Pressure Driven Microfluidic Chip And Method For Delivering A Sample At A Determined Flow Rate

Abstract

The invention relates to a pressure driven microfluidic chip for delivering a first liquid at a determined flow rate, said chip comprising a first inlet, a container connected to the first inlet, a second inlet connected to the container via a first passage, a second passage connecting the container to an outlet, wherein the first passage has a first resistance to liquid flow, and the second passage has a second resistance to liquid flow. The first resistance may be higher than the second resistance. The invention also relates to a pressure driven method of delivering a first liquid at a determined flow rate comprising using a chip first a first and second passage, wherein the first passage has a first resistance to the flow of the first liquid, and the second passage has a second resistance to flow of the second liquid.

Claims

1. A pressure driven method of delivering a first liquid at a determined flow rate, the method comprising the steps of: a) at least partly filling a container with an amount of the first liquid; b) causing a second liquid to flow into the container via a first passage, thereby forcing at least some of the first liquid out of the container, in order to discharge said at least some of the first liquid through a second passage; wherein the first passage has a first resistance to the flow of the first liquid, and the second passage has a second resistance to flow of the second liquid, wherein the first resistance is higher than the second resistance.

2. The method according to claim 1, further comprising supplying a third liquid downstream of the container in order to mix the first liquid with the third liquid at a predetermined concentration of first liquid.

3. The method according to claim 2, wherein the first liquid is supplied via a first inlet, and the second liquid is supplied via a separate, second inlet.

4. The method according to claim 1, wherein a viscosity of the second liquid is higher than a viscosity of the first liquid.

5. The method according to claim 1, wherein the first resistance is at least approximately ten times higher than the second resistance.

6. A pressure driven microfluidic chip for delivering a first liquid at a determined flow rate, said chip comprising: a first inlet, for letting the first liquid into the chip; a container connected to the first inlet, for at least temporarily containing an amount of first liquid; a second inlet connected to the container via a first passage, for letting in a second liquid into the chip; a second passage connecting the container to an outlet, allowing flow of the first liquid into the second passage, thereby delivering the first liquid; wherein the first passage has a first resistance to liquid flow, and the second passage has a second resistance to liquid flow.

7. The chip according to claim 6, wherein the first resistance is higher than the second resistance.

8. The chip according to claim 6, further comprising a third passage connected to the second passage downstream of the container for supplying a third liquid to the second passage, the chip thereby being suitable for mixing the third liquid with the first liquid.

9. The chip according to claim 6, further comprising a third inlet connected to the second and/or third passage.

10. The chip according to claim 6, wherein a minimum cross sectional area of the first passage is smaller than a minimum cross sectional area of the second passage.

11. The chip according to claim 8, wherein a minimum cross sectional area of the first passage is smaller than a minimum cross sectional area of the second passage, wherein the minimum cross sectional area of the first passage is smaller than a minimum cross sectional area of the third passage.

12. The chip according to claim 6, comprising a capillary stop valve between the container and the first passage and/or a capillary stop valve between the container and the second passage.

13. The chip according to claim 6, further comprising an absorber connected to the first inlet.

14. The chip according to claim 6, further comprising a vent connected to the first passage at a position beyond the container as seen from the inlet.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0046] The invention will be further elucidated with reference to the attached figures, wherein:

[0047] FIGS. 1A and 1B schematically show a simplified embodiment of a pressure driven microfluidic chip for delivering a first liquid at a determined flow rate;

[0048] FIGS. 2A and 2B schematically show a simplified embodiment of a pressure driven microfluidic chip for mixing a first and third liquid; and

[0049] FIGS. 3A-3D schematically show another embodiment of a microfluidic chip for mixing a first and third liquid at a determined flow rate.

DETAILED DESCRIPTION OF THE INVENTION

[0050] Across the figures, like elements are referred to using like reference numerals. Like elements of different embodiments are referred to using reference numerals increased by one hundred (100).

