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Bruker's InVivo Buy Could Expand MALDI Biotyper Workflows, Capabilities


NEW YORK (GenomeWeb) – Bruker's acquisition this month of life sciences firm InVivo Biotech Services could prove key to the development of new workflows and capabilities for the company's MALDI Biotyper platform.

Most immediately, the acquisition brings experience and capabilities in assay and kit development that Bruker will use as it seeks to expand its microbiology offerings, said Wolfgang Pusch, executive vice president for clinical MALDI solutions at Bruker.

In November, Bruker acquired PCR technology assets with which it plans to build syndromic infectious disease diagnostics to be run both on conventional PCR platforms and on the MALDI Biotyper.

The InVivo purchase is likewise "part of a broader global strategy to improve our capabilities for quick assay development, production, and [to drive] our consumable business in general," Pusch said, noting that the Hennigsdorf, Germany-based company has production facilities and expertise in moving assays from feasibility studies to actual commercial kits.

Regarding new workflows for the Biotyper, Pusch noted that antibody enrichment upfront of MALDI analysis might allow researchers and clinicians to identify microorganisms directly from patient samples without first culturing these organisms or with reduced culture times.

"The idea would be that an enrichment of antibodies could pull [target] bacteria out of [patient sample] fluids, and we could then feed that enriched sample into the normal [MALDI Biotyper] workflow," he said.

Pusch noted that Bruker was only beginning to explore this idea and that it would be a year or two before it would have any results regarding the feasibility of the process. If the company is able to develop such workflows, it would be a significant advance for MALDI-based microbial identification and microbial ID, in general.

Direct identification of microorganisms without first enriching them by culturing is a major, if perhaps still somewhat distant, goal of clinical microbiologists. As Susan Butler-Wu, director of medical microbiology at Los Angeles County-USC Medical Center, said in a 2015 interview, "one of the things we are all talking about right now is direct identification of pathogens from clinical specimens using mass spec."

Eliminating culturing could significantly shorten the time-to-result of microbial ID assays, as the step typically takes one to two days, and this in turn could allow clinicians to begin appropriate treatment more quickly.

Some groups have presented methods that could enable such direct identification. For instance, Zoltan Takats and colleagues at Imperial College London have demonstrated the use of their rapid evaporative ionization mass spectrometry (REIMS) technology (now owned by Waters) to detect bacteria directly from human colorectal tissue samples.

Direct identification has not been done using MALDI, though. If it were to prove feasible, it could be very useful, said Nathan Ledeboer, medical director for the clinical microbiology and molecular diagnostics laboratories at the Medical College of Wisconsin, noting that such a capability could decrease the MALDI Biotyper's turnaround time and expand Bruker's addressable market.

"With an antibody enrichment you should get at least 10-fold if not higher enrichment and you'll be able to better recover those organisms from a direct sample," Ledeboer said. "So rather than being overwhelmed with human protein, human DNA, you can get rid of all of that and essentially pull out just the bacterial organisms."

In addition to potentially eliminating the need for culturing, such an approach could also help MALDI platforms deal with more complicated samples.

"You could start to find ways of managing mixed species or mixed organism populations in a much more effective manner than what either Bruker or BioMérieux (which offers the competing Vitek MS MALDI microbiology system) have been able to do," Ledeboer said.

An antibody enrichment approach could also improve the ability of MALDI-based platforms to better distinguish between closely related organisms, he said. "Certainly that would be a possibility. Things like separating Shigella from [Escherichia coli], you might be able to get some added specificity with [antibody enrichment]."

It might also prove useful for detection of viruses, at task for which current MALDI systems are considered poorly suited, in significant part due to the fact that these organisms can't be enriched by culturing, Ledeboer said.

"They could design antibodies to look for a viral capsid protein or something of that effect and then use the mass spec to be able to detect that directly from the sample," he said. He noted that molecular assays provide relatively good coverage for viral detection, which might limit the upside for a company like BioMérieux that offers a broad menu of microbiology tests.

However, "from Bruker's standpoint, if you could develop a solution and be able to compete in that space that would certainly give you some opportunity," he said.

Like Pusch, Ledeboer noted that these notions were still essentially theoretical at this point. "None of this has been proven yet," he said. "How do you make an antibody that is sensitive enough or broad enough to pick up all of your organisms while maintaining a level of specificity that you need as well?" he added.

Ledeboer noted that this question is one clinical microbiologists have confronted in other contexts, such as efforts to identify biomarkers that would allow them to determine whether conditions like sepsis are caused by a bacterial or viral infection.

One approach might be to develop panels for specific questions. "You may be able to develop quite easily a set of antibodies that will look for common organisms that cause, for instance, community-acquired pneumonia, then put those antibodies into a panel that would then pick out those organisms, and those organisms could subsequently be identified using the mass spec," he said.

This sort of method, though, trades away one of mass spec's biggest advantages in the microbiology space — the ability to take an essentially unbiased approach to organism ID.

"To a certain extent you are giving up the real advantage mass spec has in that you have these giant databases to identify organisms," Ledeboer said.

He also noted that adding an antibody enrichment step would increase the cost and complexity of the assays. "One of the real advantages that mass spec delivers is the fact that it is incredibly cheap and incredibly fast. How much of that are you going to give up with this type of a process?"

That said, Ledeboer said that an antibody-MALDI workflow that was priced equivalently to existing molecular and biochemical identification assays but eliminated the need for culturing "would be huge."