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EP-4741806-A1 - PROBE HEAD, RAMAN SPECTROSCOPY INSTRUMENT COMPRISING THE PROBE HEAD, AND METHOD OF PERFORMING OPTICAL MEASUREMENTS

EP4741806A1EP 4741806 A1EP4741806 A1EP 4741806A1EP-4741806-A1

Abstract

A probe head (10) suitable for Raman spectroscopy comprises an optical pathway (110) along which it is intended that light is emitted for illuminating a sample and light returns from the sample. The probe head further comprises an internal reference target selector (25) which allows to selectively bring a reference target (253) into said optical pathway, in which case the returning light, and thus the measurement signal, originate form the reference target, and to selectively provide free passage for the light to and from the sample, in which case the returning light, and thus the measurement signal, originate form the sample. The reference target has a known Raman spectrum. Measurement values from the reference target thus enable calibration of the Raman spectroscopy measurements. The internal reference target selector enables calibration without removing the probe head from a measurement setup.

Inventors

  • BERGSTRÖM, Pär
  • Raumer, Michael
  • SCHWAB, CHRISTIAN

Assignees

  • Mettler-Toledo GmbH

Dates

Publication Date
20260513
Application Date
20241106

Claims (15)

  1. A probe head (10), the probe head comprising a sensing light optical path (110) extending between a head aperture (26) of the probe head and an optical path junction (11), wherein the optical path junction (11) is configured to receive light from an emitter optical path (120) and to guide light traveling along the emitter optical path (120) and to the optical path junction at least partially along the sensing light optical path (110) into a distal direction and towards the head aperture (26), and the optical path junction (11) is further configured to guide collimated light traveling along the sensing light optical path (110) from the head aperture (26) and to the optical path junction (11) at least partially along a receiver optical path (130), the probe head further comprising a reference target selector (25), wherein the reference target selector comprises at least one reference target (253) and wherein the reference target selector is configured to selectively place one of the at least one reference target (253) into the sensing light optical path (110) and selectively provide free optical transmission between the optical path junction (11) and the head aperture (26) and wherein the probe head comprises further a reference sensor (16), wherein the probe head is configured such that part of the light travelling along the emitter optical path (120) is guided onto the reference sensor (16).
  2. The probe head according to the preceding claim, wherein the optical path junction (11) comprises at least one of a beam splitter and a semi-transparent mirror, preferably a dichroic mirror, and wherein the emitter optical path (120) adjacent the optical path junction and the receiver optical path (130) adjacent the optical path junction are non-parallel.
  3. The probe head according to any one of the preceding claims, wherein light traveling along the emitter optical path (120) adjacent the optical path junction (11) is partially deflected at optical path junction (11) to continue traveling along the sensing light optical path (110) and partially transmits the optical path junction (11) to be guided onto the reference sensor (16) along a reference optical path (140), in particular by a reference mirror (19)
  4. The probe head according to any one of the preceding claims, wherein the head aperture (26), the optical path junction (11) and the receiver optical path (130) are arranged on a straight line, such that collimated light traveling along the sensing light optical path (110) towards the optical path junction (11) can transmit said optical path junction (11) without deflection to enter the receiver optical path (130), and wherein the probe head comprises preferably, a mirror (13) which is provided in the emitter optical path (120) to deflect light traveling along the emitter optical path (120) on the optical path junction (11).
  5. The probe head according to any preceding claim, wherein the probe head comprises at least one of an emitter port (12) or a receiver port (14), configured to receive an optical fiber, wherein the emitter port (12) is arranged and configured such that the emitter optical path (120) extend through it and wherein a collimating optic (17) is arranged in the emitter optical path (120), suitable to produce collimated light from the light leaving an optical fibre connected to the emitter port (12) and/or wherein the receiver port (14) is arranged and configured such that the receiver optical path (130) extend through it, and wherein a coupling optic (15) is arranged in the receiver optical path (130), suitable to couple collimated light into an optical fibre connected to the receiver port (14).
  6. The probe head according to any one of the preceding claims, comprising an emitter port (12), a receiver port (14) and the reference sensor (16) which are arranged such that at least the section of the emitter optical path (120) adjacent the emitter port (12), the section of the receiver optical path (130) adjacent the receiver port (14) and the section of the reference optical path (140) adjacent the reference senor (16) are parallel to each other and wherein said sections of the optical paths (120, 130, 140) are preferably at least partially separated from each other by opaque walls.
