Microfabricated structures for facilitating fluid introduction into microfluidic devices

• US 6,090,251 A
• Filed: 06/06/1997
• Issued: 07/18/2000
• Est. Priority Date: 06/06/1997
• Status: Expired due to Term

• Current Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Original Assignee: Caliper Holdings Incorporated
• Inventors: Parce, J. Wallace, Chow, Calvin Y. H., Sundberg, Steven A.
• Primary Examiner(s): Till, Terrence R.
• Assistant Examiner(s): Olsen, Kaj K.
• Application Number:
  US08/870,944
• Time in Patent Office: 1,138 Days
• Field of Search: 204/450, 204/451, 204/453, 204/601, 204/604, 204/600, 422/100, 436/174, 436/180
• 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 microfluidic system comprising:

a substrate having an upper surface, a lower surface, and a microfluidic channel disposed between the upper surface and the lower surface;

a wall in the substrate bordering a port for receiving a fluid, the port in fluid communication with the channel, the port open at the upper surface and at the lower surface of the substrate, the port having a cross-section capable of inducing sufficient capillary force in the fluid to restrain the fluid within the port; and

a mechanism to transport the fluid to the port from outside the substrate, the transport mechanism including a pin which extends downward toward the port to transfer fluid on the pin to the port.

2. A microfluidic system as claimed in claim 1, further comprising a surface disposed below the port and separated from the lower surface of the substrate for collecting and removing fluid from the port.

3. A microfluidic system as claimed in claim 2, further comprising a rod extending upward from the surface toward the port to promote decanting of the fluid from the port.

4. A microfluidic system as claimed in claim 3, wherein the lower surface comprises a hydrophobic material, and wherein the rod comprises a hydrophilic material.

5. A microfluidic system as claimed in claim 1, further comprising a plurality of ports and an associated plurality of transport mechanisms.

6. A microfluidic system comprising:

a substrate having an upper surface, a lower surface, and a microfluidic channel disposed between the upper surface and the lower surface, the lower surface of the substrate comprising a hydrophobic material;

a wall in the substrate bordering a port for receiving a fluid, the port in fluid communication with the channel, the port open at the upper surface and at the lower surface of the substrate;

a mechanism to transport the fluid to the port from outside the substrate, the transport mechanism including a pin which extends downward toward the port to transfer fluid on the pin to the port;

a surface disposed below the port and separated from the lower surface of the substrate for collecting and removing fluid from the port; and

a rod extending upward from the surface toward the port to promote decanting of the fluid from the port, the rod comprising a hydrophilic material.

7. A method for introducing a fluid into a microfluidic channel of a substrate, the method comprising:

transporting the fluid from outside the substrate to a port of the substrate through an opening in a first surface, the port extending through the substrate and having an opening on a second surface of the substrate, the microfluidic channel of the substrate being in fluid communication with the port between the first and second surfaces;

restraining the fluid within the port with a capillary force between the port and the fluid; and

moving material from the port into the channel during the restraining step.

8. A method as claimed in claim 7, wherein the moving step comprises electrokinetically injecting the material from the port into the channel.

9. A method as claimed in claim 7, further comprising expelling the fluid from the port through the second surface.

10. A method as claimed in claim 9, further comprising transporting another fluid through the first surface and into the port.

11. A method as claimed in claim 7, further comprising simultaneously transporting a plurality of fluid samples into an associated plurality of ports which extend through the substrate, retaining each sample within an associated port at least in part with capillary force, and simultaneously expelling the samples from the ports through the second surface with a pressure differential.

12. A method as claimed in claim 7, further comprising applying a vacuum to draw the fluid from the port into the channel.

13. A method as claimed in claim 7, wherein a wall material borders the port, and further comprising inhibiting smearing of the fluid along the lower surface with a hydrophobic material which is different than the wall material.

14. A method as claimed in claim 13, further comprising simultaneously expelling a plurality of fluids through the lower surface from a plurality of ports by applying a pressure differential between the upper surface and the lower surface, wherein the inhibiting step avoids cross-contamination of the fluids during the expelling step.

15. A method as claimed in claim 7, wherein the port cross-section is larger than the channel cross-section so that the port acts as a reservoir of the fluid during the moving step.

16. A method as claimed in claim 7, wherein the channel has a channel cross-section and the port has an open cross-section through the substrate from the opening on the first surface to the opening on the second surface, the open cross-section being larger than the channel cross-section, wherein the restraining step comprises inducing the capillary force with the open cross-section of the port.

17. A method for introducing a fluid into a microfluidic channel of a substrate, the method comprising:

transporting the fluid from outside the substrate to a port of the substrate through an opening in a first surface by advancing a pin downward toward the port from above the first surface so that a volume of the fluid on the pin wicks from the pin into the port, the port extending through the substrate and having an opening on a second surface of the substrate, the microfluidic channel of the substrate being in fluid communication with the port between the first and second surfaces; and

restraining the fluid within the port with a capillary force between the port and the fluid.

18. A microfluidic system comprising:

a substrate having an upper surface, a lower surface, and a microfluidic channel disposed between the upper surface and the lower surface, the lower surface comprising a hydrophobic material;

a wall in the substrate bordering a port for receiving a fluid, the port in fluid communication with the channel, the port open at the upper surface and at the lower surface of the substrate, the wall comprising a different material than the hydrophobic material and the port having a cross-section capable of inducing sufficient capillary force in the fluid to restrain the fluid within the port.

19. A microfluidic system as claimed in claim 18, further comprising a plurality of ports open at the upper surface and at the lower surface, the lower surface being sufficiently hydrophobic to avoid cross-contamination of fluids between the ports.

20. A microfluidic system as claimed in claim 19, wherein the ports define an array, and further comprising an associated array of pins advanceable downward to the ports so as to transfer the fluids from the pins to the associated ports.

21. A microfluidic system as claimed in claim 18, wherein the hydrophobic material comprises a coating.

22. A microfluidic system as claimed in claim 18, wherein the port has a cross-section capable of inducing sufficient capillary force in the fluid to restrain the fluid within the port.