Granted Patent B2

US 12,661,013 · App. 18/936,083 · Granted Jun 23, 2026

Inventor: Vladimir Pavlovich Zharov (Little Rock, AR)

A61B5/0095A61B5/0059A61B5/02007A61B5/412A61B5/415A61B5/416A61B5/418A61B5/7278A61B18/20A61K49/22G01N21/1702G01N21/39A61B8/08A61B2018/00642A61B2018/20351A61B2018/20357A61B2018/20361A61B2018/207G01N15/1425G01N15/1434G01N15/147G01N2015/1477G01N2201/0697

Abstract

Claims (29)

1 . A method of detecting target objects in vessels of a living organism, comprising:

generating a focused elongated laser beam using a lens or optical fibers as a series of consecutive laser pulses at different wavelengths in the x-ray spectra, visible spectra, terahertz spectra, or microwave spectra ranging between about 400 nm and about 2500 nm, the different wavelengths being generated at a time delay ranging between 0.1 μs and 100 μs, a pulse width ranging between about 0.1 ps and about 1000 ns, a pulse repetition rate ranging between about 1 Hz and about 500,000 Hz, and a pulse energy fluence ranging between about 0.1 mJ/cm 2 and about 1000 J/cm 2· ;

detecting one or more photoacoustic, fluorescence, and scattering light signals from the target objects with a focused ultrasound transducer and a photodetector at a sample rate ranging between about 10 KHz and about 100 MHZ;

analyzing the one or more photoacoustic, fluorescence, and scattering light signals to determine presence of the target objects and at least one characteristic of the target objects, wherein the at least one characteristic of the target objects is selected from a type of target object, a quantity of target objects, a concentration of target objects, a flow speed of target objects, a total blood volume, and combination thereof; and

triggering a therapeutic laser pulse of high energy to produce laser-induced photothermal microbubbles operated to destroy the target objects.

2 . The method of claim 1 , wherein the different wavelengths of the focused elongated laser beam are varied to optimize absorption, fluorescence and scattering of laser energy by the target objects, wherein the target objects are unlabeled cells, cell products, contrast agents, or cells labeled with one or more contrast agents and nanoparticles.

3 . The method of claim 1 , wherein the photoacoustic signals emitted by the target objects results from absorption of laser pulse energy by a variety of mechanisms including one or more of single photon absorption, two photon absorption, multi-photon absorption, Coherent Anti-Stokes Raman Scattering, optical breakdown, photothermal effect, shock waves, microbubbles and combinations thereof.

4 . The method of claim 1 , wherein the method is based on time- resolved monitoring of dynamic increases of signal amplitudes due to higher local absorption of the target objects relative to surrounding cells and tissues or decreases of signal amplitudes due to lower local absorption of the target objects relative to surrounding cells and tissues.

5 . The method of claim 1 , wherein the lens and/or the optical fibers direct the elongated laser beam to the target objects in vessels located in many different organs and tissues, including skin, lips, tongue, eyelid, interdigital membrane, retina, ear, nail pad, scrotum, lymph nodes, brain, breast, prostate, colon, spleen, liver, kidney, pancreas, heart, testicles, ovaries, lungs, uterus, muscle, and bladder.

6 . The method of claim 1 , wherein the target objects are selected from the group consisting of unlabeled single and/or clustered cells such as aggregated red blood cells, white blood cells, infected cells, bacteria, viruses, pathogens, malaria, plaques, S. aureus, E. coli , platelets, and tumor cells with intrinsic cell-specific markers producing during cell metabolism, apoptosis, necrosis, infection's invasion such as hemoglobin's forms, melanin, cytochromes, hemozoin, carotenoids, bilirubin, lipids, DNA, porphyrins, psoralens and combinations thereof.

7 . The method of claim 6 , wherein the method is for in vivo detection of circulating, unlabeled melanoma cells with melanin as intrinsic markers with wavelengths between about 650 nm and 950 nm and about 1030 nm and 1090 nm, wherein the unlabeled melanoma cells are detected by a resulting photoacoustic pulse.

8 . The method of claim 6 , wherein the method includes detecting an amplitude and photoacoustic signal rates from the target objects labeled with gold and magnetic nanoparticles using two or more antibodies and other ligands to the target objects with specific markers associated with cancer and leukocytes before and after application of a magnetic field.

