Identifying Unknown Molecules in Blood with Breakthrough Technology

Every human blood sample has about 15,000 small molecules that paint a precise picture of health. Less than 5% of these molecules are known and can be identified. What crucial information are we missing within the remaining 95%?

The team at Isospec Analytics has developed a breakthrough technology that identifies unknown molecules at scale for pharmaceutical, agritech, and nutrition companies. It’s already being used to analyze sugars and metabolites for food and agritech quality control and to support R&D. But, the real potential lies in the discovery of new biomarkers for diagnostics and drug targets.

Current Obstacles in Biomolecule Identification

Identifying unknown molecules currently takes months, slowing manufacturing pipelines and the development of life-saving medicines. It is a complex process, often requiring a combination of two methods: mass spectrometry and infrared spectroscopy.

Mass spectrometry (mass spec) is very sensitive and selective and can create a profile showing the presence of individual molecules in a sample (that’s how we know there are 15,000 molecules in a blood sample). But mass spec can’t make important distinctions between molecules of the same mass with different structures or functions. Isomers, for example have the same mass, but are structurally different and can have very different biological activities. One isomer could be linked to health, whereas the other could act as a toxin.

Infrared spectroscopy (IR) looks at the structure of all molecules in a sample at the same time, generating a single spectrum. This solves the structural resolution problem but makes it hard to extract a signature for an individual molecule.

Mass spec followed by IR is typically used to resolve individual molecules, but there are extensive purification steps in between. This process is slow, cost and labor intensive, and sometimes still requires additional techniques to further characterize the structure.

The Best of Both Worlds: Combining Mass Spec and IR

In 2022, Ahmed Ben Faleh, Stephan Warnke, and Thomas Rizzo founded Isospec Analytics to solve this problem. Their technology combines mass spec and IR into one instrument to generate molecular fingerprints with unprecedented accuracy and sensitivity—even identifying previously-unknown biomolecules.

“We are fundamentally changing the way we identify biomolecular structures,” said Dr. Faleh, “Processes that once took months can now be completed in hours with our technology.”

Isospec’s technology works by placing cryogenic infrared spectroscopy inside of a mass spectrometer. The IR fingerprints generated by this technology reflect the vibrations of the molecule which are governed by quantum mechanics. The molecular structure is computationally resolved enabling a robust and precise identification. Using this approach, there is minimal need for synthetic standards enabling detection of novel molecular structures. For example, Isospec’s technology can identify O- and N-glycan structures even when analytical standards do not exist.

Services for Product Development and Manufacturing

Isospec Analytics is focusing largely on identifying unknown biomolecules that fall within a range of 50-3,000 mass units like sugars, glycans, metabolites, and post-translationally modified proteins and lipids (i.e., glycosylated molecules). “Hundreds of thousands of unknown molecules make up the human metabolome,” says Dr. Faleh. “It’s our goal to identify them and create a database so that future biomolecule characterization and discovery projects do not run into the ‘unknown molecule barrier’ that exists today.”

Isospec currently offers access to this innovative technology through services, with a goal of one day commercializing the instrument. Their team of technical specialists provide services for product quality control that verify manufacturing consistency, identify impurities, and assess safety. For biotech and nutritional product development, the technology is being used to search for bioactive molecules and to understand environmental influences on product integrity. In addition, the team is supporting biomarker discovery and molecular verification studies for diagnostics and drug development and manufacturing.

Scaling Up to Drive Down Costs of Product Development

Isospec recently secured $1.9 million in its pre-seed funding round to scale-up operations. Funds will be used to increase automation at every step from sample preparation to testing to data analysis for even higher throughput of biomolecule discovery and identification. “This round allows us to build a software team composed of experts in data engineering,” says Dr. Faleh. “We seek to provide high throughput capabilities that drive down costs associated with the development of therapeutics and nutritional products that can provide a global impact.”

For more information, visit isospecanalytics.com.

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