The digital code driven autonomous synthesis of ibuprofen automated in a 3D-printer-based robot

An automated synthesis robot was constructed by modifying an open source 3D printing platform. The resulting automated system was used to 3D print reaction vessels (reactionware) of differing internal volumes using polypropylene feedstock via a fused deposition modeling 3D printing approach and subsequently make use of these fabricated vessels to synthesize the nonsteroidal anti-inflammatory drug ibuprofen via a consecutive one-pot three-step approach. The synthesis of ibuprofen could be achieved on different scales simply by adjusting the parameters in the robot control software. The software for controlling the synthesis robot was written in the python programming language and hard-coded for the synthesis of ibuprofen by the method described, opening possibilities for the sharing of validated synthetic ‘programs’ which can run on similar low cost, user-constructed robotic platforms towards an ‘open-source’ regime in the area of chemical synthesis

Shrink wrapping redox-active crystals of polyoxometalate open frameworks with organic polymers via crystal induced polymerisation

We report examples of crystal surface modification of polyoxometalate open frameworks whereby the use of pyrrole or aniline as monomers leads to the formation of the corresponding polymers via an oxidative polymerization process initiated by the redox active POM scaffolds. Guest-exchange experiments demonstrate that the polymers can finely tune the guest exchange rate and their structural integrity is retained after the surface modifications. In addition, the formation of polyoxometalate-based self-fabricating tubes by the dissolution of Keggin-based network crystals were also modulated by the polymers, allowing a new type of hybrid inorganic polymer with an organic coating to be fabricated

A portable 3D printer system for the diagnosis and treatment of multidrug-resistant bacteria

Summary: Multidrug-resistant bacteria are a major threat to human health, but broad-spectrum antibiotics are losing efficacy. There is a need to screen a given drug against a bacterial infection outside of the laboratory. To address this need, we have designed and built an inexpensive and easy-to-use 3D-printer-based system that allows easily readable quantitative tests for the performance of antibacterial drugs. The platform creates a sterile diagnostic device by using 3D printing, and the device is filled automatically with growth medium, and then antibiotics are sprayed onto the medium by ink-jet technology. The sample for testing can be introduced via a fluid port, and the printer hot bed is used to incubate the device, allowing operation in the field. Combining advantages from various established tests of antibacterial performance, this allows the comparison of a specific antibiotics and bacteria. Also, this system can create and test several antibiotic formulations for therapeutic use, and we demonstrate this potential by investigating a mixture of pathogens that are only killed by a mixture of drugs

2D KBr/Graphene Heterostructures-Influence on Work Function and Friction

The intercalation of graphene is an effective approach to modify the electronic properties of two-dimensional heterostructures for attractive phenomena and applications. In this work, we characterize the growth and surface properties of ionic KBr layers altered by graphene using ultra-high vacuum atomic force microscopy at room temperature. We observed a strong rippling of the KBr islands on Ir(111), which is induced by a specific layer reconstruction but disappears when graphene is introduced in between. The latter causes a consistent change in both the work function and the frictional forces measured by Kelvin probe force microscopy and frictional force microscopy, respectively. Systematic density functional theory calculations of the different systems show that the change in work function is induced by the formation of a surface dipole moment while the friction force is dominated by adhesion forces

Reconstruction of a 2D layer of KBr on Ir(111) and electromechanical alteration by graphene

A novel reconstruction of a two-dimensional layer of KBr on an Ir(111) surface is observed by high-resolution noncontact atomic force microscopy and verified by density functional theory (DFT). The observed KBr structure is oriented along the main directions of the Ir(111) surface, but forms a characteristic double-line pattern. Comprehensive calculations by DFT, taking into account the observed periodicities, resulted in a new low-energy reconstruction. However, it is fully relaxed into a common cubic structure when a monolayer of graphene is located between substrate and KBr. By using Kelvin probe force microscopy, the work functions of the reconstructed and the cubic configuration of KBr were measured and indicate, in accordance with the DFT calculations, a difference of nearly 900 meV. The difference is due to the strong interaction and local charge displacement of the K; +; /Br; -; ions and the Ir(111) surface, which are reduced by the decoupling effect of graphene, thus yielding different electrical and mechanical properties of the top KBr layer

A Multi-scale Approach for Simulations of Kelvin Probe Force Microscopy with Atomic Resolution

