NMR device for detection of analytes
This invention relates generally to detection devices having one or more small wells each surrounded by, or in close proximity to, an NMR micro coil, each well containing a liquid sample with magnetic nanoparticles that self-assemble or disperse in the presence of a target analyte, thereby altering the measured NMR properties of the liquid sample. The device may be used, for example, as a portable unit for point of care diagnosis and/or field use, or the device may be implanted for continuous or intermittent monitoring of one or more biological species of interest in a patient.
1. A device for detection of an analyte, the device comprising:
a support defining a well for holding a liquid sample comprising magnetic particles and said analyte, said magnetic particles having binding moieties linked thereto; and
an RF coil disposed about said liquid sample, said RF coil configured to detect an echo response produced by exposing said liquid sample to a bias magnetic field created using one or more magnets and an RF excitation, wherein said RF coil has a characteristic dimension from about 10 μm to about 1000 μm;
wherein said magnetic particles are deposited onto a surface of said well and wherein said magnetic particles are reconstitutable upon introduction of liquid.
2. The device of claim 1 , wherein said characteristic dimension is diameter.
3. The device of claim 1 , wherein said well and said RF coil are configured to provide a filling factor of at least about 0.7.
4. The device of claim 1 , wherein at least one of the following is less than about 1 mL:
(i) the volume circumscribed by said RF coil; and
(ii) the volume of said liquid sample.
5. The device of claim 1 , wherein at least one of the following is less than about 100 μL:
(i) the volume circumscribed by said RF coil; and
(ii) the volume of said liquid sample.
6. The device of claim 1 , further comprising an electrical element in communication with said RF coil, said electrical element configured to at least partially condition a signal corresponding to said echo response.
7. The device of claim 6 , wherein said RF coil is disposed sufficiently close to said electrical element to provide a Q factor of at least 1.
8. The device of claim 6 , wherein said RF coil is disposed sufficiently close to said electrical element to provide a Q factor of at least about 10.
9. The device of claim 6 , wherein said RF coil is integrated with said support and is disposed about said well.
10. The device of claim 6 , wherein said RF coil is disposed within one centimeter of said electrical element.
11. The device of claim 6 , wherein said RF coil is disposed within one millimeter of said electrical element.
12. The device of claim 6 , wherein said electrical element is configured to do at least one of the following:
(i) amplify said signal;
(ii) rectify said signal; and
(iii) digitize said signal.
13. The device of claim 1 , wherein said binding moieties are operative to alter an aggregation of said magnetic particles as a function of the presence or concentration of said analyte.
14. The device of claim 1 , wherein said magnetic particles are superparamagnetic nanoparticles with said binding moieties on their surfaces.
15. The device of claim 1 , wherein said device comprises at least one of said one or more magnets.
16. The device of claim 1 , wherein said RF excitation is transmitted via an RF excitation coil, separate from said RF coil disposed about said well.
17. The device of claim 1 , wherein said RF excitation is transmitted via said RF coil disposed about said well.
18. The device of claim 1 , wherein said device is fabricated on a chip.
19. The device of claim 1 , wherein at least one of said binding moieties is operative to bind to at least one of the following:
(i) said analyte;
(ii) another of said binding moieties; and
(iii) an aggregation-inducing molecule in said liquid sample, thereby producing an aggregate of multiply-linked magnetic particles as a function of the presence or concentration of said analyte in said liquid sample.
20. The device of claim 1 , wherein an aggregate of multiply-linked magnetic particles is disaggregated as a function of the presence or concentration of said analyte in said liquid sample.
21. The device of claim 1 , wherein said binding moieties comprise at least one of the following: an amino acid, a nucleic acid, an oligonucleotide, a therapeutic agent, a metabolite of a therapeutic agent, a peptide, a polypeptide, a protein, a carbohydrate, a polysaccharide, a virus, and bacteria.
22. The device of claim 1 , wherein said analyte comprises at least one of the following: a protein, a peptide, a polypeptide, an amino acid, a nucleic acid, an oligonucleotide, a therapeutic agent, a metabolite of a therapeutic agent, RNA, DNA, an antibody, an organism, a virus, bacteria, a carbohydrate, a polysaccharide, and glucose.
23. The device of claim 1 , further comprising a reader configured to receive said signal corresponding to said echo response.
24. The device of claim 23 , wherein said reader comprises an electrical element for processing said signal and a display for indicating analyte presence or concentration.
25. The device of claim 23 , wherein said reader comprises at least one of the following:
(i) a magnet for creation of said bias magnetic field; and
(ii) an RF excitation coil for providing said RF excitation.
26. The device of claim 23 , wherein said reader determines a change in T 2 relaxation time according to said signal corresponding to said echo response.