  7. A probe comprising a probe head (10) according to any preceding claim and a tube (20), comprising a proximal end and a distal aperture (21), wherein the tube is mounted with its proximal end to the probe head (10), wherein the mounted tube surrounds the head aperture (26) of the probe head (10), and extends the sensing light optical path (110) and whereby the tube comprises preferably an aperture optic (22) wherein the aperture optic (22) is arranged in the tube (20) in the sensing light optical path (110), in particular adjacent the distal aperture (21) and wherein the aperture optic (22) is adapted to focus light traveling through the tube in a proximal- distal direction and to collimate light entering the tube (20) through the distal aperture (21) and traveling in a distal-proximal direction.
  8. A Raman spectroscopy instrument, the Raman spectroscopy instrument comprising a probe head (10) according to any preceding claim, preferably a probe according to claim 8, a light source (61) and a spectrometer (62), wherein the emitter optical path (120) is configured for guiding light from the light source (61) to the optical path junction (11) and the optical path junction (11) is arranged and configured to guide said light at least partially along the sensing light optical path (110) into a distal direction, and wherein further the optical path junction (11) is arranged and configured to guide light travelling in a proximal direction along the sensing light optical path (110) at least partially along the receiver optical path (130) and to the spectrometer (62).
  9. The Raman spectroscopy instrument according to the preceding claim, wherein the Raman spectroscopy instrument further comprises a fiber optic connector (70) connecting the spectrometer (62) with the probe head (10) and comprising at least two optical fibres, a data transmission channel and preferably means for electrical power transmission.
  10. A method for performing optical measurements, comprising a basic method comprising the steps of: • emitting light and • at least partially guiding said light into a proximal-distal direction of a sensing light optical pathway (110) and • monitoring the intensity of the light guided into the proximal-distal direction of the sensing light optical pathway, by measuring a reference intensity which is proportional to the intensity of the emitted light, • at least partially guiding light returning along the sensing light optical pathway (110) in a distal-proximal direction to at least one sensor and • measuring at least one intensity of the returning light, • correcting the measured intensity of the returning light by taking the reference intensity into account which was monitored in the time frame of relevance for said measured intensity, resulting in a corrected intensity, the method for performing optical measurements further comprising the steps of • performing the basic method in at least one measurement step in which the light is directed in the proximal-distal direction to a sample (83) such that the light returning in the distal-proximal direction originates from the sample, and • performing the basic method in at least one reference step in which a reference target (253) is placed in the sensing light optical pathway (110) proximal from the sample such that the light returning along the sensing light optical pathway in the distal-proximal direction originates from the reference target (253), wherein the at least one corrected intensity of the returning light measured by the at least one sensor during the at least one reference step is used in evaluating data from the at least one corrected intensity of the returning light measured by the at least one sensor during at least one of the at least one measurement step.
  11. The method according to the preceding method claim, wherein the light emitted is monochromatic light or narrow band light having a full width at half maximum of 10 nm or less and wherein the at least one intensity of the returning light measured by the at least one sensor comprises a spectral intensity distribution of the returning light in a continuous spectral range covering a spectral range corresponding to at least 10% of the wavelength of the monochromatic emitted light or at least 10% of the wavelength of maximum intensity of the narrow band emitted light.
  12. The method according to any preceding method claim, wherein the emitted light is monochromatic light or narrow band light having a full width at half maximum of 10 nm or less and wherein a Raman spectrum including at least one of Stokes Raman scattering and/or Anti-Stokes Raman scattering is measured.
  13. The method according to any preceding method claim, wherein the sensing light optical pathway (110) is directed towards a sample (83), wherein the optical measurements are performed over a measurement period, wherein the method comprises performing at least two measurement steps during the measurement period, wherein at least one reference step is performed between the at least two measurement steps and wherein the position of the sensing light optical pathway (110) in relation to the sample (83) is maintained unchanged during the entire measurement period.
  14. The method according to the preceding claim, wherein the sensing light optical pathway (110) comprises a sensing light optical path of a probe head (10), wherein the position of the probe head (10) in relation to the sample (83) is maintained unchanged during the entire measurement period.
  15. The method according to the preceding claim, wherein the sample is provided within a containment (80), preferably a bioreactor or a line (80), and a tube (20) mounted to the probe head (10), inside which the sensing light optical path (110) extends, wherein either the tube (20) reaches into the interior of the containment (80) through a port (82), wherein the tube (20) of the probe head remains fixedly installed through the port (82) during the measurement period or the tube (20) forms itself part of the containment (80) comprising ports (82) onto which other parts of the containment (80) remain fixedly installed to during the measurement period.

