Method for selecting Raman excitation wavelength in multi-source Raman probes

Abstract

The present invention relates to the field of spectroscopy, and more particularly to a compact Raman spectroscopy system and method for providing enhanced quantitative analysis for process control. The present invention also relates to a Raman probe device for use in a Raman spectroscopy system. The method includes selecting a first excitation wavelength based on at least one characteristic of a target object, determining a range of a first Raman signal associated with the first excitation wavelength, determining a peak quantum efficiency value within the determined range of a quantum efficiency curve associated with a spectrometer, determining a target Raman shift peak of the target object, and determining a second excitation wavelength based on the peak quantum efficiency value and the target Raman shift peak.

Description

[Technical Field]

[0001] Field of Invention The present invention relates to the field of spectroscopy, and more particularly to a compact Raman spectroscopy system and method for providing enhanced quantitative analysis for process control.

[0002] Related Patents The present invention disclosed herein relates to the subject matter enumerated and taught in U.S. Patent No. 10,359,313, the contents of which are incorporated herein by reference. [Background technology]

[0003] Background of the Invention Raman spectroscopy is a well-known technique that can be used to observe vibrations, rotations, and other low-frequency modes within molecules. Raman scattering is an inelastic process in which monochromatic light, typically provided by a laser, interacts with molecular vibrations, phonons, or other excitations, causing the energy of laser photons to shift up and down. Due to the conservation of energy, the emitted photons gain or lose energy equal to the energy of their vibrational state.

[0004] Many Raman measurements are plagued by fluorescence, which necessitates the use of longer wavelength (lower energy) excitation lasers to mitigate the fluorescence that exceeds the Raman signal, thereby making it impossible to extract the Raman signal. While the use of longer excitation wavelengths facilitates the extraction of the Raman signal from fluorescent samples, it reduces the sensitivity of the silicon CCD detector that captures the spectrometer signal.

[0005] 0cm -1 ~4000cm -1 A known Raman probe that captures the entire wavenumber range of Raman spectra is completed by using the following:

[0006] (1) A single laser source equipped with a large spectrometer incorporating a long sensor to capture photons at all relevant wavenumbers with sufficient resolution, (2) A single laser source equipped with multiple spectrometers / detectors, each covering a different wavelength range (e.g., silicon and InGaAs), (3) Multiple laser sources equipped with a single spectrometer, or (4) Multiple laser sources, each equipped with a separate spectrometer configured to capture multiple Raman spectra, each covering a narrower range of wavenumbers.

[0007] Examples of the use of multiple laser technologies are disclosed below. "Novel Pressure-Induced Molecular Transformations Probed by In Situ Vibrational Spectroscopy", Yang Song, "Applications of Molecular Spectroscopy to Current Research in the Chemical and Biological Sciences," edited by Mark T. Stauffer, October 5, 2016, Chapter 8. "Spatially Compressed Dual-Wavelength Excitation Raman Spectrometer," J.B. Cooper, S. Marshall, R. Jones, M. Abdelkader, and KLWise, Applied Optics, 53, 3333 (2014). “Dual Wavelength Raman Spectroscopy: Improved Compactness and Spectral Resolution” J. Kiefer, https: / / www.americanpharmaceuticalreview.com / Featured-Articles / 354604-Dual-Wavelength-Raman-Spectroscopy-Improved-Compactness-and-Spectral-Resolution / , posted October 16, 2018.

[0008] "Raman Fusion Spectroscopy: Multiwavelength Excitation for Compact Devices," J. Kiefer, SciX2019 (October 13-18, 2019).

[0009] "Apparatus and Method for Composite Raman Multispectrum Spectrometry," BRUNEEL, Jean-Luc, BUFFETEAU, Thierry, DAUGEY, Nicolas, RODRIGUEZ, Vincent, International Publication No. 2019220047 (2019) and U.S. Patent No. 10,359,313, which has been assigned to the assignee of the assignee of this application and whose contents are incorporated herein by reference.

[0010] Each of the referenced documents focuses on capturing multiple Raman spectra using a dual-wavelength laser configuration. However, the references do not disclose means for selecting the wavelengths used for spectral analysis based on the selected material and the characteristics of the spectrometer used. Therefore, the industry needs a compact Raman probe and spectrometer system that provides improved quantitative analysis using two or more probe laser wavelengths, as well as a method for selecting laser probe wavelengths to enhance the quantitative analysis of target materials under investigation for different applications. [Overview of the Initiative] [Means for solving the problem]

[0011] Summary of the Invention The concept of Raman spectrum coupling described herein enables the use of a single, relatively compact spectrometer to collect both fingerprint and stretch Raman spectra (i.e., collected Raman wavelengths), and a method for selecting laser source wavelengths to provide enhanced quantitative analysis of a target material under investigation. According to the principles of the present invention, the fingerprint spectrum is captured using one excitation wavelength, and the stretch spectrum is captured using a second wavelength selected based on the quantum efficiency of the spectrometer and the first wavelength. By selecting one or more laser source wavelengths in the manner disclosed herein, the signal-to-noise ratio is improved to enhance the performance of quantitative analysis of the target material under investigation.

[0012] A compact dual-wavelength Raman probe is disclosed, configured to provide two or more distinct laser wavelengths selected to offer enhanced quantitative analysis of the material under investigation.

[0013] Embodiments in which two laser sources may be integrated within (or inside) the housing of a Raman probe and / or outside the housing of a Raman probe are described herein.

[0014] This specification describes embodiments in which the optical outputs emitted by two laser sources can be coupled in a common optical path, and the emitted light can be coupled using either wavelength beam coupling or geometric beam coupling by a dichroic mirror.

[0015] This specification describes embodiments of a Raman probe that utilize the co-alignment of excitation and collection light using the same optical axis.

[0016] Embodiments of a Raman probe that utilize a spatial offset between excitation and collection light using separate optical paths are described herein.

[0017] This specification describes embodiments of a method for selecting the wavelength of light emitted by two laser sources of a Raman probe, wherein the wavelength of the laser source or probe is selected partly based on the quantum efficiency of a spectrometer used for analyzing light reflected by a target material.

[0018] According to the principle of the present invention, the wavelength of the probe laser used in a dual-wavelength Raman probe is selected based on the quantum efficiency of the spectrometer, which has a single detector array (silicon, InGaAs, or any other detector array) within the spectrometer. The quantum efficiency of the detector is a measure of the ratio of collected photons to incident photons to wavelength and is a common characteristic of spectrometers supplied by manufacturers.

[0019] A method for determining a first and second excitation wavelength for use in a dual-wavelength laser spectrometer system is described herein. Such a system may comprise a first laser source configured to emit a first excitation wavelength, a second laser source configured to emit a second excitation wavelength, and a spectrometer configured to receive a first Raman signal and a second Raman signal, wherein the first Raman signal is associated with the first excitation wavelength and the second Raman signal is associated with the second excitation wavelength. The method is described herein. - A step of selecting the first excitation wavelength based on at least one property of a target object, wherein the at least one property is preferably related to fluorescence produced by the interaction between the first excitation wavelength and the target object. - A step of determining a range of a first Raman signal, preferably a fingerprint region, associated with the first excitation wavelength, - A step of determining a determined range of the quantum efficiency curve QE(λ) associated with the spectrometer, preferably a peak quantum efficiency value (λQE) within the fingerprint region, preferably a step of determining the wavelength (λQE) at which the quantum efficiency within the range of the quantum efficiency curve QE(λ) takes on a peak value associated with the spectrometer. -Target Raman shift peak (v poi ) a step of determining the target object, - The step of determining the second excitation wavelength based on the peak quantum efficiency value and the desired Raman shift peak.

[0020] A diagnostic system is further described herein, which optionally comprises a spectrometer having a known quantum efficiency, and a Raman probe device configured to provide a Raman wavelength to the spectrometer, the Raman wavelength being generated in response to excitation light irradiating a target object. The excitation light has a first wavelength λ p 2 A first light having a second wavelength λ p 1 The system comprises at least one of a second light having the following properties, wherein the first excitation wavelength is selected based on at least one property of the target object, and the second excitation wavelength is determined based on the first excitation wavelength and a wavelength substantially related to the peak value of the known quantum efficiency.

[0021] The diagnostic system may include a control unit adapted to determine a second excitation wavelength, preferably adapted to perform substantially the method described above.

