Complementary base-pair-facilitated electron tunneling for electrically pinpointing complementary nucleobases

Abstract

Molecular tips in scanning tunneling microscopy can directly detect intermolecular electron tunneling between sample and tip molecules and reveal the tunneling facilitation through chemical interactions that provide overlap of respective electronic wave functions, that is, hydrogen-bond, metal-coordination-bond, and charge-transfer interactions. Nucleobase molecular tips were prepared by chemical modification of underlying metal tips with thiol derivatives of adenine, guanine, cytosine, and uracil and the outmost single nucleobase adsorbate probes intermolecular electron tunneling to or from a sample nucleobase molecule. We found that the electron tunneling between a sample nucleobase and its complementary nucleobase molecular tip was much facilitated compared with its noncomplementary counterpart. The complementary nucleobase tip was thereby capable of electrically pinpointing each nucleobase. Chemically selective imaging using molecular tips may be coined ''intermolecular tunneling microscopy'' as its principle goes and is of general significance for novel molecular imaging of chemical identities at the membrane and solid surfaces.DNA ͉ nanobioscience ͉ scanning tunneling microscopy E lectron transfer through DNA double strands has attracted much interest (1-4) since Barton and colleagues (5) reported it in the 1990s. The processes of DNA-mediated electron transfer have been explored by spectroscopic methods for detecting photo-induced electron transfer through the DNA strands that are labeled with redox-active probes through intercalation and͞or covalent linkages (6, 7). These experiments have revealed that a DNA strand is capable of mediating electron transfer through the DNA base stacking in the strand (intrastrand pathway) (8-13). On the other hand, the contribution of the electron transfer through the complementary base pair (interstrand pathway) to the overall electron transfer in DNA has been investigated by several researchers (14,15). Here, we report on electron tunneling through the complementary base pair with nucleobase molecular tips for selectively discriminating each of the complementary nucleobases from the other nucleobases (Fig. 1a). The molecular tips are prepared by chemical modification of underlying metal tips typically with self-assembled monolayers (SAMs) of thiols and the outermost single adsorbate probes electron tunneling to or from a sample molecule. Importantly, the tunneling current increases when sample and tip molecules form chemical interactions that provide overlap of their electron wave functions, that is, hydrogen-bond interactions (16-22), metal-coordination-bond interactions (20), and charge-transfer interactions (23). We have thus far demonstrated that this phenomenon can be used for selective observation of chemical species to overcome poor chemical selectivity in conventional scanning tunneling microscopy (STM). We herein found that the electron tunneling between a sample nucleobase and its complementary nucleobase tip was much facilitated compared with its noncomplemen...

Single-nucleotide discrimination in immobilized DNA oligonucleotides with a biological nanopore

“…Certainly, the exquisite ability of (context independent) stochastic sensing to distinguish between molecules (14,49) shows what can be done with nanopores under the most favorable conditions. In the case of solid-state nanopores, it has been suggested that an active property of translocating bases (such as the ability to carry tunneling currents) might be used for sequencing (10,(50)(51)(52), but no practical demonstration of such a technique has been made. Another obvious requirement of a strand sequencing system is an ability to ''count'' bases.…”

Electrochemical tunnelling sensors and their potential applications

“…The ultimate speed of such a technology is difficult to assess at this point, because it is not only determined by the actual readout process. Lindsay and coworkers 47,48 have estimated the possible read rate to be on the order of 10 bases, based on an estimate of the residence time of the bases in their tunnelling junction, the statistical confidence level required to assign the identity of a base and the translocation force in the nanopore obtained in the previous work by Keyser et al 88 and van Dorp et al 89 Note that the force measurements by Keyser et al 88 were performed on doublestranded λ-DNA, and not single-stranded oligonucleotides used in the Lindsay experiment. This may change the magnitude of the force, but is unlikely to change the qualitative picture.…”

“…It appears that the former can cause complex current burst characteristics, which in turn contain valuable information about the molecular process itself, for example, hydrogen-bonding patterns (recognition tunnelling) 45 47,48 and the 'free-analyte' configuration where a freely diffusing analyte bridge binds to each adapter at the same time, thus bridging the tunnelling gap. In both cases, recognition events result in distinct and well-defined modulation of the tunnelling current, in terms of magnitude, event frequency and other details of the tunnelling noise.…”

“…In essence, however, it has become clear that motion of DNA in the tunnelling junction and in particular the DNA/electrode interaction would have to be controlled carefully to make sequencing-by-tunnelling in nanopore configuration a reality. This could be achieved by introducing a second set of transversal electrodes 77 or specific chemical recognition elements or 'chemical adapters' 45,47,48,84 . The key idea of the latter is that when a DNA base enters the tunnelling junction-either as an individual base or in a strand-the chemical adapters bind via hydrogen bond formation, providing a well-defined tunnelling pathway, Fig.…”

Theoretical electrical conductivity of hydrogen-bonded benzamide-derived molecules and single DNA bases

“…Ohshiro and Umezawa [12] has shown that hydrogen bonds can facilitate electron tunneling so that tunneling current decays more slowly when it is formed between a Watson-Crick complementary base pair compared to a non-complementary base pair. Also, the electron-tunneling property of different base pairs (G-C, A-T, G-T, and 2AA-T) has been investigated by Lee et al [13] with methods of complex band structure and Green's function scattering theory for I-V characteristics, showing that as more hydrogen bonds are formed between the DNA bases, higher conductance can be observed, and the decay factor for a unit cell of base pair will increase as the hydrogen bond distance increases with a linear relationship.…”