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WO2024175186A1 - Dispositif de détection optique et procédé de fonctionnement - Google Patents

Dispositif de détection optique et procédé de fonctionnement Download PDF

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Publication number
WO2024175186A1
WO2024175186A1 PCT/EP2023/054330 EP2023054330W WO2024175186A1 WO 2024175186 A1 WO2024175186 A1 WO 2024175186A1 EP 2023054330 W EP2023054330 W EP 2023054330W WO 2024175186 A1 WO2024175186 A1 WO 2024175186A1
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WIPO (PCT)
Prior art keywords
light
emitters
sample
filter
light emitters
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Ceased
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PCT/EP2023/054330
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English (en)
Inventor
Jens Hofrichter
Adler PEROTTE
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Spiden AG
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Spiden AG
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Priority to PCT/EP2023/054330 priority Critical patent/WO2024175186A1/fr
Priority to DE112023005061.9T priority patent/DE112023005061T5/de
Publication of WO2024175186A1 publication Critical patent/WO2024175186A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/65—Raman scattering
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
    • G01J3/02—Details
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
    • G01J3/02—Details
    • G01J3/0256—Compact construction
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
    • G01J3/02—Details
    • G01J3/0256—Compact construction
    • G01J3/0259—Monolithic
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
    • G01J3/02—Details
    • G01J3/10—Arrangements of light sources specially adapted for spectrometry or colorimetry
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
    • G01J3/28—Investigating the spectrum
    • G01J3/2803—Investigating the spectrum using photoelectric array detector
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
    • G01J3/28—Investigating the spectrum
    • G01J3/44—Raman spectrometry; Scattering spectrometry ; Fluorescence spectrometry
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/65—Raman scattering
    • G01N2021/653—Coherent methods [CARS]
    • G01N2021/655—Stimulated Raman
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6408—Fluorescence; Phosphorescence with measurement of decay time, time resolved fluorescence
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/645—Specially adapted constructive features of fluorimeters
    • G01N21/6452—Individual samples arranged in a regular 2D-array, e.g. multiwell plates

Definitions

  • the invention relates to a Raman detection device as well as to a method for operating such a device.
  • Background Art ??? Elastic and inelastic interactions of photons with a sample can pro- vide a wealth of information about the parameters of the sample. Classes of interactions include various elastic and Raman-type in- teractions: ??? - Elastic interactions: elastic scattering, absorption, and transmis- sion at a given optical frequency.
  • - Spontaneous Stokes or anti-Stokes Raman scattering Here, a sin- gle photon interacts with the vibrational states of the molecules in the sample.
  • - Polarized measurements This is a class of measurements that can ??? be combined with any of the others mentioned here and is based on using polarized light to probe the sample.
  • the light emitters have a full width at half maximum (FWHM) spectral width of less than 5 nm, in particular of less than 1 nm. More preferably, the light emitters have a ???
  • a plurality of light detectors The light detectors are also inte- grated on the substrate. They are advantageous arranged to receive light impinging on the first surface of the substrate.
  • At least a first filter The first filter is arranged at at least a first set ??? of the light detectors, i.e. the light impinging on said first set of light detectors has to pass the first filter.
  • the second- ary light emitter or emitters has/have an emission maximum at a second optical emis- sion frequency/frequencies ⁇ Hk, with k being 1 to K. Further, ⁇ H b ⁇ Hk. Further, the first filter transmits light at ⁇ H and blocks light ⁇ Hk for all k.
  • This type of device provides a well-defined positioning of the light emitters and detectors, and with its at least two light emitters in combination with the first filter it allows to measure a rich set of the above effects, including at least two of the following: spontaneous Stokes or anti-Stokes emission (by emitting light from the ? ? first secondary light emitter and detecting the light scattered back from the sample), elastic scattering (by emitting light from the first primary light emitter and detecting the light scattered back from the sample), stimulated Raman gain or loss (by emitting light from both emitters and detecting the light scattered back from the sample). (Note: Although, in the embodiments below, the frequency ⁇ H of ???
  • the difference between ⁇ H and ⁇ Hk is, for all k, no more than 4000 cm -1 in order to correspond to at least one typical vibrational mode.