[0022] Preferably, a computer program is described herein that includes instructions for causing the system described above to determine a second excitation wavelength by substantially performing the method described above.

[0023] According to the principles of the present invention, the probe laser wavelength can be determined for different applications based on the quantum efficiency of the spectrometer and the material in the target object, such that the desired Raman spectrum substantially coincides with the peak of the detector quantum efficiency, and thus a higher signal-to-noise ratio is achieved.

[0024] According to the principle of the present invention, the selection of the Raman excitation wavelength based on the quantum efficiency of the spectrometer allows both the fingerprint region and the stretch region of the Raman spectrum to be shifted to wavelengths in which the silicon detector (or similar detector) has relatively high quantum efficiency.

[0025] In one embodiment of the present invention, the Raman spectra of each of the two laser sources may be captured separately and then concatenated or braided together to provide a single spectral scan encompassing the entire range of data, including the fingerprint region and the stretch region, thereby enhancing the signal-to-noise ratio of the Raman signals in the stretch region.

[0026] According to one aspect of the present invention, while each dataset can be analyzed independently, it may also be possible to simultaneously collect spectra from both excitation wavelengths.

[0027] The compact dual-wavelength Raman probes disclosed herein may include optical systems for configuring the output beams of each laser source to have a circular, elliptical, or elongated cross-section that approximates a circular shape or the shape of an elongated emission region of the laser near field.

[0028] In one aspect of the present invention, light generated by a laser source may be emitted toward a target object or material under investigation, and the resulting scattered signal light is transmitted by a compact Raman probe through a light beam which may also have a corresponding elliptical cross-section. The excitation and collection paths may be colinear (i.e., co-aligned) or separate (e.g., spatial offset (see U.S. Patent Application Publication No. 20080076985) or transmission geometry (see U.S. Patent No. 8085396)). An optical fiber containing a core with dimensions approximating the returned scattered light transmits the returned scattered light to the entrance aperture of a spectrometer.

[0029] According to the principles of the dual-wavelength Raman probe disclosed herein, the dual-wavelength Raman probe may include an external cavity laser (ECL) that can be incorporated into the probe as a wavelength-stabilized laser source. See, for example, U.S. Patent No. 9,059,555, “Wavelength-Stabilized Diode Laser,” the contents of which are incorporated herein by reference. Alternatively, the ECL may be held outside the Raman probe.

[0030] According to the principles of the compact Raman probe disclosed herein, a distributed Bragg reflector (DBR) or distributed feedback (DFB) laser may include a wavelength-stabilized laser source that can be integrated integrally with the Raman probe or held externally to the Raman probe.

[0031] According to the principle of the compact two-wavelength Raman probe disclosed herein, light emitted by a laser can be used as a pump source for nonlinear optical (NLO) conversion to generate different wavelengths by, for example, second harmonic generation (SHG), third harmonic generation (THG), or any other nonlinear optical process.

[0032] According to the principle of the present invention for a compact dual-wavelength Raman probe, the selection of the second wavelength is based in part on the first wavelength and spectral efficiency of the spectrometer used to collect the Raman signal.

[0033] Brief explanation of the drawing Refer to the accompanying drawings for a better understanding of the exemplary embodiments and how they can be implemented. It is emphasized that the details shown are illustrative only and are for the purpose of describing preferred embodiments of the present disclosure, and are presented to provide what is considered to be the most useful and readily understandable description of the principles and conceptual aspects of the invention. In this regard, no attempt has been made to describe the structural details of the invention in more detail than is necessary for a basic understanding of the invention. The description with reference to the drawings will make it clear to those skilled in the art how some forms of the invention can actually be embodied. [Brief explanation of the drawing]

[0034] [Figure 1A] A block diagram of an exemplary embodiment of a dual-wavelength co-aligned / reflecting Raman probe using an external laser source is shown. [Figure 1B] A block diagram of an exemplary embodiment of a dual-wavelength co-aligned / reflecting Raman probe using an internal laser source is shown. [Figure 1C] A block diagram of an exemplary embodiment of a dual-wavelength co-aligned / transmission Raman probe using an external laser source is shown. [Figure 1D] A block diagram of an exemplary embodiment of a dual-wavelength spatial offset / transmission Raman probe is shown. [Figure 2] This graph shows the selection of laser wavelengths in a dual-wavelength Raman probe based on the principle of the present invention. [Figure 3A] A flowchart illustrating an exemplary process for selecting the laser wavelength in a dual-wavelength Raman probe according to the principle of the present invention is shown. [Figure 3B] A flowchart illustrating an exemplary process related to a dual-wavelength Raman probe based on the principle of the present invention is shown. [Figure 4A] This shows an exemplary quantum efficiency response of a silicon detector linear array with a 300 nm dispersion for two different Raman laser pump sources. [Figure 4B]This shows an exemplary quantum efficiency response of a silicon detector linear array with a 300 nm dispersion for two different Raman laser pump sources. [Figure 5A] The present invention presents a second exemplary quantum efficiency response of a silicon detector linear array having a 300 nm dispersion for two different Raman laser pump sources based on the principles of the present invention. [Figure 5B] The present invention presents a second exemplary quantum efficiency response of a silicon detector linear array having a 300 nm dispersion for two different Raman laser pump sources based on the principles of the present invention. [Figure 6A] The following shows an exemplary spectral analysis of a target material containing cyclohexane, with or without selection of the excitation wavelength according to the principle of the present invention. [Figure 6B] Figure 6A shows an enlarged cross-section of the spectral analysis. [Figure 6C] An exemplary spectral analysis of a target material containing urea is shown. [Figure 6D] This shows an exemplary spectral analysis of a target material containing water. [Figure 7] A block diagram of an exemplary embodiment of a distance-based spatial offset Raman probe configuration is shown. [Figure 8] A block diagram of another embodiment of a spatially offset Raman probe is shown. [Figure 9A] Exemplary one-dimensional and two-dimensional linear arrays for transmission of excitation wavelengths and collection of Raman wavelengths are shown. [Figure 9B] Exemplary one-dimensional and two-dimensional linear arrays for transmission of excitation wavelengths and collection of Raman wavelengths are shown. [Figure 10A] Exemplary circular or annular configurations for transmission of excitation wavelengths and collection of Raman wavelengths are shown. [Figure 10B] Exemplary circular or annular configurations for transmission of excitation wavelengths and collection of Raman wavelengths are shown. [Figure 10C] Exemplary circular or annular configurations for transmission of excitation wavelengths and collection of Raman wavelengths are shown. [Figure 10D]Exemplary circular or annular configurations for transmission of excitation wavelengths and collection of Raman wavelengths are shown. [Figure 10E] Exemplary circular or annular configurations for transmission of excitation wavelengths and collection of Raman wavelengths are shown. [Figure 10F] Exemplary circular or annular configurations for transmission of excitation wavelengths and collection of Raman wavelengths are shown. [Modes for carrying out the invention]

[0035] The figures and descriptions of the present invention described herein have been simplified to illustrate elements relevant to a clear understanding of the invention, and it should be understood that many other elements have been omitted for clarity. However, since these omitted elements are well known in the art and would not facilitate a better understanding of the invention, explanations of such elements are not provided herein. The disclosure herein also covers variations and modifications known to those skilled in the art.

[0036] Detailed explanation Figure 1A shows a block diagram of an exemplary embodiment of a compact dual-wavelength co-aligned / reflecting Raman probe configuration, similar to the configuration disclosed in Figure 5 of U.S. Patent No. 10,359,313, which discloses the use of diode lasers as light sources in Raman spectroscopy, where wavelength beam coupling by a dichroic mirror is used to couple the light output from one of the two laser sources shown along the same optical path.

[0037] In this exemplary embodiment, the dual-wavelength Raman probe 100 includes a housing 105 and two external light sources 110 and 120 (hereinafter referred to as lasers or laser sources). However, it will be recognized that the light sources 110 and 120 may also be non-laser light sources, such as superluminescent diodes, coupled to the internal optical system within the housing 100 via optical fibers 113 and 123, respectively.

[0038] Lasers 110 and 120 can emit light in a single spatial mode or in multiple spatial modes. Optical coupling units 111, 112, 121, and 122 are known devices for coupling optical fibers to instruments or devices.

[0039] The laser sources 110 and 120 may be any laser device or system, preferably wavelength-stabilized laser sources having a narrow bandwidth.

