Device and method for in vivo flow cytometry using the detection of photoacoustic waves
AssigneeBoard of Trustees of the University of Arkansas
InventorVladimir Pavlovich Zharov
Life of this patent
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Abstract
A photoacoustic flow cytometry (PAFC) device for the in vivo detection of cells circulating in blood or lymphatic vessels is described. Ultrasound transducers attached to the skin of an organism detect the photoacoustic ultrasound waves emitted by target objects in response to their illumination by at least one pulse of laser energy delivered using at least one wavelength. The wavelengths of the laser light pulse may be varied to optimize the absorption of the laser energy by the target object. Target objects detected by the device may be unlabelled biological cells or cell products, contrast agents, or biological cells labeled with one or more contrast agents.
Claims30
A device for detecting the presence of moving target objects within a circulatory vessel of a living organism at up to 15 cm away from the vessel, comprising:
- a. at least one tunable pulsed laser source functioning at one or more wavelengths between about 10 Å and about 1 cm, a pulse width ranging between about 0.1 ps and about 1000 ns, a pulse repeat rate ranging between about 1 Hz and about 500,000 Hz, and a pulse energy fluence ranging between about 0.1 mJ/cm2 and about 1000 J/cm2;
- b. at least one optical element operating to direct a pulse from the tunable laser source through the vessel in a beam with an elliptically-shaped cross-section, wherein the beam cross-section has a maximum dimension ranging between about 1 μm and about 150 μm;
- and,
- c. at least one ultrasound transducer with a sample rate ranging between about 10 kHz and about 100 MHz.
A device for performing in vivo photoacoustic flow cytometry to detect the presence of moving target objects within a circulatory vessel of a living organism at up to 15 cm away from the vessel, comprising:
- a. at least one tunable pulsed laser source functioning at one or more wavelengths between about 10 Å and about 1 cm, a pulse width ranging between about 0.1 ps and about 1000 ns, a pulse repeat rate ranging between about 1 Hz and about 500,000 Hz, and a pulse energy fluence ranging between about 0.1 mJ/cm2 and about 1000 J/cm2;
- b. at least one optical element operating to direct a pulse from the tunable laser source through the vessel in a beam with an elliptically-shaped cross-section, wherein the beam cross-section has a maximum dimension ranging between about 1 μm and about 150 μm;
- c. at least one ultrasound transducer with a sample rate ranging between about 10 kHz and about 100 MHz;
- d. an amplifier with a high frequency boundary between about 10 kHz and about 200 kHz, a low frequency boundary between about 1 MHz and about 100 MHz, and a resonance bandwidth between about 0.3 MHz and about 5 MHz;
- e. a data-recording device;
- and,
- f. a computer with a stored analysis program.
A method for detecting at least one type of moving target object within a circulatory vessel of a living organism, the method comprising:
- a. pulsing the target object moving through a vessel with at least one pulse of laser energy;
- b. detecting at least one photoacoustic pulse emitted by the target object;
- and,
- c. analyzing at least one characteristic of the detected photoacoustic pulse to determine at least one characteristic of the detected target objects.
A method of detecting moving target objects in blood or lymphatic vessels of a living organism at up to 15 cm away from the vessels, comprising:
- a. pulsing the target objects with at least one pulse of laser energy at one or more wavelengths ranging between about 400 nm and about 2500 nm, a pulse width ranging between about 0.1 ps and about 1000 ns, a pulse repeat rate ranging between about 1 Hz and about 500,000 Hz, and a pulse energy fluence ranging between about 0.1 mJ/cm2 and about 1000 J/cm2;
- b. detecting the resulting ultrasonic photoacoustic waves emitted by the target objects at a sample rate ranging between about 10 kHz and about 100 MHz;
- and,
- c. analyzing at least one characteristic of the detected photoacoustic pulse to determine at least one characteristic of the detected target objects.
A device for detecting the presence of moving target objects within a circulatory vessel of a living organism at up to 15 cm away from the vessel, comprising:
- a. at least one tunable pulsed laser source functioning at one or more wavelengths between about 10 Å and about 1 cm, a pulse width ranging between about 0.1 ps and about 1000 ns, a pulse repeat rate ranging between about 1 Hz and about 500,000 Hz, and a pulse energy fluence ranging between about 0.1 mJ/cm2 and about 1000 J/cm2.
A method for in vivo detection of a circulating, unlabelled metastatic melanoma cell, the method comprising:
- a. pulsing an area of an organism with at least one pulse of NIR laser energy at a wavelength ranging between about 650 nm and about 950 nm and a laser fluence ranging between about 20 mJ/cm2 and about 100 mJ/cm2;
- b. detecting at least one photoacoustic pulse emitted by the melanoma cell;
- and,
- c. analyzing the at least one detected photoacoustic pulse to indicate the presence of the metastatic melanoma cell in circulation.
A method for selectively destroying target objects circulating in a vessel of a living organism in vivo, comprising:
- a. detecting the target objects circulating in the vessels;
- b. triggering a pulse of laser energy delivered at a wavelength and energy level sufficient to cause the destruction of the detected target objects;
- c. monitoring frequency of detection of target objects circulating through the vessel;
- and,
- d. terminating when the frequency of detection of target objects falls below a threshold level.
Dependencies are inferred from the claim text.