From Innovation to Translation: Emerging Direct-Analysis Mass Spectrometry Platforms

Ambient and direct-analysis mass spectrometry has shifted from predominantly proof-of-concept rapid screening to increasingly robust analytical platforms with clearer translational potential. This focused critical review examines the following four emerging or strategically relevant platforms: dielectric-barrier-discharge ionization (DBDI), liquid electron ionization (LEI), paper cone spray ionization (PCSI), and sandpaper spray ionization (SPS). DBDI, PCSI, and SPS are ambient or ambient-like direct-sampling approaches. LEI is included as a complementary direct-analysis platform because its electron-ionization chemistry provides structurally informative fragmentation and can address limitations of soft-ionization methods. The review emphasizes recent advances in source and substrate engineering, analytical reproducibility, quantitative readiness, portability, and application-driven implementation. The review uses representative evidence from the literature to distinguish demonstrated analytical performance from broader translational potential, while recognizing that reported detection limits and precision values depend on the method, matrix, and analyte. Rather than cataloging all ambient ionization methodologies, the article critically evaluates the mechanistic strengths, limitations, maturity, and realistic implementation prospects of the four selected platforms in forensic, environmental, pharmaceutical, and field-analytical contexts. Collectively, these technologies illustrate a broader maturation of direct-analysis mass spectrometry, and their long-term impact will increasingly depend on quantitative validation, reproducibility, workflow standardization, and integration with practical analytical needs.