DROPLET SPACING

Abstract

We describe a microfluidic structure for spacing out droplets, the structure comprising: a main channel for guiding droplets in a spacing fluid; a first inlet for introducing droplets into the main channel; and a second inlet for introducing a spacing fluid into the main channel, wherein a cross-sectional area of the main channel decreases downstream from the first inlet. We also describe a method of spacing out droplets using a microfluidic structure.

Claims

1. A microfluidic structure for spacing out droplets, the structure comprising: a main channel for guiding droplets in a spacing fluid; a first inlet for introducing droplets into the main channel; and a second inlet for introducing a spacing fluid into the main channel, wherein a cross-sectional area of the main channel decreases in the direction of flow starting from the first inlet.

2. A microfluidic structure according to claim 1, comprising a side channel opening into the main channel at the first inlet.

3. A microfluidic structure according to claim 2, wherein at the first inlet, the side channel is angled between 30° and 90° with respect to the main channel.

4. A microfluidic structure according to claim 2, wherein the first inlet is arranged on a first side of the main channel, and wherein the main channel comprises a droplet spacing region in which the first side of the main channel is straight and a second side of the main channel opposite the first side converges towards the first side of the main channel.

5. A microfluidic structure according to claim 1, wherein the second inlet is upstream from the first inlet.

6. A microfluidic structure according to claim 1, further comprising an outlet channel from the main channel, wherein a spacing between droplets in the main channel increases as the droplets flow through the main channel into the outlet channel.

7. A microfluidic structure according to claim 1, further comprising: a dilution chamber; a droplet inlet for introducing droplets into the dilution chamber; a carrier fluid inlet for introducing a flow of carrier fluid into the dilution chamber; and a dilution chamber outlet, wherein the first inlet is configured to receive droplets from the dilution chamber outlet, and wherein the dilution chamber is configured such that droplets flow through the dilution chamber outlet arranged one behind each other.

8. A microfluidic structure according to claim 1, wherein the second inlet comprises a grid across the main channel.

9. A microfluidic structure according to claim 8, further comprising a flow-aligning structure for aligning the flow of the spacing fluid into the second inlet, wherein the flow-aligning structure is located upstream of the second inlet.

10. A microfluidic structure according to claim 8, wherein the main channel has a funnel shape.

11. A microfluidic structure according to claim 8, further comprising: a spacing chamber wherein the main channel is inside the spacing chamber, and wherein the first inlet is configured to introduce droplets into the main channel from outside a plane of the microfluidic structure; and a third inlet configured to introduce a flow of spacing fluid into the spacing chamber.

12. A microfluidic structure according to claim 8, further comprising; an outlet channel from the main channel; and a first funnel structure with a funnel opening, wherein the funnel opening has a first region configured to receive the spacer fluid and a second region configured to receive droplets from the outlet channel, and wherein the funnel structure has a funnel outlet in which, in use, droplets are spaced out further than in the output channel.

13. A microfluidic structure according to claim 12, wherein the second region is a central region of the funnel opening and the first region lies to either side of the second region,

14. A microfluidic structure according to claim 12, further comprising a funnel channel, wherein the funnel structure is inside the funnel channel, and wherein a cross-sectional area of the funnel channel decreases downstream from the funnel opening.

15. A microfluidic structure according to claim 12, wherein the funnel outlet comprises side openings configured to introduce additional spacing fluid into the funnel structure.

16. A microfluidic structure according to claim 12, further comprising a second funnel structure wherein a second region of the second funnel structure is configured to receive droplets from the funnel outlet of the first funnel structure.

17. A microfluidic structure according to claim 1, wherein the main channel has a curved shape downstream of the first inlet.

18. Use of a microfluidic structure according to claim 1, wherein the spacing fluid and/or a carrier fluid containing the droplets is an oil comprising a fluorosurfactant.

19. A method of spacing out droplets in a microfluidic structure, the method comprising: providing a main channel for guiding droplets in a spacing fluid; providing a first inlet for introducing droplets in the main channel; providing a second inlet for introducing a spacing fluid into the main channel, wherein a cross-sectional area of the main channel decreases downstream from the first inlet and the second inlet; the method further comprising: introducing droplets into the main channel from the first inlet; introducing a spacing fluid into the main channel from the second inlet; and guiding the droplets and the spacing fluid through the main channel having a decreasing cross-sectional area to increase spacing between adjacent droplets.

20. A method according to claim 19, the method comprising: providing a side channel opening into the main channel at the first inlet; and the method further comprising: guiding a spacing fluid through the main channel of the microfluidic structure from the second inlet: and introducing droplets into the main channel from the side channel opening.

