While there has been much advancement in analytical techniques, until fairly recently, there have been challenges in effectively separating molecules based on ionic charge. Traditional liquid chromatography methods may be used, but they have downsides including relatively low throughput and less than optimal resolution.
Enter Structures for Lossless Ion Manipulation (SLIM). SLIM technology was developed by Pacific Northwest National Laboratory (PNNL) and is licensed to MOBILion Systems Inc., a biotechnology company that is taking SLIM-based instruments to the commercial market. Coupled with high resolution mass spectrometry (HRMS), SLIM technology is poised to revolutionize the way we analyze biological and chemical compounds.
This technology uses structures that are designed to efficiently separate substances based on ionic charge. SLIM-based high-resolution ion mobility mass spectrometry (HRIM-MS) provides many benefits over traditional analytical methods, including speed, reproducibility, and resolution. It is destined to have far-reaching consequences in the world of medicine, as well as other areas, including national security.
SLIM technology offers improvement over traditional methods
Traditionally, liquid chromatography is used to separate molecules based on ionic charge. However, this process is relatively slow and often doesn’t provide the level of resolution required for analysis. Insufficient separation means that even when using HRMS, it can still be difficult to differentiate between molecules, especially if they are similar in terms of mass or structure.
SLIM technology is an effective alternative. This concept builds on the idea of separating ions by passing them through a long tube (an ion mobility device) that uses electric fields. Because of the distance ions need to travel, to make this solution practical, PNNL had to find a way to move ions around corners.
It succeeded and was able to create a serpentine drift pathway of more than 40 feet in length, which fits between two circuit boards of about one square foot in size. Ions are propelled through the pathway by electric fields. The process is “lossless” because the electric fields prevent the ions from hitting surfaces while traveling through the pathway.
This technology has major implications in analytics. It allows for the creation of a device for separating and detecting chemical and biological compounds that takes up very little space and may even be portable. The components can be inexpensive to produce, making the technology highly accessible.
According to Melissa Sherman, CEO of MOBILion Systems Inc., HRIM-MS has been shown to significantly improve the throughput of traditional characterization assays. “For example, a typical 30-minute released glycan analysis assay can now be run in just two minutes; a typical 60-90-minute peptide map is accomplished in five minutes with greater post-translational modification elucidation,” Sherman explains.
Additional benefits include enhanced resolution and additional structural information, all within an easily transferable method. Sherman also notes that HRIM-MS methods are analyte-agnostic. This means that their benefits can be applied to assays of different biomolecule classes (including proteins, peptides, lipids, glycans, and other metabolites) without having to change out hardware or perform extensive method development.
The implications of SLIM technology for the future of health care
Currently, the core use for SLIM-based HRIM-MS is in the analysis of biologic therapeutics, and Sherman notes that the technology is proving extremely beneficial for scientists working with complex and challenging analyte classes, such as glycans and lipids.
“HRIM-MS has shown tremendous potential to improve the characterization of biopharmaceuticals and accelerate the drug development process,” Sherman explains.
The speed of the technique offers significant advantages. “With two-to-five-minute analysis times and rapid method development that doesn’t require hardware change out, population scale sample cohorts are analyzed in weeks instead of years.” The other major benefit of the technique—improved resolution—can help to identify potential targets that may have been missed by other methods.
SLIM technology has even been used in COVID-19 vaccine development. Small and complex structures on the surface of coronavirus particles help control how the virus enters the body and defends itself. Discovering exactly how a virus works is crucial in drug and vaccine development. SLIM technology allows for better analysis of these complex surface structures.
Aside from use in research and development, PNNL suggests that SLIM-based units could be used in clinical settings such as doctors’ offices, providing speedy results for patient tests. For example, the technology could be used to find biomarkers that signal an early-stage illness and customize treatments to individual patients. Ultimately, when these improvements are scaled, SLIM-based systems could lead to better outcomes for patients and lower overall health care costs.
According to Sherman, the current goal for MOBILion Systems Inc. (which has an exclusive license to the SLIM technology) is to get it into the hands of drug developers and researchers where it can make a real difference and discoveries can be made. The company’s first commercial product will launch in June 2021 in partnership with Agilent Technologies Inc. Coupling its ion-mobility capabilities with Agilent’s highly-regarded mass spectrometry expertise, MOBILion expects to create a major impact on the biopharmaceutical characterization and clinical research markets.
And the prospects for SLIM technology don’t end there. It could have applications in national security, for example, another field in which PNNL is involved. Potential uses include the detection of toxins in the environment or screening for explosives. In the meantime, scientists at PNNL are working on expanding the power of the technology, including creating multi-level SLIM modules equipped with an “ion escalator.” Additional levels provide the opportunity for improved resolution and increasingly compact designs.