Molecular electronics sensors on a scalable semiconductor chip: A platform for single-molecule measurement of binding kinetics and enzyme activity.

For nearly 50 years, the vision of using single molecules in circuits has been seen as providing the ultimate miniaturization of electronic chips. An advanced example of such a molecular electronics chip is presented here, with the important distinction that the molecular circuit elements play the role of general-purpose single-molecule sensors. The device consists of a semiconductor chip with a scalable array architecture. Each array element contains a synthetic molecular wire assembled to span nanoelectrodes in a current monitoring circuit. A central conjugation site is used to attach a single probe molecule that defines the target of the sensor. The chip digitizes the resulting picoamp-scale current-versus-time readout from each sensor element of the array at a rate of 1,000 frames per second. This provides detailed electrical signatures of the single-molecule interactions between the probe and targets present in a solution-phase test sample. This platform is used to measure the interaction kinetics of single molecules, without the use of labels, in a massively parallel fashion. To demonstrate broad applicability, examples are shown for probe molecule binding, including DNA oligos, aptamers, antibodies, and antigens, and the activity of enzymes relevant to diagnostics and sequencing, including a CRISPR/Cas enzyme binding a target DNA, and a DNA polymerase enzyme incorporating nucleotides as it copies a DNA template. All of these applications are accomplished with high sensitivity and resolution, on a manufacturable, scalable, all-electronic semiconductor chip device, thereby bringing the power of modern chips to these diverse areas of biosensing.

Selective and Rapid Light-Induced RAFT Single Unit Monomer Insertion in Aqueous Solution.

The photocatalyst Zn(II) meso-tetra(4-sulfonatophenyl)porphyrin (ZnTPPS) is found to substantially accelerate visible-light-initiated (red, yellow, green light) single unit monomer insertion (SUMI) of N,N-dimethylacrylamide into the reversible addition-fragmentation chain transfer (RAFT) agent, 4-((((2-carboxyethyl)thio)carbonothioyl)thio)-4-cyanopentanoic acid (RAFT1 ), in aqueous solution. Thus, under irradiation with red (633 nm) or yellow (593 nm) light with 50 mpm (moles per million mole of monomer) ZnTPPS at 30 °C, the rate enhancement provided by photoinduced energy or electron transfer (PET) is ≈sevenfold over the rate of direct photoRAFT-SUMI (without catalyst), which corresponds to achieving full and selective reaction in hours versus days. Importantly, the selectivity, as judged by the absence of oligomers, is retained. Under green light at similar power, higher rates of SUMI are also observed. However, the degree of enhancement provided by PET-RAFT-SUMI over direct photoRAFT-SUMI as a function of catalyst concentration is less and some oligomers are formed.

Amphiphilic graft copolymers from end-functionalized starches: synthesis, characterization, thin film preparation, and small molecule loading.

End-functionalized macromolecular starch reagents, prepared by reductive amination, were grafted onto a urethane-linked polyester-based backbone using copper-catalyzed azide-alkyne cycloaddition (CuAAC) chemistry to produce novel amphiphilic hybrid graft copolymers. These copolymers represent the first examples of materials where the pendant chains derived from starch biopolymers have been incorporated into a host polymer by a grafting-to approach. The graft copolymers were prepared in good yields (63-90%) with high grafting efficiencies (66-98%). Rigorous quantitative spectroscopic analyses of both the macromolecular building blocks and the final graft copolymers provide a comprehensive analytical toolbox for deciphering the reaction chemistry. Due to the modular nature of both the urethane-linked polyester synthesis and the postpolymerization modification, the starch content of these novel hybrid graft copolymers was easily tuned from 28-53% (w/w). The uptake of two low molecular weight guest molecules into the hybrid polymer thin films was also studied. It was found that binding of 1-naphthol and pterostilbene correlated linearly with amount of starch present in the hybrid polymer. The newly synthesized graft copolymers were highly processable and thermally stable, therefore, opening up significant opportunities in film and coating applications. These results represent a proof-of-concept system for not only the construction of starch-containing copolymers, but also the loading of these novel polymeric materials with active agents.