21. (canceled)

22. (canceled)

23. (canceled)

24. (canceled)

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0039] These and other aspects of the invention will now be further described, by way of example only, and with reference to the accompanying figures, wherein like numerals refer to like parts throughout, and in which:

[0040] FIG. 1 shows a schematic of a microfluidic structure according to embodiments of the present invention;

[0041] FIG. 2 shows a video snapshot of droplets in a dilution chamber of a microfluidic structure according to embodiments of the present invention;

[0042] FIG. 3 shows a schematic of a microfluidic structure according to embodiments of the present invention;

[0043] FIG. 4 shows a video snapshot of droplets in a microfluidic structure according to embodiments of the present invention;

[0044] FIG. 5 shows a schematic of a microfluidic structure according to embodiments of the present invention;

[0045] FIG. 6(a) shows a schematic of a flow-aligning structure of the microfluidic structure of FIG. 5;

[0046] FIG. 6(b) shows a channel of the flow-aligning structure of FIG. 6(a);

[0047] FIG. 6(c) shows video snapshot of droplets in a microfluidic structure according to embodiments of the present invention;

[0048] FIG. 7 shows a schematic of a microfluidic structure according to embodiments of the present invention; and

[0049] FIG. 8 shows a video snapshot of droplets in a microfluidic structure according to embodiments of the present invention.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

[0050] FIG. 1 shows a schematic of a microfluidic device or structure according to an embodiment of the invention. The microfluidic structure 100 includes a main channel 102, a picodroplet inlet 104, and a spacing fluid inlet 106.

[0051] The spacing fluid inlet 106 extends from the main channel 102 so that spacing fluid travels in a continuous direction from the spacing fluid inlet 106 to the main channel 102. In this embodiment shown, the spacing fluid inlet 106 is continuous with the main channel 102 so that the fluid flowing through the spacing fluid inlet 106 spaces out droplets when entering the main channel 102.

[0052] The picodroplet inlet 104 is arranged at a side channel on a first side of the main channel 102 and is angled with respect to the main channel 102, which allows picodroplets to change direction when travelling from the picodroplet inlet 104 to the main channel 102. In this embodiment, the picodroplet inlet 104 is substantially perpendicular to the main channel 106.

[0053] The main channel 102 has a sloping sidewall 108 on a second side of the main channel 102, opposite to the picodroplet inlet 104. This means that the cross-sectional area of the main channel 102 decreases downstream from the junction with the picodroplet inlet 104. The main channel 102 is widest at the junction with the picodroplet inlet 104, and upstream at the spacing fluid inlet 106, and narrows downstream from the picodroplet inlet 104 and the spacing fluid inlet 106.

[0054] Spacing fluid is introduced into the main channel 102 from the spacing fluid inlet 106, and picodroplets are introduced into the main channel 102 from the picodroplet inlet 104. The picodroplets change direction as they enter the main channel 102, and spacing fluid enters behind them. As the main channel 102 narrows, the spacing fluid increases the distance between the picodroplets in the main channel 102.

[0055] In this embodiment, and in other embodiments shown, the spacing fluid is an oil and the droplet includes particles, cells, or entities in an aqueous suspension or solution, However, the spacing fluid may alternatively include water and the droplets may be oil droplets.

[0056] FIG. 2 shows a video snapshot of droplets in a dilution chamber 130 of a microfluidic structure according to embodiments of the present invention. The microfluidic structure includes a droplet inlet 126, a carrier fluid inlet 128, and a dilution chamber 130. Droplets enter the dilution chamber 130 from the droplet inlet 126. The droplets from the droplet inlet 126 arrive with very little carrier fluid and so minimise their surface area to volume ratio which results in the droplets arriving in a zigzag arrangement, with droplets diagonally side by side rather than being one behind each other.

[0057] Carrier fluid (in this embodiment, a carrier oil) in introduced into the dilution chamber 130 from a carrier fluid inlet 128. The dilution chamber 130 has a wider cross section on a side with the droplet inlet 126 and an outlet 132, compared to the cross section on a side with the carrier fluid inlet 128. The cross section increases more towards the side with the droplet inlet 126 and an outlet 132, with the dilution chamber 130 having a curved funnel shape. The introduction of the carrier fluid in the dilution chamber 130 aligns the droplets so that droplets flowing through the outlet 132 are in single file.

[0058] FIG. 3 shows a schematic of a microfluidic structure according to embodiments of the present invention, and FIG. 4 shows a video snapshot of droplets in the microfluidic structure of FIG. 3. The microfluidic structure of FIG. 3 includes the dilution chamber 130, droplet inlet 126, carrier fluid inlet 128 and outlet 132 of FIG. 2, with the structure of FIG. 1. The first inlet 104 is configured to receive droplets in a single file from the outlet 132. Having droplets arrive in single file improves the regular spacing of droplets within the microfluidic structure downstream from the outlet 132. In this embodiment, the first inlet 104 is parallel to the main channel 102 with droplets in carrier fluid arriving flowing in an opposite direction to the flow of spacing fluid through the spacing fluid inlet 106 and the main channel.

[0059] FIG. 5 shows a schematic of a microfluidic device or structure 200 according to a further embodiment of the invention, and FIG. 6(c) shows a video snapshot of picodroplets in the microfluidic structure 200 of FIG. 5. In this embodiment, the microfluidic structure 200 includes a main channel 202 within a spacing chamber 210, a picodroplet inlet 204 and a spacing fluid inlet 206.

