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US 12,611,640 B2Granted
Continuous flow microfluidic system
AssigneeThe University of British Columbia
InventorsEuan Ramsay, Robert James Taylor, Timothy Leaver, Andre Wild, Kevin Ou, Colin Walsh
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Abstract
The present disclosure is directed towards improved systems and methods for large-scale production of nanoparticles used for delivery of therapeutic material. The apparatus can be used to manufacture a wide array of nanoparticles containing therapeutic material including, but not limited to, lipid nanoparticles and polymer nanoparticles. In certain embodiments, continuous flow operation and parallelization of microfluidic mixers contribute to increased nanoparticle production volume.
Claims20
A mixer configured to mix a first liquid and a second liquid, the mixer comprising:
- a first toroidal mixing element having a first leg having a first hydrodynamic diameter defining a first fluidic impedance and a second leg having a second hydrodynamic diameter defining a second fluidic impedance, the first leg and the second leg leading into and being fluidly coupled to a first neck region;
- a second toroidal mixing element having a third leg and a fourth leg fluidly coupled to the first neck region, the third leg and the fourth leg leading into and being fluidly coupled to a second neck region, wherein the third leg has a third hydrodynamic diameter defining a third fluidic impedance and the fourth leg has a fourth hydrodynamic diameter defining a fourth fluidic impedance that differs from the third fluidic impedance;
- and
- a third toroidal mixing element having a fifth leg and a sixth leg fluidly coupled to the second neck region, the fifth leg and the sixth leg leading into and being fluidly coupled to an outlet, wherein the fifth leg has a fifth hydrodynamic diameter defining a fifth fluidic impedance and the sixth leg has a sixth hydrodynamic diameter defining a sixth fluidic impedance,
- wherein the first leg, the third leg, and the fifth leg are located on a first side of the mixer and the second leg, the fourth leg, and the sixth leg are located on a second side of the mixer,
- wherein at least two pairs of:
- a first pair of the first and second legs;
- a second pair of the third and fourth legs;
- and a third pair of the fifth and sixth legs are asymmetrical, and
- wherein a first ratio of the first fluidic impedance to the second fluidic impedance differs from either a second ratio of the third fluidic impedance to the fourth fluidic impedance or a third ratio of the fifth fluidic impedance to the sixth fluidic impedance.
7 more elements
The mixer of 1, wherein the first ratio is about 1:1 to about 10:1.
A system for continuous flow operation of a microfluidic chip, the system comprising:
- (1) the microfluidic chip, comprising:
- (a) a mixer configured to mix a first solution and a second solution to provide a mixed solution at a mixer outlet, the mixer comprising:
- (i) a first toroidal mixing element having a first leg having a first hydrodynamic diameter defining a first fluidic impedance and a second leg having a second hydrodynamic diameter defining a second fluidic impedance, the first leg and the second leg leading into and being fluidly coupled to a first neck region;
- (ii) a second toroidal mixing element having a third leg and a fourth leg fluidly coupled to the first neck region, the third leg and the fourth leg leading into and being fluidly coupled to a second neck region, wherein the third leg has a third hydrodynamic diameter defining a third fluidic impedance and the fourth leg has a fourth hydrodynamic diameter defining a fourth fluidic impedance that differs from the third fluidic impedance;
- (iii) a third toroidal mixing element having a fifth leg and a sixth leg fluidly coupled to the second neck region, the fifth leg and the sixth leg leading into and being fluidly coupled to the mixer outlet, wherein the fifth leg has a fifth hydrodynamic diameter defining a fifth fluidic impedance and the sixth leg has a sixth hydrodynamic diameter defining a sixth fluidic impedance,
- wherein the first leg, the third leg, and the fifth leg are located on a first side of the mixer and the second leg, the fourth leg, and the sixth leg are located on a second side of the mixer, wherein at least two pairs of:
- a first pair of the first and second legs;
- a second pair of the third and fourth legs;
- and a third pair of the fifth and sixth legs are asymmetrical, and wherein a first ratio of the first fluidic impedance to the second fluidic impedance differs from either a second ratio of the third fluidic impedance to the fourth fluidic impedance or a third ratio of the fifth fluidic impedance to the sixth fluidic impedance;
- and
- (b) a chip outlet in fluid communication with the mixer outlet through a mixed solution microchannel;
- (2) a first fluid driver configured to continuously drive the first solution into the mixer;
- (3) a second fluid driver configured to continuously drive the second solution into the mixer;
- and
- (4) a system outlet in fluid communication with the chip outlet.
12 more elements
Dependencies are inferred from the claim text.