9 . The method of claim 6 , wherein the method includes detecting an amplitude and signal rates from melanoma cells labeled with gold and magnetic nanoparticles before and after application of a magnetic field.

10 . The method of claim 6 , wherein the method includes detecting an amplitude and photoacoustic signal rates from infected cells labeled with gold or magnetic nanoparticles before and after application of a magnetic field.

11 . The method of claim 1 , wherein the method includes selectively destroying circulating unlabeled or labelled target objects with higher absorption than surrounding blood cells and tissue by detecting the target objects and triggering the therapeutic laser pulse with an increased energy level sufficient to cause thermal- based selective damage of the target objects by explosion without harming the surrounding blood cells and tissues, and monitoring falls in frequency of detection of the target objects indicating destruction efficacy.

12 . The method of claim 11 , wherein laser-induced overheating causes a temperature increase of gas inside of the microbubbles, thereby causing rupture of the microbubbles.

13 . The method of claim 1 , wherein the method is used for continuous monitoring of circulating cells for early diagnosis and treatment of metastasis, infection, sepsis, strokes, or heart attacks.

14 . A device for detecting target objects in vessels of a living organism, comprising:

a pulsed laser and an optical module configured to generate a series of consecutive laser pulses at different wavelengths for simultaneous generation of fluorescence, scattering light and photoacoustic signals from the target objects at a laser different wavelengths ranging in the x-ray spectra, visible spectra, terahertz spectra, or microwave spectra ranging between about 400 nm and about 2500 nm, the different wavelengths being generated at a time delay ranging between 0.1 μs and 100 μs, a pulse width ranging between about 0.1 ps and about 1000 ns, a pulse repetition rate ranging between about 1 Hz and about 500,000 Hz, and a pulse energy fluence ranging between about 0.1 mJ/cm 2 and about 1000 J/cm 2· ;

at least one ultrasound transducer;

at least one photodetector, wherein the at least one ultrasound transducer and the at least one photodetector are configured to simultaneously receive fluorescence, scattering light and photoacoustic signals from the target objects and generate an output;

a data recording system; and

a processor configured to:

analyze one or more of the fluorescence, scattering light, and photoacoustic signals to determine a presence of the target objects and at least one characteristic of the target objects, wherein the at least one characteristic of the target objects is selected from a type of target object, a quantity of target objects, a concentration of target objects, a flow speed of target objects, a total blood volume, and combinations thereof; and

trigger a therapeutic laser pulse of high energy to produce laser-induced photothermal bubbles operated to destroy the target objects.

15 . The device of claim 14 , wherein the pulsed laser comprises one or more of gas lasers, chemical lasers, excimer lasers, solid state lasers, microchips laser, fiber-hosted lasers, Q-switched lasers, semiconductor (diode) lasers, dye lasers and other lasers with different gain medium or combinations thereof, and the optical module is configured to convert the wavelengths of light emitted by the pulsed laser to at least one different wavelength using linear or non-linear optical elements, wherein the optical module includes one or more of mirrors, reflectors, optics fibers, optical parametric oscillators, optical crystals, etalons, monochromatic filters, optical couplers, distributed Bragg reflector structures, Lyot filters, Raman shifters, saturable components, optical beam, and wavelengths switching elements, or combinations thereof.

16 . The device of claim 14 , wherein the pulsed laser comprises one or more diode lasers configured to generate laser pulses with wavelengths ranging between about 660 nm and 1100 nm.

17 . The device of claim 14 , wherein the at least one ultrasound transducer includes unfocused and/or focused spherical and/or cylindrical ultrasound transducers at different angles to skin operated to convert the photoacoustic signals received from the target objects in a deep vessel having a depth up to 11 mm with a high resolution provided by high frequency transducers into voltage fluctuations that are subsequently amplified, digitized, stored, and/or analyzed using a high-speed computer and software capable of collecting data at a rate up to 200 megasamples per second.

18 . The device of claim 14 , wherein efficiency of acoustic matching of the at least one ultrasound transducer and tissue of an organism is enhanced by application of an acoustically and optically transparent liquid, wherein the optically transparent liquid includes water, gel, or glycerol.

Assignments (2)

Continuity (6)

References Cited (244)