Description

Technical Field The herein disclosed subject matter relates to a probe head, a probe, a Raman spectroscopy instrument comprising the probe head, and to a method of performing optical measurements as set forth in the appended claims. Background Art Raman scattering spectroscopy is a powerful method for material analysis. In brief Raman scattering describes the effect that some of the light illuminating a material may be inelastically scattered by the material, thus either exciting atoms and/or molecules, so-called Stokes Raman scattering, or receiving energy from atoms and/or molecules, so-called Anti-Stokes Raman scattering. In the first case, energy is transferred from a light quantum to the matter, i.e., the light loses energy, i.e., the scattered light has a lower frequency or a larger wavelength that the incoming light. In the latter case, energy is transferred to a light quantum, i.e., the light gains energy, i.e., the scattered light has a higher frequency or a smaller wavelength than the incoming light. In the art of Raman spectroscopy, the energy gain or energy loss of the light quanta, or photons, i.e., the so-called Raman shift, is expressed in terms of a wave number shift from an excitation light wavelength, and measured in the dimension of 1/cm. In brief, the light inelastically scattered by a material upon excitation of the material by light of a specific excitation wavelength has a characteristic Raman spectrum of intensity versus Raman shift. Hence, a spectrum of light scattered from a sample may be measured, analysed, and be compared to a database of known Raman spectra for specific materials to determine said materials in the sample. More generally, it may be said that Raman scattering is based upon illuminating a sample with monochromatic or narrow band excitation light and analysing a spectrum of scattered light comprising a spectrum which includes wavelengths different from the wavelengths comprised in the excitation light. The intensity of the Raman scattered light is lower than the intensity of the excitation light by several orders of magnitude. Moreover, it is crucial to correctly and accurately assign a measured intensity within a spectrum to the correct wavelength. In particular, when Raman spectroscopy is applied in long-term measurements, it may be desirable to calibrate the measurement setup in intervals during the measurement period. This calibration can preferably be a wave number calibration of the Raman shift and/or a calibration of the spectral response of the instrument, such as a Raman spectrometer. In addition, it was observed that the intensity of the excitation light, i.e. the light with which the sample is illuminated, can change over time, causing intensity changed in the Raman scattered light intensity which are unrelated to the measured material. Again, this effect is in particular relevant in long-term measurements and in instruments where light source and sample volume -i.e. the location of the material to be measured- are separated, spatially and/or by multiple optical components. It may therefore be desirable to provide means to detect and -if needed- correct or at least consider such excitation light intensity fluctuations during the measurement period. US 6,897,951 B1 suggests an end cap which includes a calibration material, i.e., a material having a known Raman spectrum, on an inner side thereof. The end cap is intended to be attached to a distal end of a probe to generate and detect a known Raman spectrum. This allows to calibrate the instrument and/or the spectral analysis. However, it will be appreciated that a probe head can in certain applications not remain installed in the measurement setup during the calibration procedure when the device suggested in US 6,897,951 B1 is used. Calibration may require removal of a probe head from a measurement setup, which has at least two drawbacks: On the one hand, it requires manual operation, requires removal and rearrangement of the probe head, which in turn may result in misalignment. On the other hand, in the case of a measurement setup where the sample is arranged in a containment in which the probe is partially inserted, retracting the probe from said containment implies that said containment is opened and that there is therefore the risk that the sample is contaminated with material from the environment and vice versa. Besides the risk of contaminations, it might be necessary to interrupt a monitored process taking place in said containment. US 2020/348173 A1 suggests a standard reference material interface for a Raman probe which includes a locator including a housing having a first end and a second end. The first end includes an attachment portion configured to mate with an attachment portion of the Raman probe. The locator defines a central axis that intersects the first end and the second end. The standard reference material interface also includes a hermetically sealed standard reference material enclosu