NEW YORK – Sample separation firm Mobilion Systems is making inroads into the proteomics market with its SLIM (structures for lossless ion manipulation) system.

纽约——样品分离公司Mobilion Systems正通过其SLIM（无损离子操控结构）系统在蛋白质组学市场取得进展。

Researchers have begun using the SLIM technology for applications that include single-cell proteomics, glycoproteomics, and biomarker discovery, taking advantage of its separations power to increase the sensitivity of their analyses.

研究人员已经开始利用 SLIM 技术进行单细胞蛋白质组学、糖蛋白组学和生物标志物发现等应用，利用其分离能力提高分析的灵敏度。

Some are also working with Mobilion to broaden the range of mass spectrometry instruments the system works with, which could further boost workflow performance.

一些公司还与Mobilion合作，扩大该系统适用的质谱仪范围，这可能会进一步提升工作流程性能。

Ion mobility uses differences in size, shape, and charge to separate ions in the gas phase. Mass spec vendors including Waters, Agilent, Sciex, Thermo Fisher Scientific, and Bruker offer instruments incorporating IMS devices, which proteomics researchers typically use to provide an additional layer of separation after conventional LC..

离子迁移率利用大小、形状和电荷的差异来分离气相中的离子。包括 Waters、Agilent、Sciex、Thermo Fisher Scientific 和 Bruker 在内的质谱仪厂商提供结合 IMS 装置的仪器，蛋白质组学研究人员通常使用这些设备在传统液相色谱之后提供额外的分离层。

SLIM ion mobility extends ion mobility path lengths beyond that allowed by conventional IMS systems, enabling much more extensive separations. The technology uses arrays of printed electrodes to confine ions within the ion mobility field. This makes it possible to route ions around turns without losses, meaning that an IMS drift path can be designed to run along a serpentine path, greatly increasing the length of the IMS path without increasing the footprint of the device..

SLIM离子迁移技术将离子迁移路径长度扩展到传统IMS系统所允许的范围之外，从而实现更广泛的分离。该技术使用印刷电极阵列将离子限制在离子迁移场内。这使得离子可以在转弯时无损失地移动，这意味着IMS漂移路径可以设计为沿蛇形路径运行，在不增加设备占地面积的情况下大大增加了IMS路径的长度。

Chadds Ford, Pennsylvania-based Mobilion, which licensed the SLIM technology from its inventors at Pacific Northwest National Laboratory (PNNL), has to date packaged the technology into a platform called MOBIE, which it has largely marketed for applications in biopharma like peptide mapping and monitoring of post-translational modifications.

总部位于宾夕法尼亚州查兹福特的Mobilion公司从太平洋西北国家实验室（PNNL）的发明者手中获得了SLIM技术的许可，迄今为止已将该技术整合到一个名为MOBIE的平台中，该平台主要针对生物制药领域的应用进行市场推广，例如肽图分析和翻译后修饰的监测。

Last fall, the company announced plans to move into the proteomics market with a new SLIM product called BILLIE. It also announced the formation of a proteomics advisory board..

去年秋天，该公司宣布计划通过一款名为BILLIE的新SLIM产品进入蛋白质组学市场，并宣布成立蛋白质组学顾问委员会。

With BILLIE, Mobilion is using the SLIM technology to eliminate the need for quadrupole filtering of precursor ions in mass spec experiments.

通过BILLIE，Mobilion利用SLIM技术消除了质谱实验中对前体离子进行四极杆过滤的需求。

In a typical mass spec proteomics experiment, precursor ions with a particular mass-to-charge ratio (m/z) are selected for fragmentation using the instrument's quadrupole, and the fragment ions produced are then analyzed to collect MS/MS level data. This initial selection step simplifies the sample so that high-quality data can be collected on the subset of precursors selected for fragmentation..

在典型的质谱蛋白质组学实验中，使用仪器的四极杆选择具有特定质荷比 (m/z) 的前体离子进行碎裂，然后对产生的碎片离子进行分析以收集 MS/MS 级数据。此初始选择步骤简化了样品，以便对选定用于碎裂的前体子集收集高质量数据。

However, any precursor ions not selected for fragmentation are discarded. This means the number of ions analyzed is only a small proportion of the total ions initially introduced into the mass spectrometer, which negatively impacts the sensitivity of the experiment.

然而，任何未被选中进行碎裂的前体离子都会被丢弃。这意味着所分析的离子数量仅占最初引入质谱仪的总离子的一小部分，这会对实验的灵敏度产生负面影响。

The BILLIE system enables a workflow Mobilion has termed parallel accumulation with mobility aligned fragmentation (PAMAF), in which the system provides ion mobility separation with high enough resolution that the mass spec can fragment and analyze essentially the full available ion signal without upfront quadrupole filtering..

