Write-read 3D patterning with a dual-channel nanopipette

Nanopipettes are becoming extremely versatile and powerful tools in nanoscience for a wide variety of applications from imaging to nanoscale sensing. Herein, the capabilities of nanopipettes to architect and build complex free-standing three-dimensional (3D) nanostructures are demonstrated using a simple double-barrel nanopipette device. Electrochemical control of ionic fluxes enables highly localized delivery of precursor species from one channel and simultaneous (dynamic and responsive) ion conductance probe-to-substrate distance feedback with the other for reliable high-quality patterning. Nanopipettes with 30−50 nm tip opening dimensions of each channel allowed confinement of ionic fluxes for the fabrication of high aspect ratio copper pillars, zigzag and Γ-like structures, as well as permitting the subsequent topographical mapping of the patterned features with the same nanopipette probe as used for nanostructure engineering. This approach offers versatility and robustness for high resolution 3D “printing” (writing) and read-out at the nanoscale

Importance of mass transport and spatially heterogeneous flux processes for in situ atomic force microscopy measurements of crystal growth and dissolution kinetics

It is well-established that important information about the dissolution and growth of crystals can be obtained by the investigation of step movement on single-crystal faces via in situ AFM. However, a potential drawback of this approach for kinetic measurements is that the small region of investigation may not be representative of the overall surface. It is shown that the investigation of local processes without accounting for the processes outside the region of interest can lead to significant misinterpretation of the data collected. Taking the case of gypsum dissolution as an example, we critically analyze literature data and develop 3 different finite element method models that treat in detail the coupled mass transport–surface kinetic problem pertaining to dissolution processes in a typical AFM environment. It is shown that mass transport cannot be neglected when performing in situ AFM on macroscopic surfaces even with high-convection fluid cells. Moreover, crystal dissolution kinetics determined by AFM is mainly influenced by processes occurring in areas of the surface outside the region of interest. When this is recognized, and appropriate models are applied, step velocities due to dissolution are consistent with expectations based on macroscopic measurements, and the kinetic gap that is often apparent between nanoscale and macroscopic measurements is closed. This study provides a framework for the detailed analysis of AFM kinetic data that has wide utility and applicability

Hopping intermittent contact-scanning electrochemical microscopy (HIC-SECM) as a new local dissolution kinetic probe : application to salicylic acid dissolution in aqueous solution

Dissolution kinetics of the (110) face of salicylic acid in aqueous solution is determined by hopping intermittent contact-scanning electrochemical microscopy (HIC-SECM) using a 2.5 μm diameter platinum ultramicroelectrode (UME). The method operates by translating the probe UME towards the surface at a series of positions across the crystal and inducing dissolution via the reduction of protons to hydrogen, which titrates the weak acid and promotes the dissolution reaction, but only when the UME is close to the crystal. Most importantly, as dissolution is only briefly and transiently induced at each location, the initial dissolution kinetics of an as-grown single crystal surface can be measured, rather than a surface which has undergone significant dissolution (pitting), as in other techniques. Mass transport and kinetics in the system are modelled using finite element method simulations which allows dissolution rate constants to be evaluated. It is found that the kinetics of an ‘as-grown’ crystal are much slower than for a surface that has undergone partial bulk dissolution (mimicking conventional techniques), which can be attributed to a dramatic change in surface morphology as identified by atomic force microscopy (AFM). The ‘as-grown’ (110) surface presents extended terrace structures to the solution which evidently dissolve slowly, whereas a partially dissolved surface has extensive etch features and step sites which greatly enhance dissolution kinetics. This means that crystals such as salicylic acid will show time-dependent dissolution kinetics (fluxes) that are strongly dependent on crystal history, and this needs to be taken into account to fully understand dissolution

