Abstract
The integration of the Gas Dynamic Virtual Nozzle (GDVN) and microfluidic technologies has proven to be a promising sample delivery solution for biomolecular imaging studies and has the potential to be transformative for a range of applications in physics, biology, and chemistry. Here, we review the recent advances in the emerging field of microfluidic mix-and-jet sample delivery devices for the study of biomolecular reaction dynamics. First, we introduce the key parameters and dimensionless numbers involved in their design and characterisation. Then we critically review the techniques used to fabricate these integrated devices and discuss their advantages and disadvantages. We then summarise the most common experimental methods used for the characterisation of both the mixing and jetting components. Finally, we discuss future perspectives on the emerging field of microfluidic mix-and-jet sample delivery devices. In summary, this review aims to introduce this exciting new topic to the wider microfluidics community and to help guide future research in the field.
Highlights
The three-dimensional structure determination of biological molecules is a critical step for understanding the dynamics of biological reactions and is essential for rational drug design [1]
Weber number (We) have reviewed the recent advances in the emerging field of integrated mix-and-jet microfluidic sample delivery devices
We introduced the main parameters required for the design of these integrated devices
Summary
The three-dimensional structure determination of biological molecules is a critical step for understanding the dynamics of biological reactions and is essential for rational drug design [1]. The emergence of X-ray Free-Electron Lasers (XFELs) has facilitated the measurement of complex protein structures and the associated dynamics of biomolecular systems with atomic resolution [2]. These experiments require rapid and precise delivery of the liquid sample to the X-ray interaction region in order to capture the structural changes that occur in biomolecules on sub-microsecond to millisecond timescales [3]. The use of microfluidic mix-and-jet devices capable of triggering reactions and delivering liquid samples to the X-ray beam via a free-standing jet has become a reliable technique for solving the structure of biomolecules. Microfluidic sample delivery devices have been employed for pre-mixing and deposition of liquid samples onto cryo-EM grids for time-resolved studies [7]
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