Device incorporating a microfluidic chip for separating analyte from a sample

• US 20020055167A1
• Filed: 11/07/2001
• Published: 05/09/2002
• Est. Priority Date: 06/25/1999
• Status: Active Grant

• Current Assignee: Cepheid (Danaher Corporation)
• Original Assignee: Cepheid (Danaher Corporation)
• Inventors: Chang, Ronald, Petersen, Kurt E., Northrup, M. Allen, McMillan, William A., Pourahmadi, Farzad, Christel, Lee A., Ching, Jesus, Kovacs, Gregory T.A.
• Granted Patent: US 6,664,104 B2
• Time in Patent Office: Days
• US Class Current: 435/287.2
• CPC Class Codes: B01L 2400/0622 distribution valves, valves having multiple inlets and/or outlets, e.g. metering valves, multi-way valves
• CPC Class Codes: B01L 2400/0644 rotary valves
• CPC Class Codes: C12M 47/06 Hydrolysis; Cell lysis; Extraction of intracellular or cell wall material lysis of microorganisms C12N1/06; extracting or separating nucleic acids from biological samples C12N15/1003

Abstract

A device for separating an analyte from a fluid sample comprises a cartridge having a sample port and a first flow path extending from the sample port. A microfluidic chip is positioned in the first flow path. The microfluidic chip includes an extraction chamber having an array of microstructures for capturing the analyte from the sample as the sample flows through the extraction chamber and for subsequently releasing the captured analyte into an elution fluid as the elution fluid flows through the extraction chamber. Each of the microstructures has an aspect ratio of at least 2:1. The cartridge also includes a second flow path for eluting the captured analyte from the microfluidic chip, the second flow path diverging from the first flow path after passing through the chip. At least one flow controller directs the sample into the first flow path and the eluted analyte into the second flow path.

Claims

1. A device for separating an analyte from a fluid sample, the device comprising a cartridge having:

a) a sample port for introducing the sample into the cartridge;

b) a first flow path extending from the sample port;

c) a microfluidic chip positioned in the first flow path, the microfluidic chip comprising a body having formed therein;

i) an extraction chamber;

ii) an inlet port in fluid communication with the extraction chamber;

iii) an outlet port in fluid communication with the extraction chamber, wherein the inlet and outlet ports are positioned to permit fluid flow through the extraction chamber and out of the microfluidic chip; and

iv) an array of microstructures, integrally formed with at least one wall of the extraction chamber and extending into the extraction chamber, for capturing the analyte from the sample as the sample flows through the extraction chamber and for subsequently releasing the captured analyte into an elution fluid as the elution fluid flows through the extraction chamber, wherein each of the microstructures has an aspect ratio of at least 2;

1;

d) a second flow path for eluting the captured analyte from the microfluidic chip, wherein the second flow path passes through the chip and diverges from the first flow path after passing through the chip; and

e) at least one flow controller for directing the sample into the first flow path after the sample flows through the microfluidic chip and for directing the eluted analyte into the second flow path.

2. The device of claim 1, wherein the cartridge includes a lysing region in the first flow path, upstream of the extraction chamber, for lysing cells, spores, or microorganisms in the sample.

3. The device of claim 2, wherein the lysing region comprises a lysing chamber containing a solid phase for capturing the cells, spores, or microorganisms, and wherein the lysing chamber has a wall for contacting an ultrasonic transducer to effect the transfer of ultrasonic energy to the lysing chamber.

4. The device of claim 3, wherein the solid phase comprises a membrane or filter, and the device further comprises beads in the lysing chamber for rupturing the cells, spores, or microorganisms.

5. The device of claim 2, wherein the cartridge further includes a reagent chamber in fluid communication with the lysing region for holding a lysing reagent and for releasing the lysing reagent into the lysing region.

6. The device of claim 1, wherein the cartridge comprises a plastic body defining the first and second flow paths, and wherein the chip comprises a microfabricated structure enclosed within the plastic body.

7. The device of claim 1, wherein the cartridge further includes a waste chamber in fluid communication with the microfluidic chip via the first flow path for receiving the remaining sample after the sample flows through the microfluidic chip.

8. The device of claim 1, wherein each of the microstructures has an aspect ratio of at least 4:

1.

9. The device of claim 1, wherein each of the microstructures has a ratio of cross-sectional length to width of at least 4:

1.

10. The device of claim 1, further comprising a heating element for heating the microstructures.

11. The device of claim 10, wherein the heating element comprises a resistive heating element deposited on the chip.

12. The device of claim 1, wherein the cartridge further includes a reagent chamber in fluid communication with the microfluidic chip via the second flow path for mixing the eluted analyte with a reagent.

13. The device of claim 12, wherein the cartridge further includes a reaction chamber in fluid communication with the reagent chamber for holding the analyte for amplification and detection.

14. The device of claim 1, further comprising a reaction vessel coupled to the cartridge for receiving the eluted analyte via the second flow path.

15. The device of claim 1, wherein the cartridge further includes:

i) a lysing region in the first flow path, upstream of the extraction chamber, for lysing cells, spores, or microorganisms in the sample

ii) a waste chamber, connected to the microfluidic chip via the first flow path, for receiving the remaining sample fluid after the sample flows through the microfluidic chip; and

iii) an additional chamber, connected to the chip via the second flow path, for holding the analyte for amplification or detection.

16. The device of claim 1, further comprising an external instrument for receiving the cartridge, wherein the external instrument includes a fluid motive source for forcing fluids to flow in the cartridge.

17. The device of claim 1, wherein the cartridge includes an integrated fluid motive source for forcing fluids to flow within the cartridge.

18. The device of claim 17, wherein the fluid motive source comprises at least one membrane pump.