Microcoil Magnetic Resonance Detectors

• US 20090146658A1
• Filed: 10/23/2008
• Published: 06/11/2009
• Est. Priority Date: 10/23/2007
• Status: Active Grant

• Current Assignee: ABQMR, Inc., DNAE Group Holdings Limited (Genting Bhd.), UNM Rainforest Innovations (f/k/a STC.UNM) (The University of New Mexico)
• Original Assignee: ABQMR, Inc., nanoMR, Inc. (Genting Bhd.)
• Inventors: Norvell, Meghan, Fukushima, Eiichi, McDowell, Andrew F., Esch, Victor, Sillerud, Laurel
• Granted Patent: US 8,143,896 B2
• Time in Patent Office: Days
• US Class Current: 324/309
• CPC Class Codes: G01N 24/08 by using nuclear magnetic resonance G01N24/12 takes precedence
• CPC Class Codes: G01N 24/088 Assessment or manipulation of a chemical or biochemical reaction, e.g. verification whether a chemical reaction occurred or whether a ligand binds to a receptor in drug screening or assessing reaction kinetics
• CPC Class Codes: G01N 33/54333 Modification of conditions of immunological binding reaction, e.g. use of more than one type of particle, use of chemical agents to improve binding, choice of incubation time or application of magnetic field during binding reaction
• CPC Class Codes: G01R 33/302 Miniaturized sample handling arrangements for sampling small quantities, e.g. flow-through microfluidic NMR chips
• CPC Class Codes: G01R 33/307 specially adapted for moving the sample relative to the MR system, e.g. spinning mechanisms, flow cells or means for positioning the sample inside a spectrometer
• CPC Class Codes: G01R 33/465 applied to biological material, e.g. in vitro testing
• CPC Class Codes: G01R 33/4808 Multimodal MR, e.g. MR combined with positron emission tomography [PET], MR combined with ultrasound or MR combined with computed tomography [CT]

Abstract

The present invention provides microcoil magnetic resonance based modules, detection devices, and methods for their use.

Claims

1. A module comprising

(a) a microcoil possessing an inner diameter of between 25 microns and 550 microns;

(b) a conduit disposed proximate to the microcoil, wherein the conduit is in fluid communication with a sample reservoir;

(c) an affinity column in fluid communication with the conduit and the sample reservoir; and

;

(d) a connector for connecting the module to a magnetic resonance detector.

2. The module of claim 1, wherein the affinity column is located upstream of the conduit.

3. The module of claim 1, wherein the microcoil is wound around the conduit.

4. The module of claim 1 wherein the affinity column is located at least partially within the microcoil.

5. The module of claims 1 further comprising a sequestration chamber in fluid communication with the fluidic system, wherein the sequestration chamber is located downstream from the conduit.

6. The module of claim 1 wherein the affinity column comprises two or more layers, and wherein each layer comprises a different capture agent.

7. The module of claim 1, wherein the module comprises a plurality of microcoils each possessing an inner diameter of between 25 microns and 550 microns;

wherein a conduit is disposed proximate to each microcoil;

wherein the fluidic system is in fluid communication with each conduit, and wherein the fluidic system comprises a plurality of branches.

21. A magnetic resonance detector, comprising

(a) a housing comprising a conduit guide;

(b) a permanent magnet possessing a field strength of less than or equal to 4 Tesla within the housing; and

(b) the module of claim 1, wherein the connector connects the module to the housing via the conduit guide.

8. A module comprising

(a) a plurality of microcoils each possessing an inner diameter of between 25 microns and 550 microns;

(b) a conduit disposed proximate to each microcoil, wherein the conduit is in fluid communication with a sample reservoir; and

(c) a connector for connecting the module to a magnetic resonance detector.

9. The module of claim 8, wherein the plurality of microcoils are disposed along a single flow path in the fluidic system.

10. The module of claim 8, wherein the plurality of microcoils are along independent fluid flow paths.

11. The module of claim 8, wherein the plurality of microcoils is electrically connected to form a multi-coil detection circuit.

12. The module of claim 8 further comprising one or more sequestration chambers located downstream from the microcoils.

13. The module of claim 8, further comprising at least one affinity column in fluid communication with at least one conduit.

14. The module of claim 13, wherein the at least one affinity column is located upstream of the at least one conduit.

15. The module of claim 13, wherein each individual microcoil is wound around the conduit disposed proximate to the individual microcoil.

16. The module of claim 15 wherein the at least one affinity column is located at least partially within at least one microcoil.