  • the difference between ⁇ H and ⁇ Hk is, for all k, advantageously - at least 50 cm -1 , in particular at least 100 cm -1 and/or - at least the sum of the FWHM spectral widths of the first and first secondary light emitters.
  • the first filter is advantageously a bandpass filter having a transmission maxi- mum at a first filter frequency ⁇ fH and a FWHM (full width half maximum) transmis- sion window of less than 100 cm -1 , in particular less than 50 cm -1 .
  • the maximum emission frequency ⁇ H of the first pri- ??? mary light emitter is advantageously equal to the maximum transmission frequency ⁇ fH of the first filter in order for the filter to have a good transmission for the light from the first primary light emitter.
  • the device may also comprise more than one first secondary light emitter and more than one second secondary light emitter, i.e. K > 1.
  • K the first secondary light emitter
  • first filter at ⁇ H is at least 10 times, in particular at least 100 times, most preferably at least 1000 times, larger than the transmission of the first filter at ⁇ Hk and ⁇ Lk .
  • this provides an even richer set of measurements.
  • the frequency difference between ⁇ H and ⁇ Lk is, for ? ? all K, advantageously no more than 4000 cm -1 .
  • this the frequency difference between ⁇ H and ⁇ Lk may be at least one of: - at least 50 cm -1 , in particular at least 100 cm -1 for all k and/or - at least the sum of the FWHM of the first primary light emitter and ??? the second secondary light emitter.
  • ⁇ Hk > ⁇ Lk and ⁇ H > ⁇ Lk for all k.
  • ⁇ Hk > ⁇ Lk and the frequency difference between ⁇ Hk and ⁇ Lk is equal to a frequency difference between ⁇ fH and ⁇ Hk .
  • the device may comprise at least one second primary light emitter having an emission maximum at an emission frequency ⁇ L , with ⁇ L being, for all k, different from ⁇ Hk and from ⁇ H .
  • the frequency difference between ⁇ H and ⁇ L is advantageously no more than 4000 cm -1 and/or at least - at least 50 cm -1 , in particular at least 100 cm -1 and/or - the sum of the FWHM of the first primary light emitter and the second primary light emitter.
  • the frequency difference between ⁇ Lk and ⁇ L is advantageously no more than 4000 cm -1 and/or at least - at least 50 cm -1 , in particular at least 100 cm -1 for all k - the sum of the FWHM of the second secondary light emitter and ??? the second primary light emitters for all k.
  • the device advantageously comprises a second filter arranged at at least a second set of the light detectors for filtering the light arriving at the second set of light detectors.
  • the second filter has a spectral transmission different from the first filter.
  • the second filter is advantageously matched with the second primary light emitter, i.e. it transmits light at ⁇ L and blocks P189995PC002023-02-21.
  • the first filter can be used to selectively measure the light at ⁇ H while the second filter can be used to selectively measure the light at ⁇ L .
  • the first and second filters are located on the sub- strate with a gap between them, i.e. with an elongate region extending between them ??? that is neither covered by the first filter nor by the second filter.
  • at least part of the light emitters are located in said gap.
  • the light detectors are located at a plurality of dif- ??? ferent distances from said first primary light emitter and said first secondary light emitter.
  • the light detectors are, advanta- geously, also located at a plurality of different distances from said second primary ??? light emitter and said second secondary light emitter.
  • the invention also relates to a method for operating this type of de- vice. Said method comprises at least the following steps: - Emitting light from at least one of the light emitters into a sample. - Measuring light returning from the sample by means of one or ??? more of the light detectors, and - Deriving at least one parameter of said sample from a signal of the light detectors. ???
  • Fig.1 shows a top view of a device
  • Fig.2 shows a sectional view along line II-II of Fig.1, P189995PC002023-02-21.
  • DOCX ?? Fig.3 illustrates a possible arrangement of the light emitters in more detail
  • Fig.4 is an illustration of the frequencies of the light emitters and the filters
  • ? ? Fig.5 a block circuit diagram of the device
  • Fig.6 is a second embodiment of an array of light emitters.
  • the present device is adapted to measure various inelastic and/or elastic interactions of photons with a sample.
  • the sample may e.g. be a live tissue, such as a skin region of a human, but it may e.g. also be a fluid, such as a blood sam- ple, a gas, a chemical of unknown composition, or a solid.
