Method and device for biomolecule preparation and detection using magnetic array

• US 9,689,842 B2
• Filed: 11/05/2013
• Issued: 06/27/2017
• Est. Priority Date: 12/28/2006
• Status: Active Grant

• Current Assignee: Intel Corporation
• Original Assignee: Intel Corporation
• Inventors: Su, Xing, Wu, Kai, Liu, David J
• Primary Examiner(s): Martinez, Rebecca
• Application Number:
  US14/072,336
• Publication Number:
  US 20140141526A1
• Time in Patent Office: 1,330 Days
• Field of Search: 436518, 436526, 435 71
• CPC Class Codes: B01J 2219/00576 fluorophore
• CPC Class Codes: B01J 2219/00648 by the use of solid beads
• CPC Class Codes: B01J 2219/00655 the compounds being bound to magnets embedded in or on the solid supports
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01J 2219/0074 Biological products
• CPC Class Codes: B01L 2200/0647 Handling flowable solids, e.g. microscopic beads, cells, particles
• 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 2400/0439 ultrasonic vibrations, vibrating piezo elements
• 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: B03C 1/032 Matrix cleaning systems
• CPC Class Codes: B03C 1/0335 using coils
• CPC Class Codes: B03C 1/288 disposed at the outer circumference of a recipient
• CPC Class Codes: B03C 2201/18 Magnetic separation whereby the particles are suspended in a liquid
• CPC Class Codes: B03C 2201/26 for use in medical applications
• CPC Class Codes: G01N 27/74 of fluids G01N24/00 takes precedence
• CPC Class Codes: G01N 27/745 for detecting magnetic beads used in biochemical assays concerning the assays G01N33/54326; sensors therefor G01R33/1269; automatic analysers therefor G01N35/0098
• CPC Class Codes: G01R 33/1269 of molecules labeled with magnetic beads magnetic particles for bio assay G01N33/54326

Abstract

An embodiment of the invention relates to a device for detecting an analyte in a sample. The device comprises a fluidic network and an integrated circuitry component. The fluidic network comprises multiple zones such as a sample zone, a cleaning zone and a detection zone. The fluidic network contains a magnetic particle and/or a signal particle. A sample containing an analyte is introduced, and the analyte interacts with the magnetic particle and/or the signal particle through affinity agents. A microcoil array or a mechanically movable permanent magnet is functionally coupled to the fluidic network, which are activatable to generate a magnetic field within a portion of the fluidic network, and move the magnetic particle from the sample zone to the detection zone. A detection element is present which detects optical or electrical signals from the signal particle, thus indicating the presence of the analyte.

Claims

1. A method of moving magnetic particles comprising:

magnetic particles in a fluidic network comprising a plurality of fluidic zones in a substrate, and activating a microcoil array functionally coupled to the network to thereby move the magnetic particles from one of the plurality of fluidic zones to another without fluidic movement of a fluid in the plurality of the fluidic zones.

2. The method of claim 1, wherein the magnetic particle is a magnetic affinity complex or a coded magnetic affinity complex.

3. The method of claim 2, wherein the magnetic particle comprises the magnetic affinity complex, further comprising:

introducing a sample suspected of comprising an analyte into a fluidic zone, wherein the magnetic affinity complex binds to the analyte to form a magnetic binding complex, and wherein the magnetic binding complex is moved by activating the microcoil array.

4. The method of claim 2, wherein the magnetic particle comprises a magnetic affinity complex, further comprising:

providing a signal affinity complex in the network, introducing a sample suspected of comprising an analyte into the network, combining the analyte with the magnetic affinity complex and the signal affinity complex, wherein the combination occurs simultaneously or sequentially, and wherein the magnetic affinity complex and the signal affinity complex bind to the analyte to form a sandwich binding complex, activating the array of microcoils to move the sandwich binding complex within the network.

5. The method of claim 4, wherein the network is functionally coupled to a detection element capable of detecting the presence of the sandwich binding complex within the network, and wherein the detection of the sandwich binding complex indicates the presence of the analyte.

6. The method of claim 5, wherein multiple analytes are detected.

7. The method of claim 2, wherein the magnetic particle comprises a magnetic affinity complex, further comprising:

providing a signal analyte complex in the network, introducing a sample suspected of comprising an analyte into the network, wherein the magnetic affinity complex binds to the analyte to form a magnetic binding complex, and displacing the analyte from the magnetic binding complex with the signal analyte complex to form a competitive binding complex.

8. The method of claim 7, wherein the network is functionally coupled to a detection element capable of detecting the presence of the signal analyte complex within the network, and wherein the detection of the signal analyte complex that did not form the competitive binding complex indicates the presence of the analyte.

9. The method of claim 2, wherein the magnetic particle comprises a coded magnetic affinity complex, further comprising:

introducing a sample suspected of comprising an analyte into a fluidic zone, wherein the coded magnetic affinity complex binds to the analyte to form a coded magnetic binding complex, and wherein the coded magnetic binding complex is moved by activating the microcoil array.

