Microlithographic Patterning of Oligonucleotides:  Toward Fabrication of Multilevel DNA Based Devices

Abstract

A strategy for achieving geometrical patterning of DNA is described. The approach comprises patterning of oligonucleotides on a glycidyl oxypropyl trimethoxy silane modified Si wafer by spin casting a photoresist mixture consisting of a photoacid generator and a reactive blocking group and exposing through a photomask. Highly specific micrometer-sized DNA geometrical patterns were obtained, activity (multiple hybridization−dehybridization cycles with no loss of activity) and specificity of which were assessed using labeled complementary oligonucleotides. To further use such an approach toward integration, a novel two-stage strategy has been demonstrated, where the first stage lithography was employed to pattern electrodes and a second stage alignment/exposure was employed to define oligonucleotides between the electrodes.

Epoxy-silane linking of biomolecules is simple and effective for patterning neuronal cultures

“…The interaction between the nonbonded electron pair on the nitrogen of amine group and the carbon atom of the epoxy ring leads to the sequential processes of ring opening, electron rearrangement, and the formation of a neutral oxygenhydrogen bond (Scheme 1 in Sales et al, 2002). Others have used this chemistry to immobilize various biomolecules including DNA (Pathak and Dentinger, 2003;Hang and GuiseppiElie, 2004), antibodies (Yang and Li, 2005), glucose oxidase (Van Gerwen et al, 1998), and poly(ethylene glycol) (Piehler et al, 2000) on various substrates including glass (Piehler et al, 2000;Hang and Guiseppi-Elie, 2004), silicon dioxide (Van Gerwen et al, 1998;Luzinov et al, 2000), and indiumtin oxide (Yang and Li, 2005). Robustness and the ease of the chemistry are the main advantages over the use of other organosilane linkers such as (3-mercaptopropyl) trimethoxysilane (Branch et al, 2001) or (3-aminopropyl) trimethoxysilane (Branch et al, 1998).…”

Rewritable DNA Microarrays

“…Several methods exist for immobilizing single-stranded (ss) DNA oligonucleotides onto solid surfaces. These are predominantly multistep wet chemical reactions for silicon, [19][20][21] silica, 19,22 and gold [23][24][25][26][27] substrates. The two most promising approaches have been direct assembly of thiol-terminated ssDNA molecules onto gold 28,29 (this tends to suffer from the nonspecific adsorp- † Department of Chemistry.…”

Simple micropatterning of biomolecules on a diazoketo-functionalized photoresist

“…30 For DNA patterning and streptavidin patterning, polymer C was used, as polymer B showed higher background, which could be due to the affinity of the epoxy functional group towards the amine functional group present in the p-DNA, leading to non-specific binding of p-DNA onto the unexposed regions of the resist film. 31 Fig. 1b shows a schematic representation of the simplified lithographic process for DNA patterning, which follows a procedure similar to that used for cell patterning.…”