Microfabricated structures for facilitating fluid introduction into microfluidic devices

• US 20020179447A1
• Filed: 07/30/2002
• Published: 12/05/2002
• Est. Priority Date: 06/06/1997
• Status: Active Grant

• 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.
• Granted Patent: US 6,709,559 B2
• Time in Patent Office: Days
• 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 samples into a microfluidic substrate, the method comprising:

forming a volume of each sample on an associated pin, the pins arranged in an array;

aligning the array of pins with an array of ports on the substrate; and

bringing the aligned pins and ports together so that the volumes transfer from the pins to associated ports of the substrate.

18. A filtered microfluidic system as claimed in claim 1, wherein the header channel extends circumferentially around the reservoir.

2. 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;

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

removing an unused portion of the first fluid from the port; and

inserting a second fluid into the port.

3. A method as claimed in claim 2, 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.

4. A method as claimed in claim 2, wherein fluid remains in the channel during removal of the first fluid and insertion of the second fluid.

5. A microfluidic system comprising:

a substrate having a first microfluidic channel and a capillary limit region; and

a second microfluidic channel in fluid communication with the first channel through the limit region, the second channel having a cross-sectional dimension adjacent the limit region which is larger than a cross-sectional dimension of the limit region to inhibit wicking from the limit region into the second channel.

6. A microfluidic system as claimed in claim 5, wherein a minimum cross-sectional dimension of the limit region is sufficiently smaller than a minimum cross-sectional dimension of the second channel that differential capillary forces prevent fluid from wicking from the first channel through the limit region and into the second channel when no fluid is present in the second channel.

7. A microfluidic system as claimed in claim 5, wherein the second channel includes a first end and a second end, wherein the limit region is disposed at an end of the first channel, and wherein the limit region intersects the second channel between the first and second ends.

8. A microfluidic system as claimed in claim 7, further comprising a first fluid which extends through the first channel and substantially through the capillary limit region, and a second fluid which is different than the first fluid, the second fluid disposed within the second channel.

9. A microfluidic system as claimed in claim 8, further comprising a plurality of first channels extending from a cross channel, each first channel being in fluid communication with the second channel through an associated limit region, the header channel, the first channels and the limit regions containing a polymer solution suitable for electrophoretic sample manipulation, the second channel containing a buffer fluid for electroosmotic manipulation of samples.

10. A method for controllably distributing fluids within microfluidic substrates, the method comprising:

wicking a first fluid along a first channel and into a capillary limit region; and

preventing the first fluid from wicking beyond the limit region and into a second channel with differential capillary force.

11. A method as claimed in claim 10, wherein the differential capillary force of the preventing step is produced by an increase in a minimum cross-sectional dimension from the limit region to the second channel.

12. A method as claimed in claim 10, further comprising wicking a second fluid along the second channel beyond an intersection of the second channel and the limit region to define an interface between the first fluid and the second fluid.

14. A filtered microfluidic system as claimed in claim 13, wherein the filter channel cross-sectional dimensions are capable of preventing the transport of particles from the reservoir through the filter channels which are large enough to block the microfluidic channel.

15. A filtered microfluidic system as claimed in claim 14, wherein a sum of the cross-sections of the filter channel is larger than the cross-section of the fluid channel to minimize head loss when at least one of the filter channels is blocked.

16. A filtered microfluidic system as claimed in claim 15, wherein each filter channel has a first end and a second end, the first end opening to the reservoir, the second end opening to a header channel, the microfluidic channel being in fluid communication with the filter channels through the header channel.

17. A filtered microfluidic system as claimed in claim 16, wherein the filter channels extend radially from the reservoir.

19. A filtered microfluidic system as claimed in claim 13, wherein the microfluidic channel has a minimum cross sectional dimension of within the range from about 1μ

m to 100 μ

m, and wherein the filter channels each have a minimum cross-sectional dimension which is less than about ½

of the minimum cross-sectional dimension of the microfluidic channel.

13. A filtered microfluidic system comprising a substrate having:

a reservoir;

a channel having a microfluidic fluid channel cross-section; and

a plurality of filter channels, each filter channel extending between the reservoir and the channel, each filter channel having a cross-sectional dimension which is smaller than a cross-sectional dimension of the microfluidic channel.

21. A method for filtering a fluid sample entering a microfluidic channel network, the method comprising:

introducing the fluid sample into a port;

passing the fluid sample through a plurality of filter channels in parallel, the filter channels blocking particles having cross sections which are larger than a maximum filter particle size; and

collecting the filtered fluid sample and transporting the filtered fluid sample through a microfluidic channel having a cross-section which is larger than the maximum filter size.

20. A filtered microfluidic system as claimed in claim 29, further comprising a port in fluid communication with the microfluidic channel, wherein fluid can enter the fluid channel from the port without passing through the filter channels.

22. A method as claimed in claim 21, further comprising introducing another fluid through another port and advancing the other fluid through the fluid channel and the filter channels prior to introducing the fluid sample.