Detection, measurement, and imaging of cells such as cancer and other biologic substances using targeted nanoparticles and magnetic properties thereof
The present invention provides methods and apparatuses for detecting, measuring, or locating cells or substances present in even very low concentrations in vivo in subjects, using targeted magnetic nanoparticles and special magnetic systems. The magnetic systems can comprise magnetizing subsystems and sensors subsystems, including as examples SQUID sensors and atomic magnetometers. The magnetic systems can detect, measure, or location particles bound by antibodies to cells or substances of predetermined types. Example magnetic systems are capable of detecting sub-nanogram amounts of these nanoparticles.
1. An apparatus for the detection, measurement, or location of one or more predetermined types of cancer cells or biologic substances in vivo, comprising:
(a) a magnetizing subsystem, configured to magnetize nanoparticles that are bound to one or more predetermined types of cancer cells or biologic substances in a patient; and
(b) a sensor subsystem, configured to detect a residual magnetic field in a region of the patient during a time after the net magnetic moments of nanoparticles not bound to cancer cells or biologic substances have decayed and before magnetic moments of nanoparticles bound cancer cells or biologic substances have decayed, and
(c) an analysis subsystem configured to analyze the residual magnetic field to detect, measure, or locate the one or more predetermined types of cancer cells or biologic substances in a patient.
2. An apparatus as in claim 1 , wherein the magnetizing subsystem comprises a plurality of Helmholtz coils.
3. An apparatus as in claim 1 , wherein the sensor subsystem comprises an array of gradiometers.
4. An apparatus at in claim 1 , wherein the sensor subsystem comprises a plurality of planar gradiometers.
5. An apparatus as in claim 4 , wherein at least one planar gradiometer has a baseline of about 2 cm.
6. An apparatus as in claim 4 , wherein at least one planar gradiometer is fabricated using a photolithographic process.
7. An apparatus as in claim 4 , further comprising a Superconducting Quantum Interference Device (SQUID) in communication with at least one of the plurality of planar gradiometers, wherein the SQUID is superconducting at temperatures around the temperature of liquid nitrogen.
8. An apparatus as in claim 4 , further comprising a plurality of SQUIDS, each in communication with one of the plurality of planar gradiometers, wherein the SQUIDs are superconducting at temperatures around the temperature of liquid nitrogen.
9. An apparatus as in claim 1 , wherein the sensor subsystem comprises an atomic magnetometer.
10. An apparatus as in claim 1 , wherein the sensor subsystem is configured to solve an electromagnetic inverse problem.
11. A method to detect, measure, or locate one or more predetermined types of cancer cells or biologic substances in vivo, comprising:
(a) providing an apparatus as in claim 1 ;
(b) placing a plurality of targeted nanoparticles into a patient, wherein each of the plurality of targeted nanoparticles comprises a paramagnetic nanoparticle conjugated with a targeting agent that preferentially binds with one or more predetermined types of cancer cells or biologic substances;
(c) using the magnetizing subsystem to magnetize the nanoparticles;
(d) using the sensor subsystem to determine a residual magnetic field in a region of the patient during a time after the net magnetic moments of nanoparticles not bound to cancer cells or biologic substances have decayed and before magnetic moments of nanoparticles bound cancer cells or biologic substances have decayed, and
(c) using the analysis subsystem to analyze the residual magnetic field to detect, measure, or locate one or more predetermined types of cancer cells or biologic substances.
12. A method as in claim 11 , wherein the targeted nanoparticles are labeled with antibodies that specifically bind to a predetermined type of cancer cells.
13. A method as in claim 12 , wherein the antibody-labeled paramagnetic nanoparticles comprise a magnetic core coated with a biocompatible coating to which is attached at least one specific antibody.
14. A method as in claim 13 , wherein the magnetic core comprises a ferromagnetic material.
15. A method as in claim 14 , wherein the ferromagnetic material comprises iron oxide.
16. A method as in claim 15 , wherein the magnetic core is less than 30 nanometers in diameter.
17. A method as in claim 13 , wherein the biocompatible coating comprises Dextran, carboxyl, amine, or a combination thereof.
18. A method as in claim 13 , wherein the at least one specific antibody comprises one or more of: a prostate cancer specific antibody, a breast cancer specific antibody, an ovarian cancer specific antibody, a Hodgkin's lymphoma specific antibody, a pancreatic cancer specific antibody, an antibody that specifically bind to Reed Sternberg cells associated with Hodgkin's lymphoma.
19. The method of claim 13 , wherein the at least one specific antibody comprises a CD15 or CD30 antibody.
20. The method of claim 13 , wherein the at least one specific antibody comprises CA-125.
21. The method of claim 13 , wherein the at least one specific antibody comprises HER-2 antibodies.