Weak shock compaction on granular salt.

This study conducted integrated experiments and computational modeling to investigate the speeds of a developing shock within granular salt and analyzed the effect of various impact velocities up to 245 m/s. Experiments were conducted on table salt utilizing a novel setup with a considerable bore length for the sample, enabling visualization of a moving shock wave. Experimental analysis using particle image velocimetry enabled the characterization of shock velocity and particle velocity histories.

Modular Aptamer Switches for the Continuous Optical Detection of Small-Molecule Analytes in Complex Media.

Aptamers are a promising class of affinity reagents because signal transduction mechanisms can be built into the reagent, so that they can directly produce a physically measurable output signal upon target binding. However, endowing the signal transduction functionality into an aptamer remains a trial-and-error process that can compromise its affinity or specificity and typically requires knowledge of the ligand binding domain or its structure. In this work, a design architecture that can convert an existing aptamer into a "reversible aptamer switch" whose kinetic and thermodynamic properties can be tuned without a priori knowledge of the ligand binding domain or its structure is described.

Flow-Cell-Based Technology for Massively Parallel Characterization of Base-Modified DNA Aptamers.

Aptamers incorporating chemically modified bases can achieve superior affinity and specificity compared to natural aptamers, but their characterization remains a labor-intensive, low-throughput task. Here, we describe the "non-natural aptamer array" (N2A2) system, in which a minimally modified Illumina MiSeq instrument is used for the high-throughput generation and characterization of large libraries of base-modified DNA aptamer candidates based on both target binding and specificity. We first demonstrate the capability to screen multiple different base modifications to identify the optimal chemistry for high-affinity target binding.

Discovery of indole-modified aptamers for highly specific recognition of protein glycoforms.

Glycosylation is one of the most abundant forms of post-translational modification, and can have a profound impact on a wide range of biological processes and diseases. Unfortunately, efforts to characterize the biological function of such modifications have been greatly hampered by the lack of affinity reagents that can differentiate protein glycoforms with robust affinity and specificity. In this work, we use a fluorescence-activated cell sorting (FACS)-based approach to generate and screen aptamers with indole-modified bases, which are capable of recognizing and differentiating between specific protein glycoforms.

RE-SELEX: restriction enzyme-based evolution of structure-switching aptamer biosensors.

Aptamers are widely employed as recognition elements in small molecule biosensors due to their ability to recognize small molecule targets with high affinity and selectivity. Structure-switching aptamers are particularly promising for biosensing applications because target-induced conformational change can be directly linked to a functional output. However, traditional evolution methods do not select for the significant conformational change needed to create structure-switching biosensors.

Click-Particle Display for Base-Modified Aptamer Discovery.

Base-modified aptamers that incorporate non-natural chemical moieties can achieve greatly improved affinity and specificity relative to natural DNA or RNA aptamers. However, conventional methods for generating base-modified aptamers require considerable expertise and resources. In this work, we have accelerated and generalized the process of generating base-modified aptamers by combining a click-chemistry strategy with a fluorescence-activated cell sorting (FACS)-based screening methodology that measures the affinity and specificity of individual aptamers at a throughput of ∼10 per hour.

Strategies for Creating Structure-Switching Aptamers.

Aptamer biosensor that can switch its structure upon target binding offers a powerful strategy for molecular detection. However, the process of converting an aptamer into a "structure-switching" biosensor is challenging and often relies on trial-and-error without established design principles. In this Sensor Issues, we examine a variety of design approaches for incorporating structure-switching functionality into existing aptamers, and provide thermodynamic analyses to highlight the variables that most strongly influence their performance.

Advancements in Aptamer Discovery Technologies.

Affinity reagents that specifically bind to their target molecules are invaluable tools in nearly every field of modern biomedicine. Nucleic acid-based aptamers offer many advantages in this domain, because they are chemically synthesized, stable, and economical. Despite these compelling features, aptamers are currently not widely used in comparison to antibodies.

Temporal Control of Aptamer Biosensors Using Covalent Self-Caging To Shift Equilibrium.

Aptamer-based sensors provide a versatile and effective platform for the detection of chemical and biological targets. These sensors have been optimized to function in multiple formats, however, a remaining limitation is the inability to achieve temporal control over their sensing function. To overcome this challenge, we took inspiration from nature's ability to temporally control the activity of enzymes and protein receptors through covalent self-caging.

High-throughput enantiopurity analysis using enantiomeric DNA-based sensors.

Distinguishing between the two enantiomers of a molecule is a challenging task due to their nearly identical physical properties. Time-consuming chromatography methods are typically required for this task, which greatly limits the throughput of analysis. Here we describe a fluorescence-based method for the rapid and high-throughput analysis of both small-molecule enantiopurity and concentration.

Convenient and scalable synthesis of fmoc-protected Peptide nucleic Acid backbone.

The peptide nucleic acid backbone Fmoc-AEG-OBn has been synthesized via a scalable and cost-effective route. Ethylenediamine is mono-Boc protected, then alkylated with benzyl bromoacetate. The Boc group is removed and replaced with an Fmoc group.