[0040] One class of lasers that can be used as wavelength-stabilized laser sources is external cavity lasers. See, for example, U.S. Patent No. 9,059,555 and U.S. Patent No. 9,577,409, which have been assigned to the assignee of this application and whose entire contents are incorporated herein by reference, describing exemplary external wavelength-stabilized diode lasers. The light sources 110, 120 may also be semiconductor lasers that incorporate a grating within their structure, such as distributed feedback (DFB) lasers or distributed Bragg reflector (DBR) lasers.

[0041] The laser sources 110 and 120 may also be DFB or DBR lasers coupled to a nonlinear optical element for generating second or third harmonics of shorter wavelength laser light, as is well known in the art.

[0042] The compact dual-wavelength Raman probe 100 further includes optical systems 115, 125 for configuring the output beams of the laser sources 110, 120.

[0043] Illustrative components shown in Figure 1A include lenses 116, 117, and 118 (optical system 115) for reshaping the light beam associated with laser 110 to form a beam cross-section suitable for, for example, exciting a Raman signal (or wavelength) by a target 160, and corresponding components 126, 127, and 128 (optical system 116) for reshaping the light beam associated with laser 120.

[0044] Narrowband filters 119 and 129 block spontaneous emission from the output of lasers 110 and 120.

[0045] The collimated light beams 131 and 132 are combined into a single collimated beam 138 using a first dichroic mirror 135 and a reflective mirror 136, with mirror 136 redirecting the light beam 132 toward the first dichroic mirror 135.

[0046] The first dichroic mirror 135 further passes the light beam 132 through it, redirecting the light beam 131 to form a collimated light beam 138.

[0047] In one aspect of the present invention, a single short-pass filter (not shown) having a cutoff wavelength (i.e., optical beams 131, 132) designed to allow wavelengths emitted by the first laser 110 and the second laser 120 to pass through, but to block wavelengths exceeding the longer of the two wavelengths, may be placed after the optical beams 131, 132 are combined with a collimated optical beam 138.

[0048] The probe (excitation, irradiation) light beam 138 passes through a second short-path dichroic mirror 140, which has transmission characteristics schematically shown in inset 141, to a lens 150, which focuses the combined light containing wavelengths emitted by the first laser 110 and the second laser 120 onto the target object 160 along the optical path 145.

[0049] Light scattered from the target object 160 includes Raman, Rayleigh, and fluorescent components, which can be collected by lens 150 and returned through optical path 145 toward the second dichroic mirror 140.

[0050] In this illustration, the dichroic mirror 140 is configured to reflect Raman photons with longer Stokes shifts into the collimated beam 155.

[0051] Light with wavelengths longer than the filter cutoff, including the two excitation wavelengths, mostly passes through the second dichroic mirror 140 and is almost completely removed from the beam 155.

[0052] In one aspect of the present invention, additional optical elements (not shown) can be included in the optical path of the light beam 138 in order to shape the light beam 138.

[0053] For example, the light beam 138 may be shaped into a circular beam such that the light beam 138 (i.e., the combined first and second excitation wavelengths) forms an annular region on the target object 160.

[0054] In an additional embodiment, the optical element may be configured to adjust the diameter of the annular region projected onto the target object. According to another embodiment of the present invention, additional optical elements (not shown) may be included in the optical path of the light beam 138 to shape the light beam 138 into an elliptical or elongated shape.

[0055] The spatial range of the excitation light on target 160 may be long enough to produce off-axis scattered light, which may result in reflection of a wavelength range (including wavelengths that are preferentially excluded) from beam 155 by the second dichroic mirror 140.

[0056] The dichroic mirror 140 is preferably designed such that undesirable light is removed as much as possible.

[0057] The dichroic mirror 140 may also be an edge filter designed to direct the wavelength of the Raman scattered light along a single optical fiber or axis (i.e., co-aligned) towards the spectrometer 190 while substantially filtering out other light near the pump wavelength.

[0058] In embodiments of the present disclosure in which the Stokes signal wavelength is detected, the dichroic mirror 140 is a short-pass filter that reflects wavelengths longer than the pump wavelength and substantially removes wavelengths below the pump wavelength from the light beam 155, as shown.

[0059] In one disclosed embodiment, where an anti-Stokes signal is detected, the dichroic mirror 140 is a long-pass filter that reflects wavelengths shorter than the pump wavelength and substantially removes wavelengths greater than or equal to the pump wavelength from the light beam 155.

[0060] The dichroic mirror 140 is typically used at an incident angle of 45° and, in the embodiment shown in Figure 1A, transmits light from laser sources 110 and 120 toward the target 160 under investigation. An exemplary dichroic mirror is Semrock's RAZOREDGE beam splitter. RAZOREDGE is a registered trademark of IDEX Health & Science, Inc., located in Launate Park, California.

[0061] To detect the Stokes signal, the long-path die-clock filter 170 is designed to transmit wavelengths longer than its cutoff wavelength, as shown in inset 171.

[0062] Lens 180 focuses the filtered light onto the incident facet of the optical fiber 185, which then transmits the light through the slit 191 of the compact spectrometer 190.

[0063] Filter 170 may be a dichroic filter, a volume holographic grating filter, or a fiber Bragg grating filter, and is used in combination with focusing and collecting optics, or any filter that provides the required wavelength-dependent blocking and transmission capabilities. Exemplary filters include Stopline single-notch filters, RAZOREDGE® ultra-steep long-path edge filters for Stokes detection, and ultra-steep short-path edge filters for anti-Stokes detection. STOPLINE and RAZOREDGE are registered trademarks of IDEX Health & Science, Inc., located in Laurate Park, California.

[0064] The spectrometer 190 is designed to diffract light incident through the slit 191 onto a linear silicon detector array (not shown). The range of light diffracted onto the array is limited, as is well known in the art, by the design of the spectrometer's diffraction grating and the linear range of the detector array. Thus, the grating and detector of the spectrometer can be configured such that the detector receives a limited range of wavelengths, for example, about 791 nm to 934 nm in the case of a Stokes signal. An exemplary 2048-element linear detector, when detected separately, can have a resolution of about 1 cm⁻¹ (i.e., one wavenumber, where wavenumber is a technical term in the field of optics) in both the fingerprint and stretch regions of the spectrum.

[0065] In another embodiment of the present invention, the light from lasers 110 and 120 in Figure 1A may be coupled onto a single fiber (not shown) before being presented to the dichroic mirror 140.

[0066] The elements that generate and combine light from lasers 110 and 120 do not need to be contained within the body 105, but instead may be coupled outside the body 105 by geometric or dichroic coupling and subsequently coupled into a single fiber before being presented to the dichroic mirror 140.

[0067] Figure 1B shows an exemplary embodiment of a dual-wavelength laser co-aligned / reflective Raman probe, in which the laser sources 110 and 120 are incorporated within a Raman probe housing 105.

[0068] In this second exemplary embodiment of the dual-wavelength laser Raman probe, the elements (components) and operation of the Raman probe shown in Figure 1B are the same as those discussed for the dual-wavelength Raman probe shown in Figure 1A. Since both the components and operation of the configuration shown in Figure 1B are the same as those of the dual-wavelength laser Raman probe shown in Figure 1A, the details of the components and operation of the configuration shown in Figure 1B can be understood by those skilled in the art by reading the components and operation of Figure 1A, and therefore, further discussion of Figure 1B is considered unnecessary.

[0069] Figure 1C shows an exemplary embodiment of a dual-wavelength laser co-aligned Raman / transmission probe having a Raman probe, where light output by external laser sources 110, 120 is coupled to a single light beam 138 using wavelength beam coupling by dichroic mirrors 135 and reflective mirrors 136, as described above. In this third embodiment, a second dichroic filter 140 functions to direct the excitation light from the laser source towards the target object 160 via lens 150.

[0070] Lens 150 further collects the Raman wavelength generated in response to the interaction of the excitation wavelength and transmits it to dichroic filter 140. The dichroic filter 140 then transmits the collected Raman light as an optical beam 155 to filter 170.

[0071] In this case, the filter 170 operates to remove the light from the laser sources 110 and 120 so that it is not presented to the slit 191 of the spectrometer 190.