22. A magnetic resonance detector, comprising

(a) a housing comprising a conduit guide;

(b) a permanent magnet possessing a field strength of less than or equal to 4 Tesla within the housing; and

(b) the module of claim 8, wherein the connector connects the module to the housing via the conduit guide.

17. A microcoil comprising an inner diameter of between 25 microns and 550 microns, wherein the microcoil is an effective magnetic resonance transmitter or receiver coil;

and wherein the microcoil is within or surrounds an affinity column.

18. The microcoil of claim 17, wherein the affinity column comprises two or more layers, and wherein each layer comprises a different capture agent.

19. A detection device, comprising

(a) a permanent magnet possessing a field strength of less than or equal to 4 Tesla;

(b) a microcoil disposed proximate to a magnetic field generated by the permanent magnet, wherein the microcoil possesses an inner diameter of between 25 microns and 550 microns;

(c) a conduit disposed proximate to the microcoil, wherein the conduit is in fluid communication with a sample reservoir;

(d) an affinity column in fluid communication with the conduit and the sample reservoir.

23. A method for detecting a target is a sample fluid, comprising:

(a) flowing a fluid containing one or more magnetically labeled targets through the conduit of the detection device of claim 19-22;

(b) energizing the microcoil at a frequency that permits detection of a magnetic resonance within the sample fluid; and

(c) processing a signal received from the microcoil to detect the magnetically labeled targets in the sample fluid.

20. A detection device, comprising

(a) a permanent magnet possessing a field strength of less than or equal to 4 Tesla;

(b) a plurality of microcoils each possessing an inner diameter of between 25 microns and 550 microns, wherein each microcoils is an effective magnetic resonance transmitter or receiver coil; and

(c) a conduit disposed proximate to each microcoil, wherein the conduit is in fluid communication with a sample reservoir.

24. A method for detecting a target in a sample fluid, comprising:

(a) introducing a sample fluid into a sample reservoir, wherein the sample reservoir is in fluid communication with a conduit;

(b) flowing the sample fluid into an affinity column in the conduit, wherein the affinity column comprises one or more capture agents that bind to one or more targets of interest;

(c) flowing a fluid comprising magnetic particles into the affinity column, wherein the magnetic particles are capable of binding selectively to the one or more targets of interest bound to the affinity column via the one or more capture agents, and wherein binding of the magnetic particles to the targets produces magnetic particle-target complexes;

(d) washing the affinity column to reduce the number unbound magnetic particles;

(e) eluting bound magnetic particle-target complexes from the affinity column;

(f) flowing the fluid comprising the magnetic particle-target complexes through a conduit disposed proximate to a microcoil, wherein the microcoil possesses an inner diameter of between 25 microns and 550 microns, wherein the microcoil is an effective magnetic resonance transmitter or receiver coil; and

(g) energizing the microcoil at a frequency that permits detection of a magnetic resonance within the sample fluid; and

(h) processing a signal received from the microcoil to detect magnetic particle-target complexes in the sample fluid.

25. The method of claim 24, wherein

step (f) comprises flowing fluid through a plurality of conduits disposed proximate to a plurality of microcoils each possessing an inner diameter of between 25 microns and 550 microns, wherein each microcoil is an effective magnetic resonance transmitter or receiver coil, and wherein each conduit is part of the fluidic system in fluid communication with a sample reservoir;

step (g) comprises energizing each microcoil at a frequency that permits detection of a magnetic resonance within the flowing fluid; and

step (h) comprises processing a signal received from each microcoil to detect magnetic particle-target complexes in the flowing fluid.

32. The method of any one of claims 24-27 and 29-31, wherein the signal processing comprises identifying a plurality of frequency components and a plurality of magnitude components within the signal received from the microcoil, and correlating the plurality of magnitude components and plurality of frequency components to a presence or absence of a labeled entity in the flowing fluid at a plurality of locations along an axial length of the microcoil.

26. A method for detecting a target is a sample fluid, comprising:

(a) introducing a sample fluid into a sample reservoir, wherein the sample reservoir is in fluid communication with a conduit, wherein the conduit is disposed proximate to a microcoil, wherein the microcoil possesses an inner diameter of between 25 microns and 550 microns, wherein the microcoil is an effective magnetic resonance transmitter or receiver coil;

(b) flowing the sample fluid into an affinity column in the conduit, wherein the affinity column comprises two or more layers, wherein each layer comprises one or more capture agents that bind to one or more targets of interest in the sample fluid, wherein each layer in the affinity column is capable of binding to molecules distinct from other layers; and

wherein the affinity column is located at least partially within the microcoil;

(c) flowing a fluid comprising magnetic particles into the affinity column, wherein the magnetic particles are capable of binding selectively to the one or more targets of interest, and wherein binding of the magnetic particles to the targets produces magnetic particle-target complexes;

(d) energizing the microcoil at a frequency that permits detection of a magnetic resonance within the affinity column; and

(e) processing a signal received from the microcoil to detect magnetic particle-target complexes in one or more layers of the affinity column.

