Devices, systems and methods for time domain multiplexing of reagents

• US 20030215863A1
• Filed: 04/17/2003
• Published: 11/20/2003
• Est. Priority Date: 01/28/1999
• Status: Active Grant

• Current Assignee: Caliper Life Sciences Incorporated (Revvity, Inc.)
• Original Assignee: Caliper Technologies Corp (Revvity, Inc.)
• Inventors: Parce, J. Wallace, Chow, Calvin Y.H.
• Granted Patent: US 7,276,330 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: B01L 2200/0621 Control of the sequence of chambers filled or emptied
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/049 vacuum
• 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

Abstract

Time dependent iterative reactions are carried out in microscale fluidic channels by configuring the channels such that reagents from different sources are delivered to a central reaction zone at different times during the analysis, allowing for the performance of a variety of time dependent, and/or iterative reactions in simplified microfluidic channels. Exemplary analyses include the determination of dose responses for biological and biochemical systems.

Claims

1. A method of performing successive reactions in a microfluidic device, comprising:

providing a microfluidic device comprising a reaction zone disposed within the microfluidic device, wherein the reaction zone is in fluid communication with a source of first reagent, a source of second reagent and a source of third reagent, the fluid connection between the second and third reagent sources and the reaction zone being configured to deliver the second reagent to the reaction zone prior to the third reagent;

applying a driving force to one of the reaction zone, the first reagent source, the second reagent source and the third reagent source to flow the first reagent through the reaction zone, introduce the second reagent into the reaction zone causing a first reaction between the first reagent and the second reagent, and subsequently introduce the third reagent into the reaction zone to cause a reaction between the first reagent and the third reagent.

2. The method of claim 1, wherein the fluid communication between the reaction zone and the first, second and third reagent sources is provided by a first channel fluidly connecting the source of first reagent and the reaction zone, a second channel fluidly connecting the source of second reagent and the reaction zone, and a third channel fluidly connecting the source of third reagent and the reaction zone.

3. The method of claim 2, wherein the second channel and the third channel intersect the reaction zone at a single point.

4. The method of claim 2, wherein the second channel and the third channel intersect the reaction zone at separate points.

5. The method of claim 2, wherein the third channel is longer than the second channel.

6. The method of claim 2, wherein the cross sectional area of the second channel is larger than the cross sectional area of the third channel.

7. The method of claim 6, wherein the aspect ratio of the second and third channels is greater than about 5.

8. The method of claim 1, wherein the driving force is a vacuum.

9. The method of claim 8, wherein the vacuum is applied to the reaction zone.

10. A method of performing successive reactions in a microfluidic device, comprising:

providing a microfluidic device comprising a reaction zone disposed within the microfluidic device, wherein the reaction zone is in fluid communication with a source of first reagent, a source of second reagent and a source of third reagent, the fluid connection between the second and third reagent sources and the reaction one being configured to deliver the second reagent to the reaction zone prior to the third reagent;

applying a driving force to one of the reaction zone, the first reagent source, the second reagent source and the third reagent source to flow the first reagent through the reaction zone, introduce the second reagent into the reaction zone causing a first reaction between the first reagent and the second reagent to produce a first product, and subsequently introduce the third reagent into the reaction zone to cause a reaction between the first product and the third reagent.

11. The method of claim 10, wherein the fluid communication between the reaction zone and the first, second and third reagent sources is provided by a first channel fluidly connecting the source of first reagent and the reaction zone, a second channel fluidly connecting the source of second reagent and the reaction zone, and a third channel fluidly connecting the source of third reagent and the reaction zone.

12. The method of claim 11, wherein the second channel and the third channel intersect the reaction zone at a single point.

13. The method of claim 11, wherein the second channel and the third channel intersect the reaction zone at separate points.

14. The method of claim 11, wherein the third channel is longer than the second channel.

15. The method of claim 11, wherein the cross sectional area of the second channel is larger than the cross sectional area of the third channel.

16. The method of claim 15, wherein the aspect ratio of the second and third channels is greater than about 5.

17. The method of claim 10, wherein the driving force is a vacuum.

18. The method of claim 17, wherein the vacuum is applied to the reaction zone.

19. A method of determining a dose response of a first reagent on a biochemical system, comprising:

providing a microfluidic device comprising a body structure, a reaction zone disposed within the body structure, the reaction zone being fluidly connected to a first reagent source, a second reagent source and a third reagent source, the first reagent source comprising a first reagent, the second reagent source comprising a second reagent at a first concentration and the third reagent source comprising the second reagent at a second concentration greater than the first concentration, wherein the fluid connection between the second reagent source and the reaction zone and the third reagent source and the reaction zone are configured to deliver the second concentration to the reaction zone subsequent to delivering the first concentration of the second reagent to the reaction zone;

detecting an effect of each of the first concentration of the second reagent and the second concentration of the second reagent on the first reagent within the reaction zone; and

generating a dose response curve from the detected effect.

20. The method of claim 19, wherein the fluid communication between the reaction zone and the first, second and third reagent sources is provided by a first channel fluidly connecting the source of first reagent and the reaction zone, a second channel fluidly connecting the source of second reagent and the reaction zone, and a third channel fluidly connecting the source of third reagent and the reaction zone.

21. The method of claim 20, wherein the second channel and the third channel intersect the reaction zone at a single point.

22. The method of claim 20, wherein the second channel and the third channel intersect the reaction zone at separate points.

23. The method of claim 20, wherein the third channel is longer than the second channel.

24. The method of claim 20, wherein the cross sectional area of the second channel is larger than the cross sectional area of the third channel.

25. The method of claim 24, wherein the aspect ratio of the second and third channels is greater than about 5.

26. The method of claim 19, wherein a vacuum is applied to the reaction zone.