Device and method for in vivo flow cytometry using the detection of photoacoustic waves
US-9217703-B2 · Dec 22, 2015 · US
US11237105B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-11237105-B2 |
| Application number | US-201917273814-A |
| Country | US |
| Kind code | B2 |
| Filing date | Sep 4, 2019 |
| Priority date | Sep 6, 2018 |
| Publication date | Feb 1, 2022 |
| Grant date | Feb 1, 2022 |
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A system for measuring the absorption of a laser radiation by a sample is provided. The system comprises: •(i) a pulsed laser source, suitable for emitting pulses at a repetition frequency fl and arranged so as to illuminate the sample; •(ii) an AFM probe arranged so as to be able to be placed in contact with the region of the surface of the sample on one side, the AFM probe having a mechanical resonance mode at a frequency fm; and •(iii) a detector configured to measure the amplitude of the oscillations of the AFM probe resulting from the absorption of the laser radiation by the region of the surface of the sample, characterized in that it also comprises a translation system designed to displace the sample at a frequency fp.
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The invention claimed is: 1. A system for measuring the absorption of a laser radiation by a sample with a nanometric or subnanometric spatial resolution comprising: (i) a pulsed laser source, suitable for emitting pulses at a tunable wavelength and at a repetition frequency f l and arranged so as to illuminate a portion of the sample so as to induce a thermal expansion of a region of the surface of the sample; (ii) an AFM probe comprising a beam bearing an AFM tip oriented in a so-called vertical direction and arranged so as to be able to be placed in contact with the region of the surface of the sample in which a thermal expansion is induced on one side and held mechanically on another side, the AFM probe having a mechanical resonance mode at a frequency f m ; and (iii) a detector configured to measure the amplitude of the oscillations of the AFM probe resulting from the absorption of the laser radiation by the region of the surface of the sample, wherein the system further comprises a piezoelectric translation system designed to displace the sample in said vertical direction, the displacement being modulated at a frequency f p , and in that the detector is configured to measure the amplitude of a frequency component f m of the oscillations of the AFM probe, the frequency f p being chosen so as to generate oscillations of the AFM probe at the frequency f m by a mix of acoustic waves. 2. The system for measuring the absorption of a laser radiation by a sample with a nanometric or subnanometric spatial resolution as claimed in claim 1 , wherein the frequency f p of modulation of the displacement of the piezoelectric translation system is the sum of or the difference between the frequencies f m and f l . 3. The system for measuring the absorption of a laser radiation by a sample with a nanometric or subnanometric spatial resolution as claimed in claim 1 , wherein the pulse repetition frequency f l is greater than half the mid-height spectral width of the mechanical resonance mode of resonance frequency f m . 4. The system for measuring the absorption of a laser radiation by a sample with a nanometric or subnanometric spatial resolution as claimed in claim 1 , wherein the pulse repetition frequency of the laser is tunable. 5. The system for measuring the absorption of a laser radiation by a sample with a nanometric or subnanometric spatial resolution as claimed in claim 1 , wherein the pulsed laser source is arranged so that the portion of the sample that is illuminated includes the region of the surface of the sample in contact with the tip of the AFM probe. 6. The system for measuring the absorption of a laser radiation by a sample with a nanometric or subnanometric spatial resolution as claimed in claim 1 , the pulsed laser source being arranged so that the portion of the sample that is illuminated is situated on a first face of the sample, the AFM probe being arranged so that the region of the surface of the sample in contact with the AFM probe is situated on a second face, opposite the first face. 7. A method for measuring the absorption of a laser radiation by a sample with a nanometric or subnanometric spatial resolution, the method comprising the following steps: a. illuminating a region of the surface of the sample with a pulsed laser source designed to emit pulses at a tunable wavelength and at a repetition frequency f l ; b. placing an AFM probe, comprising a beam having an AFM tip oriented in a so-called vertical direction on one side and held mechanically on another side, so as to be able to place the AFM tip in contact with the illuminated region of the surface of the sample on one side, the probe having a mechanical resonance mode at a frequency f m ; c. displacing the surface of the sample in said vertical direction using a piezoelectric translation system supporting the sample, the displacement being modulated at a frequency f p chosen so as to generate oscillations of the AFM probe at the frequency f m by a mix of acoustic waves, and d. detecting and measuring the amplitude of the oscillations of the AFM probe resulting from the absorption of the laser radiation by the surface. 8. The method for measuring the absorption of a laser radiation by a sample with a nanometric or subnanometric spatial resolution as claimed in claim 7 , wherein the laser illuminating the region of the surface of the sample has a tunable pulse repetition frequency. 9. The method for measuring the absorption of a laser radiation by a sample with a nanometric or subnanometric spatial resolution as claimed in claim 8 , wherein the steps a) to d) are reiterated by illuminating the region of the surface of the sample for successive and different pulse repetition frequencies f l . 10. The method for measuring the absorption of a laser radiation by a sample with a nanometric or subnanometric spatial resolution as claimed in claim 9 , wherein the steps a) to d) are reiterated by illuminating the region of the surface of the sample with successive and different illumination wavelengths to create an absorption spectrum from the measurements of the amplitude of the oscillations of the AFM probe corresponding to said successive illumination wavelengths. 11. The method for measuring the absorption of a laser radiation by a sample with a nanometric or subnanometric spatial resolution as claimed in claim 10 , wherein the steps a) to d) are reiterated at different regions of the surface of the sample illuminated by the laser source to create an absorption map from the measurements of the amplitudes of the oscillations of the AFM probe, said AFM probe operating in contact mode. 12. The method for measuring the absorption of a laser radiation by a sample with a nanometric or subnanometric spatial resolution as claimed in claim 10 , wherein the AFM probe operates in peak force tapping mode. 13. The method for measuring the absorption of a laser radiation by a sample with a nanometric or subnanometric spatial resolution as claimed in claim 10 , wherein the AFM probe operates in intermittent contact mode.
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