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With Purchase of Prosolia Tech, Waters Continues Building Direct Ionization Mass Spec Portfolio


NEW YORK(GenomeWeb) – Waters continues to build its direct ionization mass spec portfolio with its purchase this week of Prosolia's desorption electrospray ionization (DESI) technology.

The acquisition is part of a strategy to develop simpler, more streamlined mass spec workflows that will be accessible to non-expert users, said Jose Castro-Perez, the company's director of health sciences.

Castro-Perez said Waters plans to focus on the development of DESI-based mass spec imaging applications targeting a number of disease areas, including oncology, neurology disorders, and cardio-metabolic disease.

Much of life sciences mass spec has been dominated by LC-MS workflows, in which a sample is run through a liquid chromatography system to provide upfront separation and then into an electrospray ionization source that produces ions, which enter the mass spec and are analyzed. LC separation reduces the complexity of the sample as it enters the instrument, eliminating noise and improving the sensitivity of mass spec experiments.

However, LC separation can be time-consuming, which lowers throughput. Additionally, some LC devices — particularly nanoLC systems used for experiments like plasma proteomics — can be somewhat finicky and require expertise to operate and troubleshoot.

While high-performance LC-MS systems are still very much in demand among researchers, in recent years, the field has grown increasingly interested in simplified mass spec systems that can expand the technology's reach to users and labs with less LC-MS expertise. Direct ionization approaches that skip upfront LC, like DESI and the rapid evaporative ionization mass spectrometry (REIMS) technology that Waters acquired in 2014, fit into this trend.

"We want to make this technology accessible to more customers, not just [mass spec]-savvy customers," Castro-Perez said. "That is why we want to reduce the level of complexity for sample prep and also for the running of the instrumentation."

He said that Waters has been exploring uses for the DESI technology for around two years under a co-marketing agreement with Prosolia, which initially commercialized the approach. Through that work, Waters determined that "in the hands of a non-expert mass spectroscopist you can generate good, meaningful data," he noted. "And that is why we made this investment."

"If you look at [Waters'] overall portfolio of mass spectrometry, whether you are talking about direct-from-sample ionization techniques or you are talking about the QDa mass detector, there is a consistent [idea] of the democratization of this technology, trying to get mass spec data into more scientists' hands across more applications," said Jeff Tarmy, Waters' director of corporate communications. "That strategy is something you see across all these technology acquisitions and development initiatives."

DESI uses a stream of ionized solvent droplets, shot at an angle toward the sample of interest. These droplets extract ions from the sample, which are then directed into the mass spec for analysis. In addition to being faster and simpler than LC-MS, DESI is also simpler than MALDI, which also doesn't typically use LC but does require the addition of a matrix to the sample.

Waters offers MALDI systems, but that field in recent years has been dominated by Bruker, which achieved great success with its MALDI Biotyper microbiology system and is a leader in MALDI-based mass spec imaging, where it is currently developing MALDI imaging assays it aims to bring to the clinic.

Waters is likewise targeting imaging applications with the DESI technology, which Castro-Perez said the company sees as complementary to MALDI for imaging work. The fact that DESI does not require the addition of a matrix means it "is simpler and faster to go from sample to data," he said.

He added that some molecules DESI detects well are not well-detected by MALDI, and vice versa.

While the company's DESI efforts are research-focused at the moment, Castro-Perez said that "we want to drive this technology in the future to a point where it is mature and well-tested enough to start to think about how we could deploy it in the clinic."

In addition to the focus on oncology, neurology disorders, and cardio-metabolic disease, Waters and its collaborators are using DESI for research into imaging the microbiome and imaging drug distribution in tissue samples as part of drug metabolism studies.

The company also continues developing applications for the REIMS technology, the other main part of its direct ionization mass spec portfolio. REIMS applies electric current to samples of interest to produce gas phase ions that can then be channeled to a mass spec and analyzed. Like DESI, the technique requires no upfront sample prep or separations, making it a very fast and straightforward approach.

REIMS has shown particular promise for microbiology, where its ability to identify lipid profiles specific to particular organisms could make it useful for microbe ID, much like Bruker and BioMérieux's MALDI-based systems.

Research indicates the approach could in some cases allow for bacteria identification directly from patient samples, which would eliminate the culturing steps required by MALDI-based methods and many other microbe identification approaches.

"We see the microbiology piece as a very important area for REIMS that we want to prosecute," Castro-Perez said.

Between the DESI and REIMS acquisitions, Waters is perhaps the most active major mass spec vendor in the direct ionization space. One factor driving that development is the company's significant investment in ion mobility technology. Because direct ionization approaches don't make use of LC separations, mass spec performance suffers. However, use of ion mobility between the ionization and mass spec analysis steps can help counter this somewhat.

With DESI and REIMS experiments, "we've lost a dimension of separation on the LC side," Castro-Perez said. "But with ion mobility, we get an extra dimension, and when you separate [ions] based on drift time or collisional cross section, that really allows you to eliminate potential interferences you have in your sample."