Gold-Conjugated Protein Nanoarrays through Block-Copolymer Lithography: From Fabrication to Biosensor Design

摘要

Forming arrays of biomolecules at defined positions with spatial control and resolution down to the single-protein level is a key issue in nanobiotechnology for cell biology, protein screening, biosensors, protein-protein interaction studies, and medical implants.[1]-[7] To achieve this, it is essential to place and immobilize biomolecules at predefined positions with features on the same scale (10 nm) as the three-dimensional conformation of an individual protein molecule.[7] Various lithographic technologies, including electron-beam (e-beam) lithography,[8] nanoimprint lithography,[9], [10] scanning-probe lithography,[1]-[3] colloid lithography,[11], [12] and block-copolymer (BCP) lithography,[13], [14] may have the potential to be used to create arrays of proteins. In practice, however, pattern feature sizes smaller than 30 nm are difficult to achieve by using commercial e-beam lithography, nanoimprint lithography, and colloidal lithography. Scanning-probe techniques, which have proven very effective in the fabrication of multicomponent systems[1]-[3] and nanobioarrays with feature sizes of the order of 50 nm,[3] are time-consuming methods for large-scale production due to serial-processing limitations. Features produced by BCP lithography, on the other hand, are determined by the absolute size of the domain (5-100 nm), which is defined by the molecular weight of the copolymer and the strength of the segmental interaction between the blocks. Since the first successful works on BCP lithography,[13] dense arrays of various functional materials have been fabricated with the use of BCP thin films as templates.[14]-[16] This method is also cost effective and suitable for mass production. However, it is very difficult to place and immobilize biomolecules at the predefined positions afforded by the periodic arrays of BCP holes.