Microfluidic free interface diffusion techniques
View Patent ↗A static fluid and a second fluid are placed into contact along a microfluidic free interface and allowed to mix by diffusion without convective flow across the interface. In accordance with one embodiment of the present invention, the fluids are static and initially positioned on either side of a closed valve structure in a microfluidic channel having a width that is tightly constrained in at least one dimension. The valve is then opened, and no-slip layers at the sides of the microfluidic channel suppress convective mixing between the two fluids along the resulting interface. Applications for microfluidic free interfaces in accordance with embodiments of the present invention include, but are not limited to, protein crystallization studies, protein solubility studies, determination of properties of fluidics systems, and a variety of biological assays such as diffusive immunoassays, substrate turnover assays, and competitive binding assays.
1. A method of mixing two fluids comprising:
providing a first static fluid having a total volume;
providing a second static fluid having a total volume;
disposing a portion of the first static fluid in contact with a portion of the second static fluid to form a fluidic interface, such that a minimum volume of the first and second fluids is exposed to a steepest concentration gradient present immediately along the fluidic interface.
2. The method of claim 1 wherein portions of the first and second fluids along the interface are restricted by a dimension of a microfluidic flow channel.
3. The method of claim 2 wherein the first fluid is positioned in a first chamber, the second fluid is positioned in a second chamber, and the microfluidic flow channel connects the chambers, such that a ratio of a cross-sectional area of the first chamber to a cross-sectional area of the microfluidic flow channel is between 500 and 25,000.
4. The method of claim 1 wherein the first static fluid and the second static fluid are maintained at different temperatures.
5. The method of claim 1 wherein the minimum volume is between 1 aL to 1 uL.
6. The method of claim 1 wherein the minimum volume is between 100 aL to 100 nL.
7. The method of claim 1 wherein the minimum volume is between 1 fL to 10 nL.
8. The method of claim 1 wherein the minimum volume is between 100 fL to 1 nL.
9. The method of claim 1 wherein the minimum volume is between and 1 pL to 100 pL.
10. The method of claim 1 further comprising opening a valve to form the fluidic interface.
11. The method of claim 1 further comprising providing an elastomeric device to contain the first and second static fluids.
12. The method of claim 1 wherein providing at least the first or second static fluid comprises blind filing a fluid up to a valve.
13. The method of claim 1 further comprising utilizing a break-through value to form the fluidic interface.
14. The method of claim 1 wherein the first fluid and the second fluid are positioned in a channel, the first fluid is positioned on a first side of the channel and the second fluid is positioned on a second side of the channel with a valve positioned between the first and second sides.
15. The method of claim 14 further comprising utilizing one or more control channels overlapping at least a portion of the first side or the second side of the channel to create a plurality of chambers within the channel.
16. The method of claim 1 wherein total volume of the first static is greater than the total volume of the second static fluid.
17. The method of claim 16 wherein a ratio of the total volume of the first static to the total volume of the second static fluid is between 2 and 10.
18. The method of claim 2 wherein the dimension of the microfluidic flow channel is a width dimension of the microfluidic flow channel.