The distance dependence and atomic-scale contrast observed in nominal contact potential difference (CPD) signals recorded by KPFM on surfaces of insulating and semiconducting samples, have stimulated theoretical attempts to explain such effects. We attack this problem in two steps. First, the electrostatics of the macroscopic tip-cantilever-sample system is treated by a finite-difference method on an adjustable nonuniform mesh. Then the resulting electric field under the tip apex is inserted into a series of atomistic wavelet-based density functional theory (DFT) calculations. Results are shown for a realistic neutral but reactive silicon nano-scale tip interacting with a NaCl(001) sample. Bias-dependent forces and resulting atomic displacements are computed to within an unprecedented accuracy. Theoretical expressions for amplitude modulation (AM) and frequency modulation (FM) KPFM signals and for the corresponding local contact potential differences (LCPD) are obtained by combining the macroscopic and atomistic contributions to the electrostatic force component generated at the voltage modulation frequency, and evaluated for several tip oscillation amplitudes A up to 10 nm. Being essentially constant over a few Volts, the slope of atomistic force versus bias is the basic quantity which determines variations of the atomic-scale LCPD contrast. Already above A = 0.1 nm, the LCPD contrasts in both modes exhibit almost the same spatial dependence as the slope. In the AM mode, this contrast is approximately proportional to $A^{-1/2}$, but remains much weaker than the contrast in the FM mode, which drops somewhat faster as A is increased. These trends are a consequence of the macroscopic contributions to the KPFM signal, which are stronger in the AM-mode and especially important if the sample is an insulator even at sub-nanometer separations where atomic-scale contrast appears.Comment: 19 pages, 13 figure

A metamorphic inorganic framework that can be switched between eight single-crystalline states

The design of highly flexible framework materials requires organic linkers, whereas inorganic materials are more robust but inflexible. Here, by using linkable inorganic rings made up of tungsten oxide (P8W48O184) building blocks, we synthesized an inorganic single crystal material that can undergo at least eight different crystal-to-crystal transformations, with gigantic crystal volume contraction and expansion changes ranging from −2,170 to +1,720 Å3 with no reduction in crystallinity. Not only does this material undergo the largest single crystal-to-single crystal volume transformation thus far reported (to the best of our knowledge), the system also shows conformational flexibility while maintaining robustness over several cycles in the reversible uptake and release of guest molecules switching the crystal between different metamorphic states. This material combines the robustness of inorganic materials with the flexibility of organic frameworks, thereby challenging the notion that flexible materials with robustness are mutually exclusive

Organic synthesis in a modular robotic system driven by a chemical programming language

The synthesis of complex organic compounds is largely a manual process that is often incompletely documented. To address these shortcomings, we developed an abstraction that maps commonly reported methodological instructions into discrete steps amenable to automation. These unit operations were implemented in a modular robotic platform using a chemical programming language which formalizes and controls the assembly of the molecules. We validated the concept by directing the automated system to synthesize three pharmaceutical compounds, Nytol, rufinamide, and sildenafil, without any human intervention. Yields and purities of products and intermediates were comparable to or better than those achieved manually. The syntheses are captured as digital code that can be published, versioned, and transferred flexibly between platforms with no modification, thereby greatly enhancing reproducibility and reliable access to complex molecules

Expansion-enhanced super-resolution radial fluctuations enable nanoscale molecular profiling of pathology specimens

Expansion microscopy physically enlarges biological specimens to achieve nanoscale resolution using diffraction-limited microscopy systems1. However, optimal performance is usually reached using laser-based systems (for example, confocal microscopy), restricting its broad applicability in clinical pathology, as most centres have access only to light-emitting diode (LED)-based widefield systems. As a possible alternative, a computational method for image resolution enhancement, namely, super-resolution radial fluctuations (SRRF)2,3, has recently been developed. However, this method has not been explored in pathology specimens to date, because on its own, it does not achieve sufficient resolution for routine clinical use. Here, we report expansion-enhanced super-resolution radial fluctuations (ExSRRF), a simple, robust, scalable and accessible workflow that provides a resolution of up to 25 nm using LED-based widefield microscopy. ExSRRF enables molecular profiling of subcellular structures from archival formalin-fixed paraffin-embedded tissues in complex clinical and experimental specimens, including ischaemic, degenerative, neoplastic, genetic and immune-mediated disorders. Furthermore, as examples of its potential application to experimental and clinical pathology, we show that ExSRRF can be used to identify and quantify classical features of endoplasmic reticulum stress in the murine ischaemic kidney and diagnostic ultrastructural features in human kidney biopsies.</p