28. The method of claim 26 or 27, wherein the fluid system comprises a plurality of conduits, each disposed proximately to a separate microcoil possessing an inner diameter of between 25 microns and 550 microns, wherein each microcoil is an effective magnetic resonance transmitter or receiver coil, and wherein each conduit is part of the fluidic system in fluid communication with a sample reservoir;

wherein each microcoil is energized at a frequency that permits detection of a magnetic resonance within the sample fluid; and

a signal received from each microcoil is processed to detect magnetic particle-target complexes in the flowing fluid.

27. A method for detecting a sample in a target fluid, comprising:

(a) mixing a sample fluid with magnetic particles capable of binding to the one or more targets of interest in the sample fluid, wherein binding of magnetic particles to targets produces magnetic particle-target complexes

(b) introducing the sample fluid into a sample reservoir, wherein the sample reservoir is in fluid communication with a conduit, wherein the conduit is disposed proximate to a microcoil, wherein the microcoil possesses an inner diameter of between 25 microns and 550 microns;

(c) flowing the sample fluid into an affinity column in the conduit, wherein the affinity column comprises two or more layers, wherein each layer comprises one or more capture agents that bind to one or more targets of interest, wherein each layer in the affinity column is capable of binding to molecules distinct from other layers; and

wherein the affinity column is located at least partially within the microcoil;

(d) energizing the microcoil at a frequency that permits detection of a magnetic resonance within the affinity column; and

(e) processing a signal received from the microcoil to detect magnetic particle-target complexes in one or more layers of the affinity column.

29. A method for detecting a target in a sample fluid, comprising:

(a) introducing a sample fluid into a sample reservoir, wherein the sample reservoir is in fluid communication with a conduit, wherein the sample fluid comprises magnetic particles capable of binding selectively to one or more targets of interest in the sample fluid, and wherein binding of magnetic particles to targets produces magnetic particle-target complexes;

(b) flowing the sample fluid through the conduit disposed proximate to a microcoil, wherein the microcoil possesses an inner diameter of between 25 microns and 550 microns;

(c) energizing the microcoil at a frequency that permits detection of a magnetic resonance within the sample fluid;

(d) processing a signal received from the microcoil to detect magnetic particle-target complexes in the sample fluid;

(e) flowing a portion of the flowing fluid in which the labeled entity was detected through a conduit disposed proximate to a secondary microcoil;

(f) energizing the secondary microcoil at a frequency that permits detection of a magnetic resonance within the sample fluid; and

(g) processing a signal received from the secondary microcoil to determine a further property of the magnetic particle-target complexes.

30. A method for detecting a target in a sample fluid, comprising:

(a) introducing a sample fluid into a sample reservoir, wherein the sample reservoir is in fluid communication with a conduit, wherein the sample fluid comprises magnetic particles capable of binding selectively to one or more targets of interest in the sample fluid, and wherein binding of magnetic particles to targets produces magnetic particle-target complexes;

(b) flowing the sample fluid through the conduit disposed proximate to a microcoil, wherein the microcoil possesses an inner diameter of between 25 microns and 550 microns;

(c) energizing the microcoil at a frequency that permits detection of a magnetic resonance within the sample fluid;

(d) processing a signal received from the microcoil to detect magnetic particle-target complexes in the sample fluid;

(e) diverting a portion of the flowing fluid in which the magnetic particle-target complexes were detected into a sequestration chamber to produce a concentrated target solution.

31. A method for detecting a target in a sample fluid, comprising:

(a) introducing a sample fluid into a sample reservoir, wherein the sample reservoir is in fluid communication with a conduit, wherein the sample fluid comprises two or more targets of interest, and wherein the sample fluid comprises magnetic particles differentially bound to the two or more targets of interest to create at least a first magnetic particle-target complex and a second magnetic particle-target complex;

(b) flowing the sample fluid through the conduit disposed proximate to a microcoil, wherein the microcoil possesses an inner diameter of between 25 microns and 550 microns;

(c) energizing the microcoil at a frequency that permits detection of a magnetic resonance within the sample fluid; and

(d) processing a signal received from the microcoil to differentially detect the at least first magnetic particle-target complex and the second magnetic particle-target complex in the flowing fluid.