Philip J. Kitson

Integrated 3D-printed reactionware for chemical synthesis and analysis

Three-dimensional (3D) printing has the potential to transform science and technology by creating bespoke, low-cost appliances that previously required dedicated facilities to make. An attractive, but unexplored, application is to use a 3D printer to initiate chemical reactions by printing the reagents directly into a 3D reactionware matrix, and so put reactionware design, construction and operation under digital control. Here, using a low-cost 3D printer and open-source design software we produced reactionware for organic and inorganic synthesis, which included printed-in catalysts and other architectures with printed-in components for electrochemical and spectroscopic analysis. This enabled reactions to be monitored in situ so that different reactionware architectures could be screened for their efficacy for a given process, with a digital feedback mechanism for device optimization. Furthermore, solely by modifying reactionware architecture, reaction outcomes can be altered. Taken together, this approach constitutes a relatively cheap, automated and reconfigurable chemical discovery platform that makes techniques from chemical engineering accessible to typical synthetic laboratories.

Combining 3D printing and liquid handling to produce user-friendly reactionware for chemical synthesis and purification

We use two 3D-printing platforms as solid- and liquid-handling fabricators, producing sealed reactionware for chemical synthesis with the reagents, catalysts and purification apparatus integrated into monolithic devices. Using this reactionware, a multi-step reaction sequence was performed by simply rotating the device so that the reaction mixture flowed through successive environments under gravity, without the need for any pumps or liquid-handling prior to product retrieval from the reactionware in a pure form.

3D-printed devices for continuous-flow organic chemistry

Summary We present a study in which the versatility of 3D-printing is combined with the processing advantages of flow chemistry for the synthesis of organic compounds. Robust and inexpensive 3D-printed reactionware devices are easily connected using standard fittings resulting in complex, custom-made flow systems, including multiple reactors in a series with in-line, real-time analysis using an ATR-IR flow cell. As a proof of concept, we utilized two types of organic reactions, imine syntheses and imine reductions, to show how different reactor configurations and substrates give different products.

3D Printed High‐Throughput Hydrothermal Reactionware for Discovery, Optimization, and Scale‐Up

3D printing techniques allow the laboratory-scale design and production of reactionware tailored to specific experimental requirements. To increase the range and versatility of reactionware devices, sealed, monolithic reactors suitable for use in hydrothermal synthesis have been digitally designed and realized. The fabrication process allows the introduction of reaction mixtures directly into the reactors during the production, and also enables the manufacture of devices of varying scales and geometries unavailable in traditional equipment. The utility of these devices is shown by the use of 3D printed, high-throughput array reactors to discover two new coordination polymers, optimize the synthesis of one of these, and scale-up its synthesis using larger reactors produced on the same 3D printer. Reactors were also used to produce phase-pure samples of coordination polymers MIL-96 and HKUST-1, in yields comparable to synthesis in traditional apparatus.

3D printing of versatile reactionware for chemical synthesis

In recent decades, 3D printing (also known as additive manufacturing) techniques have moved beyond their traditional applications in the fields of industrial manufacturing and prototyping to increasingly find roles in scientific research contexts, such as synthetic chemistry. We present a general approach for the production of bespoke chemical reactors, termed reactionware, using two different approaches to extrusion-based 3D printing. This protocol describes the printing of an inert polypropylene (PP) architecture with the concurrent printing of soft material catalyst composites, using two different 3D printer setups. The steps of the PROCEDURE describe the design and preparation of a 3D digital model of the desired reactionware device and the preparation of this model for use with fused deposition modeling (FDM) type 3D printers. The protocol then further describes the preparation of composite catalyst–silicone materials for incorporation into the 3D-printed device and the steps required to fabricate a reactionware device. This combined approach allows versatility in the design and use of reactionware based on the specific needs of the experimental user. To illustrate this, we present a detailed procedure for the production of one such reactionware device that will result in the production of a sealed reactor capable of effecting a multistep organic synthesis. Depending on the design time of the 3D model, and including time for curing and drying of materials, this procedure can be completed in ∼3 d.

3D printed flow plates for the electrolysis of water: an economic and adaptable approach to device manufacture

The electrolysis of water is considered a promising route to the production of hydrogen from renewable energy sources. Electrolysers based on proton exchange membranes (PEMs) have a number of advantages including high current density, high product gas purity and the ability to operate at high pressure. Despite these advantages the high cost of such devices is an impediment to their widespread deployment. A principal factor in this cost are the materials and machining of flow plates for distribution of the liquid reagents and gaseous products in the electrochemical cell. We demonstrate the production and operation of a PEM electrolyser constructed from silver coated 3D printed components fabricated from polypropylene. This approach allows construction of light weight, low cost electrolysers and the rapid prototyping of flow field design. Furthermore we provide data on the operation of this electrolyser wherein we show that performance is excellent for a first generation device in terms of overall efficiency, internal resistances and current–voltage response. This development opens the door to the fabrication of light weight and cheap electrolysers as well as related electrochemical devices such as flow batteries and fuel cells.

Continuous parallel ESI-MS analysis of reactions carried out in a bespoke 3D printed device.

Summary Herein, we present an approach for the rapid, straightforward and economical preparation of a tailored reactor device using three-dimensional (3D) printing, which can be directly linked to a high-resolution electrospray ionisation mass spectrometer (ESI-MS) for real-time, in-line observations. To highlight the potential of the setup, supramolecular coordination chemistry was carried out in the device, with the product of the reactions being recorded continuously and in parallel by ESI-MS. Utilising in-house-programmed computer control, the reactant flow rates and order were carefully controlled and varied, with the changes in the pump inlets being mirrored by the recorded ESI-MS spectra.

Modular Redox‐Active Inorganic Chemical Cells: iCHELLs

Interfacial membrane formation by cation exchange of polyoxometalates produces modular inorganic chemical cells with tunable morphology, properties, and composition (see picture). These inorganic chemical cells (iCHELLs), which show redox activity, chirality, as well as selective permeability towards small molecules, can be nested within one another, potentially allowing stepwise reactions to occur in sequence within the cell.

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.

Digitization of multistep organic synthesis in reactionware for on-demand pharmaceuticals

A plastic plan for organic synthesis The infrastructure for chemical synthesis typically lies at either end of a spectrum: small-scale studies in ad hoc assemblies of glassware or large-scale production in capital-intensive custom reactors. Kitson et al. report a hybrid protocol that customizes a blueprint for synthesis of a target compound in a series of interconnected plastic modules, which can be assembled en masse by 3D printing (see the Perspective by Hornung). The approach, demonstrated for the commercial muscle relaxant baclofen, establishes a systematic workflow that is potentially amenable to automation: All that is necessary for synthesis and purification is the introduction of stock solutions and variation of temperature or pressure. Science, this issue p. 314; see also p. 273 A blueprint for chemical synthesis in plasticware offers an alternative to capital-intensive reactors for low-volume targets. Chemical manufacturing is often done at large facilities that require a sizable capital investment and then produce key compounds for a finite period. We present an approach to the manufacturing of fine chemicals and pharmaceuticals in a self-contained plastic reactionware device. The device was designed and constructed by using a chemical to computer-automated design (ChemCAD) approach that enables the translation of traditional bench-scale synthesis into a platform-independent digital code. This in turn guides production of a three-dimensional printed device that encloses the entire synthetic route internally via simple operations. We demonstrate the approach for the γ-aminobutyric acid receptor agonist, (±)-baclofen, establishing a concept that paves the way for the local manufacture of drugs outside of specialist facilities.