Toward nanofluidics‐based mass spectrometry for exploring the unknown complex and heterogeneous subcellular worlds

Abstract

Exploring unknown matter in an ultrasmall volume object, such as unknown subcellular matter in a single cell, requires an analytical technique that identifies unknown matter in terms of molecular structures and properties. Mass spectrometry is considered one of the best techniques for such analyses because it can identify unknown matter according to its mass‐to‐charge ratio. However, the use of mass spectrometry to identify unknown substances in such a small world has been greatly impeded due to the lack of tools to sample complex and heterogeneous analytes with ultrasmall volumes of the picoliter order, which is the volume order of a mammalian cell. We believe that nanofluidics would be an ideal tool to resolve this 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 features 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 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.

Quantitative mass spectrometry imaging: therapeutics & biomolecules

“…Lastly, for both MALDI and DESI studies, the field of fluidics has emerged for MS analysis of biomolecules at the subcellular level and displays great promise for increasing the sensitivity of molecular targets. 116,117 Incorporation of fluidics to MS is very compelling for applications dealing with small sample sizes, increasing analyte sensitivity, and the potential addition to MSI workflows. 118…”

Recent advancements in supramolecular macrocycles for two-dimensional membranes for separations

“…1,2 In addition, this phenomenon is closely related to other aspects of daily life. 3 For example, natural gas and other crude oil separation and purification products are widely used in transportation, aerospace, and other industries. However, traditional separation methods, such as fractionation and heat treatment, account for approximately 10–15% of the global energy consumption.…”

Nanofluidic Aptamer Nanoarray to Enable Stochastic Capture of Single Proteins at Normal Concentrations

“…Square nanochannels provide extremely small volumes, usually in the order of a femtoliter (fL, 10 −15 L) or less, with well-defined characteristic lengths approaching those of single molecules, thereby allowing the confinement of single molecules at high concentrations ranging from nanomolar to micromolar, which covers the so-called normal concentration range of reactant molecules in the majority of chemical syntheses and biomolecules in a single cell. [30,31] Such features provide the potential to observe, capture, detect, and react with single molecules in their original naive conditions, rather than the significantly diluted conditions required in most current single-molecule studies.…”