  • the device comprises a substrate 2, which is advantageously a semiconductor substrate. It has a first surface 4 and a second surface 6. In operation, first surface 4 typically faces the sample 8 to be investigated.
  • the device further comprises a plurality of light emitters 10, 11 and ???
  • the light emitters 10 are, advantageously, lasers with a narrow- band light emission as defined above.
  • they are vertical-cavity surface- ??? emitting laser (VCSEL).
  • VCSEL vertical-cavity surface- ??? emitting laser
  • at least some or all of them may be narrow- band LEDs such as resonant-cavity LEDs (RC-LEDs), for example.
  • the light emitters 10 are pre-selected and binned in order to match the required wave- lengths.
  • the VCSELs have a built-in tuning capability to achieve the desired wavelength and improve the matching properties.
  • the emitters are grating couplers of an integrated photonics circuit capable of tuning a plurality of narrowband emissions.
  • the light detectors 12 may be photodiodes, such as avalanche pho- todiodes (APDs), silicon photomultipliers (Si PMs) or PIN diodes. In particular, they may be or comprise Single Photon Avalanche Photodiodes (SPADs) for high sensitiv- ??? ity.
  • the device further comprises a first fil- ter 14H and a second filter 14L. P189995PC002023-02-21.DOCX ??
  • First filter 14H is arranged at a first set 12H of the light detectors 12 (denoted as 12L, 12H in Figs.1 and 2).
  • this first set 12H corresponds to the light detectors in the right of the device.
  • first filter 14H covers the first set 12H of light detectors.
  • second filter 14L is arranged at a second set 12L of the light detectors 12.
  • this second set 12L corresponds to the light detectors in the left half of the device.
  • second filter 14L co- vers the second set 12L of light detectors.
  • the first and second filters 14H, 14L are arranged on substrate 2 ???
  • Gap 16 is illustrated, in Fig.1, as a dashed rectangle. It advantageously forms a rectangular area having a longitudinal extension L parallel to the neighboring edges 15H, 15L of the first and the second filters 14H, 14L and a transversal extension T perpendicular to the neighboring edges 15H, 15L.
  • gap 16 is advantageously long and narrow, i.e. the longitudinal extension L along the edges 15H, 15L is advantageously at least 10 times larger than the mutual distance, i.e. the transversal extension T, between these edges 15H, 15L.
  • the light emitters 10, 11 are advantageously arranged in a two-di- mensional array having rows and columns, with the number of rows being advanta- ??? geously at least five times, in particular at least ten times, larger than the number of columns.
  • the array has three columns and much more than three rows, in particular at least 10 rows.
  • each row receives three light emitters of specifically matched wavelengths as described in ??? more detail below.
  • the rows of the array of light emitters extend transversally, in par- ticular perpendicularly, to the longitudinal extension L of gap 16 while the columns of the array extend parallel to the longitudinal extension L. This allows for a simple, repetitive geometry of the light emitters at the region of gap 16 along the longitudinal ??? extension L.
  • the light detectors 12 are, in the shown embodiment, also arranged in two-dimensional arrays, with each set 12H, 12L forming its own array.
  • the array of the first set 12H of light detectors 12 is covered by first filter 14H.
  • the array of the second set 12L of light detectors 12 is covered by second ??? filter 14L.
  • the arrays have columns extending parallel to the edges 15H, 15L and rows extending transversally to the edges 15H, 15L. P189995PC002023-02-21.DOCX ??
  • the rows of the detector arrays as well as the rows of the emitter array have equal spacing S1. This allows, for each row, to arrange at least some light detectors at the same relative position to the light emitters.
  • the same type of measurements i.e.
  • the rows of the arrays of the light detectors 12 ex- tend parallel to the rows of the array of the light emitters 10, 11.
  • the arrays of the light detectors 12 each comprise at least four columns extending along the longitudinal extension L of the light emit- ??? ters 10.
  • at least some of the light emitters 12 have, as men- tioned above, emission maxima at different frequencies. This is illustrated in Fig.3, ??? which shows a possible arrangement of the light emitters 12 with their emission max- ima.
  • the light emitters 10 may include first and second pri- mary light emitters 11H, 11L as well as first and second secondary light emitters 10H1, 10H2, 10H3...10HK and 10L1, 10L2, 10L3...10LK with K > 1.
