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:
initiating detection of fluids at a first measurement zone of a microfluidic system;
detecting a first wash fluid and a second wash fluid at the first measurement zone and forming a first signal corresponding to the first wash fluid and a second signal corresponding to the second wash fluid, wherein the detection step is performed by measuring light transmittance or light absorbance through the first and second wash fluids;
counting a series of signals generated from detecting a series of wash fluids passing across the first measurement zone, each signal having an intensity above or below a threshold intensity;
transmitting a first pattern of signals to a control system, the first pattern of signals comprising at least two of:
a) an intensity of the first signal;
b) a duration of the first signal;
c) a position of the first signal in time relative to a second position in time; and
d) an average time period between the first and the second signals, wherein the intensity of the first signal is indicative of a fluid type and the duration of the first signal is indicative of a volume and/or flow rate of the first fluid; 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 the number of signals having the intensity above or below the threshold intensity and/or the first pattern of 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 , wherein determining whether to modulate fluid flow in the microfluidic system comprises determining whether to stop an analysis being conducted in the microfluidic system.
4. A method as in claim 1 , 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.
5. A method as in claim 4 , wherein the component of the microfluidic system is a pump or a vacuum.
6. A method as in claim 4 , wherein the component of the microfluidic system is a valve.
7. A method as in claim 1 , further comprising comparing the first pattern of signals to a control pattern of signals or values pre-programmed into the control system.
8. A method as in claim 1 , wherein the first pattern of signals comprises an intensity of the first signal, and wherein intensity of the first signal comprises an average or maximum intensity.
9. A method as in claim 1 , wherein the first pattern of signals comprises an intensity of the first signal and a duration of the first signal.
10. A method as in claim 1 , wherein the first pattern of signals comprises an intensity of the first signal and a position of the first signal in time relative to a time of the initiation step.
11. A method as in claim 1 , wherein the first pattern of signals comprises an intensity of the first signal and an average time period between the first and second signals.
12. A method as in claim 1 , wherein the first and second fluids are immiscible with one another.
13. A method as in claim 1 , wherein the first fluid is a liquid and the second fluid is a gas.
14. A method as in claim 1 , wherein the first and second fluids are miscible with one another.
15. A method as in a claim 1 , wherein the first and second fluids are separated by a third, immiscible fluid.
16. A method as in claim 1 , comprising passing a fluid sample across the first measurement zone.
17. A method as in claim 16 , wherein the fluid sample comprises whole blood.
18. A method as in claim 1 , comprising alerting a user of an abnormality in an analysis being conducted in the microfluidic system.
19. A method as in claim 18 , comprising providing the user with information about the analysis based on detection of an abnormality during the analysis.
20. A method as in claim 19 , wherein providing the user with information comprises alerting the user via a user interface.
21. A method as in claim 19 , 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.
22. A method as in claim 19 , wherein the information provided to the user comprises information that the analysis is cancelled and/or the results should be disregarded.
23. A method as in claim 19 , comprising seeking further input from the user after providing the user with the information.
24. A method as in claim 20 , wherein the user interface comprises a screen that is part of a sample analyzer, and wherein the sample analyzer comprises the control system and at least one detector for detecting the first and second fluids at the first measurement zone.
25. A method as in claim 1 , comprising measuring light transmittance or light absorbance as a function of time.
26. 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.
27. A method as in claim 26 , wherein detecting the passing of fluids across the second measurement zone is performed without the use of a label and comprises measuring light transmittance or light absorbance through the first and second fluids at the second measurement zone.
28. A method as in claim 1 , wherein at least one signal is indicative of a component deposited from a fluid onto a surface of a channel in the first measurement zone.
29. A method as in claim 1 , comprising measuring light transmittance or light absorbance through a sample fluid and a series of wash fluids at the first measurement zone.
30. 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 the first and second fluids across the first measurement zone.
31. A method as in claim 1 , further comprising detecting a third fluid in the first measurement zone.
32. A method as in claim 31 , further comprising detecting a fourth fluid and a fifth fluid in the first measurement zone.
33. A method as in claim 16 , wherein the fluid sample is blood, serum, or plasma.
34. A method as in claim 1 , wherein the first fluid is air.
35. A method as in claim 1 , wherein the first fluid is aqueous.
36. A method as in claim 1 , wherein the detection step is performed without the use of a label.