Market Assessment for Ultrastable Cryo-electron Microscopy Holder

低温电子显微镜(Cryo-EM)中的一个重要技术问题是，当试图获得冷冻水化样品的原子分辨三维结构时，液氮冷却的振动会对分辨率产生负面影响。到目前为止，冷冻-EM的样品保持器一直依赖于使用带有液氮的杜瓦来将样品冷却到130K以下。使用液氮往往不方便，也很难实施。杜瓦内部的水结晶和相关的热点可能会通过鼓泡引起振动，限制了可获得的空间分辨率。在这种恶劣的条件下，需要大量的用户专业知识来进行单粒子低温电磁实验，并成功地实现原子空间分辨率(低于0.3纳米)。因此，需要设计稳定的低温EM支架(振动最小或没有振动)，并且可以延长冷却期，从而延长观看**时间。**滑铁卢研究人员设计了一种低温EM支架，它不需要使用液氮，从而避免了这种方法固有的持续灌装步骤，并允许在任何样品倾斜角度下进行成像，没有液体溢出。新型滑铁卢保持器是准无振动的，提供了比传统的基于液氮冷却的低温电磁保持器更低的温度。美国的临时专利申请将很快提交。*

One important technical problem in cryo-electron microscopy (cryo-EM), when trying to attain atomically resolved 3D structures of frozen hydrated specimens, is the negative effect on the resolution due to the vibration from liquid nitrogen cooling. Sample holders for cryo-EM have so far relied on the use of a Dewar with liquid nitrogen to cool down sample to temperatures below 130K. The use of liquid nitrogen is often inconvenient and difficult to implement. Water crystallization inside the Dewar and relative hot spots may induce vibration through bubbling, limiting the attainable spatial resolution. Significant user expertise is required under such adverse conditions to perform single particle cryo-EM experiments and successfully achieve atomic spatial resolution (below 0.3 nm). There is thus a need for cryo-EM holder design that is stable (minimal to no vibration) and can provide prolonged cooling periods, hence longer viewing**times.**Waterloo researchers have designed a cryo-EM holder that does not require the use of liquid nitrogen and thus avoids the constant refilling step inherent with this method and allows imaging at any arbitrary sample tilt angle with no liquid spills. The novel Waterloo holder is quasi-vibration free and provides lower temperatures than conventional cryo-EM holders based on liquid nitrogen cooling. A provisional US patent application will be filed very soon.****