Microfluidic system with integrated permeable membrane

• US 20050266582A1
• Filed: 04/14/2005
• Published: 12/01/2005
• Est. Priority Date: 12/16/2002
• Status: Abandoned Application

• Current Assignee: Cytodiscovery Incorporated
• Original Assignee: Cytodiscovery Incorporated
• Inventors: Chazan, David, Modlin, Douglas N.
• Application Number:
  US11/107,983
• Publication Number:
  US 20050266582A1
• Time in Patent Office: Days
• US Class Current: 436/164
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/0636 Focussing flows, e.g. to laminate flows
• CPC Class Codes: B01L 2200/0684 Venting, avoiding backpressure, avoid gas bubbles
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0822 Slides
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2300/10 Means to control humidity and/or other gases
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0655 pinch valves
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• 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 3/502723 characterised by venting arrangements
• CPC Class Codes: B01L 3/502738 characterised by integrated valves microvalves F16K99/0001
• 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 3/502776 specially adapted for focusing or laminating flows
• CPC Class Codes: G01N 2021/0346 : Capillary cells; Microcells
• CPC Class Codes: G01N 2021/6482 : Sample cells, cuvettes
• CPC Class Codes: G01N 2021/7763 : Sample through flow
• CPC Class Codes: G01N 2021/7769 : Measurement method of reaction-produced change in sensor
• CPC Class Codes: G01N 21/05 : Flow-through cuvettes G01N21/09 takes precedence; handling fluid samples G01N1/10
• CPC Class Codes: G01N 21/253 : for batch operation, i.e. multisample apparatus analytical automats G01N35/00
• 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 21/77 : by observing the effect on a chemical indicator
• CPC Class Codes: G01N 21/78 : producing a change of colour

Abstract

A microfluidic system for performing chemical reactions or biochemical, biological, or chemical assays utilizing a microfabricated device or “chip.” The system may include, among others, an integrated membrane fabricated from a chemically inert material whose permeability for gases, liquids, cells, and specific molecules, etc. can be selected for optimum results in a desired application.

Claims

1. A microfluidic device comprising:

a fabricated substrate having at least one inlet access port disposed in said substrate;

at least one channel disposed in said substrate and connected to said inlet access port; and

a gas permeable membrane sealably attached to said substrate to cover said channel.

2. The device of claim 1 wherein said substrate comprises a material selected from the group consisting of glass, quartz, plastic, polymer, polyethylene, polypropylene, silicone, silicon, polymethylpentene, polystyrene, Teflon, and combinations thereof.

3. The device of claim 1 wherein the dimensions of said channel in width or depth are between about 1 micron and 1,000 microns.

4. The device of claim 1 wherein said membrane has sufficient gas permeability to support living cells within said channel.

5. The device of claim 1 wherein the gas permeability of said membrane to the group of gases consisting of nitrogen, oxygen, carbon dioxide, and combinations thereof is within the range of about 0.1 to about 10 Barrer units.

6. The device of claim 1 further comprising one or more of the following:

at least one outlet access port disposed in said substrate and connected to said channel;

one or more fluid chambers disposed in said substrate and connected to said channel;

a delivery mechanism for bringing one or more gases into diffusive communication with the surface of said gas permeable membrane; and

a controller for controlling the flow rate or velocity of a fluid in the channel.

7. The device of claim 1 wherein said substrate has a microscope slide or a microplate format.

8. The device of claim 1, further comprising a coating or chemical treatment on at least one surface of said channel and/or said membrane.

9. The device of claim 1 further comprising one or more cells.

10. The device of claim 1 further comprising one or more reagents wherein at least one of said reagents is present in a concentration gradient.

11. The device of claim 1 wherein a portion of the membrane can be deflected into or away from said channel or said substrate.

12. The device of claim 11, wherein said membrane can be deflected by application of a mechanical force, pneumatic pressure, or hydraulic pressure

13. An array comprising one or more positionally distinguishable devices of claim 1.

14. The array of claim 13 comprising a plurality of devices of claim 1 and further comprising a network of channels interconnecting said devices.

15. A method of performing an assay to evaluate a property of a compound comprising the steps of:

providing a device of claim 1;

introducing said compound into said device; and

evaluating said property of said compound.

16. The method of claim 15, wherein said property is said compound'"'"'s effect on at least one measurement selected from the group consisting of absorbance, transmission, reflectance, refractive index, luminescence, fluorescence intensity, fluorescence lifetime, fluorescence polarization, fluorescence anisotropy, turbidity, color, grayscale, phase contrast, differential phase contrast, function, absolute or relative position, velocity, acceleration, morphology, electrical resistance, charge, conductance, capacitance, inductance, impedance, admittance, electric potential, chemical potential, redox potential, oxygen, carbon dioxide, nitrous oxide, pH, electrical field, magnetic field, and combinations thereof.

17. The method of claim 15 wherein said assay is selected from the group consisting of apoptosis, toxicity, metabolism, viability, vitality, function, motility, migration, proliferation, chemotaxis, cell-to-cell communication, cell signaling, ion channel flux, receptor activation or inhibition, gene expression, protein expression, receptor binding, transcriptional and translational binding, enzyme activity, protein-protein interaction, nucleic acid interaction, or combinations thereof.

18. The method of claim 15, wherein said property is said compound'"'"'s effect on at least one image collected by an optical imaging device.

19. The method of claim 15 wherein either before or after said compound is introduced into said device, said method further comprises providing introducing one or more reagents into said device such that said reagents are disposed in concentration gradients in said device.

20. A method for preparing a microfluidic device having an integrated gas permeable membrane comprising the steps of:

providing a substrate having at least one channel and at least one inlet access port wherein said inlet access port is connected to said channel; and

attaching a gas permeable membrane to said substrate to cover said channel.

21. The method for preparing the device of claim 20 further comprising:

providing a package having at least one fluid well corresponding to said at least one inlet access port; and

sealably mounting said substrate in said package to form a microfluidic device.