Active microelectronic chip devices which utilize controlled electrophoretic fields for multiplex DNA hybridization and other genomic applications

Abstract

Microelectronic DNA chip devices that contain planar arrays of microelectrodes have been developed for multiplex DNA hybridization and a variety of genomic research and DNA diagnostic applications. These devices are able to produce almost any desired electric field configuration on their surface. This ability to produce well‐defined electric fields allows charged molecules (DNA, RNA, proteins, enzymes, antibodies, nanobeads, and even micron scale semiconductor devices) to be electrophoretically transported to or from any microlocation on the planar surface of the device. Of key importance to the device function is the permeation layer which overcoats the microelectrodes. The permeation layer is generally a porous hydrogel material that allows water molecules and small ions (Na+, CI−, etc.) to freely contact the microelectrode surface, but impedes the transport of the larger analytes (oligonucleotides, DNA, RNA, proteins, etc.). The permeation layer prevents the destruction of DNA at the active microelectrode surface, ameliorates the adverse effects of electrolysis products on the sensitive hybridization reactions, and serves as a porous support structure for attaching DNA probes and other molecules to the array. In order to maintain rapid transport of DNA molecules, facilitate hybriziation, and work within constrained current and voltage ranges, low conductance buffers and various electronic pulsing scenarios have also been developed. These active microelectronic array devices allow electrophoretic fields to be used to carry out accelerated DNA hybridization reactions and to improve selectivity for single nucleotide polymorphism (SNP), short tandem repeat (STR), and point mutation analysis.

Collection, focusing, and metering of DNA in microchannels using addressable electrode arrays for portable low-power bioanalysis

“…The interelectrode spacing within the array (225 m edge-to-edge) allows relatively high electric fields (Ϸ40 V͞cm) to be achieved with a minimal applied potential (1 V). Under these conditions, a sufficient electrostatic driving force is developed to direct DNA migration while maintaining a voltage below the threshold for bubble formation arising from hydrolysis reactions at the electrode surfaces (30,31). First, a DNA sample is loaded into the microchannel with a syringe, after which the access holes are sealed to prevent evaporation.…”

“…The concept of using on-chip electrodes to achieve directed migration of oligonucleotide fragments in microfluidic devices has been recognized in the context of DNA microarrays (29)(30)(31). By using microelectronic array technology, assemblies of addressable electrodes have been designed to transport samples to particular locations on an array surface to enhance hybridization efficiency, with specificity enhanced by posthybridization reversal of the electric field (32).…”

Purification of Peptides in High-Complexity Arrays

“…Furthermore, oligonucleotide arrays are the most prominent example of how modern array technologies have helped to advance an entire sub-field of molecular biology. The arrays are synthesized by means of lithographic [2] , electrolytic [3] , or electrophoretic [4] techniques.…”

β-Thalassemia Microelectronic Chip: A Fast and Accurate Method for Mutation Detection

“…This system enables deposition and concentration of charged samples to designated test sites on a 100-microelectrode formatted cartridge (5)(6)(7)(8). Arrays consist of biotin-labeled PCR products amplified from patient DNA and immobilized on test sites through interaction with streptavidin in a permeation layer.…”