Smart Biotech Scientist | Master Bioprocess CMC Development, Biologics Manufacturing & Scale-up, Cell Culture Innovation

208: Cryogenic Infrared Ion Spectroscopy: From Mass Spec Limitations to Molecular Precision with Tom Rizzo - Part 2

David Brühlmann - CMC Development Leader, Biotech C-level Advisor, Business Strategist Episode 208

What if you could analyze every metabolite, glycan variant, and unknown impurity in your bioprocess sample—not just the targets you're looking for, but everything that's actually there? Cryogenic infrared ion spectroscopy combined (CIRIS) with AI-powered analysis transforms untargeted screening from aspiration to reality.

This episode moves from fundamental principles to practical applications. While Part 1 established how CIRIS overcomes mass spectrometry's structural limitations, Part 2 reveals what becomes possible when you can definitively identify complex mixtures: better mAb characterization, earlier disease detection, and process decisions based on complete data rather than educated guesses.

Professor Tom Rizzo returns to discuss Isospec Analytics' path from laboratory innovation to commercial service platform. His transition from academic leadership at EPFL to biotech entrepreneurship offers insights for any scientist considering whether breakthrough research deserves a startup—and what that journey actually requires.

For bioprocess scientists drowning in unidentified peaks, struggling with glycan heterogeneity, or making critical manufacturing decisions with incomplete analytical data, this conversation demonstrates how next-generation analytics powered by quantum chemistry and machine learning can illuminate what's been hidden in your samples all along.

Episode Highlights:

  • Why targeted metabolomics creates a "streetlight effect"—and how untargeted CIRIS analysis reveals the complete molecular landscape (00:00)
  • Isomer-specific glycan characterization for mAbs: distinguishing structural variants that impact efficacy and immunogenicity (03:17)
  • Advanced disease detection and biomarker discovery: identifying diagnostic signatures in complex biological matrices (05:21)
  • AI meets quantum chemistry: automated spectral library building and machine learning algorithms that accelerate molecule identification from hours to seconds (06:05)
  • From data generation to decision-making: how comprehensive analytics and AI transform bioprocess development workflows (09:23)
  • Isospec's commercial roadmap: service platform for comprehensive sample analysis and projected timeline for benchtop instrumentation (10:09)
  • Academic to entrepreneur: Tom Rizzo's perspective on leaving tenure for a startup, with practical advice for scientists evaluating the leap (12:05)
  • Personal motivation behind early diagnostics: cancer and leukemia experiences that drive Isospec's clinical applications (14:11)
  • Technical deep dive: messenger tagging methodology and achieving single-ion infrared detection sensitivity (15:41)
  • The transformative capability: adding a structural dimension to mass spec data that eliminates ambiguity in complex mixture analysis (17:55)

Mass spectrometry tells you what masses are present. Cryogenic infrared ion spectroscopy tells you what molecules they actually are. When coupled with AI-powered analysis, this combination enables truly comprehensive characterization—from process impurity identification to critical quality attribute assessment to early disease biomarker discovery.

If you're making bioprocess decisions with incomplete analytical information, managing glycan complexity in biologics development, or exploring how emerging analytical technologies could solve your toughest characterization challenges, this episode provides both the technical foundation and the commercial pathway forward.

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