10. The method of claim 9, further comprising:

moving the coded magnetic binding complex to a first affinity surface, forming a bound coded magnetic binding complex, detaching the code from the bound coded magnetic binding complex, providing a magnetic signal affinity complex, wherein the detached code binds to the magnetic signal affinity complex to form a coded magnetic signal binding complex, and activating the microcoil array to move the coded magnetic signal binding complex to the detection zone comprising a second affinity surface, forming a bound coded magnetic signal binding complex.

11. The method of claim 10, wherein the fluidic network is functionally coupled to a detection element capable of detecting the presence of the bound coded magnetic signal binding complex within the network, and wherein the detection of the bound coded magnetic signal binding complex indicates the presence of the analyte.

12. The method of claim 11, wherein multiple analytes are detected.

13. The method of claim 10, wherein the fluidic network comprises a diffusion bather configured to reduce diffusion or convective flow from a first fluidic zone to a second fluidic zone.

14. The method of claim 1, wherein the plurality of fluidic zones comprises a sample zone, a cleaning zone, and a detection zone.

15. The method of claim 1, wherein the fluidic network comprises a diffusion bather configured to reduce diffusion or convective flow from a first fluidic zone to a second fluidic zone.

16. A method of detecting an analyte, comprising:

providing a fluidic network comprising a plurality of fluidic zones in a substrate, wherein at least one fluidic zone comprises a magnetic affinity complex, introducing a sample suspected of comprising an analyte into one of the fluidic zones, wherein the magnetic affinity complex binds to the analyte to form a magnetic binding complex, one of the fluidic zones without fluidic movement of a fluid in the plurality of the fluidic zones, and detecting the magnetic binding complex using a detection element functionally coupled to the network, wherein the presence of the complex indicates the presence of the analyte.

17. The method of claim 16, wherein the fluidic network comprises a diffusion bather configured to reduce diffusion or convective flow from a first fluidic zone to a second fluidic zone.

18. A method of detecting an analyte, comprising:

providing a fluidic network comprising a plurality of fluidic zones in a substrate, wherein a magnetic affinity complex and a signal affinity complex are present in one or more of the fluidic zones, and wherein the network is functionally coupled to an array of microcoils, introducing a sample suspected of comprising an analyte into at least one of the fluidic zones, combining the analyte with the magnetic affinity complex and the signal affinity complex, wherein the combination occurs simultaneously or sequentially, and wherein the magnetic affinity complex and the signal affinity complex bind to the analyte to form a sandwich binding complex, one of the fluidic zones within the network without fluidic movement of a fluid in the plurality of the fluidic zones, and detecting the sandwich binding complex using a detection element functionally coupled to the fluidic network, wherein the detection of the sandwich binding complex indicates the presence of the analyte.

19. The method of claim 18, wherein the analyte is a protein, an antibody, or a nucleic acid.

20. The method of claim 18, wherein the fluidic network comprises a diffusion barrier configured to reduce diffusion or convective flow from a first fluidic zone to a second fluidic zone.

21. A method of detecting an analyte, comprising:

providing a fluidic network comprising a plurality of fluidic zones in a substrate, wherein a magnetic affinity complex and a signal analyte complex are present in one or more of the fluidic zones, introducing a sample suspected of comprising an analyte into at least one of the fluidic zones, combining the analyte with the magnetic affinity complex and the signal affinity complex, wherein the magnetic affinity complex binds to the analyte to form a magnetic binding complex, one of the fluidic zones within the network without fluidic movement of a fluid in the plurality of the fluidic zones, displacing the analyte from the magnetic binding complex with the signal analyte complex to form a competitive binding complex, detecting the competitive binding complex and/or the unbound signal analyte complex using a detection element functionally coupled to the fluidic network, wherein the detection of the unbound signal analyte complex or competitive binding complex indicates the presence of the analyte.

22. The method of claim 21, further comprising:

activating the array of microcoils functionally coupled to the fluidic network to move the competitive binding complex within the fluidic network prior to detecting the competitive binding complex and/or the unbound signal analyte complex.

23. A method of detecting an analyte, comprising:

providing a fluidic network comprising a plurality of fluidic zones in a substrate, wherein a coded magnetic affinity complex and a magnetic signal affinity complex are present in one or more of the fluidic zones, and wherein the network is functionally coupled to an array of microcoils, introducing a sample suspected of comprising an analyte into at least one of the fluidic zones, combining the analyte with the coded magnetic affinity complex, wherein the analyte binds to the coded magnetic affinity complex to form a coded magnetic binding complex, activating an array of microcoils functionally coupled to the fluidic network to move the coded magnetic binding complex to a different one of the fluidic zones within the network to a first affinity surface without fluidic movement of a fluid in the plurality of the fluidic zones, forming a bound coded magnetic binding complex, detaching the code from the bound coded magnetic binding complex, providing a magnetic signal affinity complex, wherein the detached code binds to the magnetic signal affinity complex to form a coded magnetic signal binding complex, and activating the microcoil array to move the coded magnetic signal binding complex to the detection zone comprising a second affinity surface, forming a bound coded magnetic signal binding complex, and detecting the bound coded magnetic signal binding complex using a detection element functionally coupled to the fluidic network, wherein the detection of the bound coded magnetic signal binding complex indicates the presence of the analyte.