An electrical framework for detection and characterization of DNA using nanoscale silicon based sensors

Samir Muzaffar Iqbal, Purdue University

Abstract

The ability to manipulate and identify the properties of single biological molecules with the potential of characterizing biological processes at the most fundamental levels can significantly facilitate rapid diagnostics and therapeutics. Fabrication of solid state devices investigating bacteria, viruses, proteins and even at such smaller sizes as of DNA can create a large arsenal of highly specific and ultrasensitive biosensors and systems. This work shows the use of two important silicon based electrical frameworks to investigate DNA molecules towards the development of a variety of biosensors. First, a novel method employing metal electrodes with nanometer scale spacing was used to examine the effects of the GC-content in the dry strands of the DNA on its DC resistance. A dramatic decrease in conductance was also reported on heating the DNA devices, analogous to an electrical fuse, attributable to complete or partial denaturing of the ds-DNA molecules that bridged the nanogaps. These findings have applications like nonoptical detection of extremely low concentrations, biophysical studies of charge transport, and control of DNA-modified materials. Second, solid state nanopores, progenitors of rapid and cheap next-generation DNA sequencing “machines”, were designed to be selective to important DNA sequences. To our knowledge, this work was the first evidence of engineering selectivity in solid state nanopores. Distinctly different translocation signatures and event frequencies were discovered for important DNA targets. This work demonstrated the first experimental evidence of facilitated transport theory based on interactions between channel binding sites and the single DNA molecule. The selective solid-state nanopores realized in an array format can open avenues to novel devices for sequencing, detection of single nucleotide polymorphism, expression analysis, etc. as well as detection of specific proteins using specific ligand-receptor systems from very few copies of the analytes. Such selectivity can be electrically measured and can be used for direct label-free sequencing and detection of nucleic acids. These devices can potentially mimic the exquisite selectivity found in natural biological channels in cell or nuclear membranes, and help unravel the physics of selective and facilitated transport of biomolecules in nanoscale channels.

Degree

Ph.D.

Advisors

Bashir, Purdue University.

Subject Area

Biomedical research|Electrical engineering

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