Device and method for particle complex handling

• US 20080160622A1
• Filed: 12/29/2006
• Published: 07/03/2008
• Est. Priority Date: 12/29/2006
• Status: Active Grant

• Current Assignee: Intel Corporation
• Original Assignee: Intel Corporation
• Inventors: Wu, Kai, Yamakawa, Mineo, Su, Xing, Liu, David J., Swartz, Kenneth B.
• Granted Patent: US 7,993,525 B2
• Time in Patent Office: Days
• US Class Current: 436/86
• 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 2400/0424 Dielectrophoretic forces
• CPC Class Codes: B01L 2400/043 magnetic forces
• CPC Class Codes: B01L 2400/0638 membrane valves, flap valves
• CPC Class Codes: B01L 2400/086 using baffles or other fixed flow obstructions
• 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 1/4044 by chemical techniques; Digestion; Chemical decomposition
• CPC Class Codes: G01N 2015/0038 Investigating nanoparticles
• CPC Class Codes: G01N 2015/0092 Monitoring flocculation or agglomeration
• CPC Class Codes: G01N 35/0098 involving analyte bound to insoluble magnetic carrier, e.g. using magnetic separation magnetic particles used in immunoassays G01N33/54326; magnetic separation in general B03C
• CPC Class Codes: G01N 35/08 using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
• CPC Class Codes: H01F 2007/068 using printed circuit coils
• CPC Class Codes: H01F 7/20 without armatures cores H01F3/00; coils H01F5/00 ; shaping metal by applying magnetic forces B21D26/14; electromagnets specially adapted for NMR applications G01R33/381
• CPC Class Codes: H01F 7/206 Electromagnets for lifting, handling or transporting of magnetic pieces or material electromagnets for guidance of vehicles, workpieces B65G21/2009; for magnetic suspension or levitation H02N15/00
• CPC Class Codes: Y10S 436/805 Optical property
• CPC Class Codes: Y10S 436/806 Electrical property or magnetic property
• CPC Class Codes: Y10T 29/49117 Conductor or circuit manufacturing
• CPC Class Codes: Y10T 29/4913 : Assembling to base an electrical component, e.g., capacitor, etc.
• CPC Class Codes: Y10T 29/49155 : Manufacturing circuit on or in base
• CPC Class Codes: Y10T 436/25 : including sample preparation

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 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 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 device comprising

a fluidic network comprising a plurality of fluidic zones, each fluidic zone being connected to the adjacent zone by a diffusion barrier, and an integrated circuitry component;

an array of magnetic microcoils functionally coupled to the fluidic network, wherein the microcoils are programmably activatable to generate a magnetic field in proximity to each microcoil and to transport a magnetic particle in the fluidic network without fluidic movement of a fluid in the plurality of the fluidic zones;

a detection element functionally coupled to the fluidic network; and

optionally comprising a vibrational element functionally coupled to the fluidic network.

2. The device of claim 1, wherein the diffusion barrier is a fluidic channel.

3. The device of claim 1, wherein the diffusion barrier is a thermally-sensitive barrier.

4. The device of claim 1, wherein the diffusion barrier is a hydrophilic-hydrophobic interface, created by completely surrounding the hydrophilic reagents by hydrophobic liquid.

5. The device of claim 1, wherein the diffusion barrier is created by a MEMS membrane valve.

6. The device of claim 1, wherein the diffusion barrier is created by dielectric phoresis.

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

8. The device of claim 7, wherein the sample zone comprises a space for holding a sample, and is selected from a reservoir, a channel, an opening, a surface, or a combination thereof.

9. The device of claim 1, wherein multiple sets of fluidic zones are present in parallel in the fluidic network.

10. The device of claim 1, wherein the array of magnetic microcoils is removeably coupled to the fluidic network.

11. The device of claim 1, wherein the array of magnetic microcoils is permanently coupled to the fluidic network.

12. The device of claim 1, wherein the detection element is selected from an optical detection element and an electrical detection element.

13. The detection element of claim 12, wherein the optical detection element is selected from, a photon multiplier tube, avalanche sensor, CCD, photodiode, a Raman detector, and a fluorescent reader, and the electrical detection element is selected from a capacity detection element, a current sensor, a voltage sensor, and a charge sensor, and an electrochemical sensor.

14. The device of claim 1, wherein the device is self-contained.

15. The device of claim 1, further in functional association with a flow controller.

16. The device of claim 7, wherein the sample zone comprises the magnetic particle selected from the group consisting of a magnetic affinity complex, a competitive binding complex and a coded magnetic affinity complex.

17. A method of using the device of claim 16 to move the magnetic particle from the sample zone to the adjacent fluidic zone by activating the array of microcoils.

18. A method of using the device of claim 16, wherein the magnetic particle comprises a magnetic affinity complex, comprising

introducing a sample suspected of comprising an analyte into the sample zone, wherein the magnetic affinity complex binds to the analyte to form a magnetic binding complex, and

activating the microcoil array to move the magnetic binding complex from the sample zone to another fluidic zone.

19. The method of claim 16, wherein one or more fluidic zones comprises a signal affinity complex.

20. The method of claim 19, wherein the magnetic particle comprises a magnetic affinity complex, comprising:

introducing a sample suspected of comprising an analyte into a fluidic zone,

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 to the detection zone of the fluidic network, and

detecting the sandwich binding complex in the detection zone, wherein the detection of the sandwich binding complex indicates the presence of the analyte.