[0072] In this third exemplary embodiment of the dual-wavelength laser Raman probe, the remaining elements (components) and operations shown in Figure 1C are the same as those discussed for the dual-wavelength Raman probe shown in Figure 1A. Since both the components and operations of the configuration shown in Figure 1C are the same as those of the dual-wavelength laser Raman probe shown in Figure 1A, the details of the components and operations of the configuration shown in Figure 1C can be understood by those skilled in the art by reading the components and operations of Figure 1A, and therefore, further discussion of Figure 1C is considered unnecessary.

[0073] Figure 1D shows an exemplary embodiment of a dual-wavelength laser spatial offset / transmission Raman probe, where light output from two external laser sources 110, 120 is coupled along the same optical path using wavelength beam coupling by dichroic mirrors 135 and 136, as previously described. The coupled light 138 is then directed towards a target object 160 by mirror 152 via a focusing lens 150. A collecting lens 151 collects the Raman light generated in response to the irradiation of the target object 160 with the coupled excitation (or illumination) light 138, and directs the collected Raman light, i.e., the light beam 155, to a filter 170, which operates to remove the excitation wavelength from the collected Raman light, as previously described.

[0074] In this fourth exemplary embodiment of the dual-wavelength laser Raman probe, the remaining elements (components) and operations shown in Figure 1D are the same as those discussed for the dual-wavelength Raman probe shown in Figure 1A. Since both the remaining components and operations of the configuration shown in Figure 1D are the same as those of the remaining components and operations of the dual-wavelength laser Raman probe shown in Figure 1A, the details of the remaining components and operations of the configuration shown in Figure 1D can be understood by those skilled in the art by reading the components and operations of Figure 1A, and therefore, further discussion of Figure 1D is considered unnecessary.

[0075] The present invention further relates to a diagnostic system, the diagnostic system comprising a spectrometer having a known quantum efficiency, and a Raman probe device configured to provide the Raman optical wavelength to the spectrometer, the Raman optical wavelength being generated in response to excitation light irradiating a target, and a Raman probe device, and the excitation light having a first wavelength λ p 2 Comprising a first light having, and at least one of a second light having a second wavelength λ p 1 Comprising, the first excitation wavelength being selected based on at least one characteristic of the target, and the second excitation wavelength being determined based on a wavelength substantially related to the first excitation wavelength and the peak value of the known quantum efficiency.

[0076] In a preferred embodiment, within the system described above, the second excitation wavelength is determined as follows.

[0077]

Equation

[0078] Where λ QE Is the wavelength substantially related to the peak of the quantum efficiency within the range defined by the first excitation wavelength, and ν poi [[ID=二十六]]Is the target Raman shift peak. More precisely, ν poi Is the wavenumber of the target Raman shift peak, given in the same dimension as 1 / λ QE . Preferably, the target Raman shift peak (ν poi ) is the stretch peak emitted by the target upon irradiation with the second laser light at the second excitation wavelength.

[0079] [[ID=三十五]] In a preferred embodiment, within the system described above, the Raman probe comprises a first lens configured to focus the first light and the second light on the target, and a filter configured to pass the Raman optical wavelength and block the first wavelength and the second wavelength from passing through the spectrometer.

[0080] In a preferred embodiment, within the system described above, the first lens is configured to collect the Raman light wavelength and provide the collected Raman light wavelength to the filter.

[0081] In a preferred embodiment, the system described above includes a second lens, which is configured to collect the Raman light wavelength and provide the Raman light wavelength to the filter.

[0082] In a preferred embodiment, the system comprises an optical device comprising at least one optical fiber configured to receive the excitation light and direct the received excitation light toward the target object, and a plurality of optical fibers configured to receive the Raman light wavelength and direct the received Raman light wavelength toward the second lens.

[0083] In a preferred embodiment, the system includes a mask that prevents a selected optical fiber from receiving the Raman light wavelength among the plurality of optical fibers.

[0084] In a preferred embodiment, the optical device in the system described above comprises a plurality of optical fibers arranged in one of a one-dimensional array of optical fibers and a two-dimensional array of optical fibers.

[0085] In a preferred embodiment, within the system described above, the optical device comprises a plurality of optical fibers arranged in a ring around a central optical fiber, and the central cable is one of the transmissive optical device and the receptive optical device.

[0086] In a preferred embodiment, within the system described above, the at least one property of the target object is associated with the fluorescence produced by the target object when irradiated with the first excitation wavelength. Preferably, the first excitation wavelength is selected to minimize the influence of fluorescence on the Raman spectroscopic signal.

[0087] The first light and the second light may be emitted simultaneously. The first excitation wavelength and the second excitation wavelength may be emitted sequentially.

[0088] In a preferred embodiment, the system comprises a first laser configured to generate the first light, which is located either inside the Raman probe or outside the Raman probe device, and / or a second laser configured to generate the second light, which is located either inside the Raman probe or outside the Raman probe device.

[0089] The present invention further relates to a Raman probe device including a first lens, wherein the first lens has a first excitation wavelength λ p 2 , the first excitation wavelength and the second excitation wavelength λ, which are determined based on at least one property of the target object. p 1 The Raman probe device is configured to receive at least one of the following, the first lens is configured to focus at least one of the first excitation wavelength and the second excitation wavelength onto the target object, the Raman wavelength is generated in response to the target object being irradiated by a corresponding one of the first excitation wavelength and the second excitation wavelength, the Raman probe device further comprises a filter, the filter is configured to pass the Raman wavelength generated in response to the target object being irradiated by a corresponding one of the first excitation wavelength and the second excitation wavelength through a spectrometer, the spectrometer has a known quantum efficiency, and the second excitation wavelength is,

[0090]

number

[0091] It was determined as such, and in the formula, λ QEv is the wavelength associated with the peak of the quantum efficiency within the range defined by the first excitation wavelength, and poi This represents the target Raman shift peak of the object.

[0092] In the preferred embodiment of the Raman probe described above, the first lens is configured to collect the Raman wavelength and present the collected Raman wavelength to the filter.

[0093] In a preferred embodiment, the Raman probe described above includes a second lens, the second lens configured to collect the Raman wavelength and present the collected Raman wavelength to the filter.

[0094] In a preferred embodiment, the Raman probe described above comprises a first laser source configured to emit the first excitation wavelength and a second laser source configured to emit the second excitation wavelength, wherein at least one of the first and second laser sources is located outside the Raman probe. Alternatively, at least one of the first and second laser sources may be located inside the Raman probe.

[0095] In a preferred embodiment of the Raman probe described above, the first excitation wavelength and the second excitation wavelength are emitted simultaneously and sequentially.

[0096] In a preferred embodiment, the Raman probe described above comprises an optical device having a plurality of optical fibers, wherein a selected optical fiber receives the first excitation wavelength and the second excitation wavelength, and a selected optical fiber receives the Raman light wavelength.

[0097] In one preferred embodiment of the Raman probe described above, the plurality of optical fibers are arranged in one of a matrix configuration and an annular configuration.

[0098] Figure 7 shows a block diagram of an exemplary embodiment of a distance-based spatial offset Raman probe configuration, where the spatial separation (or distance) 710 between the excitation light wavelength 702 and the collected light wavelength 704 enables detection of the subsurface region of the target object 160.

[0099] Hereafter, the coupled light 138 having a first excitation wavelength 210 and a second excitation wavelength 220 will be referred to as the excitation light 702, and the Raman light wavelength will be referred to as the collected light wavelength 704.

[0100] By increasing the distance 710 between the excitation light wavelength 702 and the collected light wavelength 704, the region beneath the surface of the target object 160 can be observed.

[0101] Figure 8 shows a block diagram of a second embodiment of a distance-based spatially oriented Raman probe according to the principles of the present invention. This illustrated embodiment further includes an optical device 810 that communicates optically with lenses 150 and 151, similar to the embodiment shown in Figure 1D.

[0102] In this second embodiment, the light (or excitation wavelength) emitted by the lens 150 is directed to the optical device 810 via an optically transparent material (e.g., optical fiber), and the Raman light 704 generated in response to the excitation light 702 illuminating the target object 160 can be collected by the optical device 810 and provided to the collection lens 151 via a second set of optically transparent materials (e.g., optical fiber).

[0103] For example, the optical device 810 may include an optical probe that can be used to scan a target object 160 while emitting an excitation wavelength 702 and collecting a Raman wavelength 704.

