa, it&#8217;s a follow on from my list of sequencing companies. As we&#8217;ll see inSilixa isn&#8217;t really focused on sequencing, but it&#8217;s an interesting company anyway. Business inSilixa was founded in 2012, according to Crunchbase they&#8217;ve raised 13MUSD from PointGuard Ventures and Morningside Group. They appear to have received 2 SBIR grants [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[1],"tags":[],"class_list":["post-5177","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack_shortlink":"https:\/\/wp.me\/s1RRoU-insilixa","jetpack_sharing_enabled":true,"_links":{"self":[{"href":"https:\/\/41j.com\/blog\/wp-json\/wp\/v2\/posts\/5177","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/41j.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/41j.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/41j.com\/blog\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/41j.com\/blog\/wp-json\/wp\/v2\/comments?post=5177"}],"version-history":[{"count":3,"href":"https:\/\/41j.com\/blog\/wp-json\/wp\/v2\/posts\/5177\/revisions"}],"predecessor-version":[{"id":5194,"href":"https:\/\/41j.com\/blog\/wp-json\/wp\/v2\/posts\/5177\/revisions\/5194"}],"wp:attachment":[{"href":"https:\/\/41j.com\/blog\/wp-json\/wp\/v2\/media?parent=5177"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/41j.com\/blog\/wp-json\/wp\/v2\/categories?post=5177"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/41j.com\/blog\/wp-json\/wp\/v2\/tags?post=5177"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}