Development of Electronic DNA Hybridization Detection Using Carbon Nanotube Field Effect Transistor Arrays

Abstract

Spurred by the Human Genome Project, deoxyribonucleic acid (DNA) microarrays are indispensable tools in molecular biology. In particular, they are used in the genetic profiling of human diseases, which includes identifying genes that are expressed in certain cancers. Genotyping allows more accurate identification and consequently, improved treatment. This technique has the potential to revolutionize the diagnosis of many other human ailments and be an important tool in the arsenal of modern medicine. At present however, microarray experiments involve complex protocols, often employing fluorescent labeling as well as sophisticated detection instruments. These systems are thus only affordable by very few large laboratories and pharmaceutical companies. In this work, we propose and demonstrate the feasibility of using a low-cost and improved alternative. We designed and fabricated biochips based on carbon nanotube field effect transistor arrays to detect the presence of specific DNA sequences, e.g. expressed genes, in a solution of DNA or RNA in the same manner as microarrays. The ultimate goal is to optimize the system to make it suitable for point-of-care applications. Our design utilizes CVD-grown carbon nanotube mats on a substrate of silicon oxide and metal contacts patterned using conventional microlithography. The carbon nanotube mats are covered by a thin oxide upon which single stranded DNA 'probe' molecules are immobilized. When exposed to a solution containing the complementary sequence, Watson-Crick hybridization leads to the binding of the complementary 'target' strands. Since DNA's are electrically charged through the excess electron of the phosphate backbone, this process results in the incorporation of additional negative charges at the transistor gate. This effectively causes a change in the conductance of the nanotube channel and a shift in the device threshold voltage. The voltage shift reflects the amount of extra charges deposited on the gate and based on this, the amount of captured target DNA can be precisely quantified.

We demonstrated electronic label-free detection of specific DNA binding or hybridization at the sensitivity level of 10−100 nM, and specificity limited by chemical protocols. Comparing other label-free schemes, we believe our approach is advantageous in terms of simplicity and compatibility with current microarray protocols.