[0104] The tip of the optical probe may include an optically transparent material (e.g., multiple optical fibers) that receives the excitation wavelength from lens 150, and a second, separate optically transparent material (e.g., optical fiber) that collects the Raman light wavelength and provides the collected Raman wavelength to collection lens 151.

[0105] Alternatively, the optical device 810 may be a fixed device including a platform on which a target object can be placed or accommodated. In one aspect of the present invention, the optical device 810 may include, for example, a plurality of optical fibers that receive an excitation wavelength 702 and a second plurality of optical fibers that collect, for example, a Raman wavelength 704 and provide the collected Raman wavelength to a collection lens 151.

[0106] Furthermore, the first set of optical fibers and the second set of optical fibers may be oriented, for example, as shown in Figure 7. In another embodiment, the first set of optical fibers may be oriented so that the excitation wavelength 702 is projected onto the target object 160 at a certain angle, and the second set of optical fibers may be oriented at a certain angle to the target object 160.

[0107] In yet another aspect of the present invention, the first set of optical fibers (or transparent material) may be positioned on one side of the target object 160, and the second set of optical fibers may be positioned on the other side of the target object 160.

[0108] Although the optical device 810 is shown outside the housing 110, it will be recognized that the optical device 810 may also be located inside the housing 110.

[0109] Figure 9A shows a first exemplary embodiment of an optical device 810 in which a first set of multiple optical fibers (or other optically transparent material) 910 and a second set of optical fibers 920 are arranged in a one-dimensional array. In this exemplary embodiment, the optical fibers 910 represent a transmitting device that can be used to provide an excitation wavelength or light 702 to a target object 160, and the optical fibers 920 represent a receiving device that can be used to collect Raman light or wavelength 704 and provide the collected light to a collecting lens 151 (see Figure 8).

[0110] The spatial distance 710 between the excitation wavelength 702 and the Raman wavelength 704 can be varied, for example, by using different collection fibers 920.

[0111] Figure 9B shows a second example of an optical device 810 that includes a two-dimensional array in which a first set of optical fibers 910 and a second set of optical fibers 920 are arranged in a matrix.

[0112] Similar to the arrangement shown in Figure 9A, the excitation wavelength or light 702 may be supplied to the target object 160 via fiber 910, and the Raman light 704 may be collected via optical fiber 920.

[0113] In this illustrated embodiment, the spatial distance 710 can be measured horizontally, vertically, or obliquely with respect to the transmitting and receiving fibers.

[0114] In aspects of the present invention, a mask can be used to limit the number of receiving devices that receive Raman light wavelengths. The mask can be used to determine the minimum separation (or maximum separation distance). Returning to Figure 9A, a mask (not shown) can be placed between the second and fifth rows of the receiving fiber optic cable 920 to establish a minimum separation distance between the penetrating fiber optic cable 910 and the receiving fiber optic cable 920.

[0115] This allows the separation distance to be made variable. Figures 10A to 10F show exemplary embodiments of the optical device 810 in which the optical fibers 910 and 920 are arranged in a circular or annular configuration.

[0116] Figure 10A shows an example of a centrally transmitted fiber 910 surrounded by multiple collection fibers 920.

[0117] Figure 10B shows an example of a centrally transmitted fiber 910 surrounded by two rows of multiple collection fibers 920.

[0118] Figure 10C shows an example of multiple transmission fibers 910 centered around a central collection fiber 920.

[0119] Figure 10D shows an example of a center-based transmission fiber 910 surrounded by a ring of optically transparent material 1020 for collecting Raman light 704.

[0120] Figure 10E shows an example of a center-based transmission fiber 910 surrounded by multiple collection fibers 920.

[0121] Figure 10F shows an example of a center-based collection fiber 920 surrounded by an optically transparent material 1010.

[0122] In one aspect of the present invention, the physical separation 710 of the excitation wavelength 702 from the collected wavelength 704 can be achieved by using a central irradiation (excitation) region and an annular collection region. In another aspect of the present invention, the physical separation 710 of the excitation wavelength 702 from the collected wavelength 704 can be achieved by using an annular irradiation (excitation) region and a central collection region. In yet another aspect, the collection wavelength region may be physically moved or masked from the excitation wavelength region to allow a variable distance between the excitation wavelength irradiation region and the collection light wavelength region.

[0123] In another aspect of the present invention, the excitation wavelength region and the collection wavelength region may be oriented on both sides of the target object 160 in a so-called transmission configuration.

[0124] In yet another embodiment of the present invention, the excitation wavelength 702 may be directed towards the target object 160 at a certain angle. Similarly, the collected wavelength 704 may be collected at a certain angle to the target object 160.

[0125] Exemplary embodiments of dual-wavelength co-aligned / reflective Raman probes with external lasers (Figure 1A), dual-wavelength co-aligned / reflective n-Raman probes with internal lasers (Figure 1B), dual-wavelength co-aligned / transmission Raman probes with external lasers (Figure 1C), and dual-wavelength spatially aligned / reflective Raman probes with external lasers (Figure 1D) are discussed. However, it will be understood that the excitation wavelength selection methods presented herein are also applicable to other types of dual-wavelength Raman probes (e.g., spatially aligned / reflective Raman probes with external or internal lasers) and are considered to be within the scope of the claimed invention.

[0126] Furthermore, it is known to those skilled in the art that the coupling of the excitation wavelengths described can be performed by any of a known number of known wavelength coupling methods (e.g., wavelength beam coupling or geometric beam coupling by dichroic mirrors, see U.S. Patent No. 7,420,996).

[0127] According to the principles of the present invention, the excitation lasers 110, 120 disclosed herein can be operated simultaneously, in parallel, or sequentially. Continuous operation eliminates spurious signals, such as fluorescence, that may be generated when both laser sources were to be operated simultaneously. However, it will be understood that simultaneous or parallel operation is considered, and both parallel and sequential operation of the laser sources are considered to be within the scope of the invention. Thus, when the light sources are operated in parallel, the laser light from the two light sources may be combined to couple with each other to form a single light beam consisting of two wavelengths. On the other hand, (e.g., wavelength beam, geometric beam coupling (see, for example, U.S. Patent No. 7,420,996)).

[0128] If the operation of the light sources is continuous, the laser light from one light source can be considered to "combine" with the absence of light from a second laser light source so that a single beam of a single wavelength is formed.

[0129] Examples of Raman pump wavelengths currently in use are 532 nm, 638 nm, 785 nm, 830 nm, and 1064 nm. As is known in the art, shorter pump wavelengths result in a Raman intensity of λ. -4 Since it is proportional to the Raman scattering signal, it yields a higher Raman scattering signal.

[0130] However, shorter pump wavelengths are more likely to produce fluorescence, which can overwhelm the characteristics of the Raman spectrum. The Raman signal is λ -4 While proportional to the excitation wavelength and shifting with respect to the excitation wavelength, the Raman coupling method offers the possibility of mitigating the adverse effects of fluorescence with shorter wavelength excitation sources, since fluorescence is wavelength-dependent. This makes it possible to quantify the Raman signal in the stretch band when it is not possible to quantify the Raman signal in the fingerprint region in the presence of high levels of fluorescence. Finally, specific wavelengths of short-wavelength or long-wavelength laser sources can be selected to mitigate any fluorescence resonance effects.

[0131] Furthermore, the Stokes spectrum is typically stronger than the anti-Stokes spectrum. As is well known in the art, the Stokes shift of v (measured at wavenumber, i.e., cm⁻¹) is determined by the probe wavelength λ. p The Raman signal associated with wavelength λ s This is caused by the following:

[0132]

number

[0133] Generally, the "fingerprint" region of the spectrum is approximately 2000 cm⁻¹. -1 While the "stretch" region includes wavenumbers below 2000 cm², the "stretch" region is approximately 2000 cm². -1 ~4000cm -1 Includes wavenumbers within the range.

[0134] Figure 2 shows an example of determining the fingerprint and stretch regions of spectra that can be excited by two distinct wavelengths, enabling the detection of two obtained Stokes signal spectra using a single detector array in a compact spectrometer.

[0135] According to the principle of the present invention, λ p 1 210 and λ p 2 The two probe wavelengths, indicated as 220, excite the stretch region and fingerprint region of the Raman spectrum, respectively. In this example, the second excitation wavelength λ p 1 The first excitation wavelength λ p 2 It has a shorter wavelength than 220.