[0051] FIGS. 1A and 1B show a simplified microfluidic chip 1. The chip 1 has a container 2 which can hold liquid. In the shown embodiment, the container 2 is formed by a segment of a microfluidic channel 2. Although not shown here, the channel 2 is provided as a trough in a first layer of the chip 1, and a second layer seals the channel 2 and other structures of the chip 1. Inlet and outlets can be created by making a hole in the first or second layer of the chip 1. The chip 1 also comprises a first inlet 3. The first inlet 3 is connected to the container 2, so that a first liquid 4 can be let into the container 2 via the first inlet 3. On the other side, the container 2 is connected to an outlet 5 via a second passage 11. First liquid 4 from the container 2 can therefore exit the chip 1 via the outlet 5. The chip 1 has a second inlet 6. Via the second inlet 6, a second liquid 7 can be let into the chip 1. The second inlet 6 connects to the container 2 via a first passage 8, which in this example is also a segment of a microfluidic channel 8.

[0052] The microfluidic chip 1 of FIGS. 1A and 1B is operated as follows. After first liquid 4 has been let into the container 2 (see FIG. 1A), second liquid 7 is added through the second inlet 6. The second liquid 6 therefore pushes the first liquid 4 out of the chip via the outlet 5 (see FIG. 1B). To prevent the first liquid 4 from escaping through the first inlet 3, the first inlet 3 may be sealed, or a pressure may be applied thereto. Sealing the first inlet 3 makes sure no fluid flow is possible in the channel section between the inlet 3 and the channel 2, thereby avoiding influences this channel section may have on the flow rate.

[0053] The first passage 8 includes a narrowing 9, shown here using a funnel 10. The narrowing 9 causes a flow restriction in the first passage 8. Of course, other types of narrowing could also be used, or other types of flow restrictions could be used. The flow restriction 9 creates a relatively high resistance to flow, so that the first passage 8 has a relatively high resistance to flow. The second passage 11 has no narrowing 9, so that its resistance to flow is lower. The flow rate of the first liquid 4 is determined by the pressure drop from the second inlet 6 to the outlet, and the resistance to flow of the first and second liquid 4, 7when disregarding flow to or from the first inlet 3 at the same time. As the resistance to flow in the first passage 8 is relatively high, the first passage's 8 contribution to the flow rate is significant. The contribution of the second passage 11 is analogously less significant.

[0054] The chip 1 can thus be used to deliver the first liquid 4 at a determined flow rate, even if the viscosity of the first liquid 4 varies within a sample, or from sample to sample, or is not accurately known. By simply using a second liquid 7 of a known and relatively constant viscosity, the flow rate can be determined to a relatively large extent by the known second liquid 7 rather than by the sample first liquid 4. As such, the flow rate can be determined relatively accurately.

[0055] FIGS. 2A and 2B show a chip 101 that is similar to the chip 1 of FIGS. 1A and 1B. As such, only the difference will be described below. The chip 101 of FIGS. 2A and 2B has a third passage 112 that connects to the second passage 111 downstream of the container 102. The third passage has a third inlet 113, so that a third liquid 114 can be let into the third passage 112. As an alternative the third passage 112 could be connected to the second inlet 106, so that the second and third liquid 107, 114 are the same.

[0056] By driving the third liquid 114 at the same time as the second liquid 107, the two liquids merge in the second passage 111, where they will mix. As such, a mixed fluid 115 is delivered at the output 105. Depending on the liquids involved, different mixing behavior is observed.

[0057] Instead of restricting flow of the second liquid 107 by a flow restriction caused by the geometry of the first passage 108, the resistance to liquid flow in the first passage 108 is increased by choosing a second liquid 107 with a relatively high viscosity. Similar as to in the chip 1 of FIGS. 1A and 1B, the flow rate is therefore defined to a relatively large extent by second liquid 107 flowing in the first passage 108, so that the flow rate is not as much influenced by variations in the viscosity in the first liquid 104.

[0058] The mixing ratio between the first and third liquids 104, 114 is defined by the flow rates of the liquids 104, 114. As the flow rate of the first liquid 104 is defined to a relatively large extent by the flow resistance in the first passage 108, and to a lesser extent by flow of the first liquid 104, the mixing ratio is determined to a relatively large extent by the second liquid 107 flowing through the first passage 108. As such, the chip 101 of FIGS. 2A and 2B can be used for delivering a mixed fluid 115 at a predetermined mixing ratio.

