Secrets of science magazine 01/2024

Importance of topic

Recent advances in analytical chemistry offer transformative tools for life sciences, environmental technology, clinical diagnostics and sustainable energy. Sensitive detection of Alzheimer’s biomarkers, robust blood sampling, green hydrogen production monitoring, efficient biowaste valorization and predictive pharmacogenetics underscore the field’s crucial role in addressing major societal challenges.

Study objectives and overview

• Develop mass-spectrometry methods for plasma amyloid β (Aβ) to enable noninvasive Alzheimer’s screening.
• Implement dried plasma spot (DPS) cards for simplified blood collection and multiplex biomarker analysis.
• Optimize pyrolysis of diverse biowastes to yield biochar, bioliquids and syngas for low-carbon applications.
• Validate a GC-MS/MS heart-cut method for robust detection of the new EU fuel marker BPE (butyl phenyl ether).
• Elucidate the gas-phase formation and fragmentation of bisquaternary ammonium-trifluoroacetate adducts for future anion sensors.
• Introduce DOSIURA™ as a turnkey LC-MS/MS kit for uracil/dihydrouracil quantification to screen DPD-deficient cancer patients.
• Demonstrate the critical importance of ultrapure water monitoring in PEM water electrolysis for green hydrogen production.

Methodology and instrumentation

• Immunoprecipitation coupled MALDI-TOF and LC-MS/MS (Shimadzu LCMS-IT-TOF) for direct Aβ1-40, Aβ1-42 and APP669-711 quantification.
• DPS cards with integrated separation membrane for room-temperature plasma collection and compatibility with LC-MS, ELISA and PCR assays.
• Laboratory-scale and micropyrolysis reactors interfaced to GC-MS (Frontier Lab pyrolyzer and Shimadzu GCMS-QP2010/2020 NX) plus calorimetry and TOC analysis for biowaste characterization.
• Heart-cut MDGC-FID/MS method on QP2020 NX and FID-2030 for BPE detection at sub-µg/L levels in fuels.
• ESI-MSn on Shimadzu IT-TOF to investigate covalent bisquaternary ammonium-trifluoroacetate adducts and unique fragmentation pathways.
• DOSIURA™ reagents and internal standards for rapid LC-MS/MS quantification of uracil/dihydrouracil in plasma.
• On-line process analytics: Shimadzu TOC-1000e for continuous TOC and conductivity monitoring in ultrapure water loops of PEM electrolyzers.

Key results and discussion

The IP-MS technique achieved the first reliable detection of plasma Aβ species, with composite Aβ1-40/Aβ1-42 and APP669-711/Aβ1-42 ratios yielding 94–97 % concordance with amyloid PET across two cohorts. DPS cards demonstrated > 90 % recovery, minimal hematocrit bias and ease of handling for remote blood sampling. Pyrolysis tuning enabled up to 75 % bioliquid yield or 50 % biochar from lignin-rich feedstocks; analytical workflows characterized toxic PAHs in biochars and guided process adjustments. The new BPE marker was quantified down to 2.8 µg/L, with linearity to 12 mg/L and recoveries of 93–117 % in spiked fuels. ESI-MS/MS of bisquaternary ammonium-TFA adducts revealed covalent N–O bond formation and unusual fragment ions, suggesting routes to stable anion sensing. DOSIURA™ provided < 0.5 µM precision for uracil and dihydrouracil, aligning with clinical thresholds for DPD deficiency. Continuous TOC/conductivity monitoring by TOC-1000e enabled early detection of contamination and predictive electrolyzer maintenance.

Benefits and practical applications

• Noninvasive Alzheimer’s risk screening and treatment monitoring.
• Decentralized blood sampling for biomarkers in rural/low-resource settings.
• Valorization of agricultural and municipal biowaste to materials, fuels and carbon sinks.
• Regulatory-compliant fuel marking to prevent tax fraud.
• Foundations for novel mass-spectrometry-based anion sensors.
• Personalized oncology through DPD deficiency screening to reduce chemotherapy toxicity.
• Optimized green hydrogen production via real-time water quality control.

Future trends and possibilities

Integration of high-throughput IP-MS workflows and multiplex DPS assays promises large-scale population screening for neurological and metabolic disorders. Advanced catalytic upgrading of pyrolysis oils and structured biochar composites will expand biowaste uses in bioplastics and carbon capture. Emergent MSn ion-chemistries may pave the way for direct detection of environmental anions. Standardized kits like DOSIURA™ will underpin precision medicine in chemotherapy dosing. Finally, AI-driven PAT systems will further enhance electrolyzer efficiency and reliability, accelerating the global hydrogen transition.

Conclusion

Across multiple domains, cutting-edge analytical chemistry methods and devices—from immuno-MS to process-embedded PAT—are enabling new applications that tackle neurodegeneration, sustainable energy, environmental protection and personalized medicine. Continued innovation and cross-disciplinary collaboration will be vital to translate these technological advances into societal impact.

References

• Selected peer-reviewed studies on blood Aβ IP-MS and PET correlations.
• European Medicines Agency guidelines on fluoropyrimidine dosing.
• ISO and ASTM standards for ultrapure water in electrolysis.
• Key publications on pyrolysis GC-MS analytical protocols.