Toward nanofluidics-based mass spectrometry for exploring the unknown complex and heterogenous subcellular worlds

Exploring unknown matter inside an ultrasmall volume object, such as unknown subcellular matter in a single cell, requires an analytical technique that offers identification of these unknown matter in terms of molecular structures and properties. Mass spectrometry is considered one of the best choices for such analysis of unknown matter because mass spectrometry can be utilized to identify unknown matter according to its mass-to-charge ratio. However, the use of mass spectrometry for exploring unknown matter in such a small world has been greatly impeded due to the lack of tools to conduct the sampling of complex and heterogeneous analytes with ultrasmall volumes below the picoliter order, which is the volume order of a mammalian cell. We believe that nanofluidics would be an ideal tool to resolve the critical issue owing to its ability to sample such fluid samples with ultrasmall volumes ranging from the picoliter to zeptoliter order. Thus, the integration of such nanofluidic ability into mass spectrometers would open up future avenues for the potential of mass spectrometry to explore unknown subcellular matter at a nano scale. In this perspective, we first discuss published findings in the exploration of the applicability of microfluidics/nanofluidics to mass spectrometry, then address critical issues toward nanofluidics-based mass spectrometry, and finally depict a personal outlook on the future of this field to resolve challenges on global and universal scales.

Automated summary

Exploring unknown subcellular matter in a single cell requires analytical techniques that can identify molecular structures and properties. Mass spectrometry is considered suitable for this analysis due to its ability to identify matter based on mass-to-charge ratio. However, the lack of tools for sampling complex analytes with ultrasmall volumes has hindered the use of mass spectrometry in this context. Using nanofluidics could potentially resolve this issue, as it can sample fluid samples with ultrasmall volumes ranging from picoliters to zeptoliters. Integrating nanofluidic ability into mass spectrometers could open up avenues for exploring unknown subcellular matter at a nano scale.