**5.1. The science of nanofluidics**

In nanofluidics, size (or scale) is important, likely more so than in microfluidics. For instance, at the nano-scale many dimensions of molecules are of similar size as the nano-fluidic channels that constrain them (**Figure 1**). A few scientific questions that being addressed include: How do properties of individual atoms, ions or molecules, manifest themselves as they are confined in spaces (roughly) of their own size? Would quantum effects become important [173]? Since pressure is not used to force fluids through nanochannels, should electrokinetic flow be preferred? And, as surface-to-volume ratio increases significantly (over microchannels), what is the effect of surface-charge on ions or molecules confined in nanochannels? What is the effect of surface roughness on fluid-flow? And, how do surfaces interact with ions or molecules so close to them? What are the best surface modification approaches? What is the effect of van der Waals forces and of the electric double layer (EDL) at the nm-scale? Some questions arising from technology include: how would one introduce very small volumes of analytical samples into nanofluidic channels? To facilitate discussion, assume a cylindrical nanochannel with 100 nm diameter and 1 μm length. In this case, the volume is 100 **a**tto **L**iter (**aL**). How would one introduce an aL volume sample into a nanochannel without evaporation of some of the analyte or of the solvent? Due to the infinitesimal volumes used, would single atom, ion or molecule measurement techniques be essential? In support of this, it has been estimated that in a liquid the volume of a cube with dimensions 100 nm by 100 nm by 100 nm, there are only ~6 analytes when the concentration of the analyte is 1 μm [160]. Would sample separation, pre-concentration and use of highly-sensitive detection techniques (e.g., laser induced fluorescence or LIF) become essential?