BILLIE系统实现了一个被Mobilion称为平行累积与移动对齐碎裂（PAMAF）的工作流程，该系统提供足够高分辨率的离子移动分离，使质谱仪能够在无需前置四极杆过滤的情况下进行碎片化和分析几乎全部可用的离子信号。

According to the company's projections, PAMAF will deliver a fivefold improvement in speed and a 10-fold improvement in signal-to-noise compared to existing workflows.

根据该公司的预测，与现有工作流程相比，PAMAF 将使速度提高五倍，信噪比提高十倍。

Birgit Schilling, a professor at the Buck Institute for Research on Aging and a member of Mobilion's proteomics advisory board, said that she sees the technology as being particularly promising for her lab's study of low abundance post-translational modifications linked to acute kidney injury. She noted that the boost in speed and sensitivity provided by the system aids identification of these PTMs.

Birgit Schilling是巴克老龄化研究所的教授，也是Mobilion蛋白质组学顾问委员会的成员，她表示，她认为这项技术对其实验室研究与急性肾损伤相关的低丰度翻译后修饰特别有前景。她指出，该系统在速度和灵敏度上的提升有助于这些翻译后修饰的鉴定。

Additionally, the BILLIE system's high separation power allows her to better distinguish between peptide isoforms..

此外，BILLIE 系统的高分离能力使她能够更好地区分肽同分异构体。

'With PTMs there are all these different site-localized isoforms,' Schilling said. 'And traditional workflows often have difficulty separating them and doing accurate quantification.'

“有了PTMs，这些不同的位点局部异构体就出现了，”Schilling说道。“而传统的工作流程往往难以将它们分离并进行准确的定量。”

She said that using the BILLIE system she and her colleagues have seen 'very distinct separation of many of the isoforms and isomers, and the for the first time we are really able to distinctly quantify them in our biological system of acute kidney injury.'

她说，使用BILLIE系统，她和她的同事已经看到了“许多同工型和异构体的非常明显的分离，并且我们首次能够在我们的急性肾损伤生物系统中真正明确地量化它们。”

Ben Orsburn, assistant professor of pharmacology and chemical biology at the University of Pittsburgh, has been exploring the system's utility for single-cell proteomics. Currently, the BILLIE is available only at Mobilion's lab and interfaced with Agilent QTOFs that Orsburn said are not the sort of high-end instruments typically used for proteomics research.

匹兹堡大学药理学和化学生物学助理教授本·奥尔斯伯恩一直在探索该系统在单细胞蛋白质组学中的应用。目前，BILLIE仅在Mobilion的实验室中可用，并与安捷伦QTOF质谱仪配合使用，但奥尔斯伯恩表示，这些仪器并非通常用于蛋白质组学研究的高端设备。

Even so, he said, the system was able to measure around 300 proteins per cell in his initial work with it. The Agilent QTOF without the BILLIE was unable to measure any proteins in his single-cell samples, he said..

尽管如此，他表示，在他最初使用该系统时，它能够测量每个细胞大约 300 种蛋白质。他说，没有 BILLIE 的安捷伦 QTOF 无法测量他单细胞样本中的任何蛋白质。

The 300 proteins detected with the BILLIE-Agilent QTOF combo compared to the roughly 1,500 proteins per cell Orsburn was able to achieve in the same samples with a Bruker timsTOF Ultra 2 without SLIM technology. He said that as he collected more data using the BILLIE system, the gap between the two narrowed, adding that this indicated the system's great potential, especially if it were to be coupled to a more advanced mass spectrometer..

使用BILLIE-Agilent QTOF组合检测到的300种蛋白质，相比之下，Orsburn在相同样本中使用Bruker timsTOF Ultra 2（未采用SLIM技术）能够达到每个细胞大约1500种蛋白质。他表示，随着他使用BILLIE系统收集更多数据，两种方法之间的差距逐渐缩小，并补充说这表明该系统具有巨大的潜力，特别是如果与更先进的质谱仪结合使用时。

John Yates III, professor of molecular medicine and neurobiology at The Scripps Research Institute, similarly noted that the results his lab has seen from the BILLIE system 'have been pretty impressive' even with 'pretty mediocre [mass spec] technology on the back end.'

斯克里普斯研究所分子医学与神经生物学教授约翰·耶茨三世同样指出，他的实验室从 BILLIE 系统中看到的结果“相当令人印象深刻”，即使“后端的质量谱技术相当平庸”。

In an email to

在一封电子邮件中

GenomeWeb

基因组网

, Mobilion said that it aims to make its technology compatible with 'virtually any mass detector' and noted that it has publicly demonstrated integration of the SLIM technology with a Thermo Fisher Scientific Orbitrap, a PerkinElmer triple quadrupole, an Agilent triple quadrupole, and an Agilent 6230 TOF.

，Mobilion 表示其目标是使自己的技术与“几乎任何质量检测器”兼容，并指出它已经公开演示了 SLIM 技术与赛默飞世尔科技的 Orbitrap、珀金埃尔默的三重四极杆、安捷伦的三重四极杆以及安捷伦 6230 TOF 的集成。

It added that it has completed integration with several other instruments that are still confidential..

