Signal enhancement using a switchable magnetic trap

• US 8,189,186 B2
• Filed: 12/27/2007
• Issued: 05/29/2012
• Est. Priority Date: 12/27/2007
• Status: Expired due to Fees

• Current Assignee: Lawrence Livermore National Security LLC (Government of the United States of America)
• Original Assignee: Lawrence Livermore National Security LLC (Government of the United States of America)
• Inventors: Beer, Neil Reginald
• Primary Examiner(s): LAUCHMAN, LAYLA G
• Application Number:
  US11/965,598
• Publication Number:
  US 20110215798A1
• Time in Patent Office: 1,615 Days
• Field of Search: 436/526, 356/244, 356/246
• US Class Current: 356/244
• CPC Class Codes: B01L 2200/0647 Handling flowable solids, e.g. microscopic beads, cells, particles
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• 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 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2400/043 magnetic forces
• 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: G01N 15/1404 Handling flow, e.g. hydrodynamic focusing
• CPC Class Codes: G01N 15/1484 microstructural devices
• CPC Class Codes: G01N 27/84 by applying magnetic powder or magnetic ink

Abstract

A system for analyzing a sample including providing a microchannel flow channel; associating the sample with magnetic nanoparticles or magnetic polystyrene-coated beads; moving the sample with said magnetic nanoparticles or magnetic polystyrene-coated beads in the microchannel flow channel; holding the sample with the magnetic nanoparticles or magnetic polystyrene-coated beads in a magnetic trap in the microchannel flow channel; and analyzing the sample obtaining an enhanced analysis signal. An apparatus for analysis of a sample includes magnetic particles connected to the sample, a microchip, a flow channel in the microchip, a source of carrier fluid connected to the flow channel for moving the sample in the flow channel, an electromagnet trap connected to the flow line for selectively magnetically trapping the sample and the magnetic particles, and an analyzer for analyzing the sample.

Claims

1. An apparatus for analysis of a sample, comprising:

a microchip,

a microchannel flow channel in said microchip,

a connecting channel connected to said microchannel flow channel,

a source of magnetic particles that produces magnetic particles, said source of magnetic particles connected to said connecting channel wherein said source of magnetic particles delivers said magnetic particles to said connecting channel,

a source of carrier fluid connected to said connecting channel for moving the sample in said connecting channel,

a source of the sample connected to said connecting channel,

fluorescent probes associated with said magnetic particles, said carrier fluid, and said sample,

a source of microchannel flow channel carrier fluid connected to said microchannel flow channel wherein said microchannel flow channel carrier fluid is positioned to move the sample, said magnetic particles, and said fluorescent probes from said connecting channel into said microchannel flow channel and to move the sample, said magnetic particles, and said fluorescent probes in the microchannel flow channel,

an electromagnet trap connected to said microchannel flow channel for selectively magnetically trapping the sample, said magnetic particles, and said fluorescent probes, and

an analyzer positioned at or proximate said electromagnet trap for detecting said fluorescent probes and analyzing the sample.

2. The apparatus for analysis of a sample of claim 1 further comprising a droplet maker connected to said microchannel flow channel for producing droplets containing the sample, said fluorescent probes, and said magnetic particles.

3. The apparatus for analysis of a sample of claim 1 further comprising a system for producing liquid slugs in said microchannel flow channel with said liquid slugs containing the sample, said fluorescent probes, and said magnetic particles.

4. The apparatus for analysis of a sample of claim 1 wherein said flow channel in said microchip has a cross section aspect ratio, width and depth, that is sized to prevent said magnetic particles from vertical stacking.

5. The apparatus for analysis of a sample of claim 1 wherein said electromagnet trap is a microfluidic network of parallel or branched microchannels.

6. The apparatus for analysis of a sample of claim 1 wherein said source of carrier fluid is a source of oil connected to said flow channel.

7. The apparatus for analysis of a sample of claim 1 wherein said source of carrier fluid is a source of fluorocarbon-based fluid carrier fluid connected to said flow channel.

8. The apparatus for analysis of a sample of claim 1 wherein said magnetic particles are magnetic-cored optically discrete nanoparticles.

9. The apparatus for analysis of a sample of claim 1 wherein said magnetic particles are magnetic polystyrene-coated beads.

10. The apparatus for analysis of a sample of claim 1 wherein said analyzer includes a photodiode.

11. The apparatus for analysis of a sample of claim 1 wherein said analyzer includes a CCD or CMOS array.

12. The apparatus for analysis of a sample of claim 1 wherein said analyzer includes a laser.

13. The apparatus for analysis of a sample of claim 1 wherein said analyzer includes a LED light source.

14. The apparatus for analysis of a sample of claim 1 wherein said electromagnet trap includes an electromagnet.

15. An apparatus for analysis of a sample comprising:

a microchip,

a microchannel flow channel in said microchip,

a connecting channel connected to said microchannel flow channel,

a source of magnetic particles connected to said connecting channel that delivers said magnetic particles to said connecting channel,

a source of carrier fluid connected to said connecting channel for moving the sample in said connecting channel,

a source of the sample connected to said connecting channel,

fluorescence probes associated with said magnetic particles, said carrier fluid, and said sample,

a pulsed source of carrier fluid connected to said flow channel that pulses carrier fluid into said flow channel and creates liquid slugs in said flow channel containing the sample, said magnetic particles, and said fluorescent probes,

an electromagnet trap connected to said flow channel for selectively magnetically trapping said liquid slugs containing the sample, said magnetic particles, and said fluorescent probes, and

an analyzer positioned at or proximate said electromagnet trap for detecting said fluorescent probes and analyzing the sample.

