This invention relates to a method and apparatus for controlling multi-fluid flow in a micro channel and refers particularly, though not exclusively, to such a method and apparatus that operates on electrokinetic and hydrodynamic principles. In a preferred aspect the present invention relates to a method and apparatus for controlling a position of an interface of fluids in the micro channel for switching, mixing and/or cytometering. In a more preferred aspect the present invention is also for controlling the form and position of the interface.
Most solid surfaces acquire an electrostatic charge when in contact with polar liquids. As a result, a difference in potential is developed across the interface between the negative and positive phases. The charged interface attracts ions of opposition charge (counter-ions) and repels ions of like charge (co-ions) in the liquid. The arrangement of charges that occurs near the interface leads to the development of an electric double layer. When a tangential electric field is applied along the capillary along which the liquid flows, liquids are pumped due to electroosmostic flow. The two widely used methods for the transportation of a single fluid in microfluidics are electroosmostic flow, and pressure-driven flow.
In microfluidics, the Reynolds number is small and fluid flow is laminar. Laminar fluid diffusion interfaces are created when two or more streams flow in parallel within a single micro-structure. Since the flows are laminar, there is no mixing between them. No mixing may be very useful because only diffusion occurs between the different streams of flow. Therefore, it is able to be used for extraction or separation in biological analysis. Diffusion-based microfluidic devices, such as the T-sensor® and the H-filter® have been developed for commercial use by Micronics, Inc. of Redmond, Wash., USA.
The variable viscosity of biological fluids can be problematic when the two streams of flows have different viscosities. The fluid with higher viscosity will occupy a wider portion of the channel while having a smaller velocity; whereas the fluid with lower viscosity flows at a larger velocity within a narrow portion of the channel. The two fluids will still have the same volumetric flow rate. The unmatched viscosity affects diffusion due to differences in residence time. The average residence time of the more viscous fluid will increase, while that of the less viscous fluid will decrease. To overcome this problem, it has been proposed to measure the viscosity of the fluid, and to add a viscosity-enhancing solute to the less viscous fluid. Another proposal is to control the ratio of the volumetric flow rate of the two fluids. By increasing the flow rate of the less viscous fluid, it is possible to maintain the interface of the two streams at the center of the channel. However, the unmatched average residence time remains unsolved because the less viscous fluid flows even faster, and has even shorter average residence time within the channel.
In accordance with a first preferred aspect there is provided apparatus for controlling fluid flow in a micro channel, the apparatus comprising:
(a) a first inlet for a first fluid;
(b) a second inlet for a second fluid;
(c) a first outlet;
(d) a second outlet;
(e) the micro channel being operatively and fluidically connected to the first inlet, the second inlet, the first outlet and the second outlet; the micro channel being for receiving the first fluid and the second fluid under pressure-driven flow; there being a first interface between the first fluid and the second fluid when in the micro channel; and
(f) a pair of electrodes for having a first electric field applied thereto for a controlling the first fluid flow velocity along the micro channel.
According to a second aspect there is provided a method for controlling fluid flow in a micro channel, the method comprising:
(a) supplying a first fluid through a first inlet under pressure-driven flow;
(b) supplying a second fluid through a second inlet under pressure-driven flow;
(c) the first fluid being able to flow along a micro channel to a first outlet;
(d) the second fluid being able to flow along the micro channel to a second outlet;
(e) the micro channel being operatively and fluidically connected to the first inlet, the second inlet, the first outlet and the second outlet; there being a first interface between the first fluid and the second fluid when in the micro channel; and
(f) applying an electric field to a pair of electrodes for controlling the first fluid flow velocity along the micro channel.
The micro channel has a width, the first electric field may also being for controlling the location of the first interface across the width, and residence time of the first and second fluids in the micro channel.
The first pair of electrodes may comprise a first electrode and a second electrode, the first electrode being in the first inlet and the second electrode being in the first outlet.
There may also be a third inlet also for a third fluid, the second inlet being between the first inlet and the third inlet, there being a second interface between the second fluid and the third fluid; and a third outlet; the third inlet and the third outlet being operatively and fluidically connected to the micro channel.
A second pair of electrodes for having a second electric field applied thereto may be provided for controlling the third fluid flow velocity along the micro channel from the third inlet. The second electric field may also be for controlling the location of the second interface across the width, and residence time of the first, second and third fluids in the micro channel. The second pair of electrodes may comprise a first electrode and a second electrode, the first electrode being in the third inlet and the second electrode being in the third outlet.
There may also be a fourth outlet operatively and fluidically connected to the micro channel. The second electrode of the second pair of electrodes may be in the fourth outlet.
There may also be a fifth outlet operatively and fluidically connected to the micro channel. The second electrode of the second pair of electrodes may be in the fifth outlet.
The first electric field and the second electric field may be able to be controlled for directing the second fluid to at least one of: the first outlet, the second outlet, the third outlet, the fourth outlet and the fifth outlet.
The method and apparatus may be used for at least one selected from the group consisting of: an electrokinetic flow switch, a micromixer, a micro-flow cytometer, an interface position controller, and an in-channel fluidic lens.
