Microfluidic chemostat

• US 7,407,799 B2
• Filed: 12/14/2004
• Issued: 08/05/2008
• Est. Priority Date: 01/16/2004
• Status: Expired due to Fees

• Current Assignee: California Institute of Technology
• Original Assignee: California Institute of Technology
• Inventors: Quake, Stephen R., Hansen, Carl L., Balagadde, Frederick, Kartalov, Emil
• Primary Examiner(s): Weber; Jon P
• Assistant Examiner(s): Srivastava; Kailash C
• Application Number:
  US11/012,852
• Publication Number:
  US 20050164376A1
• Time in Patent Office: 1,330 Days
• Field of Search: 435/288.5, 435/289.1, 435/294.1, 435/297.1, 435/293.1, 435/304.2, 435/306.1
• US Class Current: 435/289.1
• CPC Class Codes: B01L 2300/0861 Configuration of multiple channels and/or chambers in a single devices
• CPC Class Codes: B01L 2300/0877 Flow chambers
• CPC Class Codes: B01L 2300/10 Means to control humidity and/or other gases
• CPC Class Codes: B01L 2300/163 Biocompatibility
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0655 pinch valves
• 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 3/502738 characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: C12M 23/16 Microfluidic devices; Capillary tubes integrated microfluidic structures B01L3/5027; microreactors B01J19/0093
• CPC Class Codes: C12M 23/34 Internal compartments or partitions
• CPC Class Codes: C12M 39/00 Means for cleaning the apparatus or avoiding unwanted deposits of microorganisms apparatus for cleaning laboratory receptacles or instruments B01L13/02; cleaning in general B08B
• CPC Class Codes: C12P 1/00 Preparation of compounds or compositions, not provided for in groups C12P3/00 - C12P39/00, by using microorganisms or enzymes
• CPC Class Codes: C12P 19/04 Polysaccharides, i.e. compounds containing more than five saccharide radicals attached to each other by glycosidic bonds

Abstract

A chemostat is described that includes a growth chamber having a plurality of compartments. Each of the compartments may be fluidly isolated from the rest of the growth chamber by one or more actuatable valves. The chemostat may also include a nutrient supply-line to supply growth medium to the growth chamber, and an output port to remove fluids from the growth chamber. Also, a method of preventing biofilm formation in a growth chamber of a chemostat is described. The method may include the steps of adding a lysis agent to a isolated portion of the growth chamber, and reuniting the isolated portion with the rest of the growth chamber.

Claims

1. A chemostat chip comprising one or more chemostats, wherein each of the chemostats includes a first compartment adaptable to hold one or more cells and a second compartment adaptable to receive a lysis agent, and wherein the first and second compartments are separated by an actuatable valve that when opened can permit the one or more cells to travel from the first compartment to the second compartment, and when closed can isolate the one or more cells in the second compartment before exposing the second compartment to the lysis agent, wherein

said chemostat chip further comprises a growth chamber having a plurality of compartments;

wherein each of the compartments may be fluidly isolated from the rest of the growth chamber by one or more actuatable valves;

wherein the compartments of the growth chamber are connected in a loop;

a nutrient supply-line to supply growth medium to the growth chamber; and

an output port to remove fluids from the growth chamber.

2. The chemostat chip of claim 1, wherein an actuatable supply valve controls the delivery of the lysis agent to the compartment coupled to the supply channel.

3. The chemostat chip of claim 1, wherein the second compartment is fluidly coupled to an output channel to remove materials from the compartment.

4. The chemostat chip of claim 1, wherein the growth chamber comprises a silicone elastomer.

5. The chemostat chip of claim 1, wherein the chemostat comprises a peristaltic pump to circulate fluids in the growth chamber.

6. The chemostat chip of claim 1, wherein the growth chamber comprises a volume of about 50 nanoliters or less.

7. The chemostat chip of claim 1, wherein the growth chamber comprises a volume of about 16 nanoliters or less.

8. The chemostat chip of claim 1, wherein the growth chamber has 16 compartments.

9. The chemostat chip of claim 1, wherein during operation the chemostat chip consumes growth medium at a rate of about 40 μ

L/day or less.

10. The chemostat chip of claim 3, wherein the materials removed from the compartment comprise dissolved cell components.

11. The chemostat chip of claim 3, wherein an actuatable output valve controls the removal of the materials from the compartment.

12. The chemostat chip of claim 4, wherein the silicone elastomer is polydimethylsiloxane.

13. A chemostat chip comprising an array of chemostats, wherein each of the chemostats comprises:

a growth chamber having a plurality of compartments, wherein each of the compartments may be fluidly isolated from the rest of the growth chamber by one or more actuatable valves to give the growth chamber a variable volume;

a nutrient supply-line to supply growth medium to the growth chamber; and

an output port to remove fluids from the growth chamber.

14. The chemostat chip of claim 13, wherein the chip comprises six or more chemostats.

15. The chemostat chip of claim 13, wherein the chip has a thickness of about 5 mm or less.