Stuart Lindsay’s Publications

Publications 2013

Application of catalyst-free click reactions in attaching affinity molecules to tips of atomic force microscopy for detection of protein biomarkers.Langmuir. November 2013
Application of catalyst-free click reactions in attaching affinity molecules to tips of atomic force microscopy for detection of protein biomarkers.

Long Lifetime of Hydrogen-bonded DNA Basepairs by Force Spectroscopy. Biophys J. May 2012
Long lifetime of hydrogen-bonded DNA basepairs by force spectroscopy.

Publications 2012

Optical and electrical detection of single-molecule translocation through carbon nanotubes

Optical and Electrical Detection of Single-Molecule Transolcation

Hydrophobicity of methylated DNA as a possible mechanism for gene silencing

Hydrophobicity of Methylated DNA

DNA translocating through a carbon nanotube can increase ionic current

DNA Translocating through a carbon nonotube

Identifying Single Bases in a DNA Oligomer with Electron Tunneling. Nat Nanotechnol. December 2010.
Identifying single bases in a DNA oligomer with electron tunneling.

Mass transport through vertically aligned large diameter MWCNTs embedded in parylene

Mass Transport through vertically aligned large diameter MWCNTS

Palladium electrodes for molecular tunnel junctions

Palladium electrodes for Molecular Tunnel Junctions

1,8-Naphthyridine-2,7-diamine: A potential universal reader of Watson-Crick base pairs for DNA sequencing by electron tunneling

Base pairs for DNA sequencin by electron tunneling

Solution Synthesis of Ultrathin Single-Crystalline SnS Nanoribbons for Photodetectors via Phase Transition and Surface Processing

Solution Synthesis

Chemical Recognition and Binding Kinetics in a functionalized tunnel junction


4(5)-(2-mercaptoethyl)-1H-imidazole-2-carboxamide is a molecule that has multiple hydrogen bonding sites and a short flexible linker. When tethered to a pair of electrodes, it traps target molecules in a tunnel junction. Surprisingly large recognition-tunneling signals are generated for all naturally occurring DNA bases A, C, G, T and 5-methyl-cytosine. Tunnel current spikes are stochastic and broadly distributed, but characteristic enough so that individual bases can be identified as a tunneling probe is scanned over DNA oligomers. Each base yields a recognizable burst of signal, the duration of which is controlled entirely by the probe speed, down to speeds of 1nms 1, implying a maximum off-rate of 3s 1 for the recognition complex. The same measurements yield a lower bound on the on-rate of 1M 1s 1. Despite the stochastic nature of the signals, an optimized multiparameter fit allows base calling from a single signal peak with an accuracy that can exceed 80% when a single type of nucleotide is present in the junction, meaning that recognition-tunneling is capable of true single-molecule analysis. The accuracy increases to 95% when multiple spikes in a signal cluster are analyzed. © 2012 IOP Publishing Ltd.

Chemical Recognition and Binding kinetics in a functionalized tunnel junction

Long Lifetime of Hydrogen-Bonded DNA Basepairs by Force Spectroscopy


Electron-tunneling data suggest that a noncovalently-bonded complex of three molecules, two recognition molecules that present hydrogen-bond donor and acceptor sites via a carboxamide group, and a DNA base, remains bound for seconds. This is surprising, given that imino-proton exchange rates show that basepairs in a DNA double helix open on millisecond timescales. The long lifetime of the three-molecule complex was confirmed using force spectroscopy, but measurements on DNA basepairs are required to establish a comparison with the proton-exchange data. Here, we report on a dynamic force spectroscopy study of complexes between the bases adenine and thymine (A-T, two-hydrogen bonds) and 2-aminoadenine and thymine (2AA-T, three-hydrogen bonds). Bases were tethered to an AFM probe and mica substrate via long, covalently linked polymer tethers. Data for bond-survival probability versus force and the rupture-force distributions were well fitted by the Bell model. The resulting lifetime of the complexes at zero pulling force was ∼2 s for two-hydrogen bonds (A-T) and ∼4 s for three-hydrogen bonds (2AA-T). Thus, DNA basepairs in an AFM pulling experiment remain bonded for long times, even without the stabilizing influence of base-stacking in a double helix. This result suggests that the pathways for opening, and perhaps the open states themselves, are very different in the AFM and proton-exchange measurements. © 2012 by the Biophysical Society.

Long Lifetime of Hydrogen-Bonded DNA Basepairs by Force Spectroscopy

Synthesis, Phsiochemical Properties and Hydrogen Bonding of 4(5)-Substituted 1-H-Imidazole-2-Carboxamide, a Potential Universal Reader for DNA Sequencing by Recognition Tunneling


We have developed a chemical reagent that recognizes all naturally occurring DNA bases, a so called universal reader, for DNA sequencing by recognition tunneling in nanopores.1 The primary requirements for this type of molecules are the ability to form non-covalent complexes with individual DNA bases and to generate recognizable electronic signatures under an electrical bias. 1-H-imidazole-2-carboxamide was designed as such a recognition moiety to interact with the DNA bases through hydrogen bonding. In the present study, we first furnished a synthetic route to 1-H-imidazole-2-carboxamide containing a short ω-functionalized alkyl chain at its 4(5) position for its attachment to metal and carbon electrodes. The acid dissociation constants of the imidazole-2-carboxamide were then determined by UV spectroscopy. The data show that the 1-H-imidazole-2-carboxamide exists in a neutral form between pH 6-10. Density functional theory (DFT) and NMR studies indicate that the imidazole ring exists in prototropic tautomers. We propose an intramolecular mechanism for tautomerization of 1-H-imidazole-2-carboxamide. In addition, the imidazole-2-carboxamide can self-associate to form hydrogen bonded dimers. NMR titration found that naturally occurring nucleosides interacted with 1-H-imidazole-2-carboxamide through hydrogen bonding in a tendency of dG>dC≤laquo;dT>dA. These studies are indispensable to assisting us in understanding the molecular recognition that takes place in the nanopore where routinely used analytical tools such as NMR and FTIR cannot be conveniently applied. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis,Physiochemical Properties and Hyrdogen Bonding

Biochemistry and Semiconductor Electronics- the next big hit for silicon?


Two recent developments portend a new era for silicon electronics in biomedical applications. Firstly, highly specific chemical recognition and massively parallel sample preparation techniques are being combined with VLSI to make new kinds of analytical chips. Secondly, critical dimensions are beginning to approach the size of biomolecules, opening new pathways for physical interactions between molecules and semiconductor structures. Future generations of hybrid chemicalCMOS devices could revolutionize diagnosis and make personalized medicine cheap enough to become widespread. © 2012 IOP Publishing Ltd.

Biochemistry and Semiconductor Electronics – the next big hit for Silicon?

Insulated Gold Scanning tunneling microscopy probes for recognition tunneling in an aqueous environment


Chemically functionalized probes are required for tunneling measurements made via chemical contacts (Recognition Tunneling). Here, we describe the etching of gold STM probes suitable for chemical functionalization with moieties bearing thiol groups. Insulated with high density polyethylene, these probes may be used in aqueous electrolytes with sub pA leakage currents. The area of the exposed probe surface was characterized via the saturation current in an electroactive solution (0.1 M K 3Fe(CN) 6). Twenty five percent of the probes had an exposed region of 10 nm radius or less. © 2012 American Institute of Physics.Insulated Gold Scanning tunnelling microscopy probes for recognition tunneling in an aqueous environment

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