Feedback control in microfluidic systems
Systems and methods for controlling fluids in microfluidic systems are generally described. In some embodiments, control of fluids involves the use of feedback from one or more processes or events taking place in the microfluidic system. For instance, a detector may detect one or more fluids at a measurement zone of a microfluidic system and one or more signals, or a pattern of signals, may be generated corresponding to the fluid(s). In some cases, the signal or pattern of signals may correspond to an intensity, a duration, a position in time relative to a second position in time or relative to another process, and/or an average time period between events. Using this data, a control system may determine whether to modulate subsequent fluid flow in the microfluidic system. In some embodiments, these and other methods can be used to conduct quality control to determine abnormalities in operation of the microfluidic system.
1. A method, comprising:
passing a sample across a first measurement zone of a microfluidic system;
passing at least a first wash fluid and a second wash fluid across the first measurement zone;
measuring light transmittance or light absorbance through at least the sample, first wash fluid, and second wash fluid at the first measurement zone;
forming signals corresponding to the passing of at least the sample, first wash fluid, and second wash fluid across the first measurement zone,
wherein an intensity of each signal is indicative of the fluid passing across the first measurement zone, and wherein a duration of each signal is indicative of a volume and/or flow rate of the fluid passing across the first measurement zone; and
determining whether to modulate fluid flow in the microfluidic system and/or alerting a user of an abnormality in an analysis being conducted in the microfluidic system based at least in part on information derived from the intensity and/or duration of one or more signals.
2. A method as in claim 1 , comprising continuously or periodically detecting the passing of any fluids across the first measurement zone.
3. A method as in claim 1 , comprising determining whether to modulate fluid flow in the microfluidic system.
4. A method as in claim 3 , wherein determining whether to modulate fluid flow in the microfluidic system comprises determining whether to stop an analysis being conducted in the microfluidic system.
5. A method as in claim 3 , further comprising transmitting an electrical signal from the control system to a component of the microfluidic system that can modulate fluid flow as a result of the transmitting step.
6. A method as in claim 5 , wherein the component of the microfluidic system is a pump or a vacuum.
7. A method as in claim 5 , wherein the component of the microfluidic system is a valve.
8. A method as in claim 1 , comprising alerting a user of an abnormality in an analysis being conducted in the microfluidic system.
9. A method as in claim 8 , comprising providing the user with information about the analysis based on detection of an abnormality during the analysis.
10. A method as in claim 9 , wherein providing the user with information comprises alerting the user via a user interface.
11. A method as in claim 9 , wherein the information provided to the user comprises information that results of the analysis should not be relied upon, that the analysis needs to be performed again, that the analysis may take longer to perform, or that the user should take some action.
12. A method as in claim 9 , wherein the information provided to the user comprises information that the analysis is cancelled and/or the results should be disregarded.
13. A method as in claim 9 , comprising seeking further input from the user after providing the user with the information.
14. A method as in claim 1 , wherein the sample comprises whole blood.
15. A method as in claim 1 , wherein the sample is serum or plasma.
16. A method as in claim 1 , comprising measuring light transmittance or light absorbance as a function of time.
17. A method as in claim 1 , comprising applying a substantially constant vacuum at an outlet in fluid communication with the first measurement zone during flow of at least the first and second wash fluids across the first measurement zone.
18. A method as in claim 1 , comprising continuously or periodically detecting the passing of fluids across a second measurement zone of the microfluidic system, wherein the first and second measurement zones are positioned in series with respect to one another.
19. A method as in claim 18 , wherein detecting the passing of fluids across the second measurement zone comprises measuring light transmittance or light absorbance.
20. A method as in claim 1 , further comprising passing at least a third wash fluid and a fourth wash fluid across the first measurement zone.
21. A method as in claim 1 , wherein the first wash fluid and the second wash fluid are liquids, the method further comprising passing a gaseous plug across the first measurement zone after the passing of the second wash fluid.
22. A method as in claim 21 , comprising determining whether to modulate fluid flow in the microfluidic system and/or alerting a user of an abnormality in an analysis being conducted in the microfluidic system based at least in part on information derived from the intensity and/or duration of a signal obtained from the passing of the gaseous plug across the first measurement zone.
23. A method as in claim 1 , comprising determining whether to modulate fluid flow in the microfluidic system and/or alerting a user of an abnormality in an analysis being conducted in the microfluidic system based at least in part on information derived from the intensity and/or duration of signals obtained from the passing of the first wash fluid and the second wash fluid across the first measurement zone.
24. A method as in claim 23 , wherein the first wash fluid is a liquid and the second wash fluid is a gas.
25. A method as in claim 23 , wherein the first and second wash fluids are liquids.
26. A method as in claim 1 , comprising determining whether to modulate fluid flow in the microfluidic system and/or alerting a user of an abnormality in an analysis being conducted in the microfluidic system based at least in part on the number of wash fluids that pass across the first measurement zone.
27. A method as in claim 1 , comprising forming signals corresponding to the passing of each fluid passing across the first measurement zone.
28. A method as in claim 1 , wherein the intensity of each signal is indicative of the concentration of a component in a fluid and/or the amount of a component in a fluid passing across the first measurement zone.
29. A method as in claim 1 , wherein the intensity of each signal is indicative of the type of fluid passing across the first measurement zone.
30. A method as in claim 1 , wherein intensity is determined by an opacity of a fluid or a component of the fluid.
31. A method as in claim 1 , comparing an intensity of a signal with a threshold intensity programmed into a control system.
32. A method as in claim 1 , comprising depositing a sample component from the sample at the first measurement zone.
33. A method as in claim 32 , comprising determining opacity of the sample component or a material associated with the sample component at the first measurement zone as a function of time.
34. A method as in claim 1 , comprising determining whether to modulate fluid flow in the microfluidic system and/or alerting a user of an abnormality in an analysis being conducted in the microfluidic system based at least in part on information derived from the intensity and/or duration of a signal obtained from the passing of the sample across the first measurement zone.