  • the first primary light emitters 11H have an emission maximum at an optical frequency ⁇ H and the second primary light emitters 11L have an emission ??? maximum at an optical frequency ⁇ L.
  • the primary emitters 11H, 11L are all ar- ? ? ranged in a first one of the columns (in the shown embodiment: in the center column) of the array of light emitters.
  • the secondary light emitters 10Hk, 10Lk are arranged in second and third columns (in the shown embodiment: in the outer two columns).
  • the first secondary light emitters 10Hk are arranged in the second column and the second secondary light emitters 10Lk are ???
  • first filter 14H transmits ??? light at ⁇ H (i.e. light from the first primary light emitters 11H). However, it blocks the light at ⁇ Hk and ⁇ Lk for all k (i.e. the light from all secondary light emitters) as well as the light at ⁇ L (i.e. the light from the second primary light emitters 11L).
  • second filter 14L transmits light at ⁇ L (i.e. light from the first second light emitters 11L).
  • the frequencies ⁇ H and ⁇ L of the first and second primary light emitters are different from each other with ⁇ H > ⁇ L . ? ?
  • the frequencies ⁇ Hk , ⁇ Lk of the secondary light emitters 10Hk, 10Lk lie between ⁇ H and ⁇ L , i.e. ⁇ H > ⁇ Hk > ⁇ L for all k (3) and ??? ⁇ H > ⁇ Lk > ⁇ L for all k.
  • the frequency ⁇ Hk of the first secondary light emitter is larger than the frequency ⁇ Lk of the second secondary light emitter, i.e. ???
  • ⁇ Hk and ⁇ Lk there is a large number of different frequencies ⁇ Hk and ⁇ Lk for the secondary light emitters in order to perform measurements at a plurality of different points in the spectrum.
  • the spectral range R L between a lowest and a highest frequency ⁇ Lk, for all k is at least 3500 cm -1 .
  • the spectral range R H between a lowest and a highest frequency ⁇ Hk, for all k, is at least 1750 cm -1 .
  • Fig.4 illustrates an example of the frequencies ⁇ Lk and ⁇ Hk as a function of index k.
  • the frequencies ⁇ Lk are advantageously evenly dis- tributed over their spectral range R L
  • the frequencies ⁇ Hk are advantageously evenly distributed over their spectral range R H . ???
  • ⁇ evenly distributed advantageously implies that K > 3 and that P189995PC002023-02-21.
  • DOCX ??? - a maximum distance between any two neighboring values ⁇ Lk9 and ⁇ Lk is no more than 3 .
  • R L / (K 31) and/or - the maximum distance between any two neighboring values ⁇ Hk9 and ⁇ Lk is no more than 3 .
  • Fig.4 assumes that index k corresponds to the row number in the array of light emitters 10, 11.
  • the frequencies ⁇ Lk and ⁇ Hk are non-monotonous as a function of index k, i.e. they are neither continuously as- cending nor continuously descending as a function of k. Rather, the frequencies are ??? un-ordered along x, e.g. they are in a random order. This reduces an unwanted influ- ence of the device or sample geometry on the measured frequency response. Measurements As mentioned, the present device allows to run a variety of different ??? measurements on the sample.
  • the returning light may e.g. be light reflected from the sample or light transmitted through the am- ple and returned to the detectors e.g. by mirrors or other deflection means.
  • the light may interact with the surface of the sample and/or the in- terior of the sample.
  • spontaneous Stokes Raman scattering can be measured by de- tecting, by means of the second set 12L of detectors, scattered light from one or more of the first primary light emitters 11H. Spontaneous anti-Stokes Raman scattering can be recorded e.g. by ? ?
  • spontaneous anti-Stokes Raman scattering can be measured ??? by detecting, by means of the first set 12H of detectors, scattered light from one or more of the first primary light emitters 11L.
  • Stokes as well as anti-Stokes Raman scattering can be ??? measured at the same time.
  • the method includes at least the steps of - emitting light from one or more of the secondary light emitters; and ??? - detecting light from the sample by means of one or more of the de- tectors.
  • the scattered light is detected by one or more of the second set 12L of the detectors.
  • the scattered light is detected by one or more of the ??? first set 12H of the detectors.
