Leveraging 3D printing to enhance mass spectrometry:A review

The use of 3D printing in the chemical and analytical sciences has gained a lot of momentum in recent years. Some of the earliest publications detailed 3D-printed interfaces for mass spectrometry, which is an evolving family of powerful detection techniques. Since then, the application of 3D printing for enhancing mass spectrometry has significantly diversified, with important reasons for its application including flexible integration of different parts or devices, fast customization of setups, additional functionality, portability, cost-effectiveness, and user-friendliness. Moreover, computer-aided design (CAD) and 3D printing enables the rapid and wide distribution of scientific and engineering knowledge. 3D printers allow fast prototyping with constantly increasing resolution in a broad range of materials using different fabrication principles. Moreover, 3D printing has proven its value in the development of novel technologies for multiple analytical applications such as online and offline sample preparation, ionization, ion transport, and developing interfaces for the mass spectrometer. Additionally, 3D-printed devices are often used for the protection of more fragile elements of a sample preparation system in a customized fashion, and allow the embedding of external components into an integrated system for mass spectrometric analysis. This review comprehensively addresses these developments, since their introduction in 2013. Moreover, the challenges and choices with respect to the selection of the most appropriate printing process in combination with an appropriate material for a mass spectrometric application are addressed; special attention is paid to chemical compatibility, ease of production, and cost. In this review, we critically discuss these developments and assess their impact on mass spectrometry

3D-Printed Paper Spray Ionization Cartridge with Integrated Desolvation Feature and Ion Optics

In this work we present the application of 3D-printing for the miniaturization and functionalization of an ion source for (portable) mass spectrometry (MS). Two versions of a 3D-printed cartridge for paper spray ionization (PSI) are demonstrated, assessed, and compared. We first focus on the use of 3D-printing to enable the integration of an embedded electrostatic lens and a manifold for internal sheath gas distribution and delivery. Cartridges with and without a sheath gas manifold and an electrostatic lens are compared with respect to analytical performance and operational flexibility. The sensitivity and limit of detection are improved in the cartridge with an electrostatic lens and sheath gas manifold compared to the cartridge without (15% and over 6.5× smaller, respectively). The use of these focusing elements also improved the average spray stability. Furthermore, the range of potentials required for PSI was lower, and the distance to the MS orifice over which spray could be obtained was larger. Importantly, both setups allowed quantification of a model drug in the ng/mL range with single-stage MS, after correction for spray instability. Finally, we believe that this work is an example of the impact that 3D-printing will have on the future of analytical device fabrication, miniaturization, and functionalization

A microstructured fiber with defined borosilicate regions to produce a radial micronozzle array for nanoelectrospray ionization

This work highlights the possibility of using microstructured fibres with predefined doped regions to produce functional microstructures at a fibre facet with differential chemical etching. A specially designed silica microstructured fibre (MSF) that possesses specific boron-doped silica regions was fabricated for the purpose of generating a radial micronozzle array. The MSF was drawn from a preform comprising pure silica capillaries surrounded by boron-doped silica rods. Different etching rates of the boron-doped and silica regions at the fiber facet produces raised nozzles where the silica capillaries were placed. Fabrication parameters were explored in relation to the fidelity and protrusion length of the nozzle. Using etching alone, the nozzle protrusion length was limited, and the inner diameter of the channels in the array is expanded. However with the addition of a protective water counter flow, nozzle protrusion is increased to 60 μm with a limited increase in hole diameter. The radial micronozzle array generated nine individual electrosprays which were characterized using spray current measurements and related to theoretical prediction. Signal enhancement for the higher charge state ions for two peptides showed a substantial signal enhancement compared to conventional emitter technology.Y. Fu, S. Morency, K. Bachus, D. Simon, T. Hutama, G. T. T. Gibson, Y. Messaddeq and R. D. Oleschu

Integration of immobilized trypsin bead beds for protein digestion within a microfluidic chip incorporating capillary electrophoresis separations and an electrospray mass spectroscopy interface: Rapid Comm.Mass Spectrom.

NRC publication: Ye

Controlled, synchronized actuation of microdroplets by gravity in a superhydrophobic, 3D-printed device

Droplet manipulation over open surfaces allows one to perform assays with a large degree of control and high throughput, making them appealing for applications in drug screening or (bio)analysis. However, the design, manufacturing and operation of these systems comes with high technical requirements. In this study we employ a commercial, low-friction, superhydrophobic coating, Ultra-Ever Dry (R), on a 3D-printed microfluidic device. The device features individual droplet compartments, which allow the manipulation of discrete droplets (10-50 mu L) actuated by gravity alone. Simply by angling the device to normal in a 3D-printed holder and rocking in a "to and fro"-fashion, a sequence of droplets can be individually transferred to an electrochemical microelectrode detector and then to waste, while preserving the (chronological) order of samples. Multiple biological fluids (i.e. human saliva, urine and rat blood and serum) were successfully tested for compatibility with the device and actuation mechanism, demonstrating low slip angles and high contact angles. Biological matrix (protein) carryover was probed and effectively mitigated by incorporating aqueous rinse droplets as part of the analysis sequence. As a proof-of-concept, the enzyme-coupled, amperometric detection of glucose was carried out on individual rat serum droplets, enabling total analysis in approximate to 30 min, including calibration. The device is readily customizable, and the integration of droplet generation techniques and other sensor systems for different analytes of interest or applications can be realized in a plug and play fashion. (C) 2017 Elsevier B.V. All rights reserved

Fabrication of Patterned Superhydrophobic/Hydrophilic Substrates by Laser Micromachining for Small Volume Deposition and Droplet-Based Fluorescence

The deposition of nanoliter and subnanoliter volumes is important in chemical and biochemical droplet-based microfluidic systems. There are several techniques that have been established for the deposition/generation of small volumes including the use of surfaces with patterned differences in wettability. Many such methods require complex and time-consuming lithographic techniques. Here, we present a facile method for the fabrication of superhydrophobic surfaces with patterned hydrophilic regions by laser micromachining. A comprehensive study of fabrication parameters (laser machining speed, laser power, and patch size) on the material, patch wettability, and droplet volume is presented. Patch sizes as small as 100 μm diameter and as large as 1500 μm diameter were investigated, and volumes as low as 400 pL were observed. As an example application of such patterned materials and the deposition of small volumes, halide salts were preconcentrated on the hydrophilic patches, and their fluorescence quenching constants were rapidly calculated using a 3D-printed device coupled to a fluorescence spectrometer

Fabrication of Patterned Superhydrophobic/Hydrophilic Substrates by Laser Micromachining for Small Volume Deposition and Droplet-Based Fluorescence

The deposition of nanoliter and subnanoliter volumes is important in chemical and biochemical droplet-based microfluidic systems. There are several techniques that have been established for the deposition/generation of small volumes including the use of surfaces with patterned differences in wettability. Many such methods require complex and time-consuming lithographic techniques. Here, we present a facile method for the fabrication of superhydrophobic surfaces with patterned hydrophilic regions by laser micromachining. A comprehensive study of fabrication parameters (laser machining speed, laser power, and patch size) on the material, patch wettability, and droplet volume is presented. Patch sizes as small as 100 μm diameter and as large as 1500 μm diameter were investigated, and volumes as low as 400 pL were observed. As an example application of such patterned materials and the deposition of small volumes, halide salts were preconcentrated on the hydrophilic patches, and their fluorescence quenching constants were rapidly calculated using a 3D-printed device coupled to a fluorescence spectrometer