FEEDBACK CONTROL IN MICROFLUIDIC SYSTEMS

• US 20110253224A1
• Filed: 04/15/2011
• Published: 10/20/2011
• Est. Priority Date: 04/16/2010
• Status: Active Grant

• Current Assignee: Opko Diagnostics, LLC (Opko Health, Inc.)
• Original Assignee: Claros Diagnostics, Inc. (Opko Health, Inc.)
• Inventors: Steinmiller, David, Linder, Vincent
• Granted Patent: US 8,580,569 B2
• Time in Patent Office: Days
• US Class Current: 137/2
• CPC Class Codes: B01L 2200/025 Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2200/026 Fluid interfacing between devices or objects, e.g. connectors, inlet details
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/028 Modular arrangements
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2200/0684 Venting, avoiding backpressure, avoid gas bubbles
• CPC Class Codes: B01L 2200/143 Quality control, feedback systems
• CPC Class Codes: B01L 2200/146 Employing pressure sensors
• CPC Class Codes: B01L 2200/147 Employing temperature sensors
• CPC Class Codes: B01L 2300/021 Identification, e.g. bar codes
• CPC Class Codes: B01L 2300/023 Sending and receiving of information, e.g. using bluetooth
• CPC Class Codes: B01L 2300/027 Digital display, e.g. LCD, LED
• CPC Class Codes: B01L 2300/04 Closures and closing means
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• 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 2300/12 Specific details about materials
• CPC Class Codes: B01L 2300/14 Means for pressure control
• CPC Class Codes: B01L 2300/16 Surface properties and coatings
• CPC Class Codes: B01L 2300/168 Specific optical properties, e.g. reflective coatings
• CPC Class Codes: B01L 2300/1827 : using resistive heater
• CPC Class Codes: B01L 2300/1894 : Cooling means; Cryo cooling
• CPC Class Codes: B01L 2400/0475 : specific mechanical means and fluid pressure
• CPC Class Codes: B01L 2400/049 : vacuum
• CPC Class Codes: B01L 2400/0666 : Solenoid valves
• CPC Class Codes: B01L 2400/082 : Active control of flow resistance, e.g. flow controllers
• 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 3/502715 : characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• 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: B01L 3/502738 : characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B01L 3/502746 : characterised by the means for controlling flow resistance, e.g. flow controllers, baffles B01L3/502738 takes precedence
• CPC Class Codes: B01L 7/52 : with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: G01N 21/05 : Flow-through cuvettes G01N21/09 takes precedence; handling fluid samples G01N1/10
• CPC Class Codes: G01N 21/59 : Transmissivity G01N21/25 takes precedence
• CPC Class Codes: G01N 21/64 : Fluorescence; Phosphorescence
• CPC Class Codes: G01N 21/76 : Chemiluminescence; Bioluminescence
• CPC Class Codes: G01N 2201/02 : Mechanical
• CPC Class Codes: G01N 2201/0612 : Laser diodes
• CPC Class Codes: G01N 2201/062 : LED's
• CPC Class Codes: G01N 2201/0621 : Supply
• CPC Class Codes: G01N 2201/0697 : Pulsed lasers
• CPC Class Codes: G01N 2333/96433 : Serine endopeptidases (3.4.21)
• CPC Class Codes: G01N 33/54313 : the carrier being characterised by its particulate form
• CPC Class Codes: G01N 33/54366 : Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 33/57434 : of prostate
• CPC Class Codes: Y10T 137/0324 : With control of flow by a condition or characteristic of a fluid
• CPC Class Codes: Y10T 436/12 : Condition responsive control

Abstract

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.

Claims

1. A method comprising:

initiating detection of fluids at a first measurement zone of a microfluidic system;

detecting a first fluid and a second fluid at the first measurement zone and forming a first signal corresponding to the first fluid and a second signal corresponding to the second fluid;

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 second signals; and

determining whether to modulate fluid flow in the microfluidic system based at least in part on the first pattern of signals.

4. A method as in claim 1, comprising continuously or periodically detecting the passing of any fluids across the first measurement zone.

5. 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.

6. 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.

7. A method as in claim 1, wherein the component of the microfluidic system is a pump or a vacuum.

8. A method as in claim 1, wherein the component of the microfluidic system is a valve.

9. 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.

10. A method as in claim 1, wherein intensity of the first signal comprises an average or maximum intensity.

11. 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.

12. 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.

13. 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.

14. A method as in claim 1, further comprising counting a series of signals each having an intensity above or below a threshold intensity, and determining whether to modulate fluid flow in the microfluidic system based at least in part on the number of signals having the intensity above or below the threshold intensity.

15. A method as in claim 1, wherein the first and second fluids are immiscible with one another.

16. A method as in claim 1, wherein the first fluid is a liquid and the second fluid is a gas.

17. A method as in claim 1, wherein the first and second fluids are miscible with one another.

18. A method as in a claim 1, wherein the first and second fluids are separated by a third, immiscible fluid.

19. A method as in claim 1, wherein the first fluid is a sample.

20. A method as in claim 1, wherein the first fluid comprises whole blood.

2. A method comprising:

detecting a first fluid and a second fluid at a first measurement zone of a microfluidic system, wherein the detection step comprises detecting at least two of;

a) an opacity of the first fluid;

b) a volume of the first fluid;

c) a flow rate of the first fluid;

d) a position of the detection of the first fluid in time relative to a second position in time; and

e) an average time period between the detection of the first and second fluids; and

determining whether to modulate fluid flow in the microfluidic system based at least in part on the detection step.

3. A method of conducting quality control to determine abnormalities in operation of a microfluidic system, comprising:

detecting a first fluid at a first measurement zone of the microfluidic system and forming a first signal corresponding to the first fluid;

transmitting the first signal to a control system;

comparing the first signal to a reference signal, thereby determining the presence of abnormalities in operation of the microfluidic system; and

determining whether to stop an analysis being conducted in the microfluidic system based at least in part on results of the comparing step.

21-37. -37. (canceled)