[0060] The picodroplet inlet 204 is arranged at a first junction connected to the main channel 202 within the spacing chamber 210. The spacing fluid inlet 206 connects to the spacing chamber 210 but is upstream of the picodroplet inlet 204 and the main channel 202. The main channel has a teardrop shape narrowing towards an outlet 218.

[0061] Two funnel structures 220 are arranged downstream of the main channel. The funnel structures have inlets 212 and gaps 214 are present on the sides of the funnel structures 220 so that spacing fluid can enter the funnel structures 220 through the inlets 212 or gaps 214. The inlets 212 are arranged such that spacing fluid enters the funnel structures 220 in a direction substantially parallel to the direction of flow in the funnel structures 220. The spacing fluid entering the funnel structures 220 through the inlets 212 and gaps 214 spaces out the droplets flowing through the funnel structures 220.

[0062] The funnel structures 220 are located within a larger funnel channel 222. The funnel channel 222 has a decreasing cross-sectional area such that spacing fluid in the funnel channel 222 but outside the inner funnels 220 is forced into the funnels 220 through the inlets 212 or gaps 214 and spaces out droplets in the funnel 220.

[0063] A flow-aligning structure 216 as shown in FIG. 6(a) is located between the spacing fluid inlet 206 and the picodroplet inlet 204. The flow-aligning structure 216 includes a series of smaller channel structures as shown in FIG. 6(b), which align the flow of spacing medium or spacing fluid in a direction towards the picodroplet inlet 204 and to the main channel 202. In this embodiment, the flow aligning structure 216 is a series of rows of channels in the direction of flow through the spacing chamber 210, each having an opening aperture 226 to allow fluid to enter and one or more smaller exit apertures 228 to reduce the amount of fluid flowing through each channel. The rows of channels are offset with respect to each other, so that the exit aperture of one channel is aligned with a gap between channels in an adjacent row of channels.

[0064] A semi-circular grid structure 224 is adjacent to the flow-aligning structure 216. In this embodiment, the grid structure 224 is an array of inline filters. Some spacing fluid from the spacing fluid inlet 206 passes through the flow-aligning structure 216 and the grid structure 224, and then into the main channel 202 upstream of the picodroplet inlet 204. The rest of the flow of spacing fluid passes through the flow-aligning structure 216 and around the outside of the main channel 202 inside the spacing chamber 210. This may then enter the funnels 220 through the inlets 212 or gaps 214 along the sides of the funnels 220.

[0065] FIG. 7 shows a schematic of a microfluidic structure 300 according to a further embodiment of the present invention, and FIG. 8 shows a video snapshot of picodroplets in the microfluidic structure 300 of FIG. 7. In this embodiment, the microfluidic structure 300 includes a main channel 302 connected to a spacing chamber 310, a picodroplet inlet 304 and a spacing fluid inlet 306.

[0066] The picodroplet inlet 304 is arranged at a first junction with the spacing chamber 310, and the spacing fluid inlet 306 is arranged at a second junction with the spacing chamber 310. The main channel 302 joins the spacing chamber 310 downstream from the picodroplet inlet 304 and the spacing fluid inlet 36. The spacing fluid inlet 306 is upstream of the picodroplet inlet 304 and the main channel 302.

[0067] Similar to the embodiment shown in FIGS. 5 and 6, a flow-aligning structure 316 is located between the spacing fluid inlet 306 and the picodroplet inlet 304. The flow-aligning structure 316 includes a series of smaller dotted structures, which align the flow of spacing fluid from the spacing fluid inlet 306 in a direction towards the picodroplet inlet 304 and to the main channel 302. A semi-circular grid structure 324 is adjacent to the flow-aligning structure 316. The spacing fluid passes from the spacing fluid inlet 306 and the flow of the spacing fluid is aligned towards the picodroplet inlet 304 and the main channel 302 extending from the spacing chamber 310.

[0068] The main channel 302 has a narrowing cross section downstream from the picodroplet inlet 302 and the spacing chamber 310. The decreasing cross section of the main channel 302 slows down the flow of spacing fluid and the picodroplets and spaces out the picodroplets. In this embodiment, the main channel 302 has a curved shape so that it spirals around the spacing chamber 310. The curved or bent shape of the main channel 302 allows picodroplets to align on an outside surface of the bend of the curved main channel 302, that the picodroplets are spaced out from each other as they travel downstream of the spacing chamber 310.

[0069] Although aspects and embodiments of the invention described throughout the specification refer to picodroplets (which may be defined as droplets having a volume of less than one nano-litre), the skilled person will appreciate that aspects of the invention and embodiments generally as described herein may equally be used for droplets with other sizes. for example droplets having a volume of 1-1000 nanolitres or microdroplets.

[0070] No doubt, many other effective alternatives will occur to the skilled person. It will be understood that the invention is not limited to the described embodiments and encompasses modifications apparent to those skilled in the art lying within the spirit and scope of the claims appended hereto.