Method of producing emulsions
Devices, systems, and their methods of use, for generating droplets are provided. One or more geometric parameters of a microfluidic channel can be selected to generate droplets of a desired and predictable droplet size.
1. A method of producing droplets comprising:
a) providing a device comprising:
i) a first channel having a first proximal end, a first distal end, a first depth, and a first width, the first channel comprising a first liquid;
ii) a second channel having a second proximal end, a second distal end, a second depth, and a second width; wherein the second channel intersects the first channel between the first proximal end and the first distal end, the second channel comprising a third liquid;
iii) a droplet formation region in fluid communication with the first distal end of the first channel, wherein the droplet formation region has a width or depth greater than the first width or first depth and the droplet formation region comprises a second liquid; and
iv) a collection region in fluid communication with the droplet formation region and that collects droplets formed in the droplet formation region;
wherein the first liquid is immiscible with the second liquid, wherein the first or third liquid comprises one or more particles and wherein the device is capable of forming droplets with the second liquid flowing in response to displacement by the droplets being formed;
b) flowing the first liquid from the first channel and the third liquid from the second channel to the intersection to combine the first and third liquids;
c) flowing the combined first and third liquids to the droplet formation region to produce droplets of the first liquid, third liquid, and one or more particles dispersed in the second liquid;
d) transporting the droplets to the collection region; and
e) collecting the droplets in the collection region.
2. The method of claim 1 , wherein the droplets collected in step e) are substantially stationary.
3. The method of claim 1 , wherein a proximal-to-distal direction extends from the first proximal end to the first distal end, and the first depth decreases in the proximal-to-distal direction in at least a portion of the first channel.
4. The method of claim 1 , wherein a proximal-to-distal direction extends from the first proximal end to the first distal end, and the first depth increases in the proximal-to-distal direction in at least a portion of the first channel.
5. The method of claim 1 , wherein the first channel further comprises a groove.
6. The method of claim 1 , further comprising a first reservoir in fluid communication with the first proximal end.
7. The method of claim 6 , wherein, prior to step a), the first liquid comprises the one or more particles, and the first reservoir comprises at least a portion of the first liquid and the one or more particles.
8. The method of claim 1 , wherein step produces droplets having a single particle.
9. The method of claim 1 , wherein the first liquid is aqueous or miscible with water.
10. The method of claim 1 , wherein the density of the first liquid is lower than the density of the second liquid.
11. The method of claim 1 , wherein the density of the first liquid is higher than the density of the second liquid.
12. The method of claim 1 , wherein a proximal-to-distal direction extends from the second proximal end to the second distal end, and the second depth decreases in the proximal-to-distal direction in at least a portion of the second channel.
13. The method of claim 1 , wherein a proximal-to-distal direction extends from the second proximal end to the second distal end, and the second depth increases in the proximal-to-distal direction in at least a portion of the second channel.
14. The method of claim 1 , wherein the third liquid is aqueous or miscible with water.
15. The method of claim 1 , wherein the density of the third liquid is lower than the density of the second liquid.
16. The method of claim 1 , wherein the density of the third liquid is higher than the density of the second liquid.
17. The method of claim 1 , wherein the device further comprises a second reservoir in fluid communication with the second proximal end.
18. The method of claim 1 , wherein the second channel further comprises a groove.
19. The method of claim 1 , wherein the droplet formation region comprises a shelf region having a third depth and a third width, wherein the shelf region has at least one inlet in fluid communication with the first distal end and at least one outlet in fluid communication with the collection region.
20. The method of claim 19 , wherein the third width increases from one of the at least one inlet of the shelf region to one of the at least one outlet of the shelf region.
21. The method of claim 1 , wherein the droplet formation region comprises a step region having a fourth depth.
22. The method of claim 21 , wherein the droplet formation region further comprises a shelf region that is disposed between the first distal end and the step region.
23. The method of claim 22 , wherein the device further comprises a third channel having a third proximal end and a third distal end, wherein the third proximal end is in fluid communication with the shelf region, and wherein the third distal end is in fluid communication with the step region.
24. The method of claim 1 , wherein the droplet formation region comprises a plurality of inlets in fluid communication with the first distal end and a plurality of outlets in fluid communication with the collection region.
25. The method of claim 24 , wherein the number of inlets and the number of outlets is the same.
26. The method of claim 1 , wherein the one or more particles are beads.
27. The method of claim 26 , wherein, in step a), the first or third liquid comprises one or more biological particles, and each of the droplets produced in step c) comprise the first liquid, third liquid, a single bead, and a single biological particle.