Implantable magnetic relaxation sensors and methods of measuring a sensor's cumulative exposure to a biomarker

• US 9,918,656 B2
• Filed: 06/27/2011
• Issued: 03/20/2018
• Est. Priority Date: 06/25/2010
• Status: Active Grant

• Current Assignee: Massachusetts Institute of Technology, The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: Massachusetts Institute of Technology, The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Cima, Michael J., Huang, Paul, Ling, Yibo, Pong, Terrence, Vassiliou, Christophoros C.
• Primary Examiner(s): Roy, Baisakhi
• Application Number:
  US13/806,348
• Publication Number:
  US 20130150707A1
• Time in Patent Office: 2,458 Days
• Field of Search: 600420, 424 92, 623 217
• CPC Class Codes: A61B 2562/0285 Nanoscale sensors
• CPC Class Codes: A61B 5/0031 Implanted circuitry
• CPC Class Codes: A61B 5/055 involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• 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 33/50 based on the determination of relaxation times , e.g. T1 measurement by IR sequences; T2 measurement by multiple-echo sequences
• 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

An implantable magnetic relaxation sensor is provided that comprises superparamagnetic nanoparticies functionalized with one or more agents that bond with a biomarker of interest. The sensor is configured for minimally-invasive implantation into a human or animal, and is configured to indicate the implanted sensor'"'"'s cumulative exposure to the biomarker of interest by analysis using magnetic resonance relaxometry.

Claims

1. An implantable magnetic relaxation sensor comprising:

superparamagnetic nanoparticles functionalized with one or more agents that irreversibly bond with a biomarker of interest;

wherein the sensor is configured for minimally-invasive implantation into a human or animal; and

wherein the sensor is configured to operate as a dosimeter to indicate the implanted sensor'"'"'s cumulative exposure to the biomarker of interest with a single reading of the sensor by analysis using magnetic resonance relaxometry.

2. The sensor of claim 1, wherein the one or more agents comprise an antibody.

3. The sensor of claim 2, wherein the one or more agents comprise antibodies for myoglobin, cTnI, CK-MB, or a combination thereof.

4. The sensor of claim 3, wherein the biomarker of interest is myoglobin, cTnI, CK-MB, or a combination thereof;

and wherein the sensor is configured to indicate the sensor'"'"'s cumulative exposure to myoglobin, cTnI, CK-MB, or a combination thereof after the sensor has been implanted and the sensor is analyzed using magnetic resonance relaxometry.

5. The sensor of claim 4, wherein the sensor is sensitive to cTnI in a range of 10-100 ng/mL.

6. The sensor of claim 4, wherein the sensor is sensitive to myoglobin in a range of 100 ng/mL to 1 μ

g/mL.

7. The sensor of claim 4, wherein the sensor is sensitive to CK-MB in a range of 100 ng/mL to 1 μ

g/mL.

8. The sensor of claim 1, wherein the nanoparticles comprise iron oxide.

9. The sensor of claim 1, further comprising a sensor body having at least one reservoir, wherein the nanoparticles are contained within the at least one reservoir.

10. The sensor of claim 9, wherein the nanoparticles are retained within the at least one reservoir by one or more size-exclusion membranes.

11. An implantable magnetic relaxation sensor comprising:

superparamagnetic nanoparticles functionalized with one or more antibodies that irreversibly bond with myoglobin, cTnI, CK-MB, or a combination thereof;

wherein the sensor is configured to operate as a dosimeter to indicate the sensor'"'"'s cumulative exposure to myoglobin, cTnI, CK-MB, or a combination thereof with a single reading of the sensor by analysis using magnetic resonance relaxometry after the sensor has been implanted, and wherein the sensor comprises a sensor body having at least one reservoir, wherein the nanoparticles are contained within the at least one reservoir.

12. The sensor of claim 11, wherein the nanoparticles comprise iron oxide.

13. The sensor of claim 11, wherein the nanoparticles are retained within the at least one reservoir by one or more size-exclusion membranes.

14. The sensor of claim 11, wherein the sensor is sensitive to cTnI in a range of 10-100 ng/mL.

15. The sensor of claim 11, wherein the sensor is sensitive to myoglobin in a range of 100 ng/mL to 1 μ

g/mL.

16. The sensor of claim 11, wherein the sensor is sensitive to CK-MB in a range of 100 ng/mL to 1 μ

g/mL.