  • Elastic scattering, absorption, and/or transmission can be measured by emitting light from one or more of the primary light emitters 11H, 11L ??? and by measuring the light by means of one or more of the detectors 12. This works because the filters 14H, 14L pass light from the corresponding type of primary light emitters. P189995PC002023-02-21.DOCX ??? Hence, the present device is suited to e.g.
  • the method includes at least the steps of: - emitting light from one or more of the primary light emitters; and - detecting light from the sample by means of one or more of the de- ??? tectors.
  • the light is emitted from one or more of the first pri- mary light emitters 11H and the scattered light is detected by one or more of the first set 12H of the detectors, and/or the light is emitted from one or more of the second primary light emitters 11L and the scattered light is detected by one or more of the ??? second set 12H of the detectors.
  • elastic scattering, absorption and/or transmission can also be measured without the filters.
  • all of the secondary emitters can be used to cover a broad frequency range of elastic scattering measurements. ???
  • CARS Coherent anti-Stokes Raman spectroscopy
  • the resulting light will have the frequency 2 . ⁇ Hk 3 ⁇ Lk.
  • This light which has a frequency higher than ⁇ Hk and ⁇ Lk, should pass the high frequency filter, i.e. first filter 14H, in order to be detected by the first set 12H of detectors.
  • first filter 14H is advantageously a bandpass filter having a maximum transmission frequency ⁇ fH.
  • ⁇ Hk 3 ⁇ Lk ⁇ fH, i.e.: P189995PC002023-02-21.
  • DOCX ??? ⁇ Hk 3 ⁇ Lk ⁇ fH 3 ⁇ Hk .
  • the method for operating the device comprises the steps of - concurrently emitting light into the sample from two of the sec- ondary light emitters 10Hk, 10Lk at first and second different optical frequencies, and ??? - detecting light returning from the sample by means of the light de- tectors 12 at an optical frequency equal to two times the first optical frequency minus one time the second optical frequency.
  • the first optical frequency is higher than the second optical frequency.
  • at least one of the first secondary ??? light emitters 10Hk is used to generate the first optical frequency and at least one of the second secondary light emitters 10Lk is used to generate the second optical fre- quency.
  • the returning light at two times the first optical frequency minus one time the second optical frequency advantageously corresponds to the maximum ??? transmission frequency ⁇ fH of first optical filter 14H.
  • Stimulated Raman gain and stimulated Raman loss For measuring stimulated Raman gain (SRG) or stimulated Raman loss (SRL), a pump beam at a frequency ⁇ 1 is sent into the sample together with a ??? Stokes beam at a frequency ⁇ 2. If ⁇ 13 ⁇ 2 corresponds to the energy of a resonant ex- cited state of the molecules of the sample, there is a strong coupling between the two beams resulting in an energy transfer from the pump beam to the Stokes beam.
  • the intensity gain of the Stokes beam is detected, in SRL meas- urements the intensity loss of the pump beam is detected.
  • the loss or ??? gain can be measured by modulating the intensity of one of the beams and detecting this modulation in the other beam, see e.g. Liao et al. in Science Advances 1(9), 2015 (DOI: 10.1126/sciadv.1500738). P189995PC002023-02-21.DOCX ???
  • SRG is measured by using the light from one or more of the second primary light emitters 11L at frequency ⁇ L as the Stokes beam and the light from any of the secondary light emitters 10Hk, 10Lk or of the first primary light emitters 11H as the pump beam.
  • the intensity of the light at frequency ? ? ⁇ L returning from the sample is measured by means of one or more of the second set 12L of light detectors.
  • SRL is measured by using the light from one or more of the first primary light emitters 11H at frequency ⁇ H as a pump beam and the light from any of the secondary light emitters 10Hk, 10Lk or of the second primary light ??? emitters 11L as the Stokes beam.
  • the intensity of the light at frequency ⁇ H returning the sample is measured by means of one or more of the first set 12H of light detec- tors.
  • a spectrum of SRL and/or SRG can be measured by using several of the secondary light emitters 10Hk, 10Lk for different measurements. ???
  • the method comprises the steps of - concurrently emitting light into the sample from at least one of the primary light emitters 11H, 11L and from at least one of the secondary light emitters 10Hk, 10Lk and ??? - detecting returning light at an optical frequency of the at least one of the primary light emitters 11H, 11L by means of the light detectors 12.
