3D printed nozzles on a silicon fluidic chip

Abstract

Serial femtosecond crystallography is a new method for protein structure determination utilizing intense and destructive X-ray pulses generated by free-electron lasers. The approach requires the means to deliver hydrated protein crystals to a focused X-ray beam and replenish them at the repetition rate of the pulses. A liquid-jet sample delivery system where a gas dynamic virtual nozzle is printed directly on a silicon-glass microfluidic chip using a 2-photon-polymerization 3D printing process is implemented. This allows for rapid prototyping and high-precision production of nozzles to suit the characteristics of a particular sample and opens up the possibility for high-throughput and versatile sample delivery systems that can integrate microfluidic components for sample detection, characterisation, or control. With the hybrid system described here, stable liquid jets with diameters between 1.5 µm at liquid flow rate of 1.5 µl/min and more than 20 µm at liquid flow rate of 100 µl/min under atmospheric and vacuum conditions are generated. The combination of 2D lithography with direct 3D printing may streamline the integration of free-form-features and also facilitate scale-up production of such integrated microfluidic devices that may be useful in many other applications such as flow cytometry and optofluidics.

Ultracompact 3D microfluidics for time-resolved structural biology

“…This permits highly miniaturized devices and performance improvements through accurate 3D flow optimization. By reducing print time per device to as little as 0.3% of the time to print comparable 2pp microfluidics 3,4 allows for fast design optimization through rapid prototyping, but also the realization of largerscale designs. This will in particular help advance applications that combine flow-focusing and mixing, such as formulating emulsion and multiple emulsion-based materials 62 , active pharmaceutical ingredient nano-particles 63 , or tunable fiber spinning 64 , as well as scaling up their production to exceed liters per hour ranges.…”

“…In particular, twophoton stereolithography (2pp) is one of the few 3D printing methods that achieve free-form geometries with submicron precision. Originally pioneered for micro/nano-optics applications 2 , the utility of 2pp for microfluidic engineering remained limited as devices required several hours of print time per chip 3,4 . The ability to create free-form features with submicron accuracy promise performance improvements for microfluidic engineering.…”

Recent Advances and Future Perspectives on Microfluidic Mix-and-Jet Sample Delivery Devices

“…Bohne et al [ 49 ] have reported on a hybrid fabrication method consisting of 2PP 3D printing the nozzle head onto a 2D microfluidic silicon-glass chip fabricated via lithography. The method omits the assembly steps for connecting the nozzle tip to the liquid sample and gas channels, which previously required gluing of the capillaries to the nozzle tip.…”

“…Their fast-imaging setup takes advantage of an illumination source consisting of a Karl Storz xenon lamp generating a uniform background, which was coupled to a pulsed laser source to improve the time resolution. Bohne et al [ 49 ] used the same setup as Beyerlein et al [ 30 ] for measurements of liquid jets created by their 3D printed device under atmospheric pressure conditions. They used an environmental scanning electron microscope (SEM, EVO MA 25, Carl Zeiss AG, Oberkochen, Germany) to conduct the measurements under near-vacuum conditions of 100 Pa.…”

3D printed droplet generation devices for serial femtosecond crystallography enabled by surface coating

“…This approach involves a polymerization reaction initiated by near-infrared femtosecond laser pulses focused into a photosensitive material volume, followed by the removal of non-photopolymerized material, with advantages including micrometre resolution, availability of transparent photoresists and fast design modification (Waheed et al, 2016;Lee et al, 2008). This 3D printing approach has been utilized to develop nozzles for SFX sample delivery (Bohne et al, 2019;Nelson et al, 2016;Wiedorn et al, 2018). Although droplets can be generated using devices with different geometries, we have focused on a T-junction geometry because of its simplicity and well characterized droplet formation physical parameters (Thorsen et al, 2001;Nisisako et al, 2002;Zheng et al, 2003;Li & Ismagilov, 2010;Garstecki et al, 2006;Husny & Cooper-White, 2006;Zhu & Wang, 2016).…”