As the field of nanofluidics matures, fundamental discoveries are being applied to lab-on-a-chip analyses. The unique behavior of matter at the nanoscale is adding new functionality to devices that integrate nanopores or nanochannels. (To listen to a podcast about this feature, please go to the Analytical Chemistry website at pubs. acs.org/journal/ancham.)Advances in microfabrication and miniaturized analysis have resulted in increasingly sophisticated microfluidic systems that are fulfilling the promise of true "labs-on-a-chip" or "micro total analysis systems" by integrating multiple processing steps on a single device.1 Furthermore, improved fabrication techniques have placed the nanoscale regime within reach, even for laboratories with limited fabrication facilities. 2 These advances are allowing scientists to explore fluidic systems containing conduits that approach molecular-length scales. Incorporation of biological and synthetic nanochannels in fluidic devices holds great promise for new analytical applications because there are forces and phenomena at this scale that are absent or negligible in larger microchannels.3 Critical considerations in designing these devices include double-layer overlap (DLO) and the resulting ion permselectivity; localized enhancement of electric fields; and the increased influence of diffusion, surface-to-volume ratio, surface charge, and entropy. Through these effects, nanoscale components can improve routine processing and add new functionality to microfluidic devices. The goals of this article are to highlight progress in integrated micro-and nanofluidic devices, to demonstrate how nanofluidic components may benefit each function performed during chemical analysis (sample preparation, fluid handling and injection, separation, and detection), and to encourage creative thinking about future applications as this technology matures. This article focuses on devices containing one or more nanochannels or nanoporess fluidic features with at least one dimension typically e100 nm. We will discuss discrete features e0.5 µm, as opposed to nanoporous monoliths 4 or membranes with tortuous paths, 5 which are reviewed elsewhere.Some of the earliest work in nanofluidics used native and engineered protein pores in lipid bilayers to characterize a range of molecules, including polymers, nucleic acids, metal ions, and organic molecules, by resistive-pulse sensing.
10Protein pores provide excellent reproducibility with respect to their dimensions and internal chemistry and readily self-insert into a bilayer from solution. However, lipid bilayers on-chip are relatively fragile compared to the glass, polymer, and semiconductor substrates typical for microfluidic applications. As a result, many groups are pursuing emerging nanofabrication methods to produce nanochannels in hard and soft materials. Figure 1 shows integrated micro-and nanofluidic devices in which nanopores or channels are formed by a variety of methods, including track-etching polymer membranes, 6 sacrificial layer deposition, 7 ...