  • the intensity of the at least one of the secondary light emitters 10Hk, 10Lk is electronically modulated, and the signal from the light detec- tors 12 is analyzed for the modulation in order to detect the gain or loss.
  • the design where several rows of said array(s) P189995PC002023-02-21.DOCX ??? of detectors run parallel to a gap 16 at the light emitters 10, 11 is particularly advanta- geous.
  • the present device can also be used to perform fluorescence meas- urements, e.g. as described in https://en.wikipedia.org/wiki/Fluorescence_spectros- ??? copy.
  • light of at least one of the light emitters in particular of the first primary light emitters 11H and/or any of the secondary light emitters 10Hk, 10Lk, is sent into the sample, and light at a lower fre- quency returning from the sample is measured by means of the second set 12L of the ??? light detectors 12.
  • light from several of the light emitters at different wavelengths is sent into the sample. Fluorescence can be distinguished over Stokes Raman emission by its temporal behavior. Whereas Raman is quasi-instantaneous, fluorescence has a characteristic temporal response ranging from nanoseconds to microseconds, which??? requires fast detectors and fast light pulses to separate the Raman signal from the flu- orescence.
  • the fluorescent emission itself is also of value as its lifetime can be an indication of the species to be analyzed in the tissue or sample. More specifically, time-correlated single-photon counting (TSPC) can be employed to assess the temporal behavior of fluorescence. When done spa- ??? tially, the fluorescence lifetime can be mapped across the tissue or same in a tech- nique called florescence life-time imaging (FLIM). Moreover, SPADs can allow also for time-stamping or time-gating to assess the arrival time of photons. However, since fluorescence often has a significantly higher amplitude compared to the Stokes Ra- man emission, the Stoke Raman emission is ignored and temporal properties are not ??? used to isolate it further.
  • TSPC time-correlated single-photon counting
  • the method includes at least the steps of P189995PC002023-02-21.
  • DOCX ??? emitting light at a first optical frequency from one or more of the light emitters, in particular from the first primary emitters 11H or from one or more of the secondary light emitters 10Hk, 10Lk at a first optical frequency; and - detecting light at a second optical frequency, lower than the first ? ? optical frequency, returning from the sample by means of one or more of the light de- tectors, in particular by means of one or more of the second set (12L) of light detec- tors (12).
  • the measurement is performed for several of the light emitters having different optical frequencies.
  • the ??? advantageously, the ???
  • the present device may further comprise one or more optical polari- zation filters arranged at least at some of the light detectors. Such a filter 20 is shown in dotted lines in Fig.1. It may optionally also extend over at least some of the light ??? emitters 10, 11 in order to polarize the emitted light. There may be several such polarization filters 20 of different polari- zation.
  • the filters may be linear or circular polarization filters.
  • the method advantageously comprises the steps of - emitting light into the sample from one or more of the light emit- ters 10Hk, 10Lk, 11H, 11L and ??? - measuring light returning from the sample by at least some of the light detectors 12, wherein the returning light is filtered by one or more optical polar- izers 20.
  • the invention relates to a method for operating the device comprising the steps of: - Concurrently operating several of the light emitters 10, 11 while ??? electronically modulating the light intensity of at least two of the light emitters with different modulation frequencies; and - Analyzing signals from the light detectors 12 for frequency com- ponents at the different modulation frequencies.
  • the light emitters 10 may be lit up in a ??? plurality of different patterns, with at least some of said patterns having several of the emitters lit at the same time.
  • Fig.5 shows an example of the circuitry of a de- vice as described here. It comprises a control unit 22, such as a microprocessor. Con- trol unit 22 is connected to drivers 24, 26 for individually driving the light emitters 10, 11 as well as to circuitry (such as amplifiers and A/D converters) 28 for pro- ??? cessing the signals from the detectors 12. Control unit 22 may be adapted to carry out the methods as de- scribed herein, and/or it may interface with an external computer that controls the de- vice for carrying out the methods. ???
  • the device may comprise further emitters.
  • the density of light emitters in the spectral range R H is higher than in the lower half of the spectral range R L , which leads ??? to a lower spectral resolution of measurements in the lower half of R L .
  • the secondary light emitters fulfilling Eq. (6) or (7) are ar- ranged in the same row. This is not strictly required.