Quantifying Strain via Buckling Instabilities in Surface Modified Polymer Brushes.

A compressive strain applied to bilayer films (e.g. thin film adhered to a thick substrate) can lead to buckled or wrinkled morphologies, which has many important applications in stretchable electronics, anti-counterfeit technology, and high-precision micro and nano-metrology. A number of buckling-based metrology methods have been developed to quantify the residual stress and viscoelastic properties of polymer thin films. However, in some systems (e.g. solvent-induced swelling or thermal strain), the compressive strain is unknown or difficult to measure. We present a quantitative method of measuring the compressive strain of wrinkled polymer films and coatings with knowledge of the "skin" thickness, wrinkle wavelength, and wrinkle amplitude. The derived analytical expression is validated with a well-studied model system, e.g., stiff, thin film (PS) bonded to a thick, compliant substrate (PDMS). After validation, we use our expression to quantify the applied swelling strain of previously reported wrinkled poly(styrene-alt-maleic anhydride) brush surfaces. Finally, the applied strain is used to rationalize the observed persistence length of aligned wrinkles created during atomic force microscopy (AFM) lithography and subsequent solvent exposure.

Sequential and one-pot post-polymerization modification reactions of thiolactone-containing polymer brushes.

Thiolactone chemistry has garnered significant attention as a powerful post-polymerization modification (PPM) route to mutlifunctional polymeric materials. Here, we apply this versatile chemistry to the fabrication of ultrathin, multifunctional polymer surfaces via aminolysis and thiol-mediated double modifications of thiolactone-containing polymer brushes. Polymer brush surfaces were synthesized via microwave-assisted surface-initiated polymerization of DL-homocysteine thiolactone acrylamide. Aminolysis and thiol-Michael double modifications of the thiolactone-functional brush were explored using both sequential and one-pot reactions with bromobenzyl amine and 1H,1H-perfluoro-N-decyl acrylate. X-ray photoelectron spectroscopy and argon gas cluster ion sputter depth profiling enabled quantitative comparison of the sequential and one-pot PPM routes with regard to conversion and spatial distribution of functional groups immobilized throughout thickness of the brush. While one-pot conditions proved to be more effective in immobilizing the amine and acrylate within the brush, the sequenital reaction enabled the fabrication of multifunctional, micropattterned brush surfaces using reactive microcontact printing.

Fabrication of single-chain nanoparticles through the dimerization of pendant anthracene groups via photochemical upconversion.

We report on the use of visible light as the driving force for the intramolecular dimerization of pendant anthracene groups on a methacrylic polymer to induce the formation of single-chain nanoparticles (SCNPs). Using a 532 nm green laser light source and platinum octaethylporphyrin as a sensitizer, we first demonstrated the use of TTA-UC to dimerize monomeric anthracene, and subsequently applied this concept to dilute poly((methyl methacrylate)-stat-(anthracenyl methacrylate)) samples. A combination of triple-detection size-exclusion chromatography, atomic force microscopy, and UV-visible spectroscopy confirmed the formation of the SCNPs. This report pioneers the use of TTA-UC to drive photochemical reactions in polymeric systems, and showcases the potential for TTA-UC in the development of nanoobjects.

Buckling Instabilities in Polymer Brush Surfaces via Postpolymerization Modification.

We report a simple route to engineer ultrathin polymer brush surfaces with wrinkled morphologies using post-polymerization modification (PPM), where the length scale of the buckled features can be tuned from hundreds of nanometers to one micrometer using PPM reaction time. We show that partial crosslinking of the outer layer of the polymer brush under poor solvent conditions is critical to obtain wrinkled morphologies upon swelling. Characterization of the PPM kinetics and swelling behavior via ellipsometry and the through-thickness composition profile via time-of-flight secondary ion mass spectroscopy (ToF-SIMS) provided keys insight into parameters influencing the buckling behavior.