Method and apparatus for measuring a spectral sample response

• US 10,101,268 B2
• Filed: 12/18/2015
• Issued: 10/16/2018
• Est. Priority Date: 12/23/2014
• Status: Active Grant

• Current Assignee: Ludwig-Maximilians-Universitat Munchen, Max-Planck-Gesellschaft Zur Foerderung Der Wissenschaften e.V. (Max-Planck-Gesellschaft zur Frderung der Wissenschaften e)
• Original Assignee: Ludwig-Maximilians-Universitat Munchen, Max-Planck-Gesellschaft Zur Foerderung Der Wissenschaften e.V. (Max-Planck-Gesellschaft zur Frderung der Wissenschaften e)
• Inventors: Apolonskiy, Alexander, Pupeza, Ioachim, Krausz, Ferenc, Fill, Ernst
• Primary Examiner(s): Nur, Abdullahi
• Application Number:
  US15/538,018
• Publication Number:
  US 20180003623A1
• Time in Patent Office: 1,033 Days
• CPC Class Codes: C07D 231/12 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: G01N 2021/3595 using FTIR
• CPC Class Codes: G01N 21/35 using infrared light G01N21/39 takes precedence
• CPC Class Codes: G01N 21/3586 by Terahertz time domain spectroscopy [THz-TDS]
• CPC Class Codes: G01N 2201/06113 Coherent sources; lasers
• CPC Class Codes: G01N 2201/0697 Pulsed lasers

Abstract

A method of measuring a spectral response of a biological sample (1), comprises the steps generation of probe light having a primary spectrum, irradiation of the sample (1) with the probe light, including an interaction of the probe light and the sample (1), and spectrally resolved detection of the probe light having a modified spectrum, which deviates from the primary spectrum as a result of the interaction of the probe light and the sample (1), said modified spectrum being characteristic of the spectral response of the sample (1), wherein the probe light comprises probe light pulses (2) being generated with a fs laser source device (10). Furthermore, a spectroscopic measuring apparatus is described, which is configured for measuring a spectral response of a biological sample (1).

Claims

1. A method of measuring a spectral response of a biological sample, comprising the steps:

generation of probe light having a primary spectrum,

irradiation of the sample with the probe light, including an interaction of the probe light and the sample, and

spectrally resolved detection of the probe light having a modified spectrum, which deviates from the primary spectrum as a result of the interaction of the probe light and the sample, said modified spectrum being characteristic of the spectral response of the sample,

wherein

the probe light comprises probe light pulses being generated with a fs laser source device;

the detection step comprises time-domain sampling a temporal shape of the probe light pulses after the intersection with the sample, and

the spectral response of the sample is obtained based on a Fourier transformation of the temporal shape of the probe light pulses.

2. The method according to claim 1, wherein the probe light pulses have at least one of the features

the probe light pulses have a pulse duration below a reciprocal frequency width of a spectrum including spectral response features occurring in the modified spectrum,

the probe light pulses have a pulse duration below 50 fs before the irradiation of the sample,

the probe light pulses have an average power above 50 mW before the irradiation of the sample,

the primary spectrum covers at least one frequency octave,

the primary spectrum covers a wavelength range including wavelengths of at least one of at least 5 μ

m and at most 15 μ

m, and

the primary spectrum is a continuous or quasi-continuous spectrum.

3. The method according to claim 1, wherein

the spectral response is at least one of an absorption spectrum and a reflection spectrum of the sample.

4. The method according to claim 1, having at least one of the features

the sample comprises at least one of a solid, a liquid, an aerosol, a gas and a vapor, and

the sample is arranged in a multipass cell or an enhancement cavity.

5. The method according to claim 1, wherein the fs laser source device includes

a driving source creating driving pulses, and

a difference frequency generation (DFG) unit generating the probe light pulses by intra-pulse frequency differences of the driving pulses.

6. The method according to claim 1, wherein the fs laser source device includes

a fiber laser,

an Yb-YAG disk laser, or

a Ho-YAG disk laser.

7. The method according to claim 1, wherein

the time-domain sampling step comprises electro-optic sampling of the probe light pulses, wherein

the probe light pulses and sampling pulses are superimposed with varying temporal relationship in an electro-optic probe element for sampling the temporal shape of the probe light.

8. The method according to claim 7, wherein

the sampling pulses comprise parts of driving pulses used for the generation of the probe light pulses, said sampling pulses being directed to the electro-optic probe element with varying delay relative to the probe light pulses.

