A Numerical Study of Sub-Millisecond Integrated Mix-and-Inject Microfluidic Devices for Sample Delivery at Synchrotron and XFELs

Abstract

Microfluidic devices which integrate both rapid mixing and liquid jetting for sample delivery are an emerging solution for studying molecular dynamics via X-ray diffraction. Here we use finite element modelling to investigate the efficiency and time-resolution achievable using microfluidic mixers within the parameter range required for producing stable liquid jets. Three-dimensional simulations, validated by experimental data, are used to determine the velocity and concentration distribution within these devices. The results show that by adopting a serpentine geometry, it is possible to induce chaotic mixing, which effectively reduces the time required to achieve a homogeneous mixture for sample delivery. Further, we investigate the effect of flow rate and the mixer microchannel size on the mixing efficiency and minimum time required for complete mixing of the two solutions whilst maintaining a stable jet. In general, we find that the smaller the cross-sectional area of the mixer microchannel, the shorter the time needed to achieve homogeneous mixing for a given flow rate. The results of these simulations will form the basis for optimised designs enabling the study of molecular dynamics occurring on millisecond timescales using integrated mix-and-inject microfluidic devices.

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

“…Microfluidic SU8 on glass lithographic fabrication [39][40][41] Simple fabrication achieving high resolution combined with chemical and mechanical inertness and design lexibility.…”

“…The nanometer-thick sheet could have transformative potential for applications in infrared, X-ray, electron spectroscopy studies. Hejazian et al [39][40][41] have proposed a novel SU8 on glass technique to fabricate mix-and-inject devices suitable for experiments at both the synchrotron and XFEL. The use of SU8 for the fabrication of the microchannels provides high chemical inertness and X-ray stability, which is further supported by a glass body to increase the mechanical rigidity making it suitable for enduring high pressures.…”

Towards real-time analysis of liquid jet alignment in serial femtosecond crystallography

“…Maintaining a constant sample supply is challenging, as both systematic drifts and random fluctuations in the relative position of the X-ray beam and liquid jet can occur over time. The most commonly employed sample delivery system for SFX is the gas dynamic virtual nozzle (GDVN) (Gorel et al, 2020;Sobolev et al, 2020;Gru ¨nbein et al, 2019;Vakili et al, 2022;DePonte et al, 2008); more recent versions of this injector include double-flow-focusing nozzles (DFFNs) (Oberthuer et al, 2017;Vakili et al, 2022) or incorporate rapid mixing (Hejazian et al, 2021). The jet characteristics, such as its diameter, length and speed, can be controlled via the liquid and gas flow rates and the geometry of the nozzle(s) used.…”

Observations of phase changes in monoolein during high viscous injection

“…This technique is used at both X-ray free-electron lasers (XFELs) and synchrotron facilities and is an effective method for replenishing sample following interaction with the X-ray beam, which either destroys the crystal or induces radiation damage (Nogly et al, 2016;Berntsen et al, 2019;Hadian-Jazi et al, 2021;Wiedorn et al, 2018;Abbey et al, 2016). Serial crystallography is also an important tool for time-resolved crystallography used to correlate structure with reaction dynamics by collecting diffraction data on millisecond-tofemtosecond timescales (Orville, 2018;Hejazian et al, 2021a). Depending on the specific requirements in terms of sample quantities and environment (Darmanin et al, 2016), there are a number of different options for delivering the crystals to the X-ray beam (Hejazian et al, 2021b).…”