21. The method of claim 20, wherein the analyte is a protein, an antibody, or a nucleic acid.

22. The method of claim 20, wherein multiple analytes are detected.

23. The method of claim 16, wherein the magnetic particle comprises a competitive binding complex comprising a magnetic affinity complex and a signal analyte complex, further comprising:

introducing a sample suspected of comprising an analyte into the sample zone,

displacing the signal analyte complex from the competitive binding complex with analyte from the sample, and

detecting a signal from the signal analyte complex that was displaced from the competitive binding complex.

24. The method of claim 23, wherein the analyte is a small molecule.

25. The method of claim 16, wherein the magnetic particle comprises a coded magnetic affinity complex, comprising:

introducing a sample suspected of comprising an analyte into the sample zone, wherein the coded magnetic affinity complex binds to the analyte to form a coded magnetic binding complex,

activating the microcoil array to move the coded magnetic binding complex from the sample zone to a first affinity surface to immobilize the binding complex,

detaching the code from the 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,

activating the microcoil array to move the coded magnetic signal binding complex to the detection zone comprising a second affinity surface to immobilize the binding complex, and

detecting the coded magnetic signal binding complex in the detection zone.

26. The method of claim 16, wherein the magnetic particle comprises a magnetic affinity complex, comprising:

introducing a sample suspected of comprising an analyte into a fluidic zone and combining it with the magnetic affinity complex to form a magnetic binding complex,

activating the array of microcoils to move the magnetic binding complex to a zone of the fluidic network comprising a coded affinity complex, wherein the coded affinity complex is not magnetic, and wherein the magnetic binding complex and the coded affinity complex form a coded sandwich binding complex,

activating the array of microcoils to move the coded sandwich binding complex to a zone of the fluidic network comprising a signal affinity complex, wherein the coded sandwich binding complex and signal affinity complex form a super-binding complex,

activating the array of microcoils to move the super-binding complex to the detection zone of the fluidic network, and

detecting the super-binding complex in the detection zone, wherein the detection of the super-binding complex indicates the presence of the analyte.

27. A method comprising

fabricating a fluidic network comprising a plurality of fluidic zones on a substrate, wherein at least one of the fluidic zones is a sample zone designed to hold a sample and a magnetic particle,

fabricating one or more diffusion barriers on the substrate, wherein a diffusion barrier connects each fluidic zone to the adjacent fluidic zone;

and

forming an integrated circuitry component for storing data on the substrate.

28. The method of claim 27, further comprising functionally connecting a magnetic microarray to the substrate, wherein the microcoils are programmably activatable to generate a magnetic field in proximity to each microcoil and to transport the magnetic particle in the fluidic network without fluidic movement of a fluid in the plurality of the fluidic zones.

29. The method of claim 27, further comprising functionally connecting a detection element to the substrate, wherein the detection element is an optical detection element or an electrical detection element.

30. The method of claim 27, further comprising functionally connecting a vibration element to the substrate, wherein the vibration element is capable of vibrating the fluid within one or more fluidic zones.

31. The method of claim 27, wherein fabricating the plurality of fluidic zones on a substrate comprises combining two or more solid supports.

32. The method of claim 27, wherein fabricating the diffusion barrier comprise fabricating a fluidic channel.

33. The method of claim 27, wherein fabricating the diffusion barrier comprises fabricating a thermally-sensitive barrier.

34. The method of claim 27, wherein the diffusion barrier is a hydrophilic-hydrophobic interface, created by completely surrounding the hydrophilic reagents by hydrophobic liquid.

35. The method of claim 27, wherein the diffusion barrier is created by a MEMS membrane valve.

36. The method of claim 27, wherein the diffusion barrier is created by dielectric phoresis.

37. The method of claim 27, wherein the plurality of fluidic zones comprises a sample zone, a cleaning zone, and a detection zone.

38. A device comprising:

a substrate containing a plurality of fluidic zones, each fluidic zone being connected to the adjacent fluidic zone by a diffusion barrier,

wherein each fluidic zone comprises a fluid,

wherein one or more fluidic zones comprises a magnetic particle, and

wherein the device is adapted to permit transport of the magnetic particle from one fluidic zone to an adjacent fluidic zone substantially without moving the fluid between the fluidic zones.

39. The device of claim 38, wherein the diffusion barrier is a fluidic channel and/or a thermally-sensitive barrier.

40. The device of claim 38, wherein the diffusion barrier is a hydrophilic-hydrophobic interface, created by completely surrounding the hydrophilic reagents by hydrophobic liquid.

41. The device of claim 38, wherein the diffusion barrier is created by a MEMS membrane valve.

42. The device of claim 38, wherein the diffusion barrier is created by dielectric phoresis.

43. The device of claim 38, wherein the magnetic particle is a magnetic affinity complex, a competitive binding complex and/or a coded magnetic affinity complex.

44. The device of claim 38, wherein the plurality of fluidic zones comprises a sample zone, a cleaning zone, and a detection zone.

45. The device of claim 44, wherein the sample zone comprises a space for holding a sample, and is selected from a reservoir, a channel, an opening, a surface, or a combination thereof.

46. The device of claim 44, further comprising an additional fluidic zone adapted for the storage of one or more reagents.

47. The device of claim 44, wherein the detection zone comprises a reaction substrate that is capable of interacting with a catalytic element to form a reaction product.

48. The device of claim 38, wherein multiple sets of fluidic zones are present in parallel in the device.

49. The device of claim 38, wherein one or more fluidic zones comprises a signal affinity complex.

50. The device of claim 38, further comprising an integrated circuitry component.