May 1, 2015 (Vol. 35, No. 9)
Protea Biosciences Is Commercializing an Ambient Ionization Mass Spec Technique
Laser ablation electrospray ionization (LAESI®) provides direct molecular imaging of all types of tissues within minutes, without touching the sample. This mass spectrometry technology promises to be disruptive, while integrating easily into current laboratory and bioinformatics workflows.
“We are all used to antibody and radiolabeling,” Stephen Turner, chairman and CEO of Protea Biosciences Group, tells GEN. “But LAESI needs no labeling and no sample preparation. You just look for the molecules of interest.”
LAESI mass specrometry imaging was developed at George Washington University by Akos Vertes, Ph.D., and exclusively licensed to Protea Biosciences. It simultaneously identifies hundreds to thousands of endogenous or exogenous molecules per analysis—including proteins, peptides, lipids, and metabolites—with micron resolution. Within one hour, a full proteomic, metabolomic, and lipidomic profile of a specific area of tissue can be performed.
Basically, the LAESI technology combines laser ablation from a mid-range infrared laser with a secondary electrospray ionization (ESI) process. The laser’s energy is absorbed by water molecules in the sample tissue, creating a stream of gas-phase particles. The stream, rising above the tissue sample, encounters an ESI plume, and sample particles from the stream become ionized. Once ionized, the molecules are swept into a mass spectrometer for analysis.
“There’s no need for sample preparation,” Turner emphasizes. Because the sample need not be handled, analysis is convenient, fast, and free of bias.
The results are screened against large molecular databases, and molecular maps can be created using the company’s ProteaPlot software showing the two- and three-dimensional distribution of molecules within the sample. At the molecular level, LAESI can distinguish between tumors and nontumors, “even though the histology might appear similar,” Turner says.
This fully automated platform can be used to analyze fresh and frozen tissues, formalin-fixed paraffin-embedded (FFPE) tissue, living cells, biofluids, and even rehydrated blood. “One of our customers has used it to analyze contact lenses,” Turner remarks.
Citing a time study of drug migration in a mouse digestive track, with imaging at 10, 30, and 60 minutes, Turner points out that such studies were impossible using mass spectrometry before LAESI. “You had to ‘grind and find’—do extractions and then do HPLC,” he explains. “Then you could not image the data.” With LAESI, however, imaging can be done multiple times on the same subject, and early enough in trials to allow compounds to be reformulated if necessary.
The first applications are in pharmaceutical research and cancer diagnostics. Collaborations are underway for lung, colon, skin, and breast diagnoses. “We are developing collaborations to further pharmaceutical research and to develop a new class of products for cancer,” Turner notes. LAESI also is being used for the molecular profiling of 3D microtissues.
Protea Biosciences’ business model is three-pronged:
- Selling the LAESI DP-1000 instrument to companies or academic institutions for in-house research.
- Providing mass spectrometry imaging services. (“Many of our clients are biologists who want better data,” Turner adds.)
- Collaborating in the area of tissue analytics.
In January, Protea Biosciences announced a research collaboration with Memorial Sloan Kettering Cancer Center (MSKCC). “We provide tissue analytics for diagnostic development,” Turner explains. “Scientists use molecular information to help them make difficult diagnoses. Biopsies are used, but when there is a scarcity of tissue, LAESI is particularly beneficial.”
Also in January, Protea Biosciences launched a service that uses histology-guided mass spectrometry imaging (HG-MSI), a combination of traditional microscopy and molecular imaging. In this service, tissue samples are reviewed by pathologists or clinical researchers at their own laboratories. Then the samples are sent to Protea Biosciences on slides, which are then digitized. The pathologists may then access their tissue images through Protea Biosciences’ web portal and use the HG-MSI software to identify cells to query for molecular information.
“HG-MSI complements histology,” Turner asserts. “[Using this software,] pathologists can annotate the tissue and specify which subpopulations of cells should be analyzed separately. Pathologists’ workflows aren’t changed. Instead, we are adding information to their routine.”
That information takes the form of differences among subpopulations of cells that may help identify and characterize biomarkers. Such additional discrimination may improve the accuracy of diagnoses and lead to more informed drug selection for physicians and better development for biotech companies.
Protea Biosciences has a nonexclusive co-marketing agreement with Waters and is interested in forming others. It also has an analytic collaboration with InSphero.
The latter endeavor generates molecular profiles of 3D microtissues for the liver and a wide range of tumors. “These 3D tissues behave more like human tissue, so predictability is enhanced,” Turner says. “This partnership allows us to generate molecular profiles and offer them alongside Insphero tissue to help drug developers assess the efficacy of novel agents.”
The first data was presented last autumn. Protea Biosciences expects the first molecularly profiled 3D tissue services to launch this year.
Protea Biosciences’ user base is growing, along with its product and service offerings. Already, the LAESI user base includes SRI International, Dana-Farber Cancer Institute, GE Global Research, Princeton University, Purdue University, the University of Oklahoma, the U.S. Department of Agriculture, and others. In January, Protea Biosciences, as part of a research consortium, received a DARPA grant of up to $14.6 million to develop rapid threat assessment technology.
Protea Biosciences Group
Location: 955 Hartman Run Road, Morgantown, WV 26507
Phone: (304) 292-2226
Principal: Stephen Turner, Chairman and CEO
Number of Employees: 39
Focus: Protea Biosciences Group is a molecular imaging company. Its technology can allow direct imaging of molecules in virtually any tissue or liquid sample without the need for sample preparation.