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.


General experimental remarks
All chemical reagents and solvents were purchased from Sigma Aldrich and used without further purification.

Design software:
The 3D-printed device used in this work was designed on the freely distributed 3D CAD software Autodesk123D® (http://www.123dapp.com/) although any 3D modelling/CAD software with the ability to export models in an STL file (Supporting Information File 2) format would suffice for this, and there are a number of suitable alternative free/open source candidates available on the internet.
The device design was exported as an STL file (available from the authors), which was then interpreted by Bits from Bytes Axon 2 software, which produces a 3D printer instruction file (BFB file), which was subsequently transferred to the 3DTouch TM 3D printer. The printing was conducted in a layer-by-layer fashion by the 3DTouch TM printer, and the device was printed using polypropylene (PP) and fitted with standard PTFE 1/16" (1.6 mm) OD tubing and standard screw connectors. The inlet tubing was subsequently connected to the pumps, whilst the outlet was fitted with a T-device for dilution and a polyether ether ketone (PEEK) microsplitter valve with PEEK tubing to control the flow to the ESI-MS.

Device setup:
The overall dimensions of the device are 46.5 × 80 mm. It takes five hours to print, and the inner path of the device is about 1.5 mm in diameter. The total internal capacity of the device is roughly 0.65 mL, and the actual reaction capacity is about 0.57 mL. The printed device weighs about 20 g and can be valued at approximately US$ 0.40 (€ 0.30). The total cost of the PEEK accessories was US$ 230 (€ 180) and the Tricontinent C-3000 syringe pumps with the associated S3 hardware cost US$ 1000 (€ 770) per pump. Therefore the total cost was approximately US$ 4200 (€ 3300).
All solutions were pumped by means of Tricontinent C-3000 syringe pumps equipped with 1 mL syringes for the starting materials, and with a 5 mL syringe for the dilution step. An in-house-developed LabView application was employed to program the pumps to deliver the desired flow rates. Figure S1: The device setup, where the numbers denote the four pumps used, where pump A, B and C have 1 mL syringes, and pump D has a 5 mL syringe. The pale blue channels represent the tubing, the T denotes the T-piece where the dilution takes place, whilst M denotes the PEEK microsplitter valve, which splits the flow so that only the required amount will reach the ESI-MS. Check-valves were fitted between the pumps and inlet A-C, about 1.5 cm from the device, to avoid backflow and diffusion when the pumps were idle.
As seen in Figure S2, it is evident that there is no backflow or diffusion issue for inlet C when only pumps A and B are moving as the solution is still colourless between the inlet and the check-valve for this inlet. On closer inspection it can be seen that a blue area is in front of the purple area within the reactor device. This is because pump A S4 runs twice as fast as pump B, and therefore the area at the front is only Methylene Blue. To avoid this problem during our experiments we ignored the first two runs, allowing the device to be properly filled first.