Microfluidic apparatus to control liposome formation
An apparatus to create a homogenous liposome population without post-processing using laminar flow/diffusive mixing, and for reducing waste discharge of the therapeutic or compound to be encapsulated and delivered by the liposomes.
1. A microfluidic apparatus for producing laminar flow for the formation of liposomes of uniform size having a mean diameter of 40 nanometers to 300 nanometers with a standard deviation of less than 10% for liposomes having a diameter smaller than 80 nm, comprised of:
a substrate including
a lipid channel through which a miscible lipid stream flows
wherein said lipid channel having a channel depth to width ratio of greater than 2 to 1 and;
wherein said lipid channel has a volumetric flow rate between 0.1 microliter/minute and 1 milliliter/minute resulting in a non-overlapping flow stream;
a laminar flow delivery compound channel having a channel depth to width ratio of greater than 2 to 1 and through which a miscible delivery compound stream flows;
a laminar flow buffer channel having a channel depth to width ratio of greater than 2 to 1 and through which a miscible buffer stream flows;
a laminar flow reaction which includes a convective diffusing mixing interface;
wherein loading efficiency may be varied by adjusting the ratio of the volumetric flow rate through said buffer channel and
said delivery compound channel;
at least one liposome outlet channel; and
at least one waste channel;
wherein said lipid channel, said delivery compound channel, said buffer channel, said liposome outlet channel, and said at least one waste channel are of dimensions that support laminar flow; and
a sealing component bonded to the top surface of said substrate.
2. The apparatus of claim 1 wherein said at least one buffer channel and said at least one delivery compound channel intersect at a second convective diffusive mixing interface to form a miscible fluid mixing channel.
3. The apparatus of claim 2 wherein said at least one buffer channel and said at least one delivery compound channel intersect at an angle sufficient to maintain laminar flow.
4. The apparatus of claim 2 wherein said at least one buffer channel and said at least one delivery compound channel intersect at an angle of 30 to 150 degrees.
5. The apparatus of claim 2 wherein said miscible fluid mixing channel intersects said at least one lipid channel to form said reaction channel.
6. The apparatus of claim 2 wherein said miscible fluid mixing channel intersects said at least one lipid channel at an angle sufficient to maintain laminar flow.
7. The apparatus of claim 2 wherein said miscible fluid mixing channel intersects said at least one lipid channel at an angle of 30 to 150 degrees.
8. The apparatus of claim 1 wherein said at least one lipid channel has a width of 0.1 to 500 micrometers and a length of 1 to 100 millimeters.
9. The apparatus of claim 1 wherein said at least one delivery compound channel has a width of 0.1 to 500 micrometers and a length of 1 to 100 millimeters.
10. The apparatus of claim 1 wherein said at least one buffer channel has a width of 0.1 to 500 micrometers and a length of 1 to 100 millimeters.
11. The apparatus of claim 1 wherein the volumetric flow rate of said lipid stream through said at least one lipid channel is 100 microliters per minute.
12. The apparatus of claim 1 wherein loading efficiency may be varied by adjusting the length of said at least one delivery compound channel.
13. A method of controlling the loading efficiency of the microfluidic apparatus of claim 1 comprising;
adjusting the volumetric flow rate of a buffer stream through a buffer channel; and
adjusting the volumetric flow rate of a delivery compound stream through a delivery compound channel.
14. The method of claim 13 which further includes the step of controlling the concentration of a delivery compound in said delivery compound stream.
15. The method of claim 14 wherein said concentration of said delivery compound is controlled by adjusting the length of said delivery compound channel.