IP Library Granted Patent US 9,795,697
Granted Patent B2
US 9,795,697 · App. 12/196,392 · Granted Oct 24, 2017

Liquid containment for integrated assays

Inventors: Vincent Linder (Tewksbury, MA); David Steinmiller (Menlo Park, CA); Jason Taylor (Windham, NH)
Assignee: OPKO Diagnostics, LLC
A61L2/0082B01L3/502715B01L3/502784B01L2200/025B01L2200/0673B01L2300/069B01L2300/087B01L2300/0816B01L2300/161B01L2400/0406B01L2400/0487
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Quick Facts
Patent No.
US 9,795,697
App. No.
12/196,392
Granted
Oct 24, 2017
Kind
B2
Abstract

Microfluidic systems including liquid containment regions and methods associated therewith for performing chemical, biological, or biochemical analyzes are provided. Liquid containment regions of a microfluidic device may include regions that capture one or more liquids flowing in the device, while allowing gases or other fluids in the device to pass through the region. This may be achieved, in some embodiments, by positioning one or more absorbent materials in the liquid containment region for absorbing the liquids. This configuration may be useful for removing air bubbles from a stream of fluid and/or for separating hydrophobic liquids from hydrophilic liquids. In certain embodiments, the liquid containment region prevents any liquid from passing through the region. In some such cases, the liquid containment region may act as a waste area by capturing substantially all of the liquid in the device, thereby preventing any liquid from exiting the device. This arrangement may be useful when the device is used as a diagnostic tool, as the liquid containment region may prevent a user from being exposed to potentially-harmful fluids in the device.

Claims (57)

1. A method, comprising:

in a device including a microfluidic network containing a first plug comprising a first liquid and a second plug comprising a second liquid stored in one or more channels of the device, wherein the first and second plugs are separated by a fluid immiscible with the first and second liquids, and wherein a port of the one or more channels of the device is sealed, performing the steps of:

unsealing the port;

inserting both an inlet and an outlet of a sample introduction component containing a sample into ports of the device, wherein upon insertion, the inlet of the sample introduction component is downstream of the first and second plugs, and the outlet of the sample introduction component is upstream of a reaction area of the microfluidic network;

introducing the sample into the device downstream of the first and second plugs;

passing the sample across the reaction area of the microfluidic network;

passing at least a portion of the first liquid and/or the second liquid across the reaction area after the step of passing the sample across the reaction area;

absorbing at least a portion of the first liquid and at least a portion of the second liquid with an absorbent material contained in a liquid containment region positioned downstream of the reaction area and upstream of an outlet of the microfluidic network; and

controlling a rate of flow of a liquid in the channel by applying a source of fluid flow to the channel,

wherein the act of absorbing does not substantially control the flow rate of a liquid flowing in the channel upstream of the liquid containment region and wherein the rate of flow is at least 10 times greater than the rate of absorbing.

2. A method as in claim 1 , wherein controlling the rate of flow of the liquid comprises applying a vacuum source to an outlet of the device.

3. A method as in claim 1 , wherein controlling the rate of flow of the liquid comprises applying a positive pressure to an inlet of the device.

4. A method as in claim 1 , wherein controlling a rate of flow of a liquid comprises controlling the rate of flow of the liquid upstream of the liquid containment region.

5. A method as in claim 1 , wherein the fluid immiscible with the first and second liquids is a gas.

6. A method as in claim 5 , further comprising allowing the gas to escape from the outlet of the device.

7. A method as in claim 6 , wherein the gas escapes from the outlet of the device by flowing around the absorbent material.

8. A method as in claim 6 , wherein the gas escapes from the outlet of the device by flowing through pores of the absorbent material.

9. A method as in claim 1 , wherein the fluid immiscible with the first and second liquids is a third liquid.

10. A method as in claim 9 , further comprising absorbing the third liquid with the absorbent material contained in the liquid containment region.

11. A method as in claim 1 , wherein the total volume of liquids introduced into the device is less than the volume of the liquid containment region.

12. A method as in claim 1 , wherein the total volume of liquids flowing in the device is less than the volume of the liquid containment region.

13. A method as in claim 1 , wherein none of the liquid flowing in the device exits the device during use.

14. A method as in claim 1 , wherein the microfluidic network does not include any channel intersections.

15. A method as in claim 1 , wherein the liquid containment region comprises a first, hydrophilic absorbent material and a second, hydrophobic absorbent material.

16. A method as in claim 1 , wherein the first and second liquids are aqueous solutions and the third liquid is hydrophobic.

17. A method as in claim 1 , comprising absorbing substantially all of the liquid flowing in the device in the liquid containment region.

