Continuous flow systems with bifurcating mixers
Disclosed herein are continuous flow systems having bifurcated fluidic flow mixers. The mixers operate, at least partially, by Dean vortexing. Accordingly, the mixers are referred to as Dean Vortex Bifurcating Mixers (“DVBM”). DVBMs utilize Dean vortexing and bifurcation of the fluidic channels that form the mixers to achieve the goal of optimized microfluidic mixing.
1 . A system for continuous flow operation of a microfluidic chip, the system comprising:
(1) the microfluidic chip, comprising:
(a) a first inlet configured to receive a first solution;
(b) a second inlet configured to receive a second solution; and
(c) a bifurcating mixer configured to mix the first solution and the second solution, the bifurcating mixer comprising:
(i) an inlet microchannel in fluid communication with the first and second inlets, the inlet microchannel leading into a first leg channel having a first hydrodynamic diameter defining a first fluidic impedance and a second leg channel having a second hydrodynamic diameter defining a second fluidic impedance, the first leg channel and the second leg channel defining a first mixing toroid and leading into a first neck region;
(ii) the first neck region leading into a third leg channel having a third hydrodynamic diameter defining a third fluidic impedance and a fourth leg channel having a fourth hydrodynamic diameter defining a fourth fluidic impedance that differs from the third fluidic impedance, the third leg channel and the fourth leg channel defining a second mixing toroid and leading into a second neck region; and
(iii) the second neck region leading into a fifth leg channel having a fifth hydrodynamic diameter defining a fifth fluidic impedance and a sixth leg channel having a sixth hydrodynamic diameter defining a sixth fluidic impedance, the fifth leg channel and the sixth leg channel defining a third mixing toroid and in fluid communication with a chip outlet of the microfluidic chip,
wherein the first leg channel, the third leg channel, and the fifth leg channel are located on a first side of the bifurcating mixer and the second leg channel, the fourth leg channel, and the sixth leg channel are located on a second side of the bifurcating mixer,
wherein at least two pairs of: a first pair of the first and second leg channels; a second pair of the third and fourth leg channels; and a third pair of the fifth and sixth leg channels are asymmetrical, and
wherein a first ratio of the first fluidic impedance to the second fluidic impedance differs from at least one of 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
(d) the chip outlet in fluid communication with the bifurcating mixer;
(2) a first continuous flow fluid driver configured to continuously drive the first solution into the first inlet of the microfluidic chip;
(3) a second continuous flow fluid driver configured to continuously drive the second solution into the second inlet of the microfluidic chip; and
(4) a system outlet in fluid communication with the chip outlet.
2 . The system of claim 1 , wherein the first ratio is about 1:1 to about 10:1.
3 . The system of claim 1 , wherein the second neck region forms a neck angle from 90 degrees to 150 degrees with respect to the first neck region, the neck angle being defined as a shortest angle formed between a first line passing through centers of the first mixing toroid and the second mixing toroid, and a second line passing through centers of the second mixing toroid and the third mixing toroid.
4 . The system of claim 1 , wherein the first leg channel has a first length and the second leg channel has a lesser second length.
5 . The system of claim 1 , wherein the third leg channel has a third length and the fourth leg channel has a fourth length, the third length being less than the fourth length.
6 . The system of claim 5 , wherein the first ratio differs from the second ratio, and wherein the second ratio is different than the third ratio.
7 . The system of claim 1 , wherein the first neck region forms a neck angle with the inlet microchannel from 90 degrees to 150 degrees.
8 . The system of claim 1 , wherein the first solution comprises an active pharmaceutical ingredient.
9 . The system of claim 1 , wherein the second solution comprises a particle-forming material in a second solvent.
10 . The system of claim 1 , wherein the first solution comprises a nucleic acid in a first solvent and the second solution comprises lipid particle-forming materials in a second solvent.
11 . The system of claim 1 , wherein the microfluidic chip is sterile.
12 . The system of claim 1 , further comprising a dilution element comprising a third continuous flow fluid driver configured to continuously drive a dilution solution from a dilution solution reservoir into the system, via a dilution channel, between the chip outlet and the system outlet.
13 . The system of claim 1 , further comprising a waste outlet in fluid communication with a waste valve between the chip outlet and the system outlet, wherein the waste valve is configured to controllably direct fluid towards the waste outlet.
14 . The system of claim 1 , wherein the system includes a disposable fluidic path.
15 . A sterile package comprising a microfluidic chip according to the system of claim 1 sealed within the sterile package, wherein the microfluidic chip is sterile.
16 . The system of claim 1 , wherein the first ratio is an inverse of the second ratio.
17 . The system of claim 1 , wherein the first leg has a first cross section and the second leg has a second cross section that differs from the first cross section.
18 . The system of claim 1 , wherein the first fluidic impedance equals the fourth fluidic impedance.
19 . The system of claim 1 , wherein the second fluidic impedance equals the third fluidic impedance.
20 . The system of claim 1 , wherein at least one of the first mixing toroid, the second mixing toroid, or the third mixing toroid has a variable radius.
21 . The system of claim 1 , wherein the first mixing toroid has a first radius and the second mixing toroid has a second radius that differs from the first radius.