Quantitative and holistic views of crystal dissolution processes

This thesis is concerned with the development and application of novel theoretical and experimental methodologies to study crystal dissolution processes across multiple lengthscales. In particular, it presents a versatile in situ multimicroscopy approach, comprising atomic force microscopy (AFM), scanning ion-conductance microscopy (SICM), and optical microscopy (OM) that is readily combined with finite element method (FEM) simulations. The methodology permits the quantitative 3D visualization of microcrystal morphology during dissolution with well-defined, high mass transport rates, enabling both the measurement of face-dependent dissolution rates and the elucidation of the dissolution mechanism. The approach also allows the determination of interfacial concentrations and concentration gradients, as well as the separation of kinetic and mass transport limiting regimes. The high resolving power and versatility of this new methodology is demonstrated on four different crystalline compounds with very different characteristics. First, the dissolution kinetics of individual faces of single furosemide microcrystals are investigated by OM-SICM and FEM modeling. It is found that the (001) face is strongly influenced by surface kinetics, while the (010) and (101) faces are dominated by mass transport. Dissolution rates are shown to vary greatly between crystals, with a strong dependence on crystal morphology and surface properties. A similar approach is then used to investigate changes in both crystal morphology and surface processes during the dissolution of bicalutamide single crystals, achieving high resolution with in situ AFM. It is shown that dissolution involves roughening and pit formation on all dissolving surfaces, and that this has a strong influence on the overall dissolution rate. FEM simulations determine that mass transport contributions increase as dissolution proceeds due to a continuous increase of the intrinsic dissolution rate constant, promoted by the exposure of high index microfacets. The methodology is further developed to show that kinetic data obtained from OMSICM and AFM, which provide differing measures of kinetic parameters, are in good agreement when the different mass transport regimes of the two experimental configurations are accounted for. The robustness of the methodology is verified via studies of L-cystine crystals, while also providing insights into the dissolution mechanism by visualizing hexagonal spirals descending along screw dislocations. Finally, the ability of the methodology to characterize processes with fast surface kinetics is demonstrated by the study of the proton-promoted dissolution of calcite single crystals. The approach allows the accurate determination of the near-interface concentration of all species during dissolution, as well as the intrinsic dissolution rate constant of the {104} faces, showing that surface kinetics play an important role in the dissolution process. Overall, this methodology provides a significant advance in the analysis and understanding of dissolution processes at a single crystal level, revealing the intrinsic properties of crystal faces and providing a powerful platform from which future studies can be developed

Face-discriminating dissolution kinetics of furosemide single crystals : in situ three-dimensional multi-microscopy and modeling

A versatile in situ multi-microscopy approach to study the dissolution kinetics of single crystals is described, using the loop diuretic drug furosemide as a testbed to demonstrate the utility of the approach. Using optical microscopy and scanning ion-conductance microscopy in combination, the dissolution rate of individual crystallographically independent crystal faces can be measured quantitatively while providing a direct visualization of the evolution of crystal morphology in real time in three dimensions. Finite element method models using experimental data enables quantitative analysis of dissolution fluxes for individual faces and determination of the limiting process—mass transport or interfacial kinetics—that regulates dissolution. A key feature of the approach is that isolated crystals (typically <60 μm largest characteristic dimension) in solution during dissolution experience high and well-defined diffusion rates. The ability to obtain this quantitative information for individual crystal faces suggests a pathway to understanding crystal dissolution at the molecular level and regulating bioavailability, for example, through manipulation of crystal morphology

Tracking the dissolution of calcite single crystals in acid waters : a simple method for measuring fast surface kinetics

A combined optical microscopy-finite element method modeling approach reveals the kinetics of proton attack on calcite.</p

Alkyne-Functionalized Coumarin Compound for Analytic and Preparative 4‑Thiouridine Labeling

Bioconjugation of RNA is a dynamic field recently reinvigorated by a surge in research on post-transcriptional modification. This work focuses on the bioconjugation of 4-thiouridine, a nucleoside that occurs as a post-transcriptional modification in bacterial RNA and is used as a metabolic label and for cross-linking purposes in eukaryotic RNA. A newly designed coumarin compound named 4-bromomethyl-7-propargyloxycoumarin (PBC) is introduced, which exhibits remarkable selectivity for 4-thiouridine. Bearing a terminal alkyne group, it is conductive to secondary bioconjugation via “click chemistry”, thereby offering a wide range of preparative and analytical options. We applied PBC to quantitatively monitor the metabolic incorporation of s⁴U as a label into RNA and for site-specific introduction of a fluorophore into bacterial tRNA at position 8, allowing the determination of its binding constant to an RNA-modification enzyme