Fluidic connectors and microfluidic systems

• US 10,408,824 B2
• Filed: 11/24/2015
• Issued: 09/10/2019
• 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:
  US14/951,095
• Publication Number:
  US 20160077087A1
• Time in Patent Office: 1,386 Days
• Field of Search: 422 681, 422502, 422503, 422504, 436 43, 436174, 436180, 436164, 436 63
• 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.

Claims

1. A method comprising:

in a fluidic device containing a first fluid, wherein the first fluid is stored in a region of the device that includes a fluid-tight, piercable seal, performing the steps of;

unsealing the fluid-tight seal;

introducing a sample into the fluidic device after the unsealing step by inserting a sample introduction component containing the sample into a port of the fluidic device, wherein the sample introduction component, when inserted into the port of the fluidic device, is downstream of the region containing the first fluid and upstream of a reaction area of the fluidic device;

passing the sample across the reaction area of the fluidic device;

passing the first fluid across the reaction area after the step of passing the sample across the reaction area; and

determining a component of the sample at the reaction area.

2. The method of claim 1, wherein the sample introduction component remains attached to the fluidic device during the steps of passing the sample and the first fluid across the reaction area.

3. The method of claim 1, wherein the fluid-tight seal is a cover on a port of the fluidic device.

4. The method of claim 3, comprising inserting a sample introduction component containing the sample into the port of the fluidic device, thereby causing the cover of the port to be pierced or broken.

5. The method of claim 1, wherein the step of introducing the sample into the fluidic device comprises applying a vacuum to an outlet of the fluidic device to cause the sample to flow from the sample introduction component into the fluidic device.

6. The method of claim 1, wherein the first fluid is stored in a microfluidic channel having at least one cross-sectional dimension of less than 1 mm.

7. The method of claim 1, wherein the first fluid is a wash fluid.

8. The method of claim 1, wherein the sample introduction component comprises an inlet and an outlet, and the method comprises inserting both the inlet and outlet into ports of the fluidic device.

9. The method of claim 1, wherein the first fluid is stored along with a second fluid, and wherein the first and second fluids are separated by a third fluid that is immiscible with said first and second fluids.

10. The method of claim 9, wherein the third fluid which is immiscible with the first and second fluids is a gas.

11. The method of claim 1, wherein the first fluid is water or a buffer.

12. The method of claim 1, wherein the first fluid comprises a metal precursor.

13. The method of claim 1, wherein the reaction area comprises a channel having at least one cross-sectional dimension of less than 100 microns.

14. The method of claim 13, wherein the reaction area comprises at least one meandering channel region.

15. The method of claim 1, wherein the reaction area comprises at least two meandering channel regions connected in series.

16. The method of claim 15, wherein each of the at least two meandering channel regions comprises a chemical and/or biological species disposed therein that can undergo a chemical and/or biological reaction.

17. The method of claim 16, wherein the chemical and/or biological reaction is a binding event between at least two binding partners, and wherein at least one of the binding partners comprises an antibody.

18. The method of claim 1, wherein the reaction area comprises a substantially dry reagent contained therein.

19. The method of claim 13, wherein the reaction area comprises at least one of an antibody or an antigen adsorbed to a surface of the channel.