Metal electrode based 3D printed device for tuning microfluidic droplet generation frequency and synchronizing phase for serial femtosecond crystallography
Inventors
Ros, Alexandra • Kim, Daihyun • ECHELMEIER, Austin • Cruz Villarreal, Jorvani • EGATZ-GOMEZ, Ana • QUINTANA, Sebastian
Assignees
Arizona State University ASU • Arizona State University Downtown Phoenix campus
Publication Number
US-10969350-B2
Publication Date
2021-04-06
Expiration Date
2038-05-22
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Abstract
Methods and systems are provided for serial femtosecond crystallography for reducing the vast amount of waste of injected crystals practiced with traditional continuous flow injections. A micrometer-scale 3-D printed water-in-oil droplet generator device includes an oil phase inlet channel, an aqueous phase inlet channel, a droplet flow outlet channel, and two embedded non-contact electrodes. The inlet and outlet channels are connected internally at a junction. The electrodes comprise gallium metal injected within the 3-D printed device. Voltage across the electrodes generates water-in-oil droplets, determines a rate for a series of droplets, or triggers a phase shift in the droplets. An external trigger generates the droplets based on the frequency of an XFEL utilized in droplet detection, thereby synchronizing a series of droplets with x-ray pulses for efficient crystal detection. The generated droplets can be coupled to an SFX with XFEL experiment compatible with common liquid injector such as a GDVN.
Core Innovation
The invention provides a micrometer-scale 3-D printed water-in-oil droplet generator device with embedded non-contact electrodes for use in serial femtosecond crystallography (SFX). The device includes an oil phase inlet channel, an aqueous phase inlet channel, a droplet flow outlet channel, and two embedded gallium metal-based electrodes. These channels connect at a junction, and the electrodes are positioned on opposite sides of the linear channel section where the oil and aqueous phases meet, enabling precise initiation and control of droplet generation through induced electric fields.
The core problem addressed is the large amount of waste from injected protein crystals in traditional continuous flow injections for SFX experiments, caused by the mismatch between crystal delivery and the pulsed nature of x-ray free electron lasers (XFELs). Since protein crystals are precious and often available in limited quantities, minimizing sample waste is a critical challenge for efficient data collection in crystallography.
The invention's system utilizes the combination of a 3-D printed droplet generator and metallic non-contact electrodes to generate, tune, and synchronize water-in-oil droplets with x-ray pulse timing from XFELs. The electrodes, when supplied with electric potentials, can control the formation rate and phase of droplets, making it possible to match droplet delivery to the timing of X-ray pulses. Additionally, phase synchronization may be achieved by introducing sacrificial oil at a downstream T-junction or via electric triggering, widening experimental flexibility. The method is stated to be compatible with common liquid injectors such as gas dynamic virtual nozzles (GDVN) and can be adapted to various XFEL pulse structures, reducing sample waste and optimizing protein crystal usage.
Claims Coverage
There is one independent claim in the patent, with additional dependent claims. The main inventive features are extracted below.
3-D printed water-in-oil droplet generator device with embedded non-contact electrodes
A device consisting of: - An oil phase inlet channel - An aqueous phase inlet channel - A droplet flow outlet channel - Two embedded non-contact electrodes The channels are connected at a junction within the device. The junction includes a linear channel section in which the oil phase inlet is coaxially coupled to the droplet flow outlet. The two embedded non-contact electrodes are positioned on opposite sides of the linear channel section of the junction, arranged on an axis intersecting the linear section at the location where the aqueous phase inlet connects to the oil phase inlet. The device enables generation of water-in-oil droplets via local electric fields induced by the electrodes, with capabilities for tuning droplet formation and synchronization.
The independent claim focuses on a 3-D printed microfluidic device for generating water-in-oil droplets with embedded non-contact electrodes, specifically configured regarding electrode placement and fluidic junction geometry, to enable controlled droplet generation and synchronization.
Stated Advantages
Reduces the volume of sample required for full data sets in SFX experiments compared to traditional continuous stream methods.
Decreases sample consumption and sample waste by synchronizing droplet generation to x-ray pulse frequency.
Enables tenability with droplet size and channel geometries, reducing the risk of clogging and adapting to different sizes of protein crystals.
Gallium metal-based non-contact electrodes prevent degradation and damage of biological samples and reduce problems such as Joule heating and hydrolysis.
Device fabrication is simple and does not require complex microfabrication tools or steps.
Offers increased control of droplet frequency and size, and possesses the ability to synchronize the phase of droplet generation.
Documented Applications
Serial femtosecond crystallography (SFX) experiments using x-ray free electron lasers (XFELs) for efficient protein crystal structure determination.
Coupling generated droplets to common liquid injectors such as gas dynamic virtual nozzles (GDVNs) compatible with SFX and XFEL setups.
Application at existing and future XFEL facilities worldwide, including devices tested on the European XFEL with protein crystal samples.
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