Method and system for background suppression in magneto-motive photoacoustic imaging of magnetic contrast agents

1. A method for detecting magnetic target objects within a moving fluid, comprising:

(a) introducing a plurality of magnetic particles having photoacoustic properties to a moving fluid comprising target objects to provide magnetically-labeled target objects;

(b) applying a magnetic field to an area of interest through which the fluid flows to accumulate the magnetically-labeled target objects in the area of interest to provide accumulated magnetically-labeled target objects in a first position;

(c) measuring a first photoacoustic signal from the accumulated magnetically-labeled target objects in the first position;

(d) manipulating the magnetic field in the area of interest to move at least a portion of the accumulated magnetically-labeled target objects in a predetermined pattern directly related to the magnetic field manipulation; and

(e) measuring one or more photoacoustic signals from the accumulated magnetically-labeled target objects during and after magnetic field manipulation.

2. The method of claim 1 , wherein measuring one or more photoacoustic signals from the accumulated magnetically-labeled target objects during and after magnetic field manipulation comprises measuring a sequence of photoacoustic signals from the accumulated magnetically-labeled target objects during and after magnetic field manipulation.

3. The method of claim 1 , wherein measuring one or more photoacoustic signals from the accumulated magnetically-labeled target objects during and after magnetic field manipulation comprises measuring one or more photoacoustic signals from the accumulated magnetically-labeled target objects during and immediately after magnetic field manipulation.

4. The method of claim 1 further comprising comparing the sequence of photoacoustic signals during magnetic field manipulation to provide a background suppressed photoacoustic signal.

5. The method of claim 4 , wherein comparing the sequence of photoacoustic signals during magnetic field manipulation provides a background suppressed photoacoustic image of the accumulated magnetically-labeled target objects.

6. The method of claim 1 , wherein manipulating the magnetic field results in acquiring photoacoustic signals from the accumulated magnetically-labeled target objects at two separate spatial locations.

7. The method of claim 6 further comprising comparing the photoacoustic signals acquired from the accumulated magnetically-labeled target objects at two separate spatial locations to provide a background suppressed photoacoustic signal.

8. The method of claim 7 , wherein comparing the photoacoustic signals acquired at two separate spatial locations provides a background suppressed photoacoustic image of the accumulated magnetically-labeled target objects.

9. The method of claim 1 , wherein applying a magnetic field to an area of interest comprises situating at least one magnet in a location sufficiently proximate to the area of interest to subject the area to an effective magnetic field.

10. The method of claim 9 , wherein a uniform polarizing magnetic field applied primarily in one direction is combined with a collection of superimposed magnetic fields with significant spatial gradients in the component aligned with the direction of the polarizing magnetic field.

11. The method of claim 10 , wherein three mutually orthogonal gradient fields are applied.

12. The method of claim 10 , wherein any of the applied magnetic fields are permanent or time varying.

13. The method of claim 1 , wherein measuring a first photoacoustic signal comprises delivering at least one laser pulse to the area of interest effective to generate a photoacoustic signal from the accumulated magnetically-labeled target objects at the first position.

14. The method of claim 1 , wherein a single element ultrasonic transducer is used to record the photoacoustic signals.

15. The method of claim 1 , wherein a one-dimensional or two-dimensional ultrasonic array transducer is used to record the photoacoustic signals.

16. The method of claim 1 , wherein manipulating the magnetic field comprises physically moving all or part of the magnets.

17. The method of claim 1 , wherein manipulating the magnetic field comprises changing currents in electromagnets providing all or part of the applied fields.

18. The method of claim 10 , wherein manipulating the magnetic field comprises physically moving all or part of the magnets producing the gradient fields.

19. The method of claim 10 , wherein manipulating the magnetic field comprises changing currents in electromagnets providing all or part of the gradient fields.

20. The method of claim 1 , wherein measuring a second photoacoustic signal comprises delivering at least one laser pulse to the area of interest effective to generate a photoacoustic signal from the accumulated magnetically-labeled target objects during magnetic field manipulation.

21. The method of claim 1 further comprising subjecting the accumulated magnetically-labeled target objects to an additional process selected from removal for biochemical or genetic analysis; non-invasive eradication using high-energy pulses selected from laser pulses, microwave pulses, or ultrasound pulses; magnetic purging; mechanical removal; needle extraction; or any combination thereof.

22. The method of claim 1 , wherein the magnetic particles having photoacoustic properties are nanoparticle complexes or a microparticle complexes selected from metal-magnetic complexes, quantum dot-magnetic complexes, carbon nanostructure-magnetic complexes, or mixtures thereof.