16. An apparatus for analysis of a sample, comprising:

a microchip,

a microchannel flow channel in said microchip,

a connecting channel connected to said microchannel flow channel,

a source of magnetic particles connected to said connecting channel that delivers said magnetic particles to said connecting channel,

a source of carrier fluid connected to said connecting channel for moving the sample in said connecting channel,

a source of the sample connected to said connecting channel,

fluorescent probes associated with said magnetic articles said carrier fluid, and said sample,

a droplet maker connected to said flow channel for producing droplets containing the sample, said fluorescent probes, and said magnetic particles,

an electromagnet trap connected to said flow channel for selectively magnetically trapping said droplets containing the sample, said fluorescent probes, and said magnetic particles, and

an analyzer positioned at or proximate said electromagnet trap for detecting said fluorescent probes and analyzing the sample.

17. The apparatus for analysis of a sample of claim 16 wherein said microchannel flow channel in said microchip has a cross section aspect ratio, width and depth, that is sized to prevent said magnetic particles from vertical stacking.

18. A method of analyzing a sample on a microchip, comprising the steps of:

providing a microchannel flow channel in the microchip;

providing a connecting channel connected to said microchannel flow channel,

providing a source of carrier fluid connected to said connecting channel for moving the sample in said connecting channel,

providing a source of the sample connected to said connecting channel,

providing a source of magnetic nanoparticles or magnetic polystyrene-coated beads connected to said connecting channel,

providing fluorescent probes associated with the sample, with said carrier fluid, and with said magnetic nanoparticles or magnetic polystyrene-coated beads;

moving the sample with said fluorescent probes and said magnetic nanoparticles or magnetic polystyrene-coated beads in said connecting channel into said microchannel flow channel and in said microchannel flow channel,

trapping the sample with said fluorescent probes and said magnetic nanoparticles or magnetic polystyrene-coated beads in a magnetic trap in said microchannel flow channel, and

providing an analyzer positioned at or proximate said electromagnet trap for detecting said fluorescent probes and analyzing the sample.

19. The method of analyzing a sample on a microchip of claim 18 further comprising the step of forming microreactor droplets in said microchannel flow channel, said microreactor droplets containing the sample, said fluorescent probes, and said magnetic nanoparticles or magnetic polystyrene-coated beads.

20. The method of analyzing a sample on a microchip of claim 18 further comprising the step of forming liquid slugs in said microchannel flow channel, said liquid slugs containing the sample, said fluorescent probes, and said magnetic nanoparticles or magnetic polystyrene-coated beads.

21. The method of analyzing a sample on a microchip of claim 18 wherein said step of providing a source of magnetic nanoparticles or magnetic polystyrene-coated beads connected to said connecting channel comprises providing a source of magnetic nanoparticles connected to said connecting channel.

22. The method of analyzing a sample on a microchip of claim 18 wherein said step of providing a source of magnetic nanoparticles or magnetic polystyrene-coated beads connected to said connecting channel comprises providing a source of magnetic-cored optically discrete nanoparticles connected to said connecting channel.

23. The method of analyzing a sample on a microchip of claim 18 wherein said step of providing a source of magnetic nanoparticles or magnetic polystyrene-coated beads connected to said connecting channel comprises providing a source of magnetic polystyrene-coated beads connected to said connecting channel.

24. The method of analyzing a sample on a microchip of claim 18 wherein said step of providing a microchannel flow channel in the microchip comprises providing a microchannel flow channel cross section aspect ratio, width and depth, that prevents said magnetic nanoparticles or magnetic polystyrene-coated beads from vertical stacking.

25. The method of analyzing a sample on a microchip of claim 18 further comprising the step of flowing reagent over and through the sample and said magnetic nanoparticles or magnetic polystyrene-coated beads in said magnetic trap.

26. A method of analyzing a sample, comprising the steps of:

providing a microchannel flow channel;

providing a connecting channel connected to said microchannel flow channel,

providing a source of carrier fluid connected to said connecting channel for moving the sample in said connecting channel,

providing a source of the sample connected to said connecting channel,

providing a source of magnetic nanoparticles or magnetic polystyrene-coated beads connected to said connecting channel,

providing fluorescent probes associated with the sample, with said carrier fluid, and with said magnetic nanoparticles or magnetic polystyrene-coated beads;

providing a droplet maker connected to said connecting channel and to said flow channel for producing droplets containing the sample, said fluorescent probes, and said magnetic nanoparticles or magnetic polystyrene-coated beads,

moving said droplets with the sample, with said fluorescent probes, and with said magnetic nanoparticles or magnetic polystyrene-coated beads in said microchannel flow channel;

holding said droplets with the sample, with said fluorescent probes, and with said magnetic nanoparticles or magnetic polystyrene-coated beads in a magnetic trap in said microchannel flow channel; and

providing an analyzer positioned at or proximate said electromagnet trap for detecting said fluorescent probes and analyzing the sample obtaining an enhanced analysis signal.

27. The method of analyzing a sample of claim 26 further comprising the step of holding the sample, said fluorescent probes, and said magnetic nanoparticles or magnetic polystyrene-coated beads in said magnetic trap in said microchannel flow channel while washing the sample or exposing the sample to reagents or exposing the sample to other conditions.