27. The device of claim 1 , wherein said device is portable.
28. The device of claim 1 , wherein said device weighs less than about 1 kilogram.
29. A device for detection of an analyte, said device comprising a plurality of wells for holding a liquid sample comprising magnetic particles and said analyte, said magnetic particles having binding moieties linked thereto, and, for each of said wells:
an RF coil disposed about said well, said RF coil configured to detect an echo response produced by exposing said liquid sample in said well to a bias magnetic field created using one or more magnets and an RF excitation;
wherein at least one well has a known characteristic substantially unaffected by said analyte and is used for calibration.
30. The device of claim 29 , further comprising, for each of said wells:
an electrical element in communication with said RF coil, said electrical element configured to at least partially condition a signal corresponding to said echo response.
31. The device of claim 30 , wherein, for each of said wells, said respective RF coil is disposed within one centimeter of said electrical element in communication with said RF coil.
32. The device of claim 30 , wherein said electrical element is configured to do at least one of the following:
(i) amplify said signal;
(ii) rectify said signal; and
(iii) digitize said signal.
33. The device of claim 30 , wherein said RF coil is disposed sufficiently close to said electrical element to provide a Q factor of at least 1.
34. The device of claim 29 , wherein magnetic particles having different binding moieties are disposed in different wells for detection of multiple analytes.
35. The device of claim 29 , wherein magnetic particles having the same binding moieties are disposed in different wells for replicate measurements, thereby improving accuracy.
36. The device of claim 29 , wherein magnetic particles having the same binding moieties are disposed in different wells for detection of varying analyte concentrations in said liquid sample.
37. The device of claim 29 , wherein different wells have different concentrations of binding moieties disposed therein.
38. The device of claim 29 , wherein said RF excitation is transmitted via an RF excitation coil, separate from said each RF coil disposed about said each well.
39. The device of claim 38 , wherein said RF excitation coil is disposed about said plurality of wells.
40. The device of claim 29 , wherein said analyte comprises at least one of the following: a protein, a peptide, a polypeptide, an amino acid, a nucleic acid, an oligonucleotide, a therapeutic agent, a metobolite of a therapeutic agent, RNA, DNA, an antibody, an organism, a virus, bacteria, a carbohydrate, a polysaccharide, and glucose.
41. The device of claim 29 , wherein said binding moieties comprise at least one of the following: an amino acid, a nucleic acid, an oligonucleotide, a therapeutic agent, a metabolite of a therapeutic agent, a peptide, a polypeptide, a protein, a carbohydrate, a polysaccharide, a virus, and bacteria.
42. The device of claim 29 , further comprising a reader configured to receive, for each of said wells, a signal corresponding to said echo response from said respective well.
43. The device of claim 42 , wherein said receiver comprises an electrical element for processing said signals and a display for indicating analyte presence or concentration.
44. A device comprising:
a support defining one or more wells for holding a liquid sample; and
disposed on said support, for reconstitution within said one or more wells, dried superparamagnetic particles having binding moieties linked thereto, wherein said binding moieties are operative to alter an aggregation of said magnetic particles in said liquid sample as a function of the presence or concentration of an analyte in said liquid sample.
45. The device of claim 44 , further comprising, for each of said one or more wells, an RF coil disposed about said well and an electrical element in communication with said RF coil, wherein said RF coil is configured to detect an echo response produced by exposing said liquid sample in said well to a bias magnetic field created using one or more magnets and an RF excitation, wherein said electrical element is configured to at least partially condition a signal corresponding to said echo response.
46. A device for detection of an analyte, the device comprising:
a support defining a well for holding a liquid sample comprising magnetic particles and said analyte, said magnetic particles having binding moieties linked thereto; and
an RF coil disposed about said liquid sample, said RF coil configured to detect an echo response produced by exposing said liquid sample to a bias magnetic field created using one or more magnets and an RF excitation, wherein said RF coil has a characteristic dimension from about 10 μm to about 1000 μm;
wherein said device is implantable, and is operable without skin-penetrating wires.
47. A device for detection of an analyte, said device comprising a plurality of wells for holding a liquid sample comprising magnetic particles and said analyte, said magnetic particles having binding moieties linked thereto, and, for each of said wells:
an RF coil disposed about said well, said RF coil configured to detect an echo response produced by exposing said liquid sample in said well to a bias magnetic field created using one or more magnets and an RF excitation;
wherein magnetic particles having different binding moieties are disposed in different wells for detection of said analyte, said different binding moieties promoting aggregation or disaggregation of said magnetic particles in proportion to concentration of said analyte.
48. A device for detection of an analyte, said device comprising a plurality of wells for holding a liquid sample comprising magnetic particles and said analyte, said magnetic particles having binding moieties linked thereto, and, for each of said wells:
an RF coil disposed about said well, said RF coil configured to detect an echo response produced by exposing said liquid sample in said well to a bias magnetic field created using one or more magnets and an RF excitation;
wherein said magnetic particles are deposited onto a surface of one or more of said plurality of wells.
49. The device of claim 48 , wherein said magnetic particles are reconstitutable upon introduction of liquid.