Electron spin resonance for medical imaging

Patent metadata

Field	Value
Publication number	US-9857447-B2
Application number	US-201314041212-A
Country	US
Kind code	B2
Filing date	Sep 30, 2013
Priority date	Sep 28, 2012
Publication date	Jan 2, 2018
Grant date	Jan 2, 2018

Abstract

A method includes generating, from an integrated oscillator circuit, an oscillating output signal and generating, by an integrated power amplifier (PA) circuit, an amplified oscillating output signal based on the oscillating output signal. The method further includes receiving, by integrated receiver amplifier circuit, an electron spin resonance (ESR) signal from biological samples that include a magnetic species and generating, by the integrated receiver amplifier circuit, an amplified ESR signal based on the received ESR signal. The method further includes receiving, by the integrated receiver amplifier circuit, an electron spin resonance (ESR) signal from magnetic nanoparticles that are loaded with drugs or attached to human cells.

First claim

What is claimed is:

1. A method of obtaining an electron spin resonance (ESR) signal from a biological sample using an integrated electron spin resonance circuit chip having a chip substrate, the method comprising:
generating, from an integrated oscillator circuit, an oscillating output signal;
generating, by an integrated power amplifier (PA) circuit, an amplified oscillating output signal based on the oscillating output signal; and
receiving, by integrated receiver amplifier circuit, an ESR signal from the biological sample that includes a magnetic species;
generating, by the integrated receiver amplifier circuit, an amplified ESR signal based on the received ESR signal;
down-converting, by an integrated mixer circuit, the amplified ESR signal to a baseband signal; and
generating, by an integrated baseband amplifier circuit, an amplified baseband signal based on the baseband signal,
wherein the integrated oscillator circuit, the integrated PA circuit, the integrated receiver amplifier circuit, and integrated mixer circuit, and the integrated baseband amplifier circuit are all disposed on the chip substrate.

2. The method of claim 1 , wherein the magnetic species is one selected from a group consisting of a molecule, an atom, an ion, a free radical, and a nanoparticle.

3. The method of claim 2 , wherein the magnetic species is a nanoparticle and the nanoparticle is a super paramagnetic iron oxide nanoparticle (SPION).

4. The method of claim 1 , wherein the magnetic species comprises a reporter molecule that interacts with a magnetic molecule in the biological sample.

5. The method of claim 4 , wherein the magnetic molecule is Oxygen (O 2 ).

6. The method of claim 4 , wherein the reporter molecule is one selected for a group consisting of carbon particulate, a molecule with a nitroxides bond, and a tri-aryl-methyl (trityl) molecule with a protected electron on the central methyl carbon.

7. The method of claim 4 , wherein a relaxation rate of the reporter molecule is proportional to a concentration of the magnetic molecule in the biological sample.

8. The method of claim 7 , wherein the relaxation rate is one selected from a group consisting of T 1 relaxation rate, T 2 relaxation rate, and T 2 * relaxation rate.

9. The method of claim 1 , wherein generating the amplified oscillating output signal further comprises pulsing the amplified output signal to excite a time domain ESR signal in the biological sample.

10. The method of claim 9 , wherein pulsing the amplified output signal includes:
generating, by an integrated digital pulse generator circuit, a voltage pulse,
wherein the integrated digital pulse generator circuit is disposed on the chip substrate.

11. The method of claim 10 , further comprising:
providing the voltage pulse to a gate terminal of a switching transistor to switch the amplified oscillating output signal, wherein the switching transistor is connected to an input terminal of the PA circuit.

12. The method of claim 11 , further comprising pulling down a bias voltage of an input transistor of the PA circuit to switch the amplified oscillating output signal in response to the voltage pulse from the integrated digital pulse generator circuit.

13. The method of claim 9 , wherein the time domain ESR signal is an electron spin relaxation signal.

14. The method of claim 13 , wherein the electron spin relaxation signal provides information related to one selected from a group consisting of T 1 , T 2 , and T 2 *.

