Fluidic connectors and microfluidic systems

• US 8,202,492 B2
• Filed: 05/01/2008
• Issued: 06/19/2012
• Est. Priority Date: 05/04/2007
• Status: Active Grant

• Current Assignee: Opko Diagnostics, LLC (Opko Health, Inc.)
• Original Assignee: Opko Diagnostics, LLC (Opko Health, Inc.)
• Inventors: Linder, Vincent, Steinmiller, David, Sia, Samuel K.
• Primary Examiner(s): Sines, Brian J
• Application Number:
  US12/113,503
• Publication Number:
  US 20080273918A1
• Time in Patent Office: 1,510 Days
• Field of Search: 422/50, 422/68.1, 422/502, 422/503, 436/43, 436/63
• US Class Current: 422/503
• CPC Class Codes: B01L 2200/025 Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/0689 Sealing
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2200/12 Specific details about manufacturing devices
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/021 Identification, e.g. bar codes
• CPC Class Codes: B01L 2300/041 Connecting closures to device or container
• CPC Class Codes: B01L 2300/0627 Sensor or part of a sensor is integrated
• CPC Class Codes: B01L 2300/0672 Integrated piercing tool
• CPC Class Codes: B01L 2300/0838 Capillaries
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• CPC Class Codes: B01L 2300/12 Specific details about materials
• CPC Class Codes: B01L 2400/049 vacuum
• 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 3/502707 characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/502761 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: B01L 3/563 Joints or fittings in general F16L; Separable fluid transfer means to transfer fluids between at least two containers, e.g. connectors
• CPC Class Codes: B01L 3/565 Seals in general F16L
• CPC Class Codes: C12Q 1/6834 : Enzymatic or biochemical coupling of nucleic acids to a solid phase
• CPC Class Codes: G01F 22/00 : Methods or apparatus for measuring volume of fluids or fluent solid material, not otherwise provided for
• CPC Class Codes: G01N 21/6428 : Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 33/5302 : Apparatus specially adapted for immunological test procedures
• CPC Class Codes: G01N 33/5304 : Reaction vessels, e.g. agglutination plates for solid-phase systems G01N33/543
• CPC Class Codes: G01N 33/5306 : Improving reaction conditions, e.g. reduction of non-specific binding, promotion of specific binding
• CPC Class Codes: G01N 33/54366 : Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 33/545 : Synthetic resin
• CPC Class Codes: Y10T 403/22 : with fluid pressure responsive component
• CPC Class Codes: Y10T 436/11 : Automated chemical analysis
• CPC Class Codes: Y10T 436/25 : including sample preparation
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

Fluidic connectors, methods, and devices for performing analyses (e.g., immunoassays) in microfluidic systems are provided. In some embodiments, a fluidic connector having a fluid path is used to connect two independent channels formed in a substrate so as to allow fluid communication between the two independent channels. One or both of the independent channels may be pre-filled with reagents (e.g., antibody solutions, washing buffers and amplification reagents), which can be used to perform the analysis. These reagents may be stored in the channels of the substrate for long periods amounts of time (e.g., 1 year) prior to use. Prior to connection of the fluid connector and the substrate, the fluid path may be filled with a sample (e.g., blood). The sample may be obtained, for example, by pricking a finger of a user until blood is drawn from the finger into the fluid path (e.g., by capillary forces). Upon connection of the fluidic connector and the channels of the substrate, the sample can pass through a reaction area within the first channel of the substrate. This process can allow components of the sample to interact with components disposed in the reaction area. Afterwards, reagents from the second channel can flow to the reaction area via the fluid path, allowing components in the reaction area to be processed (e.g., amplified to produce detectable signal). Components in the reaction area can then be determined using various methods of detection.

Claims

1. A device in combination with at least first and second reagents, comprising:

a substrate comprising a microfluidic system comprising a first microfluidic channel including at least one inlet and one outlet, a second microfluidic channel including at least one inlet and one outlet, and a reaction area in fluid communication with the second microfluidic channel;

a first reagent disposed in the first microfluidic channel, wherein the first reagent is a liquid reagent;

a seal covering, the inlet of the first microfluidic channel and a seal covering the outlet of the first microfluidic channel so as to store the first reagent in the first microfluidic channel;

a second reagent disposed in the reaction area, wherein the second reagent is a substantially dry reagent; and

a fluidic connector that can be connected to the substrate, wherein the fluidic connector comprises a fluid path including a fluid path inlet and a fluid path outlet, wherein upon connection, the fluid path inlet connects to the outlet of the first microfluidic channel to allow fluid communication between the fluid path and the first microfluidic channel, and the fluid path outlet connects to the inlet of the second microfluidic channel to allow fluid communication between the fluid path and the second microfluidic channel,

wherein the first and second microfluidic channels are not in fluid communication with one another absent connection via the fluidic connector.

2. A device in combination with at least first and second reagents as in claim 1, wherein the microfluidic system is an open-loop system.

