Method for degassing liquid droplets by electrical actuation at higher temperatures
Inventors
Gupta, Tanya • Slominski, Luke M. • ZHITOMIRSKY, David • Paolini, Jr., Richard J.
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Assignees
Member
NucleraNuclera develops automated benchtop platforms and integrated systems for rapid protein expression, optimization, and purification, utilizing cell-free synthesis, digital microfluidics, and software-driven workflows. Their technology enables miniaturized and scalable protein prototyping—including challenging targets such as membrane proteins—directly at the lab bench. Nuclera serves academic and industrial researchers, focusing on reducing turnaround time for functional protein access and streamlining screening and production. The company has secured significant funding to enable broad commercialization, expanded their leadership team to support scale-up, and continues to drive advancements in drug discovery, proteomics, and experimental automation.
Nuclera develops automated benchtop platforms and integrated systems for rapid protein expression, optimization, and purification, utilizing cell-free synthesis, digital microfluidics, and software-driven workflows. Their technology enables miniaturized and scalable protein prototyping—including challenging targets such as membrane proteins—directly at the lab bench. Nuclera serves academic and industrial researchers, focusing on reducing turnaround time for functional protein access and streamlining screening and production. The company has secured significant funding to enable broad commercialization, expanded their leadership team to support scale-up, and continues to drive advancements in drug discovery, proteomics, and experimental automation.
Publication Number
US-11946901-B2
Publication Date
2024-04-02
Expiration Date
Abstract
A method for degassing a microfluidic droplet by combining electrowetting and heating to induce formation of gaseous bubbles in the droplet. In an embodiment the methods are carried out on an active matrix of electrowetting electrodes including a hydrophobic coating. A carrier fluid is flowed against the droplet motion propelled by electrowetting to facilitate rapid removal of the gasses departing the droplet.
Core Innovation
A method for degassing a microfluidic droplet by subjecting the droplet to a combination of electrowetting and heating, wherein the combined action induces formation of gaseous bubbles in the droplet. The method is carried out on a microfluidic device comprising a bottom plate with a plurality of electrodes covered by a bottom hydrophobic layer, a top plate with a top electrode covered by a top hydrophobic layer, a spacer creating a microfluidic region, a controller operatively coupled to a set of switches to provide an actuation voltage, and a heating element configured to provide thermal energy to at least a portion of the microfluidic region.
The background problem addressed is that degassing small volumes of liquid droplets is challenging with traditional methods such as freeze thawing, purging, or sonication because these methods can cause changes in sample concentration due to solvent evaporation, damage to biological molecules, and sample contamination. The invention promotes rapid nucleation and coalescence of gaseous impurities into bubbles by combined electrowetting and heating and facilitates removal of the bubbles by moving the droplet along an electrode path and/or flowing a carrier fluid to detach and remove the gaseous bubbles.
Claims Coverage
The patent includes two independent claims and seven main inventive features.
Bottom plate with plurality of electrodes covered by a bottom hydrophobic layer
A bottom plate comprising a plurality of electrodes operatively coupled to a set of switches, and including a bottom hydrophobic layer covering the plurality of electrodes.
Top plate with top electrode and top hydrophobic layer
A top plate comprising a top electrode and a top hydrophobic layer covering the top electrode, with a spacer separating the top and bottom plates to create a microfluidic region.
Controller and heating element configured to actuate electrodes and provide thermal energy
A controller operatively coupled to the set of switches and configured to provide an actuation voltage to at least a portion of the plurality of electrodes, and a heating element configured to provide thermal energy to at least a portion of the microfluidic region.
Combined electrowetting and heating to induce gaseous bubble formation
Actuating at least one of the plurality of electrodes while directing thermal energy from the heating element to the microfluidic region to subject the droplet to combined electrowetting and heating, wherein the combined action induces formation of gaseous bubbles in the droplet.
Moving droplet along an electrode path to detach bubbles
Moving the droplet along an electrode path in the microfluidic region in a first direction to detach the gaseous bubbles from the droplet.
Carrier fluid flow to assist bubble removal
Flowing a carrier fluid in a second direction opposite to or perpendicular to the first direction to facilitate removal of gaseous bubbles from the droplet.
System with processor programmed to perform degassing method
A system comprising the microfluidic device and a processor operably programmed to subject the droplet to the degassing method by actuating electrodes and directing thermal energy to induce gaseous bubble formation and moving the droplet along an electrode path to detach the gaseous bubbles.
The independent claims cover a microfluidic device architecture combining electrode arrays with hydrophobic working surfaces, a controller and heating element to apply combined electrowetting and heating that induces gaseous bubble formation in droplets, means to move droplets along electrode paths to detach bubbles, optional carrier fluid flow to aid removal, and a system embodiment with a processor programmed to perform the degassing method.
Stated Advantages
Capable of handling very small sample sizes and well-suited to applications in the life sciences involving minute amounts of aqueous solutions of biological and pharmaceutical samples.
Degassing and separation of evolved gases can be performed simultaneously, resulting in a faster, simpler process.
No need to apply a vacuum to remove gaseous impurities.
Method is conducted at much lower frequencies compared to sonication, thereby preserving the integrity of fragile biological samples such as proteins, cell fragments, or organelles.
Documented Applications
Manipulation of minute amounts of aqueous solutions of biological and pharmaceutical samples in life sciences.
Sample preparation, assays, and synthetic chemistry performed with tiny quantities of samples and reagents.
Use with biochemical protocols including nucleic acid amplification protocols, affinity-based assay protocols, enzymatic assay protocols, gene sequencing protocols, protein sequencing protocols, and protocols for analyses of biological fluids.
Synthesis of oligonucleotides and handling of nucleic acid molecules.
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