At least one fourth inlet may be provided that is operatively and fluidically connected to the micro channel and being for a fourth fluid. There may be one fourth inlet between the second and third inlets. Alternatively, there may be a pair of fourth inlets; a first of the pair of fourth inlets may be located between the first and second inlets, and a second of the pair of fourth inlets may be located between the second inlet and the third inlet. The fourth fluid may be a protection fluid for separating the first fluid from the second and third fluids. Alternatively, the fourth fluid may be two sample fluids, the second fluid being a protection fluid for separating the two sample fluids.
The first and second electric fields may be controlled for narrowing a stream width of the second fluid for flow focusing of the second fluid. The method and apparatus may be for mixing at the micro scale, the first and second electric fields may be used for narrowing the stream width of the second and fourth fluids for controlling diffusion path and diffusion time.
A controller may be provided for controlling at least one of the first electric field and the second electric field for controlling the location of at least one of the location of the first interface and the location of the second interface.
There may be provided a pair of additional electrodes axially of the micro channel, and a pair of further electrodes at the top and bottom of the micro channel, the further electrodes being for controlling a curved shape of the first interface, and the additional electrodes being for controlling the focal length and position of the curved shape.
In order that the present invention may be fully understood and readily put into practical effect, there shall now be described by way of non-limitative example only preferred embodiments of the present invention, the description being with reference to the accompanying illustrative drawings.
In the drawings:
The first embodiment is shown in
Solution 16 may be, for example, an aqueous NaCl solution (concentration 0.7×10−3M) and solution 17 may be, for example, an aqueous glycerol (volume concentration 14%). The solutions 16, 17 are introduced through inlets A and C respectively. The schematic cross-sectional view of the two fluids flow inside the straight channel is shown in
Similarly, the holdup of the aqueous glycerol 17 is e1=1−e2.
When the two fluids 16, 17 are in contact with the wall of the channel 20, the negatively charged surface 20 will influence the distribution of free ions in the NaCl solution 16 to form an electrical double layer near the channel wall 20. But the aqueous glycerol 17 will only minimally form an electrical double layer as there are few free ions. Thus the electroosmotic flow will only affect the NaCl solution 16. When a positive voltage is applied between A and B (A as the positive electrode, B as the negative electrode), the electroosmotic force will force the NaCl solution 16 to flow in the same direction as the pressure-driven flow. If the negative electric field is applied (A is negative, B is positive), an opposite electroosmotic flow will result which is against the pressure-driven flow.
A fluorescent dye such as, for example, fluorescein disodium salt C20H10Na2O5, (also called Acid Yellow 73) may be added to the NaCl solution 16 for image collection. When the fluorescein is illuminated by a mercury lamp, a coupled charge device (CCD) camera or other similar device may be used for image capturing to enable measurements to be taken. The same volumetric flow rates of the two inlet flows A and C may be ensured through the use of identical syringes driven by a single syringe pump.
The parameters considered in the graphs of
Due to the same pressure drop across E and F, in order to achieve the same volumetric flow rates, the more viscous fluid has to spread to a larger width, i.e. a higher liquid holdup. When a positive electric field is applied, the NaCl solution 16 has a lower “viscosity”, since the electroosmotic flow is the same direction as the pressure-driven flow so that the electroosmotic effect aids the flow of the NaCl solution 16.
The relationship between the NaCl holdup, e2 at different flow rates under the fixed electric field is shown in
Therefore, by adjusting the magnitude and the direction of the applied electric field the position of interface 24 between the two fluids 16, 17 can be controlled, as can be the average residence time for the fluids. The H-shaped microfluidics structure 10 can therefore be used as a diffusion-based analysis device as it provides the same average residence time for the two fluids.
A second preferred from of microfluidic flow switch is shown in a
Without changing the flow rate, the spread widths of the three laminar streams of fluids 416, 417 and 418 can be adjusted by adjusting the direction and strength of the electric-field, based on the working principle described above. The sample fluid 417 can therefore be guided into different outlets by controlling the direction and strength of the voltage applied to electrodes 421 and 422.
With
As shown in
To get a sample fluid of a high purity, the electric fields can be adjusted in such a way that the sample fluid 417 width is slightly larger then the outlet width.
Besides flow switching, the device can be used for the purposes of flow focusing. It is possible to squeeze the sample fluid 417 into a very thin flow to allow only a single cell or several cells to pass as is shown in
To reduce diffusion or reaction between the control fluid 416, 418 and the sample fluid 417, another protection fluid 419 can be introduced to separate the two, as shown in
Also, it is possible to switch more than one sample fluid 417 as shown in
Other design based on this working principle is possible. FIGS. 11 to 13 show a Y-shaped flow switch under different work modes, e.g. switching sample fluid to one or more outlets. In
Although the electrodes 14, 421 and 422 are described and illustrated as being in the inlets and outlets, they may be located in channel 20, 420 adjacent the inlets and outlets; or at the junction of the inlets and the channel, and/or the junction of the outlets and the channel.
Whilst there has been described in the foregoing description preferred embodiments of the present invention, it will be understood by those skilled in the technology concerned that many variations or modifications in details of design or construction may be made without departing from the present invention.
This application claims priority from U.S. Provisional Patent Application No. 60/618,603 filed Oct. 15, 2004, which is hereby incorporated herein in its entirety for all purposes.
Number | Date | Country | |
---|---|---|---|
60618603 | Oct 2004 | US |