3. A device in combination with at least first and second reagents as in claim 1, wherein the first microfluidic channel comprises a third reagent disposed therein.

4. A device in combination with at least first and second reagents as in claim 3, wherein the third reagent is a liquid reagent.

5. A device in combination with at least first and second reagents as in claim 4, wherein the first and third reagents are separated by a fluid that is immiscible with said first and third reagents.

6. A device in combination with at least first and second reagents as in claim 1, comprising a seal covering the inlet of the second microfluidic channel and a seal covering the outlet of the second microfluidic channel.

7. A device in combination with at least first and second reagents as in claim 1, wherein the second reagent in the second microfluidic channel comprises at least one of an antibody or an antigen.

8. A device in combination with at least first and second reagents as in claim 1, wherein the second reagent in the second microfluidic channel is adsorbed to a surface of the second microfluidic channel.

9. A device in combination with at least first and second reagents as in claim 1, wherein the seal covering the inlet and/or the seal covering the outlet of the first microfluidic channel is a tape.

10. A device in combination with at least first and second reagents as in claim 1, wherein the reaction area allows detection of a chemical and/or biological reaction in the reaction area.

11. A device in combination with at least first and second reagents as in claim 1, wherein the reaction area comprises at least one meandering channel region.

12. A device in combination with at least first and second reagents as in claim 11, wherein the reaction area comprises at least two meandering channel regions connected in series.

13. A device in combination with at least first and second reagents as in claim 12, wherein each of the at least two meandering channel regions comprises a chemical and/or biological species that can undergo a chemical and/or biological reaction.

14. A device in combination with at least first and second reagents as in claim 1, wherein the reaction area comprises at least one cross-sectional dimension of less than 100 microns.

15. A device in combination with at least first and second reagents as in claim 1, wherein the microfluidic system includes less than 2 channel intersections.

16. A device in combination with at least first and second reagents as in claim 1, wherein the microfluidic system does not include any channel intersections.

17. A device in combination with at least first and second reagents as in claim 1, wherein the fluid path of the fluidic connector has a first volume and further comprises a volume control element that allows introduction of a controlled volume of fluid less than the first volume into the fluid path prior to connection of the fluidic connector to the microfluidic system.

18. A device in combination with at least first and second reagents as in claim 1, further comprising a source of vacuum that can be connected to an outlet.

19. A device in combination with at least first and second reagents as in claim 1, wherein the fluidic connector comprises at least one non-fluidic feature complementary to a feature of the substrate so as to form a non-fluidic connection between the fluidic connector and the substrate upon connection.

20. A device in combination with at least first and second reagents as in claim 1, wherein the fluidic connector comprises at least one feature complementary to a feature of the substrate so as to form an irreversible connection between the fluidic connector and the substrate.

21. A device in combination with at least first and second reagents as in claim 1, wherein the fluidic connector further comprises a sampling element that can receive a fluid sample from a biological entity.

22. A device in combination with at least first and second reagents as in claim 21, wherein the fluidic connector can allow transfer of fluid from the biological entity to the fluid path.

23. A device in combination with at least first and second reagents as in claim 1, comprising an alignment element associated with the substrate, extending from the substrate and comprising a cavity constructed and arranged to receive and engage the fluidic connector and thereby position the connector in a predetermined, set configuration relative to the substrate.

24. A device in combination with at least first and second reagents as in claim 23, wherein the fluidic connector is adapted to be inserted into the alignment element by a sliding motion.

25. A device in combination with at least first and second reagents as in claim 23, wherein the alignment element extends approximately perpendicular to the substrate.

26. A device in combination with at least first and second reagents as in claim 23, wherein the alignment element comprises an engaging component constructed and arranged to engage a portion of the fluidic connector to create a substantial resistance to movement of the fluidic connector relative to the alignment element upon the alignment element receiving the fluidic component.

27. A device in combination with at least first and second reagents as in claim 5, wherein the fluid immiscible with the first and third reagents is a gas.

28. A device in combination with at least first and second reagents as in claim 27, wherein at least one of the first and second reagents is a rinse solution.

29. A device in combination with at least first and second reagents as in claim 1, wherein the substrate comprises more than one substrate layers that are mated to one another.

30. A device in combination with at least first and second reagents as in claim 1, wherein the fluid path of the fluidic connector contains a sample or a reagent disposed therein prior to connection of the fluidic connector to the substrate.

31. A device in combination with at least first and second reagents as in claim 1, wherein the fluidic connector comprises a substantially planar substrate comprising a channel formed in at least a portion of the substantially planar substrate.

32. A device in combination with at least first and second reagents as in claim 1, wherein the fluidic connector comprises a monolithic device comprising a channel formed in at least a portion of the monolithic device.

33. A device in combination with at least first and second reagents as in claim 1, wherein the fluid path of the fluidic connector has a volume between 1 μ

L and 1000 μ

L.

34. A device in combination with at least first and second reagents as in claim 1, wherein the fluidic connector comprises a tube.