[0136] Furthermore, exemplary wavelength ranges related to the fingerprint region Δv2,223, expressed in wavenumber, are shown. The illustrated fingerprint region 213 corresponds to the first excitation wavelength λ p 2 λ is the Raman signal wavelength associated with 220. s 21 From 225 to λ s 22 It is indicated that it will be extended to 227.

[0137] wavelength λ s 21 215 and λ s 22 217 are the shift values ​​V, respectively. 21 and V 22 wavelength λ p 2 Determined from 220, shift value V 21 and V 22 This can be determined from equation 1 above.

[0138] In this illustrated example, the Raman signal wavelength λ s 21 225 is the first excitation wavelength λ in order to avoid saturation of the spectrometer by backscattered pump light. p2 While the conventional method shifts the Raman signal wavelength from 220 by 1-2 nm (nanometers), the Raman signal wavelength λ s 22 227 is determined by calculating the wavelength associated with the wavenumber range Δv2223 of the fingerprint.

[0139]

number

[0140] Furthermore, the wavelength range associated with the Raman signal stretch region Δv1,213 is shown in wavenumber. The stretch region shown in the figure corresponds to the second excitation wavelength λ p 1 λ, the Raman signal wavelength associated with 210 s 11 215 and λ s 12 It is indicated as an extension of Route 217.

[0141] wavelength λ s 11 215 and λs 12 217 is λ p 1 Wavelength shift value V from 210 11 and V 12 Each is determined by the value V 11 and V 12 This can be determined from equation 1 above.

[0142] Therefore, the Raman signal wavelength λ s 11 215 allows the spectrometer's detector element to be used for both pump lasers λ s 21 It was selected to essentially match 225, while the Raman signal wavelength λ s 12 217 is determined by calculating the wavelength associated with the stretch wavenumber range Δv1213, λ s 11 and λ s 12 The difference between these two values ​​defines the stretch range.

[0143]

Number

[0144] Furthermore, an exemplary quantum efficiency curve QE(λ) 230 of a spectrometer used for collection and analysis of Raman signals generated by the first and second excitation wavelengths is shown.

[0145] Therefore, by appropriately selecting the second excitation wavelength λ p 1 210 and the first excitation wavelength λ p 2 220, Raman signals generated in both the stretch region and the fingerprint region can be captured by the detector element of a single spectrometer.

[0146] For the purpose of explaining the subject matter regarded as the present invention to those skilled in the art, the fingerprint region wavenumber range and the stretch region wavenumber range are approximately equal, i.e., Δv1≒Δv2, and λ s 11 ≒λ s 21 and λ s 21 ≒λ s 22 results.

[0147] Furthermore, the second excitation wavelength λ p 1 210 and the first excitation wavelength λ p 2 220 can be selected to provide capture of both the fingerprint region and the stretch region using the same detector array, but the selection of wavelengths λ p 1 210 and λ p 2 220 according to the principles of the present invention provides an improvement in the analysis performance of the spectrometer.

[0148] Figure 3 shows a flowchart 300 of an exemplary process for determining the wavelength of a dual-wavelength Raman probe according to the principle of the present invention.

[0149] According to the principle of the present invention, in step 310, the first excitation wavelength (i.e., λ p 2 ) is selected. The first excitation wavelength is associated with the fingerprint region of the Raman signal reflected or scattered by the target object when irradiated with the first excitation wavelength.

[0150] First excitation wavelength λ p 2 The first excitation wavelength λ is selected to be as short as possible to relax the fluorescence of the Raman spectrum produced by inelastic scattering of the first excitation wavelength by the target material. p 2 This is determined based on the specific fluorescence properties of the Raman target sample 160 under investigation and when irradiated with the excitation wavelength.

[0151] For example, the first excitation wavelength λ for target classes of materials such as heavy petroleum (oil), biological materials, pharmaceutical materials, and transparent liquids. p 2 It will be known in the art that these can be selected as 1064 nm, 830 nm, 785 nm, and 532 nm, respectively.

[0152] For the purpose of teaching the claimed invention, a wavelength such as 785 nm (nanometers) may be selected as the first excitation wavelength, where 785 nm is selected to minimize the fluorescence produced by the target object when irradiated with the first excitation wavelength.

[0153] The desired range of fingerprint region wavenumbers (Δv2) in step 320 is determined by the desired spectral range and resolution (e.g., 2000 cm²) of the spectrometer. -1 ) will be selected based on the following criteria.

[0154] First excitation wavelength λ p2 The selection of Δv2 is determined by the longest measurement wavelength (λ) of the spectrometer. s 22 ) (Step 330) is defined as follows:

[0155]

number

[0156] In this example, the first excitation wavelength λ is 785 nm. p 2 Using the longest measurement wavelength λ s 22 This can be determined as 931 nm from equation 4 above.

[0157] Next, an examination of the quantum efficiency spectrum associated with the spectrometer used for acquiring and analyzing the Raman signal is performed to determine the peak wavelength QE(λ) (i.e., wavelength λ) of the spectrometer quantum efficiency response in the determined fingerprint region. p 2 (λ s 21 (approximately equal to) and λ s 22 (Step 340) can be determined.

[0158] The quantum efficiency curve QE(λ) provides a measure of the efficiency of a spectrometer that collects Raman signals over a known wavelength band. For example, for the purpose of illustrating a claimed invention, a quantum efficiency response curve (λ) within a determined fingerprint region is used. QE This can be determined from current or previous measurements of the spectrometer's response characteristics.

[0159] For example, for the purpose of explaining the claimed invention to a person skilled in the art, with reference to Figure 2, the peak (maximum) quantum efficiency (λ) of the quantum efficiency response curve 230 within the determined fingerprint region 223. QE )235 can be determined. For the purpose of teaching the claimed invention, the peak quantum efficiency in this illustrated example can be determined to be 800 nm.

[0160] Next, in step 350, the target Raman shift peak (v poi This allows us to determine the specific chemical compound (i.e., the target) being investigated.

[0161] For example, for the purpose of illustrating the claimed invention to those skilled in the art, the target Raman shift peak of a particular target object is 3000 cm⁻¹. -1 It can be determined that this is related to the wavenumber.

[0162] Next, in step 360, a second excitation wavelength (λ) for quantitative analysis in the stretch region is selected. p 1 ) can be determined as follows:

[0163]

number

[0164] Therefore, the second excitation wavelength (λ p 1 This can be determined based on the desired Raman shift peak associated with a particular target object and the peak quantum efficiency of the spectrometer within a fingerprint region defined by the selection of a first excitation wavelength.

[0165] First excitation wavelength (λ p 2 From an exemplary wavelength selected as 220, to 3000 cm -1 Exemplary example of the Raman shift peak (v poi ) and peak quantum efficiency (λ QE Regarding 235, the second excitation wavelength (λ p 1 )210 can be determined to be 645nm.

[0166] As can be understood, the selection of the second excitation wavelength in the manner disclosed in Equation 5 is the peak wavelength (λ) of the spectrometer's quantum efficiency within the fingerprint region. QE This results in a match between the target wavelength and the Raman peak.

[0167] Therefore, the analysis of the Raman signal associated with the second excitation wavelength is performed at, or substantially close to, the peak quantum efficiency of the spectrometer, which results in better analytical performance of the target object.

[0168] The selection of the second excitation wavelength is determined based on the peak quantum efficiency, as shown in Equation 5, and the most outstanding spectral performance can be achieved when the determined second excitation wavelength coincides with the peak quantum efficiency. However, it will be recognized that non-peak quantum efficiency values ​​can also be used to determine the second excitation wavelength. However, the wavelength λ at which the quantum efficiency within the range of the quantum efficiency curve QE(λ) takes its peak value related to the spectrometer is not considered. QE It is preferable that the following is determined. That is, according to the principles of the present invention, the term “peak” as used in relation to the term “peak quantum efficiency” does not have to be the “peak” or maximum value as it is commonly used. Rather, the term “peak” as used herein is considered to be a range around the maximum (or peak) value of the spectral quantum efficiency. For example, the range may be defined as ±10% of the number of wavelengths of the maximum spectral quantum efficiency. Similarly, the range may be defined as ±15% of the number of wavelengths of the maximum spectral quantum efficiency. In another example, the range may be defined as the number of wavelengths within 3 dB of the maximum spectral quantum efficiency. For example, referring to Figure 2, points 240a and 240b represent the 3 dB (or half-power) point relative to the peak quantum efficiency of 235.

