NMR device for detection of analytes

• US 8,102,176 B2
• Filed: 09/02/2008
• Issued: 01/24/2012
• Est. Priority Date: 08/31/2005
• Status: Active Grant

• Current Assignee: T2 Biosystems, Inc
• Original Assignee: T2 Biosystems, Inc
• Inventors: Lee, W. David
• Primary Examiner(s): Shrivastav, Brij
• Application Number:
  US12/231,426
• Publication Number:
  US 20090134869A1
• Time in Patent Office: 1,239 Days
• Field of Search: 324300-322, 431/7.1, 435/7.1, 435/725, 422/65, 422/82.01, 422/69, 600407-445, 436/526
• 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: G01R 33/281 Means for the use of in vitro contrast agents G01R33/282 takes precedence; involving use of a contrast agent in MR imaging G01R33/5601; in vivo contrast agents A61K49/0002
• CPC Class Codes: G01R 33/285 Invasive instruments, e.g. catheters or biopsy needles, specially adapted for tracking, guiding or visualization by NMR
• 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 33/34007 Manufacture of RF coils, e.g. using printed circuit board technology; additional hardware for providing mechanical support to the RF coil assembly or to part thereof, e.g. a support for moving the coil assembly relative to the remainder of the MR system
• CPC Class Codes: G01R 33/34053 Solenoid coils; Toroidal coils
• CPC Class Codes: G01R 33/34061 Helmholtz coils
• CPC Class Codes: G01R 33/34069 Saddle coils
• CPC Class Codes: G01R 33/34084 implantable coils or coils being geometrically adaptable to the sample, e.g. flexible coils or coils comprising mutually movable parts
• CPC Class Codes: G01R 33/341 comprising surface coils
• CPC Class Codes: G01R 33/44 using nuclear magnetic resonance [NMR] G01R33/24, G01R33/62 take precedence
• CPC Class Codes: G01R 33/465 applied to biological material, e.g. in vitro testing
• CPC Class Codes: G01R 33/5601 involving use of a contrast agent for contrast manipulation, e.g. a paramagnetic, super-paramagnetic, ferromagnetic or hyperpolarised contrast agent

Abstract

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.

Claims

1. A device configured for detection of an analyte using NMR comprising:

a support defining one or more wells for holding a liquid sample;

an RF coil, 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 and 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.

2. The device of claim 1, wherein said support defines an array of said wells.

3. The device of claim 1, wherein said device is a component of an analyte detection system.

4. The device of claim 1, further comprising an RF excitation coil for transmitting said RF excitation, wherein said RF excitation coil is separate from said one or more RF coils disposed about said one or more wells.

5. The device of claim 1, further comprising a reader configured to receive, for each of said wells, said signal corresponding to said echo response from said respective well.

6. A device configured for detection of an analyte using NMR comprising a support defining one or more wells for holding a liquid sample, said sample comprising magnetic particles and an analyte, said magnetic 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 said analyte in said liquid sample, and wherein at least one of said wells has a varying cross section such that, in the presence of a magnetic field, aggregations of said particles move from an area of larger cross section to an area of smaller cross section, thereby concentrating said analyte carried with said aggregations.

7. The device of claim 6, 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.

8. The device of claim 6, 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 said aggregations.

9. The device of claim 6, 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.

10. The device of claim 6, 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.

11. A method of measuring one or more analytes in a sample comprising:

obtaining a sample for measuring one or more analytes; and

measuring the presence of the one or more analytes in the sample using a device configured for detection of an analyte using NMR, the device comprising;

a support defining one or more wells for holding a sample and magnetic particles, the magnetic particles having binding moieties linked thereto, wherein said binding moieties are operative to alter an aggregation phenomena of the magnetic particles in the sample as a function of the presence or concentration of analyte in said sample; and

an RF coil disposed about each of the one or more wells, said RF coil configured to detect an echo response produced by exposing the sample to a bias magnetic field created using one or more magnets and an RF excitation;

wherein an echo response detected from the sample exposed to the bias magnetic field and RF excitation is indicative of detection of the one or more analytes in the sample, thereby measuring the presence of the one or more analytes.

12. The method of claim 11, wherein said method is performed in vivo.

13. The method of claim 11, wherein said measuring step comprises determining the concentration of said one or more analytes.

14. A device configured for detection of an analyte using NMR, 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.

15. The device of claim 14, wherein said wells are arranged in an array.

16. The device of claim 15, wherein said array is substantially two-dimensional.

17. The device of claim 14, configured to allow distribution of liquid into said plurality of wells.

18. The device of claim 14, wherein a substrate defines said plurality of wells, and wherein each of said RF coils is integrated with said substrate and is disposed about its respective well.