James W. Schneider

Length‐dependent DNA separations using multiple end‐attached peptide nucleic acid amphiphiles in micellar electrokinetic chromatography

End‐labeled free‐solution electrophoresis (ELFSE) is an alternative approach to gel‐based methods for size‐based electrophoretic separation of DNA. In ELFSE, an electrically neutral “drag‐tag” is appended to DNA to add significant hydrodynamic drag, thereby breaking its constant charge‐to‐friction ratio. Current drag‐tag architecture relies on covalent attachment of polymers to each DNA molecule. We have recently proposed the use of micellar drag‐tags in conjunction with sequence‐specific hybridization of peptide nucleic acid amphiphiles (PNAAs). This work investigates the effect of multiple PNAA attachment on DNA resolution using MEKC. Simultaneous PNAA hybridization allows for the separation of long DNA targets, up to 1012 bases, using micellar drag‐tags. Each PNAA handle independently interacts with the micellar phase, reducing the overall mobility of this complex relative to individual PNAA binding. The sequence‐ and size‐based dependence of this separation technique is maintained with multiple PNAA binding over a range of DNA sizes. Results are accurately described by ELFSE theory, yielding α = 54 for single‐micelle tagging and α = 142 for dual‐micelle tagging. This method is the first example of a non‐covalent drag‐tag used to separate DNA of 1000 bases based on both size and sequence.

Quasi-equilibrium AFM measurement of disjoining pressure in lubricant nanofilms II: Effect of substrate materials.

Atomic force microscopy (AFM) was used to measure the disjoining pressures of perfluoropolyether lubricant films (0.8-4.3 nm of Fomblin Z03) on both silicon wafers and hard drive disks coated with a diamondlike carbon overcoat. Differences in the disjoining pressure between the two systems were expected to be due to variations in the strength of van der Waals interactions. Lifshitz theory calculations suggest that this substrate switch will lead to relatively small changes in disjoining pressure as compared to the more pronounced effects reported due to changes in lubricant chemistry. We demonstrate the sensitivity of our AFM method by distinguishing between these similar systems.

Sequence-Specific Oligonucleotide Purification Using Peptide Nucleic Acid Amphiphiles in Hydrophobic Interaction Chromatography

We present a methodology to perform sequence‐specific separations of oligonucleotides using peptide nucleic acids covalently linked to alkane chains, or “PNA amphiphiles (PNAAs)”. The PNAA/DNA duplexes are discriminated from unbound DNA using hydrophobic interaction chromatography on a phenyl‐substituted Sepharose column. Nearly quantitative recovery is achieved at concentrations of 50 μM after incubation of oligomers with a stoichiometric amount of PNAA for 1 min or so. The method exhibits high sequence specificity, selectivity, and resolution when applied to mixtures of various oligomers up to 60 base pairs in length.

Optimization of ELFSE DNA sequencing with EOF counterflow and microfluidics

We present a nonlinear optimization study of different implementations of the DNA electrophoretic method “End‐labeled Free‐solution Electrophoresis” in commercial capillary electrophoresis systems and microfluidics to improve the time required for readout. Here, the effect of electro‐osmotic counterflows and snap‐shot detection are considered to allow for detection of peaks soon after they are electorphoretically resolved. Using drag tags available in micelle form, we identify a design capable of sequencing 600 bases in 2.8 min.

Introduction to Editorial Board Members: Professor Matthew V. Tirrell

Professor Matthew Tirrell is the founding Pritzker Director of the Institute for Molecular Engineering at the University of Chicago. He received a BS degree in Chemical Engineering from Northwestern University, and he received a PhD in Polymer Science and Engineering from the University of Massachusetts. Prof. Tirrell began his academic career at the University of Minnesota in Chemical Engineering where he earned the Shell Distinguished Chair in Chemical Engineering and established himself as a leader in the study of the polymer interfaces, adhesion, and self-assembly. In the early 1990s, he was named the Head of the Department of Chemical Engineering at Minnesota and later held the Earl E. Bakken Chair of Bio-

Introduction to Editorial Board Members: Matthew V. Tirrell

Professor Matthew Tirrell is the founding Pritzker Director of the Institute for Molecular Engineering at the University of Chicago. He received a BS degree in Chemical Engineering from Northwestern University, and he received a PhD in Polymer Science and Engineering from the University of Massachusetts. Prof. Tirrell began his academic career at the University of Minnesota in Chemical Engineering where he earned the Shell Distinguished Chair in Chemical Engineering and established himself as a leader in the study of the polymer interfaces, adhesion, and self-assembly. In the early 1990s, he was named the Head of the Department of Chemical Engineering at Minnesota and later held the Earl E. Bakken Chair of Bio-

Introduction to Editorial Board Members: Professor Matthew V. Tirrell: Editorial

Professor Matthew Tirrell is the founding Pritzker Director of the Institute for Molecular Engineering at the University of Chicago. He received a BS degree in Chemical Engineering from Northwestern University, and he received a PhD in Polymer Science and Engineering from the University of Massachusetts. Prof. Tirrell began his academic career at the University of Minnesota in Chemical Engineering where he earned the Shell Distinguished Chair in Chemical Engineering and established himself as a leader in the study of the polymer interfaces, adhesion, and self-assembly. In the early 1990s, he was named the Head of the Department of Chemical Engineering at Minnesota and later held the Earl E. Bakken Chair of Bio-

Projective Integration with an Adaptive Projection Horizon

Abstract We present an algorithm for projective integration that is computationally efficient for integrating systems of differential equations with multiple time-scales. Adaptive projective integration is a technique that uses a few inner integration steps to generate data to fit to a local reduced-order model. This reduced-order model is then used to extrapolate forward in time to estimate the states at some future time. This inner-outer integration is iterated until the desired integration is complete. The method uses an adaptive projective horizon to control for error generation during the integration. By examining an example Brusselator system, consisting of three non-linear differential equations, we show two orders of magnitude savings in computational time using adaptive projective integration over explicit Eulers method.

Optimal Design of Microfluidic Devices for Rapid DNA Separations

Abstract DNA separation is required to be rapid to be a useful component in DNA analysis devices. Different microfluidic device structures can be exploited to separate DNA with high throughput. We presents a framework for determining the optimal microfluidic device structure for rapid DNA separation through solving a nonlinear programming problem. Optimally designed spiral and serpentine microfluidic device configurations are shown to give comparable results for separating up to 425 bases of DNA using the micelle end-labeled free solution electrophoresis technique. The minimum run time for the serpentine microfluidic device configuration separating up to 425 bases of DNA is 5.1 minutes.