Fluidic devices and methods for multiplex chemical and biochemical reactions

• US 8,765,454 B2
• Filed: 02/18/2005
• Issued: 07/01/2014
• Est. Priority Date: 02/18/2004
• Status: Expired due to Fees

• Current Assignee: LC Sciences LC
• Original Assignee: Erdogan Gulari, Xiaochuan Zhou, Xiaollan Gao
• Inventors: Zhou, Xiaochuan, Gulari, Erdogan, Gao, Xiaollan
• Primary Examiner(s): FORMAN, BETTY J
• Application Number:
  US10/589,860
• Publication Number:
  US 20110143964A1
• Time in Patent Office: 3,420 Days
• Field of Search: None
• US Class Current: 435/287.2
• CPC Class Codes: B01L 2200/0605 Metering of fluids
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2300/161 Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0688 surface tension valves, capillary stop, capillary break
• 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 7/52 with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples amplification or hybridisation processes per se C12Q1/68; controlling sequential reactions for synthesis B01J19/0046
• CPC Class Codes: C07H 21/04 with deoxyribosyl as saccharide radical
• CPC Class Codes: C12Q 1/686 Polymerase chain reaction [PCR]
• CPC Class Codes: C12Q 2537/143 Multiplexing, i.e. use of multiple primers or probes in a single reaction, usually for simultaneously analyse of multiple analysis
• CPC Class Codes: C12Q 2565/501 being an array of oligonucleotides
• CPC Class Codes: C12Q 2565/629 being a microfluidic device

Abstract

The present invention describes microfluidic devices that provide novel fluidic structures to facilitate the separation of fluids into isolated, pico-liter sized compartments for performing multiplexing chemical and biological reactions. Applications of the novel devices including biomolecule synthesis, polynucleotide amplification, and binding assays are also disclosed.

Claims

1. A microfluidic reaction device comprising:

a) a plurality of chambers each having a first conduit and a second conduit;

b) a first tapered transport channel having an interior surface, said first transport channel being in flow communication with at least one said chamber through connection with said first conduit;

c) a second tapered transport channel having an interior surface said second transport channel being in flow communication with at least one said chamber through connection with said second conduit;

d) a first serpentine bypass channel attached to the first tapered transport channel; and

e) a second serpentine bypass channel attached to the second tapered transport channel.

2. The microfluidic device of claim 1, wherein the interior surfaces of said first transport channel comprise a hydrophobic film.

3. The microfluidic device of claim 1, further comprising oil in said first and second transport channels and aqueous solution in said chambers.

4. The microfluidic device of claim 1, further comprising gas in said first and second transport channels and aqueous solution in said chambers.

5. The microfluidic device of claim 1, further comprising beads in said chambers.

6. The microfluidic device of claim 1, wherein the chambers and capillary chambers.

7. A microfluidic reaction device comprising:

(a) a plurality of chambers each having a first conduit and a second conduit;

(b) a first tapered transport channel having an interior surface, said first transport channel being in flow communication with at least one said chamber through connection with said first conduit; and

(c) a second tapered transport channel having an interior surface, said second transport channel being in flow communication with at least one said chamber through connection with said second conduit, wherein passing a fluid through the microfluidic device provides a volume flow rate across the plurality of chambers which is substantially uniform and wherein a first serpentine bypass channel is attached to the first tapered transport channel and a second serpentine bypass channel attached to the second tapered transport channel.

8. The microfluidic device of claim 7 wherein the flow rate variation among the chambers is 5%.

9. The microfluidic device of claim 7 wherein the flow rate variation among the chambers is 10%.

10. The microfluidic device of claim 7 wherein the flow rate variation among the chambers is 20%.

11. The microfluidic device of claim 7 wherein at least one oligonucleotide comprising a first primer and a second primer is attached to at least one chamber and wherein a first cleavable moiety is located between the first and second primer and a second cleavable moiety is located between the primers and the chamber.

12. The microfluidic device of claim 11 wherein the first and second cleavable moiety is reverse uridine.

13. The microfluidic device of claim 11, wherein the oligonucleotide further comprises one or more binding probe sequences.

14. The microfluidic device of claim 13, wherein the cross-section area of the bypass channel is substantially larger than the first conduit.

15. A symmetric microfluidic reaction device comprising:

(a) a plurality of chambers having a first conduit and a second conduit;

(b) a first tapered transport channel having an interior surface, said first transport channel being in flow communication with at least one said chamber through connection with said first conduit;

(c) a second tapered transport channel having an interior surface, said second transport channel being in flow communication with at least one said chamber through connection with said second conduit;

(d) a first serpentine bypass channel attached to the first tapered transport channel;

(e) a second serpentine bypass channel attached to the second tapered transport channel; and

(f) an inlet and outlet channel such that a fluid can be passed though the device either through the inlet or outlet channel.

16. A microfluidic reaction device comprising:

a) a plurality of chambers each having a first conduit and a second conduit wherein each chamber is surrounded by a bypass channel such that the bypass channel is in fluid communication with the first and second conduit wherein the cross-section area of the bypass channel is substantially larger than the first conduit;

b) a first tapered transport channel having an interior surface, said first transport channel being in flow communication with at least one said chamber through connection with said first conduit; and

c) a second tapered transport channel having an interior surface said second transport channel being in flow communication with at least one said chamber through connection with said second conduit.