[0059] FIGS. 3A and 3B show a chip 201 which can be used for delivering a mixed fluid 215 at a predetermined mixing ratio, by reducing the influence of viscosity variations in a first fluid 204. The chip 201shown empty in FIG. 3Aincludes first, second and third inlets 203, 206, 213 and outlet 205. The chip 201 further includes a container 202. The container 202 in this example is formed by a chamber machined from a first layer of material of the chip 201, and closed by a second layer of material of the chip 201. Of course other production methods are also possible, such as embossing or etching. The passages 208, 211, 212 and other parts of the microfluidic flow system of the chip are formed in the same way. The container 202 includes pillars 216 to prevent collapsing. The first inlet 203 connects to the container 202. Near the first inlet, an overflow channel 217 is provided which connects to a wick 218. The second inlet 206 also connects to the container 202, via a first passage 208. The first passage 208 is separated from the container via a first capillary stop valve 219. Until triggered, the first capillary stop valve 219 stops liquid from exiting the container 202 into the first passage 208. The first passage 208 includes a vent 221, which is placed beyond the container 202 as seen from the second inlet 206. The outlet 205 is also connected to the container 202, via a second passage 211. The second passage 211 is separated from the container 202 via a second capillary stop valve 220. Until triggered, the second capillary stop valve 220 stops liquid from exiting the container into the second passage 211. Finally, the third inlet 213 is connected to the second passage via a third passage 212. The third passage 212 connects to the second passage 211 downstream of the second capillary stop valve 220, i.e. further towards the outlet 205. The capillary stop valves 219, 220 form the smallest cross sectional through flow areas of the first and second passages 208, 211 respectively. The cross sectional area of the first capillary stop valve 219 is smaller than the cross sectional area of the second capillary stop valve 220. As such, the resistance to flow is highest in the first capillary stop valve 219.

[0060] The chip 202 is used as follows. First, an empty chip 201 is provided (see FIG. 3A). Second, first liquid 204 is inserted through the first inlet 203 (see FIG. 3B). The first liquid 204 fills the container 202. During filling, air present in the container 202 exits through the vent 221. It is also possible air exits through the first, second and third passages 208, 211, 212 when the second and third inlets 206, 213 and the outlet 205 are left free during filling. If too much first liquid 216 is inserted, a surplus will flow via the bypass channel 217 towards the wick 218 in order to be absorbed. As such, the wick 218 prevents capillary stop valves 219, 220 from triggering when a surplus of first liquid 204 is supplied. Third, a second liquid 207 is let in through second inlet 206, until the first passage 208 is filled. During filling of the first passage 208, air from the first passage exits through the vent 221. When the second liquid 207 reaches the first capillary stop valve 219, said stop valve 219 is triggered, thereby allowing flow. However, as the second capillary stop valve 220 remains untriggered, both the first and second liquid 204, 207 stop flowing. Fourth, third liquid 214 is supplied via the third inlet 213 until the third passage 212 is filled. While filling, air exits the third passage 212 via the second passage 211 and the outlet 205. When the third liquid 214 reaches the second capillary stop valve 220, said stop valve 220 is triggered, thereby allowing flow. Then, by creating a pressure differential from the second and third inlets 206, 213 to the outlet 205, the second and third liquids 207, 214 will flow in the direction indicated by arrows f207 and f214 respectively (see FIG. 3D). As such, the second liquid 207 pushes the first liquid 204 out of the container 202, through the second capillary stop valve 220 into the second passage 211 towards the outlet 205. At the same time, third liquid also flows into the second passage 211 towards the outlet 205, so that the first and third liquid 204, 214 is mixed. The resulting mixed fluid 215 flows from the container 202 towards the outlet 205 as is shown using an arrow f215.

[0061] It is noted that while flowing, the second liquid 207 contacts the first capillary stop valve 219, and the first liquid 204 contacts the second capillary stop valve 220. Since the first capillary stop valve 219 is smallest, it has a relatively high resistance to flow. As such, the viscosity of the second liquid 208, in combination with the first capillary stop valve 219 is defining to a relatively large extent for the flow rate of the first liquid 204 downstream. As such, variations in the viscosity of the first liquid 204 are of less influence. The same principle can be employed by choosing a second liquid 208 with a higher viscosity than the first liquid 204, even without having different geometries for the capillary stop valves 219, 220 or the first and second passages 208, 211. Of course, a combination of these strategies is also possible.

[0062] Although the invention has been described hereabove with reference to a number of specific examples and embodiments, the invention is not limited thereto. Instead, the invention also covers the subject matter defined by the claims, which now follow.