DNA-Mediated Electrochemistry

The base pair stack of DNA has been demonstrated as a medium for long-range charge transport chemistry both in solution and at DNA-modified surfaces. This chemistry is exquisitely sensitive to structural perturbations in the base pair stack as occur with lesions, single base mismatches, and protein binding. We have exploited this sensitivity for the development of reliable electrochemical assays based on DNA charge transport at self-assembled DNA monolayers. Here, we discuss the characteristic features, applications, and advantages of DNA-mediated electrochemistry

Functionalized hyperbranched polymers via olefin metathesis

Hyperbranched polymers are highly branched, three-dimensional macromolecules which are closely related to dendrimers and are typically prepared via a one-pot polycondensation of AB_(n≥2) monomers.^1 Although hyperbranched macromolecules lack the uniformity of monodisperse dendrimers, they still possess many attractive dendritic features such as good solubility, low solution viscosity, globular structure, and multiple end groups.^1-3 Furthermore, the usually inexpensive, one-pot synthesis of these polymers makes them particularly desirable candidates for bulk-material and specialty applications. Toward this end, hyperbranched polymers have been investigated as both rheology-modifying additives to conventional polymers and as substrate-carrying supports or multifunctional macroinitiators, where a large number of functional sites within a compact space becomes beneficial

Efficient Localization of Discontinuities in Complex Computational Simulations

Surrogate models for computational simulations are input-output approximations that allow computationally intensive analyses, such as uncertainty propagation and inference, to be performed efficiently. When a simulation output does not depend smoothly on its inputs, the error and convergence rate of many approximation methods deteriorate substantially. This paper details a method for efficiently localizing discontinuities in the input parameter domain, so that the model output can be approximated as a piecewise smooth function. The approach comprises an initialization phase, which uses polynomial annihilation to assign function values to different regions and thus seed an automated labeling procedure, followed by a refinement phase that adaptively updates a kernel support vector machine representation of the separating surface via active learning. The overall approach avoids structured grids and exploits any available simplicity in the geometry of the separating surface, thus reducing the number of model evaluations required to localize the discontinuity. The method is illustrated on examples of up to eleven dimensions, including algebraic models and ODE/PDE systems, and demonstrates improved scaling and efficiency over other discontinuity localization approaches

Multiplexed DNA-Modified Electrodes

We report the use of silicon chips with 16 DNA-modified electrodes (DME chips) utilizing DNA-mediated charge transport for multiplexed detection of DNA and DNA-binding protein targets. Four DNA sequences were simultaneously distinguished on a single DME chip with 4-fold redundancy, including one incorporating a single base mismatch. These chips also enabled investigation of the sequence-specific activity of the restriction enzyme Alu1. DME chips supported dense DNA monolayer formation with high reproducibility, as confirmed by statistical comparison to commercially available rod electrodes. The working electrode areas on the chips were reduced to 10 μm in diameter, revealing microelectrode behavior that is beneficial for high sensitivity and rapid kinetic analysis. These results illustrate how DME chips facilitate sensitive and selective detection of DNA and DNA-binding protein targets in a robust and internally standardized multiplexed format

A continuous analogue of the tensor-train decomposition

We develop new approximation algorithms and data structures for representing and computing with multivariate functions using the functional tensor-train (FT), a continuous extension of the tensor-train (TT) decomposition. The FT represents functions using a tensor-train ansatz by replacing the three-dimensional TT cores with univariate matrix-valued functions. The main contribution of this paper is a framework to compute the FT that employs adaptive approximations of univariate fibers, and that is not tied to any tensorized discretization. The algorithm can be coupled with any univariate linear or nonlinear approximation procedure. We demonstrate that this approach can generate multivariate function approximations that are several orders of magnitude more accurate, for the same cost, than those based on the conventional approach of compressing the coefficient tensor of a tensor-product basis. Our approach is in the spirit of other continuous computation packages such as Chebfun, and yields an algorithm which requires the computation of "continuous" matrix factorizations such as the LU and QR decompositions of vector-valued functions. To support these developments, we describe continuous versions of an approximate maximum-volume cross approximation algorithm and of a rounding algorithm that re-approximates an FT by one of lower ranks. We demonstrate that our technique improves accuracy and robustness, compared to TT and quantics-TT approaches with fixed parameterizations, of high-dimensional integration, differentiation, and approximation of functions with local features such as discontinuities and other nonlinearities

DNA-Mediated Electrochemistry of Disulfides on Graphite

The electrochemistry of disulfides incorporated into the sugar−phosphate backbone of pyrene-modified DNA has been examined on highly oriented pyrolytic graphite (HOPG). Two signals, one irreversible, one reversible, are observed at −160 and −290 mV versus normal hydrogen electrode, respectively. The inclusion of a single base mismatch in the DNA duplex below the location of the disulfide leads to a significant attenuation in the electrochemical signal, while the inclusion of a mismatch above the disulfide has little effect on the electrochemistry observed. Thus disulfide reduction in the DNA backbone appears to be DNA-mediated. The redox couples found show a strong pH dependence consistent with formation of a disulfide radical anion or 2e- reduction of the disulfide to the two thiols. These data demonstrate that DNA electrochemistry can be utilized to promote disulfide reduction at a distance mediated by the DNA duplex

Scanning Electrochemical Microscopy of DNA Monolayers Modified with Nile Blue

Scanning electrochemical microscopy (SECM) is used to probe long-range charge transport (CT) through DNA monolayers containing the redox-active Nile Blue (NB) intercalator covalently affixed at a specific location in the DNA film. At substrate potentials negative of the formal potential of covalently attached NB, the electrocatalytic reduction of Fe(CN)63− generated at the SECM tip is observed only when NB is located at the DNA/solution interface; for DNA films containing NB in close proximity to the DNA/electrode interface, the electrocatalytic effect is absent. This behavior is consistent with both rapid DNA-mediated CT between the NB intercalator and the gold electrode as well as a rate-limiting electron transfer between NB and the solution phase Fe(CN)63−. The DNA-mediated nature of the catalytic cycle is confirmed through sequence-specific and localized detection of attomoles of TATA-binding protein, a transcription factor that severely distorts DNA upon binding. Importantly, the strategy outlined here is general and allows for the local investigation of the surface characteristics of DNA monolayers both in the absence and in the presence of DNA binding proteins. These experiments highlight the utility of DNA-modified electrodes as versatile platforms for SECM detection schemes that take advantage of CT mediated by the DNA base pair stack