Nanofluidics for sub-single cellular studies: Nascent progress, critical technologies, and future perspectives

In the field of cell studies, there is a burgeoning trend to further downscale the investigation from a single-cell level to a sub-single-cell level. Subcellular matter is the basic content in cells and correlates with cell heterogeneity. Sub-single cellular studies focus on the subcellular matter in single cells and aim to understand the details and heterogeneity of individual cells in terms of the subcellular matter or even at the single component/vesicle/molecule level. Hence, sub-single cellular studies can provide deeper insights into fundamental cell biology and the development of new diagnostic and therapeutic technologies and applications. Nonetheless, the contents of a single cell are not only ultra-small in volume but also extremely complex in composition, far exceeding the capabilities of most tools used in current cell studies. We believe that nanofluidics holds great potential in providing ideal tools for sub-single cellular studies, not only because of their capability to handle femtoliter/attoliter-scale samples, but also because of their possibility to manipulate and analyze subcellular matters at the single component/vesicle/molecule level in a high-throughput manner. In this review, we summarize the efforts in the field of nanofluidics for sub-single cellular studies, focusing on nascent progress and critical technologies that have the potential to overcome the technical bottlenecks. Some challenges and future opportunities to integrate with information sciences are also discussed. Nanofluidics is promising for further evolving cell research from a current single-cell level to a future sub-single cellular level to bridge life sciences and information sciences. Some nascent progress and critical technologies are focused, and future perspectives of the field are discussed. [Display omitted] .