15. The method of claim 1 wherein the magnetic species is a free radical generated by exposing the biological sample to ionizing radiation.

16. The method of claim 1 , wherein the biological sample is an alanine (CH 3 CH(NH 2 )COOH) phantom.

17. The method of claim 1 , wherein the magnetic species is a melanin pigment molecule.

18. The method of claim 1 , wherein the biological sample a tissue sample.

19. The method of claim 18 , wherein the tissue sample originates from a tumor.

20. The method of claim 1 , wherein the ESR signal is used in early detection of cancer.

21. The method of claim 1 , wherein the ESR signal is used to monitor drug delivery.

22. The method of claim 1 , wherein the integrated ESR circuit chip is disposed within a patient at least during a time the ESR signal is obtained.

23. The method of claim 22 , wherein the integrated ESR circuit chip is disposed within an ovary of the patient.

24. The method of claim 22 , where in the biological sample comprises the patient's tissue.

25. The method of claim 1 , wherein a filling factor of a resonator used to detect the ESR signal is substantially 1.

26. The method of claim 1 , wherein a filling factor of a resonator used to detect the ESR signal is from 0.01 to 1.

27. A method of detecting an electron spin resonance (ESR) signal, the method comprising:
exciting a magnetic nanoparticle that is functionalized with a cancer specific antibody using an oscillating magnetic field, wherein a biological sample comprises the patient's tissue, wherein the oscillating magnetic field causes the magnetic nanoparticle to emit an ESR signal, and wherein the oscillating magnetic field is generated by an amplified oscillating output signal for an integrated electron spin resonance circuit chip having a chip substrate;
receiving the ESR signal;
generating, from an integrated oscillator circuit, an oscillating output signal;
generating, by an integrated power amplifier (PA) circuit, the amplified oscillating output signal based on the oscillating output signal;
receiving, by integrated receiver amplifier circuit, the ESR signal;
generating, by the integrated receiver amplifier circuit, an amplified ESR signal based on the received ESR signal;
down-converting, by an integrated mixer circuit, the amplified ESR signal to a baseband signal; and
generating, by an integrated baseband amplifier circuit, an amplified baseband signal based on the baseband signal.

28. The method of claim 27 , wherein the cancer specific antibody is anti-prostate-specific G-protein coupled Receptor.

29. The method of claim 27 , wherein the cancer specific antibody is anti-μ-opioid receptor.

30. The method of claim 27 , wherein the integrated ESR circuit chip is disposed within a patient at least during a time the ESR signal is obtained.

31. The method of claim 27 , wherein the integrated ESR circuit chip is disposed within an ovary of the patient.

32. The method of claim 27 , wherein a filling factor of a resonator used to detect the ESR signal is substantially 1.

33. The method of claim 27 , wherein a filling factor of a resonator used to detect the ESR signal is from 0.01 to 1.

34. A method of detecting an electron spin resonance (ESR) signal, the method comprising:
exciting a magnetic nanoparticle, wherein the magnetic nanoparticle comprises a drug, and the magnetic nanoparticle is disposed within a carrier, wherein the oscillating magnetic field causes the magnetic nanoparticle disposed within the carrier to emit an ESR signal, and wherein the oscillating magnetic field is generated by an amplified oscillating output signal for an integrated electron spin resonance circuit chip having a chip substrate;
receiving the ESR signal from the magnetic nanoparticle disposed within t

Assignees

• Yang Xuebei
• Chen Charles
• Seifi Payam
• Babakhani Aydin
• Univ Rice William M

Inventors

• Yang Xuebei
• Chen Charles
• Seifi Payam
• Babakhani Aydin

Classifications

• G01R33/302

  Miniaturized sample handling arrangements for sampling small quantities, e.g. flow-through microfluidic NMR chips · CPC title

• G01R33/60 Primary

  using electron paramagnetic resonance (G01R33/24, G01R33/62 take precedence) · CPC title