  • the secondary light emitters 10Hk, 10Lk for a given k may also be arranged in different rows. Advantageously, though, they are located close to each other, e.g. at least in neighboring rows, for hav- ing a better overlap of their light fields in the sample. ???
  • First and second filter 14H, 14L can be used to measure, at least in ??? part, different processes as follows: - First filter 14H can, as described above, be used to detect one or more of spontaneous anti-Stokes Raman scattering, SRL, and CARS as well as the measurement of elastic processes at frequency ⁇ H. - Second filter 14L can, as described above, be used to detect one or ???
  • first and second filters 14H, 14L ??? are bandpass filters.
  • first filter 14H may also be a P189995PC002023-02-21.
  • DOCX ??? high-pass filter that transmits frequency ⁇ H but blocks at the frequencies of the sec- ondary emitters.
  • second filter 14L may also be a low-pass filter that transmits frequency ⁇ L but blocks the frequencies of the secondary emitters.
  • the primary emitters 11H, 11L are not ? ? covered by any of the filters.
  • the first primary light emitters 11H may be covered by the first filter 14H and/or the second primary light emitters 11L may be covered by the second filter 14L.
  • the number of first primary light emitters 11H and the number of second primary light emitters is the same, and this number is ??? equal to K/2. This is not strictly necessary, though.
  • N1 is the number N1 of first primary light emitters and N2 the number of second primary light emitters, both N1 and N2 are advantageously at least as large as K/8, in particular at least as large as K/4. ???
  • Fig.6 shows an embodiment of the array of light emitters having only two columns, where the pairs of the first and second pri- mary light emitters are arranged on the same rows, with two rows of secondary light emitters being arranged between each two neighboring rows of first primary light emitters. Further pairs of secondary light emitters may be added.
  • a Raman detection device comprises an array of light emitters in- cluding first and second primary light emitters (11H, 11L) and a plurality of second- ary light emitters (10Hk, 10Lk), with the optical frequencies of the secondary light emitters (10Hk, 10Lk) lying between the optical frequencies of the primary light ??? emitters (11H, 11L).
  • the array of light emitters is arranged between two arrays of light detectors (12H, 12L).
  • the light detectors (12H, 12L) are covered by two light filters (14H, 14L).
  • the light filters (14H, 14L) are bandpass filters for the frequencies of the first and second primary light emitters (11H, 11L). While there are shown and described presently preferred embodi-??? ments of the invention, it is to be distinctly understood that the invention is not lim- ited thereto but may be otherwise variously embodied and practiced within the scope of the following claims. ?

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  • General Physics & Mathematics (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Life Sciences & Earth Sciences (AREA)
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  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)

Abstract

La présente invention concerne un dispositif de détection Raman qui comprend un réseau d'émetteurs de lumière comprenant des premier et second émetteurs de lumière primaires (11H, 11L) et une pluralité d'émetteurs de lumière secondaires (10Hk, 10Lk), les fréquences optiques des émetteurs de lumière secondaires (10Hk, 10Lk) se trouvant entre les fréquences optiques des émetteurs de lumière primaires (11H, 11L). Le réseau d'émetteurs de lumière est disposé entre deux réseaux de détecteurs de lumière (12H, 12L). Les détecteurs de lumière (12H, 12L) sont recouverts par deux filtres de lumière (14H, 14L). Les filtres de lumière (14H, 14L) sont des filtres passe-bande pour les fréquences des premier et second émetteurs de lumière primaires (11H, 11L). Ce dispositif est approprié pour effectuer et analyser un grand nombre de différents processus de diffusion optique élastique et inélastique sur un échantillon ou un tissu.
PCT/EP2023/054330 2023-02-21 2023-02-21 Dispositif de détection optique et procédé de fonctionnement Ceased WO2024175186A1 (fr)

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WO2006061565A1 (fr) 2004-12-09 2006-06-15 The Science And Technology Facilities Council Analyse spectrale raman de tissus et de fluides situes sous une surface
WO2011022418A2 (fr) * 2009-08-17 2011-02-24 The Regents Of The University Of California Systèmes de capteurs sans fil externes et internes distribués pour la caractérisation d'une structure et d'une condition biomédicale de surface et de sous-surface
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WO2021116766A1 (fr) * 2019-12-11 2021-06-17 Rockley Photonics Limited Module de détection optique
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