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

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

On the fly multi-modal observation of ligand synthesis and complexation of Cu complexes in flow with ‘benchtop’ NMR and mass spectrometry

Exploring complex chemical systems requires reproducible and controllable ways to access non-equilibrium conditions. Herein we present a programmable flow system that can do both ligand synthesis and complexation on the fly, and the conditions of the reaction can be monitored using two simultaneous techniques, namely NMR and mass spectrometry. By using this approach we monitored the formation of unknown complexes, followed by crystallization that resulted in the characterisation of their structures giving 5 new compounds (4 isolated and fully characterised) which can be formulated as: Cu2(L1)4(μ-CO3)](BF4)2 (2); [Cu3(L1)6(μ-CO3)](PF6)2(OH)2 (3) [Cu2(L2)2](BF4)2 (4) and [Cu(L2)2](BF4)2·CH3CN (5)

3D-printed devices for continuous-flow organic chemistry

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

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

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

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

3D designed and printed chemical generators for on demand reagent synthesis

Modern science has developed well-defined and versatile sets of chemicals to perform many specific tasks, yet the diversity of these reagents is so large that it can be impractical for any one lab to stock everything they might need. At the same time, isssues of stability or limited supply mean these chemicals can be very expensive to purchase from specialist retailers. Here, we address this problem by developing a cartridge -oriented approach to reactionware-based chemical generators which can easily and reliably produce specific reagents from low-cost precursors, requiring minimal expertise and time to operate, potentially in low infrastructure environments. We developed these chemical generators for four specific targets; transition metal catalyst precursor tris(dibenzylideneacetone)dipalladium(0) [Pd2(dba)3], oxidising agent Dess-Martin periodinane (DMP), protein photolinking reagent succinimidyl 4,4’-azipentanoate (NHS-diazirine), and the polyoxometalate cluster {P8W48}. The cartridge synthesis of these materials provides high-quality target compounds in good yields which are suitable for subsequent utilization

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

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

Automatic generation of 3D-printed reactionware for chemical synthesis digitization using ChemSCAD

We describe a system, ChemSCAD, for the creation of digital reactors based on the chemical operations, physical parameters, and synthetic sequence to produce a given target compound, to show that the system can translate the gram-scale batch synthesis of the antiviral compound Ribavirin (yield 43% over three steps), the narcolepsy drug Modafinil (yield 60% over three steps), and both batch and flow instances of the synthesis of the anticancer agent Lomustine (batch yield 65% over two steps) in purities greater than or equal to 96%. The syntheses of compounds developed using the ChemSCAD system, including reactor designs and analytical data, can be stored in a database repository, with the information necessary to critically evaluate and improve upon reactionware syntheses being easily shared and versioned

Digital control of multistep hydrothermal synthesis by using 3D printed reactionware for the synthesis of metal–organic frameworks

Hydrothermal‐synthesis‐based reactions are normally single step owing to the difficulty of manipulating reaction mixtures at high temperatures and pressures. Herein we demonstrate a simple, cheap, and modular approach to the design reactors consisting of partitioned chambers, to achieve multi‐step synthesis under hydrothermal conditions, in digitally defined reactionware produced by 3D printing. This approach increases the number of steps that can be performed sequentially and allows an increase in the options available for the control of hydrothermal reactions. The synthetic outcomes of the multi‐stage reactions can be explored by varying reaction compositions, number of reagents, reaction steps, and reaction times, and these can be tagged to the digital blueprint. To demonstrate the potential of this approach a series of polyoxometalate (POM)‐containing metal–organic frameworks (MOFs) unavailable by “one‐pot” methods were prepared as well as a set of new MOFs