Methods and software for designing microfluidic devices

• US 6,500,323 B1
• Filed: 03/26/1999
• Issued: 12/31/2002
• Est. Priority Date: 03/26/1999
• Status: Expired due to Term

• Current Assignee: Caliper Technologies Corp (Revvity, Inc.)
• Original Assignee: Caliper Technologies Corp (Revvity, Inc.)
• Inventors: Chow, Andrea W., Chow, Calvin Y. H., Kopf-Sill, Anne R.
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): NOGUEROLA, ALEXANDER STEPHAN
• Application Number:
  US09/277,367
• Time in Patent Office: 1,376 Days
• Field of Search: 204/450, 204/451, 204/454, 204/453, 204/600, 204/601, 204/602, 204/604, 422/70, 422/99, 422/100, 702/19, 702/22
• US Class Current: 204/450
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0838 Capillaries
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/084 Passive control of flow resistance
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502707 characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: B01L 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: G01N 27/44791 Microapparatus sample containers with integrated microfluidic structures B01L3/5027
• CPC Class Codes: G06F 30/28 using fluid dynamics, e.g. using Navier-Stokes equations or computational fluid dynamics [CFD]

Abstract

Methods and systems for designing optimized fluidic channel networks for performing different analytical operations, which include the steps of selecting a driving force, identifying at least a first reaction parameter, and designing the channel network by determining channel lengths and cross-sectional dimensions that are optimized for the reaction requirements in view of the selected driving force. Preferred methods are used to design integrated microscale fluidic systems.

Claims

1. A method of making a microfluidic device incorporating at least one external capillary element for performing a given analysis comprising:

providing a microfluidic device including at least one capillary element having a first end and a second end, wherein said first end of said capillary element intersects a channel network of said microfluidic device at a first intersection, said channel network comprising at least first, second and third channel segments;

providing a material transport system comprising one or more of a pressure, vacuum or electrokinetic driving force for moving fluidic materials through the channel network of the microfluidic device; and

choosing a length, cross-section, or combination thereof of the first, second and third channel segments and the driving force to satisfy at least two analysis requirements for the given analysis, the first analysis requirement including minimizing an effect of spontaneous injection at the first intersection, and the second analysis requirement being selected from one or more of reaction time, separation time, reagent concentration, reagent volume, separation resolution, mixing ratio, and reaction temperature.

2. The method of claim 1 wherein the material transport system is selected to be pressure-based driving force which comprises a vacuum applied at at least one point in the channel network.

3. The method of claim 2 wherein the at least one point of the channel network comprises a port disposed in a body structure which houses the channel network, the port being in fluid communication with at least one of the first, second and third channel segments.

4. The method of claim 1 wherein the material transport system is selected to be a pressure-based driving force which comprises a positive pressure applied to at least one point in the channel network.

5. The method of claim 4 wherein the at least one point of the channel network comprises a port disposed in a body structure which houses the channel network, the port being in fluid communication with at least one of the first, second and third channel segments.

6. The method of claim 1 wherein said choosing a length, cross-section, or combination thereof for the first, second and third channel segments if performed by first computing a flow rate in each of said channel segments and said capillary element based at least in part on a calculation of an optimal value of flow resistance in each of said channel segments and said capillary element.

7. The method of claim 6 further comprising choosing the microfluidic device to include at least a fourth channel segment, wherein the flow rate in each channel segment is calculated by first calculating the flow rate Q₁ through the capillary element based on the following equation:

$Q_1=\frac{P_1-P_5-\left(P_2-P_1\right)<br><br>\left(\frac{R_4+R_5}{R_2}\right)-\left(P_3-P_1\right)<br><br>\left(\frac{R_4+R_5}{R_3}\right)}{\text{\hspace{1em}<br><br>}<br><br>R_1+R_4+R_5+\frac{R_1}{R_2}<br><br>\left(R_4+R_5\right)+\frac{R_1}{R_3}<br><br>\left(R_4+R_5\right)}$

wherein R₁-R₅ represent flow resistance values for each of the capillary element and the first, second, third and fourth channel segments, respectively, and P₁, P₂, P₃, and P₅ represent pressure values applied to the second end of the capillary element and to first, second and third ports fluidly coupled to said first, second, and third channel segments, respectively.

8. The method of claim 7 wherein the flow resistances of the first, second, and third channel segments and capillary element are determined based on lumped circuit analysis.

9. The method of claim 1 wherein the material transport system is selected to be an electrokinetic driving force.

10. The method of claim 9 wherein the electrokinetic driving force is selected to apply an electric field across at least one of the first, second and third channel segments.

11. The method of claim 10 wherein the driving force comprises an electric field applied concurrently across at least two of the first, second and third channel segments.

12. The method of claim 1 wherein the material transport system comprises a hybrid pressure-based and electrokinetic driving force.

13. The method of claim 12 wherein the hybrid driving force is selected to apply a positive or negative pressure to a point in at least one of the first, second or third channel segments and an electric field applied across a length of at least one of the first, second and third channel segments.

14. The method of claim 1 wherein the second analysis requirement comprises reaction time, and a first length of the first channel segment is provided such that reagents flowing through the first channel segment are present within the first channel segment for at least the reaction time.

15. The method of claim 1 wherein the second analysis requirement comprises separation time for constituent elements of fluid reagents under an applied electric field, and a first length of the first channel segment is provided such that reagents flowing through the first channel are present within the first channel segment for at least the separation time.

16. The method of claim 1 wherein the second analysis requirement comprises separation time for constituent components of a fluid material, and the first, second and third channel segments are chosen of a sufficient length such that the constituent elements in the fluid material transported through at least one of the channel segments are present within the one channel for the separation time, whereby the constituents separate.

17. The method of claim 1 wherein the microfluidic device comprises a planar body structure, the channel network being disposed within the planar body structure, the method further comprises configuring the first, second and third channel segments in the body structure of the microfluidic device such that the channel network has a footprint that is between about 0.25 cm² and about 200 cm².

18. The method of claim 1 wherein the microfluidic device comprises a planar body structure, the channel network being disposed within the planar body structure, the method further comprises configuring the first, second and third channel segments in the body structure of the microfluidic device such that the channel network has a footprint that is between about 0.25 cm² and about 6 cm².

19. The method of claim 1 wherein the microfluidic device comprises a planar body structure, the channel network being disposed within the planar body structure, the method further comprising providing at least one of the first, second and third channel segments with a depth of at least 10 μ

m.

20. The method of claim 1 wherein the at least first, second and third channel segments have cross-sectional dimensions of from about 0.1 μ

m to about 500 μ

m.

21. The method of claim 1 wherein the first channel segment comprises a reaction channel segment, and the second and third channel segments comprise reagent channels that are in fluid communication with the reaction channel segment.

22. The method of claim 21 wherein the first end of the capillary element is fluidly connected to the reaction channel segment at the first intersection.

23. The method of claim 1 further comprising selecting at least two or more second analysis requirements for the given analysis.