We discuss the origins, motivation, invention, development, applications, and future of chemical lift-off lithography, in which a specified pattern of a self-assembled monolayer is removed, i.e., lifted off, using a reactive, patterned stamp that is brought into contact with the monolayer. For Au substrates, this process produces a supported, patterned monolayer of Au on the stamp in addition to the negative pattern in the original molecular monolayer. Both the patterned molecular monolayer on the original substrate and the patterned supported metal monolayer on the stamp are useful as materials and for further applications in sensing and other areas. Chemical lift-off lithography effectively lowers the barriers to and costs of high-resolution, large-area nanopatterning. On the patterned monolayer side, features in the single-nanometer range can be produced across large (square millimeter or larger) areas. Patterns smaller than the original stamp feature sizes can be produced by controlling the degree of contact between the stamp and the lifted-off monolayer. We note that this process is different than conventional lift-off processes in lithography in that chemical lift-off lithography removes material, whereas conventional lift-off is a positive-tone patterning method. Chemical lift-off lithography is in some ways similar to microtransfer printing. Chemical lift-off lithography has critical advantages in the preparation of biocapture surfaces because the molecules left behind are exploited to space and to orient functional(ized) molecules. On the supported metal monolayer side, a new two-dimensional material has been produced. The useful important chemical properties of Au (vis-à-vis functionalization with thiols) are retained, but the electronic and optical properties of bulk Au or even Au nanoparticles are not. These metal monolayers do not quench excitation and may be useful in optical measurements, particularly in combination with selective binding due to attached molecular recognition elements. In contrast to materials such as graphene that have bonding confined to two dimensions, these metal monolayers can be straightforwardly patterned-by patterning the stamp, the initial monolayer, or the initial substrate. Well-developed thiol-Au and related chemistries can be used on the supported monolayers. As there is little quenching and photoabsorption, spectroscopic imaging methods can be used on these functionalized materials. We anticipate that the properties of the metal monolayers can be tuned by varying the chemical, physical, and electronic connections made by and to the supporting molecular layers. That is, the amount of charge in the layer can be determined by controlling the density of S-Au (or other) connections and the molecular backbone and functionality, which determine the strength with which the chemical contact withdraws charge from the metal. This process should work for other coinage-metal substrates and additional systems where the binding of the outermost layers to the substrate is weaker than the molecule-substrate attachment.

Precise self-assembled monolayer chemistries and microfluidic technology are combined to create small-molecule biorecognition arrays. Small-molecule neurotransmitters or precursors are spatially encoded on monolayer-modified substrates. This platform enables multiplexed screening of G-protein-coupled receptors (GPCRs) from complex media via protein-ligand interactions. Preserving access to all epitopes of small molecules is critical for GPCR recognition. The ability to address multiple small molecules on solid substrates and to sort protein mixtures based on specific affinities is a critical step in creating biochips for proteomic applications. © 2013 American Chemical Society.

Nucleotide arrays require controlled surface densities and minimal nucleotide-substrate interactions to enable highly specific and efficient recognition by corresponding targets. We investigated chemical lift-off lithography with hydroxyl- and oligo(ethylene glycol)-terminated alkanethiol self-assembled monolayers as a means to produce substrates optimized for tethered DNA insertion into post-lift-off regions. Residual alkanethiols in the patterned regions after lift-off lithography enabled the formation of patterned DNA monolayers that favored hybridization with target DNA. Nucleotide densities were tunable by altering surface chemistries and alkanethiol ratios prior to lift-off. Lithography-induced conformational changes in oligo(ethylene glycol)-terminated monolayers hindered nucleotide insertion but could be used to advantage via mixed monolayers or double-lift-off lithography. Compared to thiolated DNA self-assembly alone or with alkanethiol backfilling, preparation of functional nucleotide arrays by chemical lift-off lithography enables superior hybridization efficiency and tunability.

Self-assembled monolayers are a unique class of nanostructured materials, with properties determined by their molecular lattice structures, as well as the interfaces with their substrates and environments. As with other nanostructured materials, defects and dimensionality play important roles in the physical, chemical, and biological properties of the monolayers. In this review, we discuss monolayer structures ranging from surfaces (two-dimensional) down to single molecules (zero-dimensional), with a focus on applications of each type of structure, and on techniques that enable characterization of monolayer physical properties down to the single-molecule scale.