9. The method according to claim 1, comprising the further step

evaluation of the spectral response of the sample from a subject under investigation for obtaining diagnostically relevant information.

10. The method according to claim 9, wherein the evaluation step includes at least one of

identifying diagnostically relevant substances based on specific bands in the modified spectrum,

comparing at least a portion of the modified spectrum with a stored spectral response previously collected with another sample of the subject under investigation, and

comparing at least a portion of the modified spectrum with reference data of other subjects.

11. The method according to claim 1, wherein the probe light pulses have at least one of the features

the probe light pulses have a pulse duration below 20 fs before the irradiation of the sample,

the probe light pulses have an average power above 500 mW before the irradiation of the sample,

the primary spectrum covers at least two frequency octaves, and

the primary spectrum covers a wavelength range including wavelengths of at least one of at least 3 μ

m and at most 30 μ

m.

12. A spectroscopic measuring apparatus being configured for measuring a spectral response of a biological sample, comprising

a fs laser source device being arranged for an irradiation of the sample with probe light pulses having a primary spectrum, and

a detector device being arranged for a spectrally resolved detection of the probe light pulses after an interaction thereof with the sample, wherein;

the detector device is configured for the spectrally resolved detection of a modified spectrum deviating from the primary spectrum of the probe light pulses,

the detector device is configured for time-domain sampling a temporal shape of the probe light, and

the spectral response of the sample can be obtained based in a Fourier transformation of the temporal shape of the sample light.

13. The spectroscopic measuring apparatus according to claim 12, wherein the fs laser source device is configured for generating the probe light pulses with at least one of the features

the probe light pulses have a pulse duration below a reciprocal frequency width of a spectrum including spectral response features occurring in the modified spectrum,

the probe light pulses have a pulse duration below 50 fs,

the probe light pulses have an average power above 50 mW,

the primary spectrum covers at least one frequency octave,

the primary spectrum covers a wavelength range including wavelengths of at least one of at least 5 μ

m and at most 15 μ

m, and

the primary spectrum is a continuous spectrum.

14. The spectroscopic measuring apparatus according to claim 12, further comprising at least one of

a sample holder device being arranged for accommodating the sample, wherein the fs laser source device, the sample holder device and the detector device are arranged relative to each other such that the detector device is capable of detecting at least one of absorption and reflection spectra of the sample, and

a multipass cell or an enhancement cavity being arranged for providing multiple passes of the probe light pulses through the sample.

15. The spectroscopic measuring apparatus according to claim 14, wherein

the sample holder device is configured for accommodating the sample as at least one of a solid, a liquid, an aerosol, a gas and a vapor.

16. The spectroscopic measuring apparatus according to claim 12, wherein the fs laser source device includes

a driving source creating driving pulses, and

a difference frequency generation (DFG) unit generating the probe light pulses by intra-pulse frequency differences of the driving pulses.

17. The spectroscopic measuring apparatus according to claim 12, wherein the fs laser source device includes

a fiber laser,

an Yb-YAG disk laser, or

a Ho-YAG disk laser.

18. The spectroscopic measuring apparatus according to claim 12, wherein

the detector device includes an electro-optic sampling unit with an electro-optic probe element for sampling the temporal shape of the probe light after the interaction with the sample.

19. The spectroscopic measuring apparatus according to claim 18, wherein

the fs laser source device includes a beam splitter for providing portions of driving pulses used for generating the probe light pulses as sampling pulses, and

a delay unit is arranged for providing the sampling pulses at the electro-optic probe element with varying delay relative to the probe light pulses.

20. The spectroscopic measuring apparatus according to claim 12, further including

a calculation device being configured for evaluating the spectral response of the sample from a subject under investigation and obtaining diagnostically relevant information.

21. The spectroscopic measuring apparatus according to claim 20, wherein the calculation device includes at least one of:

a filter unit identifying diagnostically relevant substances on the basis of specific bands in the modified spectrum,

a first comparing unit comparing at least a portion of the modified spectrum with a stored spectral response previously collected with another sample of the subject under investigation, and

a second comparing unit comparing at least a portion of the modified spectrum with reference data of other subjects.

22. The spectroscopic measuring apparatus according to claim 12, wherein the fs laser source device is configured for generating the probe light pulses with at least one of the features

the probe light pulses have a pulse duration below 20 fs,

the probe light pulses have an average power above 500 mW,

the primary spectrum covers at least two frequency octaves, and

the primary spectrum covers a wavelength range including wavelengths of at least one of at least 3 μ

m and at most 30 μ

m.