Fabrication of Protein Dot Arrays via Particle Lithography

Abstract

The ability to pattern a surface with proteins on both the nanometer and micrometer scale has attracted considerable interest due to its applications in the fields of biomaterials, biosensors, and cell adhesion. Here we describe a simple particle lithography technique to fabricate substrates with hexagonally patterned dots of protein surrounded by a protein-repellant layer of poly(ethylene glycol) (PEG). Using this bottom-up approach, dot arrays of three different proteins (fibrinogen, P-selectin, and human serum albumin) were fabricated. The size of the protein dots (450 nm - 1.1 μm) was independent of the protein immobilized, but could be varied by changing the size of the latex spheres (diameter = 2 - 10 μm) utilized in assembling the lithographic bead monolayer. These results suggest that this technique can be extended to other biomolecules and will be useful in applications where arrays of protein dots are desired.

Surface Patterning with Colloidal Monolayers

“…Thus, patterning of intrinsically interesting materials with nanoscale dimensions has been achieved; including graphene, [137] carbon nanotubes [138] or proteins. [139] The creation of ordered arrays of pillars in conventional substrate materials as silicon or glass induces superhydrophobicity [14] and has been used to prepare antireflective [140] and self-cleaning materials. [15] The nanoscale periodicity has also been shown to influence cell adhesion that switched from adhesive to non-adhesive in dependence on the order and spacing in nanoscale gold arrays.…”

Nanostructured Polymer Brushes by UV‐Assisted Imprint Lithography and Surface‐Initiated Polymerization for Biological Functions

“…Among these applications the ability to pattern biomolecules to surfaces is of great importance in, for example, biotechnology, biosensors,10 immune assays,11 and cell‐adhesion studies. Current methods of protein patterning include both “top‐down” techniques such as microcontact printing,12, 13 or e‐beam litho­graphy14, 15 and “bottom‐up” methods such as block copolymer and particle lithography 16–19. All these approaches rely on the combination of micro/nanofabrication for localized surface modification and the subsequent chemical activation aimed at specific protein immobilization.…”

Oriented Protein Nanoarrays on Block Copolymer Template

“…These resulting protein chips are mainly low‐density arrays. To achieve potentially high‐density arrays, bottom‐up strategies by self‐assembly of block copolymers (BCP), micelles, and particles have been applied. BCP, with two immiscible blocks covalently linked together, can microphase‐separate into well‐ordered spot areas of chemical contrast with size of ≈20 nm and center‐to‐center spot distance of ≈30 nm .…”