23. The method of claim 1 , wherein the magnetic particles having photoacoustic properties are metal-coated nanostructures.

24. The method of claim 1 , wherein the magnetic particles having photoacoustic properties comprise one or more targeting moieties for selective binding to the target object.

25. The method of claim 24 , wherein targeting moieties are selected from antibodies, ligands, antigens, or cell marker proteins.

26. The method of claim 1 , wherein the target objects are selected from biomarkers, therapeutic drugs, toxins, microparticles, nanoparticles, viruses, or cells.

27. The method of claim 26 , wherein the biomarkers are selected from proteins, antibodies, hormones, single-stranded DNA fragments, double-stranded DNA fragments, or RNA fragments.

28. The method of claim 26 , wherein the cells are abnormal cells.

29. The method of claim 26 , wherein the cells are selected from pathogenic bacteria, pathogenic fungal cells, pathogenic protists, sickle cells, inflamed cells, or cancer cells.

30. The method of claim 29 , wherein the cancer cells are metastatic cancer stem cells.

31. The method of claim 30 , wherein the metastatic cancer stem cells result from a cancer selected from melanoma, leukemia, brain cancer, breast cancer, colon cancer, prostate cancer, ovarian cancer, pancreatic cancer, or testicular cancer.

32. The method of claim 1 , wherein the fluid is a biofluid of a living organism.

33. The method of claim 32 , wherein the biofluid is selected from blood, lymph, cerebrospinal fluid, urine, chyme, cytosol, tears, or interstitial fluid.

34. The method of claim 1 , wherein the area of interest through which the fluid flows is a circulatory vessel.

35. The method of claim 34 , wherein the circulatory vessel is selected from a blood vessel, a lymphatic vessel, an extracorporeal shunt, or any combination thereof.

36. The method of claim 1 , wherein introducing the plurality of magnetic particles having photoacoustic properties to a moving fluid comprises administering the magnetic particles intravenously to a subject to be evaluated for the presence of target objects.

37. The method of claim 1 , wherein the magnetically-labeled target objects are detected at a detection sensitivity ranging from about 1 to about 100 target objects per mL of the moving fluid.

38. A device for the manipulation and detection of a magnetically-labeled target object within a moving fluid, comprising:

(a) one or more first magnets effective for establishing a magnetic field in an area of interest within moving fluid containing magnetically-labeled target objects, wherein the magnetic field is effective to accumulate the magnetically-labeled target objects in the area of interest;

(b) one or more second magnets effective for establishing a magnetic field including both a polarizing field and gradient fields in an area of interest within moving fluid containing magnetically-labeled target objects, wherein the magnetic field is effective to move accumulated magnetically-labeled target objects from a first position to a second position within the area of interest;

(c) one or more light energy sources for delivering incident energy to the accumulated magnetically-labeled target objects in the area of interest, wherein the incident energy is sufficient to generate a photoacoustic signal from the accumulated magnetically-labeled target objects; and

(d) one or more photoacoustic transducers for receiving the photoacoustic signal from the accumulated magnetically-labeled target objects.

39. The device of claim 38 , wherein the first magnet is a permanent or pulsed magnet or electromagnet.

40. The device of claim 38 , wherein the second magnet is a permanent or pulsed magnet or electromagnet.

41. The device of claim 38 , wherein the first or second magnet comprises a magnetic material selected from the group consisting of hematite (Fe 2 O 3 ), magnetite (Fe 3 O 4 ), manganese-zinc ferrite (Mn a Zn (1−a) Fe 2 O 4 ), nickel-zinc ferrite (Ni a Zn (1−a) Fe 2 O 4 ), barium oxide, strontium oxide, and combinations thereof.

42. The device of claim 38 , wherein the first or second magnet is a cylindrical neodymium-iron-boron (NdFeB) magnet with Ni—Cu—Ni coating.

43. The device of claim 38 , wherein the light energy source is a laser.

44. The device of claim 38 , wherein the light energy source is a pulse laser.

45. The device of claim 38 , wherein the photoacoustic transducer is a single element ultrasonic transducer, a one-dimensional ultrasonic array transducer, or a two-dimensional ultrasonic array transducer.

46. The device of claim 38 , wherein the device has the form of a cuff adapted to receive or conform to a suitable body part.

47. The device of claim 46 , wherein the body part is selected from an arm, a finger, a leg, a toe, a wrist, an elbow, a shoulder, an ankle, a hip, a knee, or neck.