NMR device for detection of analytes

• US 8,344,731 B2
• Filed: 07/27/2010
• Issued: 01/01/2013
• 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 B
• Application Number:
  US12/844,685
• Publication Number:
  US 20110018538A1
• Time in Patent Office: 889 Days
• Field of Search: 324300-322, 600407-445
• US Class Current: 324/318
• 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 for measuring the NMR relaxation rate of protons in a blood sample, the device comprising:

(a) a reader configured to receive a signal from the blood sample, the reader comprising (i) one or more permanent magnets defining a magnetic field, (ii) an RF excitation coil for transmitting an RF excitation to the blood sample, (iii) an RF coil configured to detect an NMR relaxation response produced by exposing the blood sample to the magnetic field and the RF excitation, (iv) an electrical element in communication with the RF coil, the electrical element configured to amplify, rectify, transmit, and/or digitize the signal corresponding to the NMR relaxation response, and (v) a display for indicating the NMR relaxation rate of the protons in the blood sample;

(b) a support defining a well holding the blood sample comprising magnetic particles and having the RF coil disposed about the well, the RF coil configured to detect an NMR relaxation response produced by exposing the blood sample to a bias magnetic field created using the one or more permanent magnets and the RF excitation; and

(c) a removable cartridge sized for convenient insertion into and removal from the device and having a compartment comprising one or more populations of magnetic particles.

2. The device of claim 1, wherein the well and the RF coil are configured to provide a filling factor of at least about 0.1.

3. The device of claim 1, wherein the well has a volume of less than about 300 μ

L.

4. The device of claim 1, wherein the well and the RF coil are configured such that the volume circumscribed by the RF coil is less than about 300 μ

L.

5. The device of claim 1, wherein the RF coil has a characteristic dimension from about 10 μ

m to about 1000 μ

m.

6. The device of claim 1, further comprising a tube for holding the blood sample, the tube having a varying cross section.

7. The device of claim 1, wherein the bias magnetic field has a strength of from about 0.45 Tesla to about 7 Tesla.

8. The device of claim 1, further comprising a display for indicating a physical property of the blood sample.

9. The device of claim 8, wherein the physical property is the viscosity of the blood sample.

10. A method for measuring the NMR relaxation rate of protons in a blood sample, the method comprising:

(a) placing the blood sample in a device of claim 1, the device comprising a support defining a well holding a blood sample comprising magnetic particles and having an RF coil disposed about the well, the RF coil configured to detect an NMR relaxation response produced by exposing the blood sample to a bias magnetic field created using one or more magnets and an RF excitation;

(b) contacting the blood sample with the magnetic particles in the presence of the bias magnetic field;

(c) exposing the sample to an RF excitation; and

(d) following step (c), detecting an NMR relaxation response produced by the protons in the blood sample.

11. The method of claim 10, further comprising, on the basis of step (d), measuring a physical property of the blood sample.

12. The method of claim 11, wherein the physical property is the viscosity of the blood sample.

13. The method of claim 10, wherein the well and the RF coil are configured to provide a filling factor of at least about 0.1.

14. The method of claim 10, wherein the well has a volume of less than about 300 μ

L.

15. The method of claim 10, wherein the well and the RF coil are configured such that the volume circumscribed by the RF coil is less than about 300 μ

L.

16. The method of claim 10, wherein the RF coil has a characteristic dimension from about 10 μ

m to about 1000 μ

m.

17. The method of claim 10, further comprising a tube for holding the liquid sample, the tube having a varying cross section.