Scientists at the Arizona State University have developed a reader that can discriminate between DNA’s four Nitrogenous bases, namely Adenine, Guanine, Cytosine and Thiamine. The detailed paper is to be published in Nano Letters and is entitled “Electronic Signatures of all Four DNA Nucleosides in a Tunnelling Gap.” The research was headed by ASU Regents’ professor Stuart Lindsay, Ph.D.

The team had earlier (2008) demonstrated the capability of reading individual DNA sequences but in order to do so they had to use four separate readers, each designed to recognize and record the presence of one of the four bases. Subsequently they fed DNA sequences through a Carbon nanotube and used scanning tunnelling and atomic force microscopy to make measurements. The microscopes have electrodes at the tips and these are held close to the DNA sample. Fluctuations in current are correlated to the presence of specific bases.

The latest invention modifies the same principle. Only in this case there are two electrodes one at the end of a microscope probe and the other on the surface, acting like a pair of charged tweezers. The ends of each are chemically modified to catch hold of the DNA between them. The beauty of the method is the gap between the electrodes is adjusted in such a way that when a single base of the DNA passes through 2.5 nanometer gap between 2 gold electrodes, it sticks on there and the fluctuation in current (a small increase in this case) is recorded. The accuracy is so adjusted that if the gap was any bigger, then smaller bases would not be captured and conversely if it were any larger then molecules could bind in varied configurations and the resultant signal would be highly confused. The reader strikes a balance to give just the right gap required to measure and identify each individual base. Each of the chemical bases of the DNA genetic code gives a unique electrical signature as they pass between the gap in the electrodes.

“What we did was to narrow the number of types of bound configurations to just one per DNA base,” Dr. Lindsay explains. “The beauty of the approach is that all the four bases just fit the 2.5 nanometer gap, so it is one size fits all but only just so!”

“We’ve now made a generic DNA sequence reader and are the first group to report the detection of all four DNA bases in one tunnel gap,” according to Dr. Lindsay. “Also, the control experiments show that there is a certain (poor) level of discrimination with even bare electrodes (the control experiments) and this is in itself a first, too.

“We were quite surprised about binding to bare electrodes because, like many physicists, we had always assumed that the bases would just tumble through. But actually, any surface chemist will tell you that the bases have weak chemical interactions with metal surfaces.”

Next, Lindsay’s group is hard at work trying to adapt the reader to work in water-based solutions, a critically practical step for DNA sequencing applications.