Patterning biomolecule at sub-30 nm resolution by electron beam lithography.

Patterning biomolecule at nanoscale is important for applications in biosensors, bio-nanoelectromechanical(Bio-NEMS) devices and fundamental biological studies. This dissertation describes the fabrication of biomolecule nanopatterns at sub-30 nm resolution by combination of top down electron beam lithography (EBL) with molecular self-assembly from the bottom up. The ultimate goal is to obtain nanoarrays of intact protein, virus particles and DNA nanostructures on silicon substrate at sub-30 nm scale with well-defined size and spacing. In order to effectively bind biomolecules to silicon surfaces without disruption to their structure, I studied the adsorption behavior of tailspike protein and cowpea mosaic virus (CPMV) particles on cationic, anionic and hydrophobic surfaces. Self-assembled monolayers (SAMs) were employed to tailor the silicon surface properties. Cationic APTES demonstrated high binding affinity to protein, virus particles and DNA nanostructures through electrostatic interactions and did not promote aggregation, so it was picked as the anchor pad for biomolecule attachment on silicon. Nanopatterned APTES SAMs on SiO2 fabricated by EBL and molecular liftoff were used to guide deposition of tailspike protein, CPMV and DNA nanostructures on silicon wafers. Arrays of single DNA nanostructures down to sub-30 nm resolution with binding selectivity up to 30:1 were achieved. However, lower binding selectivity was obtained on the resulting protein and virus patterns due to a higher amount of non-specific binding on the SiO2 background. In order to reduce the non-specific binding of biomolecules on SiO2, a poly(ethylene)glycol SAM was studied as an EBL resist. Proteins and virus particles adhered to the e-beam exposed region on PEG SAM and formed sub-30 nm resolution patterns with remarkable increase in binding selectivity. The ability to make chemical modifications to the e-beam exposed regions gives this patterning method flexibility for patterning a wide range of biomolecules. The power and versatility of using EBL to pattern biomolecules at sub-30 nm resolution with well-defined feature size, shape, and spacing is demonstrated. In conjunction with standard semiconductor fabrication techniques, the patterning method developed here could be used to build functional biomedical and diagnostic devices. For example, gold nanoparticles patterned on SiO2 by a similar approach have been used to fabricate single-electron transistor by Finkelstein etal.