Measurement of ice thickness and quality to optimise and qualify robotic cryo-plunger

** Linkam的自动低温电子显微镜（cryo-EM）样品制备系统，以解决cryo-EM工作流程中的不一致性和瓶颈问题 ** cryo-EM的发展为生物研究和药物发现的研究人员提供了蛋白质和细胞成分的高分辨率结构信息。2017年，cryo-EM获得了诺贝尔奖（[https：//www.nobelprize.org/prizes/chemistry/2017/press-release/][0]）。传统的cryo-EM依赖于在玻璃化冰中快速冷冻样品（蛋白质颗粒或细胞成分），以将结构保存到分子水平。这可以通过插入式冷冻来实现，然而，用于插入式冷冻的典型机器和过程大多是手动的并且使用常规的吸墨纸。这种依赖于用户的过程总是导致一致性差，并被认为是整个冷冻EM工作流程的瓶颈。Linkam CryoGenium机器人样品制备系统的新颖设计使用Linkam的专利设计自动调整样品膜厚度，优化了冷冻EM的样品冷冻过程。CryoGenium为受控的低温条件提供了一个单一的平台，并消除了样品制备过程中任何不期望的用户依赖性影响。目前的A4 i项目旨在使用一组定义的样品对玻璃化样品（冰）质量进行结构化调查。冰的厚度由能量过滤器测量和内置的冷冻EM成像系统确定。这组定量测量将更好地了解仪器设置与样品结果质量之间的关系。与传统的样品冷冻方法相比，将实现基于统计参数的进一步系统优化，以进一步提高重复性和样品均匀性。该项目的第二个目标是通过这项扩展试验的反馈来提高仪器和软件的用户友好性。总体而言，这种新设备可以帮助进一步建立cryo-EM作为研究细胞和分子结构的常规工具，对理解疾病机制和药物设计具有重要意义。[0]：https://www.nobelprize.org/prizes/chemistry/2017/press-release/网站

**Automatic cryogenic electron microscopy (cryo-EM) sample preparation system from Linkam to tackle inconsistency and bottlenecks in cryo-EM workflow**The development of cryo-EM has made high resolution structural information of proteins and cellular components available to researchers in biological studies and drug discovery. A Nobel prize for cryo-EM was awarded in 2017 ([https://www.nobelprize.org/prizes/chemistry/2017/press-release/][0]).Conventional cryo-EM relies on the rapid freezing of samples (protein particles or cellular components) in vitrified ice to preserve structures down to molecular level. This can be achieved by plunge-freezing, however, the typical machines and processes used for the plunge freezing are mostly manual and use conventional blotting paper. This substantial user-dependent process always lead to poor consistency, and is considered as a bottleneck of the overall cryo-EM workflow.The novel design of the Linkam CryoGenium robotic sample preparation system has optimised the sample freezing process of cryo-EM using a Linkam - patented design for the adjustment of the sample film thickness automatically. CryoGenium provides a single platform for controlled cryogenic conditions and eliminates any undesirable user-dependent effects during the sample preparation process.This current A4i project intends to perform a structured investigation of vitrified sample (ice) quality using a defined set of samples. The ice thickness is determined by energy filter measurements and a built-in cryo-EM imaging system. The set of quantitative measurements will give better insights into the relationship between instrument settings and the quality of sample results. Further system optimisation based on statistical parameters will be achieved to further improve repeatability and sample uniformity compared to conventional sample freezing methods. A secondary goal of the project is to enhance the user-friendliness of the instrument and software with feedback from this extended trial.Overall this new device can help to further establish cryo-EM as a routine tool to study cellular and molecular structures with implications for the understanding disease mechanisms and the design of drugs.[0]: https://www.nobelprize.org/prizes/chemistry/2017/press-release/