Reimagining Ion Separation Through Lossless Innovation

MOBIE was our first product, and BILLIE is our upcoming proteomics platform concept that we’re previewing at this conference. But the common thread is they're both based on SLIM platform technology.

We hold an exclusive license to SLIM, which stands for Structures for Lossless Ion Manipulation. It’s based on printed circuit board technology and represents a major leap forward in separation science. The platform is highly customizable and tunable. By modifying the electrodes and electronics on the circuit boards, we can achieve very different outcomes in separation and analytical performance.

The easiest way to think about it is to first consider the “gold standard”: liquid chromatography integrated with mass spectrometry (LC-MS). Liquid chromatography relies on pumps, solvents, and tubing, all of which must be adjusted based on the analyte class. In contrast, SLIM offers a more universal, digital approach to separation.

I like to compare it to photography. Traditional film required you to send off the film and get it developed using chemicals — some shots came out great, others didn’t. With digital photography, everybody's a photographer! It’s instant gratification, and everybody can take high-quality pictures using their phones or cameras. That’s what SLIM is doing for separations: it’s digitizing the process, delivering immediate, real-time results with improved quality.

MOBIE is our first commercial product, designed for small and large molecule analysis typically performed using liquid chromatography–quadrupole time-of-flight (LC-QTOF) systems. BILLIE, on the other hand, features a different printed circuit board architecture tailored specifically for proteomics. The unmet need in proteomics, especially with current gold standard instruments, is the ability to identify more proteins in less time. BILLIE addresses this by enabling deeper proteome coverage with faster acquisition speeds.

It works by separating analytes based on their collision cross section. When an analyte is ionized using electrospray ionization, it adopts a natural conformation—its size, shape and structure. If you imagine drawing a sphere around that structure, the diameter of that sphere is its collision cross section. On our printed circuit board, which features a serpentine-shaped separation path, we apply voltages to drive the ionized analytes along that path. As they travel, the smaller “spheres” move faster through the system, while larger ones lag behind. So the separation is based on size, shape and charge.

It's not only about separating the analytes, we also can elucidate structures. For instance, when analyzing per- and polyfluoroalkyl substances (PFAS) on MOBIE, we can distinguish between linear and branched forms. Because their conformations differ, their collision cross sections differ, and they separate accordingly. Since this occurs in the gas phase, we’re working with gas-phase kinetics rather than liquid-phase kinetics, which means separations happen in milliseconds instead of minutes to hours, as in LC.

Collision cross section is an inherent physical property, versus a chemical property, so it's more reproducible. To sum up, it's faster, more reproducible and we separate things that LC can't always separate. It's just a different modality on a number of fronts.

BILLIE represents a fundamentally new way to approach ion fragmentation analysis. For the past five decades, tandem mass spectrometry (MS/MS) has followed the same basic workflow: isolate a specific ion population, fragment it, and analyze the fragments using multiple stages of mass analysis. Nearly every tandem mass spectrometer on the market today starts this process using a quadrupole.

A quadrupole acts as a filter; it selectively transmits certain ions and discards the rest. While this works well, it comes with a major drawback: you’re throwing away a large portion of your potential data.

Our approach is different. Instead of filtering ions, we separate them in time. Ions travel through our system and arrive at the collision cell at different moments, allowing us to analyze them all without exclusion. This not only boosts sensitivity, since no ions are discarded, but also improves speed. Traditional quadrupoles have to switch between settings, introducing delays. Our method enables continuous ion separation and eliminates downtime. We can also factor in the improvements in specificity: because we're adding this additional dimension of separation, we can improve the specificity of analysis so that you can more easily tell one analyte from another. 

Another key innovation is our PAMAF mode, short for Parallel Accumulation Mobility Aligned Fragmentation. It’s a data-independent acquisition (DIA) method that captures fragmentation data for all ions, regardless of what’s co-eluting. Researchers have wanted to do this for decades, but it wasn’t feasible until now. SLIM technology gives us the separation power needed to make this possible, especially for complex samples.

There’s a big trend – especially within the proteomics space – for limited sample amount analysis and single-cell analysis. In those situations, every ion that you can get from the sample to the detector matters. With BILLIE, we can increase ion transmission by 10- to 100-fold, giving researchers a major advantage in sensitivity and data completeness.

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There are several different ways you can configure the instrument, but maybe the one with the broadest appeal would be for rapid, full proteome coverage. Today’s leading instruments can identify 8,000 to 10,000 proteins—we can achieve that with PAMAF mode, but we do it faster. That’s because of our high spectral generation rate, which allows us to maintain protein ID numbers while dramatically increasing speed.

It also enables deeper proteome exploration into proteoforms—variations of proteins that include post-translational modifications (PTMs). The high specificity of our separation allows us to detect PTMs that might otherwise go unnoticed, offering richer insights into protein function and regulation. Because our system samples at a high rate, we preserve data integrity even at faster LC speeds, maintaining resolution across peaks and improving quantitation accuracy. And in PAMAF mode, we achieve 100% ion transmission through the quadrupole. That’s especially critical for low-abundance or single-cell samples, where every ion counts.

In short, we’ve built a system with lossless transmission and virtually limitless potential.

From the beginning, we established a Customer Success Team to ensure that users get the most value from our instruments and to support their success in the lab. That focus has been central to our approach as we’ve grown.

At two of our breakfast seminars at ASMS, we highlighted customers who used MOBIE to generate data they couldn’t obtain before. That’s a point of pride for us—we’ve built a strong feedback loop, supported by a robust quality management system, that helps us continuously refine our technology. Even as a small startup, we've given this process the same attention that you'd expect from a much larger company.

Being a smaller company has actually been an advantage. We've been able to focus on quality when it comes to our customer interactions and the customers that we've chosen to work with, as opposed to chasing numbers that may not lead to meaningful impact. As a result, we've been able to get routine feedback from each one of our customers on how we can improve not only our product, but also as a vendor.

When it comes to new products, we have a rigorous and robust process that starts with a product idea. Knowing that we're going to be bringing a new proteomics product using a novel technology into a space that is already very competitive, we need to make sure we understand what is missing. And then that meets the other side of the conversation, which is, can our technology meet those needs?

Ultimately, our goal is to help customers succeed. Whether it's with MOBIE today or BILLIE tomorrow, everything we do is guided by the question: Are we enabling our users to do something they couldn’t do before? If the answer is yes, then we're doing our job right.

At the 10,000-foot level, it's about improving speed, sensitivity, and specificity. When you're aiming for the highest quality analytical results, you want accurate quantitation, rapid throughput, low detection limits and confidence in what you're measuring. Specificity is key—it’s what allows you to say, “I know this is exactly what I think it is.”

In terms of BILLIE and our operation mode, it's about delivering the highest quality analytical results. And in the proteomics world, that means speed, sensitivity, specificity and more accurate quantitation – and not having to make sacrifices for one over the other.

I'll just add that, in the proteomics space, over the past 5–10 years there has been this explosion in capabilities. Mass spectrometry can now do things that were unimaginable a decade ago, and it’s unlocked the potential to extract deep biological insights. Researchers are no longer just asking what proteins are present, they’re designing studies to tackle major disease questions, and that often means analyzing thousands of samples.

To do that, they need higher throughput and better efficiency than current instruments can provide. BILLIE is designed to meet that next level of demand. Scientists are looking for what's next—and this is it.