Microfabricated structures for facilitating fluid introduction into microfluidic devices

• US 6,451,188 B1
• Filed: 03/30/2000
• Issued: 09/17/2002
• Est. Priority Date: 06/06/1997
• Status: Expired due to Term

• Current Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Original Assignee: Caliper Technologies Corp (Revvity, Inc.)
• Inventors: Parce, J. Wallace, Chow, Calvin Y. H., Sundberg, Steven A.
• Primary Examiner(s): Warden, Sr., Robert J.
• Assistant Examiner(s): Olsen, Kaj K.
• Application Number:
  US09/539,671
• Publication Number:
  US 20020084185A1
• Time in Patent Office: 901 Days
• Field of Search: 204/453, 204/604, 436/180, 422/100
• US Class Current: 204/453
• CPC Class Codes: B01J 19/0093 Microreactors, e.g. miniaturised or microfabricated reactors laboratory containers with capillary fluid transport in microfabricated channels or chambers B01L3/5027
• CPC Class Codes: B01J 2219/00783 Laminate assemblies, i.e. the reactor comprising a stack of plates
• CPC Class Codes: B01J 2219/00826 Quartz
• CPC Class Codes: B01J 2219/00831 Glass
• CPC Class Codes: B01J 2219/00833 Plastic
• CPC Class Codes: B01J 2219/00853 Employing electrode arrangements
• CPC Class Codes: B01J 2219/00891 Feeding or evacuation
• CPC Class Codes: B01J 2219/00909 using filters
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0418 electro-osmotic flow [EOF]
• CPC Class Codes: B01L 2400/0421 electrophoretic flow
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0688 surface tension valves, capillary stop, capillary break
• CPC Class Codes: B01L 3/0244 using pins
• CPC Class Codes: B01L 3/0262 using touch-off at substrate or container
• CPC Class Codes: B01L 3/5025 : for parallel transport of multiple samples
• CPC Class Codes: B01L 3/50255 : Multi-well filtration
• 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 3/502723 : characterised by venting arrangements
• 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 3/502753 : characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation separation in general B01D; microapparatus for analysis using electrophoresis G01N27/44791; sample preparation G01N1/28
• CPC Class Codes: G01N 2035/00237 : Handling microquantities of analyte, e.g. microvalves, capillary networks
• CPC Class Codes: G01N 2035/1037 : Using surface tension, e.g. pins or wires
• CPC Class Codes: G01N 27/44743 : Introducing samples
• CPC Class Codes: G01N 27/44791 : Microapparatus sample containers with integrated microfluidic structures B01L3/5027
• CPC Class Codes: Y10T 436/25125 : Digestion or removing interfering materials
• CPC Class Codes: Y10T 436/25375 : Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

Fluid introduction is facilitated through the use of a port which extends entirely through a microfluidic substrate. Capillary forces can be used to retain the fluid within the port, and a series of samples or other fluids may be introduced through a single port by sequentially blowing the fluid out through the substrate and replacing the removed fluid with an alternate fluid, or by displacing the fluid in part with additional fluid. In another aspect, microfluidic substrates have channels which varying in cross-sectional dimension so that capillary action spreads a fluid only within a limited portion of the channel network. In yet another aspect, the introduction ports may include a multiplicity of very small channels leading from the port to a fluid channel, so as to filter out particles or other contaminants which might otherwise block the channel at the junction between the channel and the introduction port.

Claims

1. A method for introducing a plurality of fluids into a microfluidic substrate, the method comprising:

inserting a first fluid into a port of the substrate, the port extending entirely through the substrate from an upper surface to a lower surface thereof;

transferring a portion of the first fluid from the port into a microfluidic channel of the substrate;

removing a non-transferred portion of the first fluid from the port; and

inserting a second fluid into the port.

2. A method as claimed in claim 1, wherein the first fluid is inserted through a first surface of the substrate and removed through a second surface of the substrate substantially opposite the first surface in location.

3. A method as claimed in claim 2, further comprising applying differential pressure between the first surface and the second surface to urge the first fluid from the port.

4. A method as claimed in claim 3, wherein the differential pressure comprises a differential gas pressure.

5. A method as claimed in claim 4, wherein a plurality of non-transferred portions of fluid are removed from a plurality of ports by differential pressure.

6. A method as claimed in claim 5, wherein the plurality of non-transferred portions are removed simultaneously by the differential pressure.

7. A method as claimed in claim 5, wherein a first material defines walls of the ports, and wherein a second material defines the second surface between the ports, the second material being more hydrophobic than the first material.

8. A method as claimed in claim 5, further comprising simultaneously transferring fluids from a plurality of fluid dispensing structures to the plurality of ports.

9. A method as claimed in claim 8, wherein the fluids are transferred from outer surfaces of a plurality of pins.

10. A method as claimed in claim 5, further comprising collecting the non-transferred portions of fluid with a fluid collection surface, and decanting the non-transferred portions of fluid from the ports with structures protruding upward from the fluid collection surface.

11. A method as claimed in claim 1, wherein at least some of the portion of the first fluid remains in the channel during removal of the first fluid and insertion of the second fluid.

12. A method as claimed in claim 11, wherein a plurality of differing fluids sequentially have portions transferred from the port to the channel while at least some of the portion of the first fluid is disposed within a microfluidic channel system of the substrate.

13. A method as claimed in claim 1, wherein capillary forces between the first fluid and walls of the ports are sufficient to restrain the first fluid in the port between insertion of the first fluid and removal of the first fluid from the port.