它补充说，它已经完成了与另外几种其他仪器的整合，这些仪器目前仍处于保密状态。

This month, a team led by Mobilion researchers published

本月，由Mobilion研究人员领导的团队发表了

a study

一项研究

in

在

Analytical Chemistry

分析化学

demonstrating use of SLIM technology with a Thermo Fisher Orbitrap Exploris 480, finding that it boosted protein identifications by more than twofold in an analysis of 2 ng HeLa cell samples.

展示了一种使用赛默飞Orbitrap Exploris 480的SLIM技术，发现在对2纳克HeLa细胞样本进行分析时，蛋白质鉴定数量提升了两倍以上。

Yates' lab has been using the BILLIE for glycopeptide analysis, which involves distinguishing between large numbers of peptide variants.

耶茨的实验室一直在使用 BILLIE 进行糖肽分析，这涉及到区分大量的肽变体。

'Some of the [glycosylation] sites we look at have many tens of glycan variants at a particular site,' he said. 'A separation tool like SLIM could allow us to separate the heterogeneity of glycopeptides better so that when we put them in the mass spectrometer they are at least much more fractionated.'.

“我们研究的[糖基化]位点中，有些在特定位置上有几十种聚糖变异体，”他说道。“像SLIM这样的分离工具可以让我们更好地分离糖肽的异质性，这样当我们将它们放入质谱仪时，它们至少会更加分馏。”

Yates said that more than SLIM replacing quadrupoles, he is interested in the possibility of it replacing liquid chromatography.

耶茨表示，与其说他对 SLIM 取代四极杆感兴趣，不如说他对它可能取代液相色谱更感兴趣。

'Many of the problems we have in proteomics revolve around LCs,' he said. 'It's always been a big pain in the neck. I'd like to see it get disrupted.'

“我们在蛋白质组学中遇到的许多问题都围绕着液相色谱，”他说道。“它一直是个棘手的问题。我希望看到它被颠覆。”

Others, including former PNNL research Richard Smith, one of the inventors of SLIM technology, have also

其他人，包括 SLIM 技术的发明者之一、前 PNNL 研究员理查德·史密斯，也

raised this possibility

提出了这种可能性

. And last year, researchers including Mobilion CTO Daniel DeBord, published

并且去年，包括Mobilion首席技术官丹尼尔·德博德在内的研究人员发表了

a paper

一张纸

in the

在

Journal of Proteome Research

蛋白质组研究杂志

discussing ion mobility as a replacement for LC in proteomic workflows.

讨论将离子迁移率作为蛋白质组学工作流程中液相色谱的替代方案。

Yates said that since moving into proteomics, Mobilion has made 'huge progress, fast.' He highlighted data analysis as one area likely to present challenges for the company, noting that vendors introducing new technologies to market are commonly at the mercy of outside developers — either academic or commercial — to begin using their system and building software for it..

耶茨表示，自从进入蛋白质组学领域以来，Mobilion已经取得了“快速的巨大进步”。他强调数据分析是可能给公司带来挑战的一个领域，并指出将新技术引入市场的供应商通常依赖外部开发者——无论是学术界还是商业界——来开始使用他们的系统并为其开发软件。

Mobilion has worked with proteomics firm Biognosys (which is majority owned by Bruker) to integrate PAMAF data into that company's Spectronaut software. It has also worked to integrate PAMAF data into the popular DIA mass spec software DIA-NN. Schilling said that she and her colleagues were able to import their PAMAF data into Skyline — one of the widely used proteomics software packages — and work with it in that environment..

Mobilion 已与蛋白质组学公司 Biognosys（其大部分股份由 Bruker 持有）合作，将 PAMAF 数据整合到该公司的 Spectronaut 软件中。它还致力于将 PAMAF 数据整合到广受欢迎的 DIA 质谱软件 DIA-NN 中。Schilling 表示，她和她的同事能够将他们的 PAMAF 数据导入 Skyline（一种广泛使用的蛋白质组学软件包），并在该环境中进行操作。

Mobilion said that it is also working in-house and with outside collaborators to develop new tools designed specifically for the analysis of PAMAF-enabled mass spec data.

Mobilion 还表示，公司正在内部以及与外部合作者共同开发专为 PAMAF 质谱数据分析设计的新工具。

Mobilion has not provided a timeline for when it plans to release a commercial version of the BILLIE system for purchase by individual labs. It said it is currently 'iterating on the key performance benchmarks presented' at the recent American Society for Mass Spectrometry (ASMS) annual meeting as well as 'integrating feedback from the ASMS community.' It is also finalizing the selection of the mass spec platform on which it will launch the system..

Mobilion 尚未提供其计划发布 BILLIE 系统商业版本的时间表，该系统将面向个体实验室销售。公司表示，目前正在“迭代最近在美国质谱学会 (ASMS) 年会上展示的关键性能基准”，并“整合来自 ASMS 社区的反馈”。同时，Mobilion 还在最终确定将用于推出该系统的质谱平台的选择。