Valveless microfluidic device

• US 9,709,469 B2
• Filed: 11/11/2012
• Issued: 07/18/2017
• Est. Priority Date: 11/11/2011
• Status: Active Grant

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Zhong, Wenwan, Zhong, Runtao
• Primary Examiner(s): Kim, Young J
• Application Number:
  US13/674,054
• Publication Number:
  US 20140030717A1
• Time in Patent Office: 1,710 Days
• Field of Search: None
• CPC Class Codes: B01L 2200/0647 Handling flowable solids, e.g. microscopic beads, cells, particles
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/087 Multiple sequential chambers
• CPC Class Codes: B01L 2400/043 magnetic forces
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/502761 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: B01L 3/502784 specially adapted for droplet or plug flow, e.g. digital microfluidics automatic analysis using a stream of discrete samples in a tube system G01N35/08
• CPC Class Codes: B01L 7/525 with physical movement of samples between temperature zones
• CPC Class Codes: C12N 15/1013 by using magnetic beads
• CPC Class Codes: G01N 1/34 Purifying; Cleaning processes or apparatus for extracting or separating nucleic acids from biological samples C12N15/1003

Abstract

Provided are methods, devices and systems for analyte detection using a microfluidic device.

Claims

1. A valveless microfluidic system comprising

a substrate;

a plurality of wells located on the substrate;

at least one channel fluidly connecting each of the wells from an inlet to an outlet,

each well comprising a reagent or buffer and the channel comprising a liquid that is immiscible with the reagent or buffer;

wherein each of the plurality of wells confines an aqueous droplet comprising the reagent or buffer that is surrounded by the immiscible liquid, wherein the aqueous droplet does not evaporate or disperse into the at least one channel; and

wherein a first well of the plurality of wells comprises a magnetic bead comprising an analyte binding molecule.

2. The microfluidic system of claim 1, wherein the fluidic system comprises a plurality of channels and a plurality of wells fluidly connected with each channel.

3. The microfluidic system of claim 1, wherein the analyte binding molecule comprises an oligonucleotide, peptide, polypeptide, antibody or nanoparticle.

4. The microfluidic system of claim 1, further comprising a magnet for moving the magnetic beads through the at least one channel, the magnet positioned relative to the substrate to provide a magnetic field that manipulates the magnetic bead.

5. The microfluidic system of claim 4, further comprising a computer controller for moving the magnet relative to the substrate.

6. The microfluidic system of claim 1, wherein each well comprises an aqueous droplet and the at least one channel comprises an oil.

7. The microfluidic system of claim 1, wherein the buffer is selected from the group consisting of a binding buffer, a purification buffer, a wash buffer, a lyse buffer, an elution buffer or any combination of the foregoing.

8. The microfluidic system of claim 1, wherein the plurality of wells are each independently selected from the group consisting of a sample well, a wash well, a trap well, a collection well, an elution well and a control well.

9. The microfluidic system of claim 8, wherein the at least one channel fluidly connecting each of the plurality of wells comprises varying dimensions between types of the plurality of wells.

10. The microfluidic system of claim 9, wherein the at least one channel between a sample well and a wash well is wider than the at least one channel between the wash well and the elution well.

11. A kit comprising the microfluidic system of claim 1.

12. A method of purifying an analyte comprising passing a sample comprising an analyte through the at least one channel and the plurality of wells from the inlet to the outlet of the microfluidic system of claim 1, wherein one or more wells of the plurality of wells comprises a purification buffer, lyse buffer or a combination thereof and isolating the analyte from the outlet.

13. The method of claim 12, wherein a magnetic bead comprising the analyte binding molecule is moved through the at least one channel by movement of a magnet adjacent to the microfluidic device.

14. The method of claim 12, wherein the method purifies an oligonucleotide.

15. The method of claim 12, wherein the method amplifies and purifies an oligonucleotide.