NEW YORK (GenomeWeb) – Startup Mobilion Systems is commercializing ion mobility technology developed at Pacific Northwest National Laboratory that could significantly boost the sensitivity and throughput of mass spec experiments.
According to CEO Melissa Sherman, the Exton, Pennsylvania-based company aims to have a beta version of the technology it can place in customer labs by 2020. It currently has two devices in house that it is offering to customers on a fee-for-service basis.
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.
The PNNL IMS device uses structures for lossless ion manipulations (SLIM) technology to extend ion mobility path lengths beyond that allowed by conventional IMS systems, potentially enabling much more extensive separations. SLIM systems use arrays of printed electrodes to confine ions within the ion mobility field. They also make 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.
In a 2017 paper published in Analytical Chemistry, PNNL researchers presented a 13.5-m-long SLIM system that fit into a space of around 1.5 square feet. The device also included an ion switch that allowed them to direct ions through the IMS system multiple times, using it for as many as 81 passes, or 1.1 km in total length, without experiencing decreased signal intensity.
Since then, the researchers have achieved path lengths of more than 2 km, said Richard Smith, director of proteomics research at PNNL and one of the leaders of the IMS development effort.
Smith was senior author on a study published last month in Analytical Chemistry in which he and his colleagues used the device to separate four sets of β-amyloid tryptic peptide epimers.
Citing this work as an example, he said that his team has been "making much higher resolution measurements than ever done previously with ion mobility and has been able to separate things that haven't been previously."
One area where the PNNL team has improved on the 2017 device is addressing potential issues with multi-pass runs. While that approach can significantly extend the path length, it also leads to peak lapping as ions with higher mobility overtake and lap ions with lower mobility during their multiple cycles through the path, which could create overlapping peaks that could complicate analysis and counter the device's separating power.
To address this, Smith and his colleagues developed an approach called CRIMP (compression ratio ion mobility programming) that he said compresses the ion peaks at points throughout the run to counter the tendency of peaks to disperse during the separation process.
Ultimately, he said, the researchers plan to develop a version of the device using what they call an "ion elevator" that would allow them to move ions between stacked sets of serpentine IMS paths. He called that effort "a work in progress," but said he believed it would ultimately allow for "really high resolution [separations] over very broad regions of ion mobility."
Smith said he believed the technology would initially gain a foothold in small molecule and metabolomic work, where it could help with problems like distinguishing between different isomers of lipids or oligosaccharides.
Applications within proteomics are likely a little further off, he said, though he noted that he and his colleagues have used the technology for phosphoproteomic analyses, finding that it offered a significant boost in sensitivity. He added that he envisioned the device as being particularly useful for proteomic analysis of extremely small samples, such as laser-capture microdissected tumor tissue or single-cell samples.
"This is an area there is more and more interest in… and there are some great challenges in terms of how much information you can extract from a single cell," he said. " When you think about how many protein molecules you have in a cell, and the number of peptides you would produce from those proteins, it's really quite a large number. The real challenges are manipulating very small samples and squeezing the most information from the ions that can be produced from that sample."
He suggested that the SLIM IMS technology might be coupled with single-cell sample prep approaches like the NanoPOTS platform developed at PNNL, to improve such analyses.
Sherman said that thus far Mobilion has seen interest mainly from pharma firms looking to use the SLIM technology for characterization of biotherapeutics and analysis of the patients receiving those biotherapeutics.
On the biotherapeutic characterization side of things, the technology provides improved resolution for glycoprotein analysis, she said, while on the patient side it enables better biomarker discovery or clinical trial stratification.
"What [drug companies] want to be able to do is to connect the dots between the exact biotherapeutic that's given and the biology of the patients that receive them," Sherman said. "We can provide a more comprehensive … high-throughput analysis of the patient's biomarker panel. And then we can connect that to responder, non-responder status, for example, in a clinical trial, which allows the pharmaceutical companies then to do better patient stratification for later phases of clinical trials and optimize the success of those clinical trials as they get into phase II and phase III studies."
Because IMS separations are much faster than liquid chromatography, the technology offers the promise of both improving the speed and performance of an assay, Sherman said.
"In some cases, you could insert SLIM into an LC-MS workflow and it will give you another point of validation and verification that helps confirm the identity of the analyte you are looking for," she said. Alternately, "maybe if your LC run was an hour long, you could cut that to 10 minutes and then SLIM becomes the workhorse separation component."
In some cases, she added, incorporating SLIM allows for eliminating liquid chromatography altogether.
Ion mobility is an area of significant interest for mass spec vendors, with most major life science mass spec firms offering an IMS technology that can be coupled with their mass specs.
Sherman said that Mobilion has "a number of partnerships and collaborations at various stages of development with [several] of the big five mass spec companies. We are integrating SLIM with a variety of different mass specs, and we are working with a variety of different mass spec manufacturers to have SLIM integratable with their platforms."
She added that the company's first SLIM product will be sold as a device "integrated with an existing installed base of mass spectrometers," though she declined to say what company's installed base that would be.
While Mobilion currently offers the SLIM technology on a fee-for-service basis, the company has no plans to do so once it has instruments ready for sale. "It's just a way to bridge the gap," Sherman said.
Mobilion has 11 employees and has been privately funded by seed investors to date. Sherman said the company is currently in the midst of a Series A funding round. She declined to say how much funding the company was targeting.