[0169] According to another aspect of the present invention, a particular range can be determined by a desired increase in the signal-to-noise ratio of the received Raman spectrum.

[0170] Therefore, the determination of the second excitation wavelength-based equation 5 can be expressed more generally as follows:

[0171]

number

[0172] In the formula, δ represents the range around the maximum (peak) quantum efficiency value. Therefore, according to the principle of the present invention, the term "peak" is considered to be one of the maximum value of the spectrometer's response spectrum and the range relating to the maximum value of the spectrometer's response spectrum.

[0173] Figure 3B shows an exemplary process for operating a two-wavelength Raman probe according to the principle of the present invention.

[0174] According to the principle of the present invention, the first spectral Raman component generated by the excitation of the target object by the first excitation wavelength is captured, filtered, received, processed, and stored as shown in steps 310, 365, 368, 371, and 374, respectively. More specifically, the target object is excited by the first excitation wavelength (i.e., λ p 2 The target is irradiated by a first excitation wavelength, which is selected to minimize the fluorescence produced by the target when irradiated by the first excitation wavelength. The Raman scattered light reflected or scattered by the target is captured in step 365.

[0175] Next, the Raman scattered light is filtered in step 368 and supplied to the spectrometer in step 371.

[0176] In step 374, the spectral analysis performed on the reflected or scattered signal provided to the spectrometer is then stored in step 374.

[0177] In step 360, as described above, a second excitation wavelength (i.e., λ) is determined based on the first excitation wavelength and the quantum efficiency of the spectrometer within the fingerprint region determined based on the first excitation wavelength. p 1 ) will be decided.

[0178] According to the principle of the present invention, after the second excitation wavelength is determined based on Equation 5 above, the determined second excitation wavelength can be evaluated with respect to the wavelength performance of a conventional laser device in order to determine the suitability of using a conventional laser with a known wavelength output.

[0179] In other words, by evaluating the wavelengths of one or more selected conventional lasers with respect to Equation 6, it is possible to determine which of the selected conventional lasers can be used instead of a specially designed laser that outputs a wavelength based on Equation 5.

[0180] The second Raman component generated by the excitation of the target object 160 with the determined second excitation wavelength is captured, filtered, received, processed, and stored as shown in steps 377, 381, 384, 387, and 390, respectively. Specifically, the target object 160 is irradiated with the second excitation wavelength in step 377.

[0181] Scattered or reflected Raman wavelengths related to the second excitation wavelength are captured (step 381) and filtered in step 384.

[0182] In step 387, the Raman wavelength is provided to the spectrometer, and in step 390, the results of the spectral analysis performed by the spectrometer are stored.

[0183] In step 395, the first and second Raman spectral component data are concatenated or combined, with the first Raman spectral component being used to determine the identification of the compound in the target 160, and the second Raman spectral component being used to determine the concentration of the compound in the target. Alternatively, the first and second Raman spectra may be processed independently to provide a more detailed analysis of the target. The selection of the first and second excitation wavelengths according to the principle of the present invention improves quantitative analysis because the Raman spectra coincide (or substantially coincide) with the peak of the spectrometer's quantum efficiency in the fingerprint region. The increase in the signal-to-noise ratio of the accepted Raman signal caused by the coincidence of the Raman signal with the peak of the spectrometer's quantum efficiency results in increased distinctiveness of the target (or the component under analysis within the target).

[0184] Therefore, the dual-wavelength laser Raman probes described herein provide, for example, an opportunity to monitor a pharmaceutical bioreactor (i.e., a sealed container in which bacteria grow in an aqueous liquid). In another embodiment, the H-stretch band may be used as a calibration standard, with the CH and NH stretch bands being monitored. For example, the CH and NH stretch bands can be used to determine changes in proteins within a pharmaceutical bioreactor as proteins are produced by bacteria and food (carbohydrates) is consumed. According to another application of the dual-wavelength laser Raman probes disclosed herein, the concentration of an additive may be determined by calibration using the Raman signal of pure water.

[0185] Figures 4A and 4B show a typical silicon detector quantum efficiency curve (Figure 4A) and a corresponding table (Figure 4B) showing the expected quantum efficiency versus wavenumber for a first Raman pump laser source in the 300 nm wavelength dispersion range.

[0186] Referring to Figure 4A, which shows an example of quantum efficiency versus wavenumber and efficiency related to wavelength shift associated with a 785 nm pump laser source, at 200 cm² -1 The wavelength shift of the 785nm excitation wavelength, which is related to wavenumber, provides a quantum efficiency of 96%, and 3600cm². 1Wavenumber-related wavelength shift provides an efficiency of 1%. Therefore, 200 cm -1 Analysis of the Raman shift wavelength associated with the 785 nm excitation wavelength at 3600 cm² -1 The analysis of the Raman shift wavelength associated with the 785 nm excitation wavelength is significantly better than that of the spectrometer at 200 cm². -1 This is because it is significantly higher than the Raman shift wavelength at that point.

[0187] Figure 4B shows a table of the quantum efficiency of the spectrometer associated with the 785 nm excitation wavelength for different wavelength shifts.

[0188] Figures 5A and 5B show the efficiency improvements and corresponding tables obtained for the selection of the excitation wavelength according to the principle of the present invention.

[0189] According to the principle of the present invention, the selection of a second excitation wavelength (e.g., 680 nm) based on the first wavelength and the spectral efficiency of the spectrometer is 200 cm². -1 It offers a quantum efficiency of 90%, but at 3600 cm² -1 The wavelength shift related to the wavenumber provides a quantum efficiency of 82%. Therefore, the selection of a second excitation wavelength according to the principle of the present invention results in a significant improvement in the analysis of the Raman signal.

[0190] Therefore, the selection of two excitation wavelengths by matching the peak of the quantum efficiency curve to a specific wavenumber band of interest, according to the principle of the present invention, leads to an improvement in the signal processing capability of the spectrometer.

[0191] An example of how to select the first and second excitation wavelengths can be determined as follows:

[0192] [Table 1]

[0193] Therefore, the selection of a second excitation wavelength of 827.0676692 nm according to the principle of the present invention provides an improved and enhanced signal-to-noise ratio in the Raman signal being analyzed.

[0194] Furthermore, in extended stretched bandwidth signals, the entire extended stretched bandwidth can be used for additional data, either as input for chemometric algorithms or as orthogonal data to validate data from fingerprint regions.

[0195] For example, the Raman probe excitation wavelength selection method described herein can be used in medical diagnostics because it can monitor the CH and NH bands using OH band water, as well as fats and proteins using water.

[0196] Analysis of the CH band and NH band with improved or enhanced signal analysis performance as described herein may be useful in diagnosing inflammation or other pathological conditions.

[0197] The Raman probe excitation wavelength selection method described herein can be used for pharmaceutical process analysis of compounds grown in water (H2O) because analysis of such compounds using near-infrared (NIR) spectroscopy is not effective.

[0198] The Raman probe excitation wavelength selection method described herein can be used to analyze petrochemicals, as the CH band is important and water is generally a pollutant.

[0199] Generally speaking, the present invention encompasses the use of the apparatus described herein in medical diagnostics and in analysis related to petrochemical processing or bioreactors.

[0200] Figures 6A and 6B show an example of enhancing Raman signal processing using a wavelength laser pump source in the stretched band region according to the principle of the present invention for cyclohexane.

[0201] Specifically, FIG. 6A shows a fingerprint region associated with a target containing cyclohexane and a spectral analysis associated with a stretch region. FIG. 6B shows an enlarged version of the stretch region shown in FIG. 6A.

[0202] FIG. 6A shows two Raman spectra 610 and 615, where spectrum 610 is obtained using a laser excitation signal with a wavelength of 785 nm, and spectrum 615 is obtained using 785 first excitation wavelengths of 785 nm and a second excitation wavelength of 680 nm, and the 680 nm wavelength is selected according to the principles of the invention disclosed herein.

[0203] According to the principles of the invention, the two-wavelength Raman probe technology disclosed herein enables new applications in the process automation market. For example, the use of the -H stretch region versus the fingerprint region can provide improved quantitative measurement of concentration changes or predictive quantification of concentration. For example, a two-wavelength Raman probe with wavelength selection as shown herein may be directly applicable to enhance the following analyses.