18. A method as in claim 1 , wherein the liquid containment region is a waste reservoir.

19. A method, comprising:

in a device including a microfluidic network containing a first liquid comprising a first component for a chemical and/or biological reaction and a wash solution stored in one or more channels of the device, wherein a port of the one or more channels of the device is sealed, performing the steps of:

unsealing the port;

inserting both an inlet and an outlet of a sample introduction component containing a sample into ports of the device, wherein upon insertion, the inlet of the sample introduction component is downstream of the first and second plugs, and the outlet of the sample introduction component is upstream of a reaction area of the microfluidic network;

introducing the sample into the device downstream of the first liquid and wash solution;

passing the sample across a reaction area of the microfluidic network;

passing the wash solution across the reaction area after the step of passing the sample across the reaction area;

passing the first liquid across the reaction area after the step of passing the wash solution across the reaction area, and causing a chemical and/or biological reaction to occur between the first component contained in the first liquid and a second component immobilized at the reaction area;

absorbing at least a portion of the first liquid with an absorbent material contained in a liquid containment region positioned upstream of an outlet of the microfluidic network; and

controlling a rate of flow of a liquid in the channel by applying a source of fluid flow to the channel,

wherein the act of absorbing does not substantially control the flow rate of a liquid flowing in the channel upstream of the liquid containment region and wherein the rate of flow is at least 10 times greater than the rate of absorbing.

20. A method as in claim 1 , wherein the device comprises a detector positioned downstream of the liquid containment region.

21. A method as in claim 1 , wherein the absorbent material is not accessible via an outlet of the device.

22. A method as in claim 1 , wherein a total volume occupied by the absorbent material prior to first use of the device, including the volume occupied by any pores present in the absorbent material, is less than 100% but greater than 40% of the volume of the liquid containment region.

23. A method as in claim 1 , wherein the liquid containment region comprises a disinfectant stored therein prior to use of the device.

24. A method as in claim 1 , wherein the first and second plugs are stored in the channel of the device prior to first use of the device.

25. A method as in claim 24 , wherein the first and second plugs are not in fluid communication with the liquid containment region prior to first use of the device.

26. A method as in claim 20 , wherein the detector is adapted and arranged such that upon detection of a liquid downstream of the liquid containment region, a signal is sent to a control system which can shut down or modulate a source of fluid flow that controls the rate of flow of liquids in the channel.

27. A method as in claim 1 , comprising detecting a component contained in the first fluid and/or the second fluid at the reaction area using a detector associated with the reaction area.

28. A method as in claim 1 , wherein the reaction area includes a first component immobilized therein, the method comprising causing a chemical and/or biological interaction to occur between the first component and a second component contained in the second liquid.

29. A method as in claim 28 , wherein the first liquid comprises a wash solution, the method comprising passing the first liquid across the reaction area prior to the step of causing the chemical and/or biological interaction to occur.

30. A method as in claim 2 , comprising applying the vacuum source at a constant pressure during the step of passing at least a portion of the first liquid and/or the second liquid across the reaction area and the absorbing step.

31. A method as in claim 1 , wherein the microfluidic network comprises a connecting channel fluidly connecting the outlet with the liquid containing region, and wherein the connecting channel has a length of at least 1 cm.

32. A method as in claim 31 , comprising trapping any of the first or second liquids exiting the liquid containment region in the connecting channel.

33. A method as in claim 19 , wherein the microfluidic network comprises a connecting channel fluidly connecting the outlet with the liquid containing region, and wherein the connecting channel has a length of at least 1 cm.

34. A method as in claim 33 , comprising trapping any of the first or second liquids exiting the liquid containment region in the connecting channel.

35. A method as in claim 1 , wherein the liquid containment region is in fluidic communication with the outlet.

36. A method as in claim 19 , wherein the liquid containment region is in fluidic communication with the outlet.

37. A method as in claim 1 , wherein the step of introducing the sample into the device comprises transferring the sample from the sample introduction component to the device while the first and second plugs are substantially stationary.

38. A method as in claim 1 , wherein the sample introduction component remains attached to the device during the steps of passing the sample and the first plug across the reaction area.

Assignments (5)
CORRECTIVE ASSIGNMENT TO CORRECT THE ASSIGNEE NAME AND NATURE OF CONVEYANCE PREVIOUSLY RECORDED ON REEL 027956 FRAME 0020. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNEE NAME IS CLAROS MERGER SUBSIDIARY, LLC UNDER THE NAME OF CLAROS DIAGNOSTICS, LLC AND NATURE OF CONVEYANCE IS A MERGER. Recorded May 31, 2012
From: CLAROS DIAGNOSTICS, INC.
To: CLAROS MERGER SUBSIDIARY, LLC UNDER THE NAME OF CLAROS DIAGNOSTICS, LLC
Reel/Frame 028306/0319 →
CHANGE OF NAME Recorded Mar 29, 2012
From: CLAROS DIAGNOSTICS, INC.
To: CLAROS DIAGNOSTICS, LLC
Reel/Frame 027956/0020 →
CHANGE OF NAME Recorded Mar 29, 2012
From: CLAROS DIAGNOSTICS, LLC
To: OPKO DIAGNOSTICS, LLC
Reel/Frame 027956/0076 →
NUNC PRO TUNC ASSIGNMENT Recorded Dec 3, 2008
From: LINDER, VINCENT; STEINMILLER, DAVID; TAYLOR, JASON
To: CLAROS DIAGNOSTICS, INC.
Reel/Frame 021921/0392 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 8, 2008
From: LINDER, VINCENT; STEINMILLER, DAVID; TAYLOR, JASON
To: CLAROS DIAGNOSTICS, INC.
Reel/Frame 021648/0089 →
Continuity (2)
Provisional Application 60994412 · Sep 19, 2007
Related Publication 20090075390A1 · Mar 19, 2009