[0204] · % of petroleum products in water · % of contaminants in water · % of sugar in water · % of protein in water · % of sugar / protein versus time in a biopharmaceutical process reaction · Identification of bacterial by-products (e.g., Are you producing what is desired?) · Ratio of the intensity of one set of peaks to another set of peaks (e.g., reducing the complexity of system calibration) · Monitoring the intensity of one or more peaks over time.

[0205] · Sensitivity improvement (S / N improvement) by reducing the noise floor · Optimization of the Raman band of interest and the quantum efficiency of the detector (e.g., amplifying the signal in the alkyne band) · Pass / fail analysis (e.g., identifying the presence or absence of a specific band).

[0206] Briefly, a two-wavelength Raman probe system having first and second excitation wavelengths impinges on a target, and the reflected or scattered wavelength by the target is collected and analyzed by a spectrometer. According to the principle of the present invention, the excitation wavelengths are selected based on the quantum efficiency of the target and the spectrometer (or within a known range) in order to improve the signal-to-noise ratio of the Raman signal by substantially matching the Raman signal with the peak quantum efficiency of the spectrometer. The collection of Raman signals that substantially match the peak quantum efficiency of the spectrometer results in an improvement in the signal-to-noise ratio of the Raman signal.

[0207] The present invention has been described with respect to "wavelengths" emitted by a laser source or manipulated by Raman scattering and Rayleigh scattering, but it will be recognized that the term "wavelength" is a technical term and refers to a wavelength or wavelength band near a nominal desired wavelength. The present invention has been described with reference to specific embodiments. However, those skilled in the art will recognize that various modifications and changes can be made without departing from the scope of the invention as set forth in the claims. Accordingly, this specification is to be considered in an illustrative rather than a limiting sense, and all such modifications are intended to be included within the scope of the invention. Benefits, other advantages, and solutions to problems have been described above with respect to specific embodiments. Benefits, advantages, and solutions to problems, as well as any element that may give rise to or make more prominent any benefit, advantage, or solution, should not be construed as an important, required, or essential feature or element of any or all of the claims.

[0208] For the purposes of the present invention, the term "wavelength" may be used as an abbreviation for the expression "light of (a particular) wavelength". Those skilled in the art will recognize that in these cases the expressions are interchangeable.

[0209] Those skilled in the art will, for the purposes of the present invention, understand that wavenumber (ν, usually cm -1You will understand that the θ (given in nm) and wavelength (λ, usually given in nm) must be converted to the same dimension for computational purposes.

[0210] As used herein, the terms “equip,” “include,” “contain,” “have,” “possess,” or any other variation thereof are intended to encompass non-exclusive inclusion. For example, a process, method, article or apparatus that includes a list of elements is not necessarily limited to those elements alone, and may include other elements not expressly enumerated or specific to such process, method, article or apparatus. Furthermore, unless expressly stated otherwise, the term “or” refers to an inclusive “or” rather than an exclusive “or.” For example, condition A or B is satisfied by one of the following: A is true (or exists) and B is false (or does not exist). A is false (or does not exist) and B is true (or exists). Both A and B are true (or exist).

[0211] The terms “a” or “an” as used herein are for the purpose of describing elements and components of the present invention. This is done for the convenience of the reader and to provide a general meaning of the present invention. The use of these terms in the description herein should be understood to include one or at least one. In addition, unless otherwise specified, the singular form also includes the plural form. For example, a reference to a composition containing a “compound” includes one or more compounds. As used herein and in the appended claims, the term “or” is generally used to include “and / or” unless the content clearly indicates otherwise.

[0212] In this specification, all numerical values, whether expressly indicated or not, are to be taken as being modified by the term “approximately.” The term “approximately” generally refers to a range of numbers that a person skilled in the art would consider equivalent to (i.e., having the same function or result as) the listed values. In any case, the term “approximately” may include numbers rounded (or down) to the nearest significant figure.

[0213] It is explicitly intended that all combinations of those elements that perform substantially the same function in substantially the same way to achieve the same result are within the scope of the invention. The substitution of elements from one embodiment to another described is also fully intended and contemplated.

Claims

1. First excitation wavelength (λ) for use in a dual-wavelength laser spectrometer system ｐ ２ ) and the second excitation wavelength (λ ｐ １ A method for determining ), wherein the system is - A first laser source (110) configured to emit a first excitation wavelength (220), and a second laser source (120) configured to emit a second excitation wavelength (210), - A spectrometer (190) configured to receive a first Raman signal and a second Raman signal, wherein the first Raman signal is associated with a first excitation wavelength (220) and the second Raman signal is associated with a second excitation wavelength (210), comprising: The aforementioned method, - A step of selecting the first excitation wavelength based on at least one characteristic of the target object (160), wherein the at least one characteristic is preferably related to fluorescence produced by the interaction between the first excitation wavelength (220) and the target object (160), and the first excitation wavelength (220) is selected to reduce the influence of the fluorescence on the first Raman signal. - A step of determining the range of the first Raman signal associated with the first excitation wavelength (220), preferably the fingerprint region, - From current or previous measurements of the response characteristics of the spectrometer, the determined wavelength range of the quantum efficiency curve QE(λ) associated with the spectrometer, preferably the peak quantum efficiency value (λ) within the fingerprint region. ＱＥ A step of determining the peak quantum efficiency value (λ ＱＥ ) is the wavelength (λ) at which the quantum efficiency within the range of the quantum efficiency curve QE(λ)(230) takes its peak value related to the spectrometer. ＱＥ The peak quantum efficiency value (λ) is defined as λ ＱＥ ) and - Determine the Raman shift peak (v ｐｏｉ ) for the target substance; - The step of determining the second excitation wavelength (210) based on the peak quantum efficiency value and the desired Raman shift peak, The second excitation wavelength is, [Math 1] The method by which this is determined.

2. The target Raman shift peak (ν ｐｏｉ The method according to claim 1, wherein the stretch peak is a stretch peak emitted by the target object when irradiated with laser light at the second excitation wavelength (210), and the stretch peak is related to the peak quantum efficiency value in the stretch region, which is the range of the second Raman signal related to the second excitation wavelength (210).

3. The method according to claim 1 or 2, wherein the at least one property of the target object relates to the wavelength and intensity of fluorescence of the target object when irradiated with the first excitation wavelength (220).

4. It is a diagnostic system, - A spectrometer (190) with known quantum efficiency, - A Raman probe device (100) configured to provide a Raman light wavelength to a spectrometer (190) having a known quantum efficiency, wherein the Raman light wavelength is generated in response to excitation light irradiating a target object (160), and comprises: The excitation light has a first excitation wavelength λ ｐ ２ A first light comprising (220), and a second excitation wavelength λ ｐ １ A second light comprising (210), wherein the first excitation wavelength (220) is selected to reduce the influence on the Raman signal of fluorescence produced by the interaction between the first excitation wavelength (220) and the target (160) based on at least one property of the target (160), and the second excitation wavelength (210) is determined based on the first excitation wavelength (220) and wavelengths substantially related to the known peak value of quantum efficiency, The second excitation wavelength (210) is, [Math 2] It was determined that, in the formula, λ ＱＥ v is the wavelength in the range defined by the first excitation wavelength, preferably substantially related to the peak value of the quantum efficiency within the fingerprint region, and v ｐｏｉ The diagnostic system is characterized by the target Raman shift peak of the aforementioned target object.

5. The diagnostic system according to claim 4, wherein the second excitation wavelength (210) is selected based on the quantum efficiency of the spectrometer within a fingerprint region (223) defined by the first excitation wavelength (220) and the desired Raman shift peak of the target object (160).

6. The aforementioned system, A diagnostic system according to any one of claims 4 to 5, comprising a control unit adapted to determine the second excitation wavelength (210) by performing the method described in any one of claims 1 to 3.

7. The control unit determines the second excitation wavelength (210) - A step of determining the range of the first Raman signal emitted by the target object (160) related to the first excitation wavelength (220), preferably the fingerprint region (223), - Within the determined range of the quantum efficiency curve QE(λ), preferably within the fingerprint region (223), the wavelength (λ) at which the quantum efficiency takes its peak value related to the spectrometer (190) ＱＥ ) and - The target Raman shift peak (ν) of the target object (160) ｐｏｉ ) and The diagnostic system according to claim 6, adapted to be determined by the step of determining the second excitation wavelength (210) based on the peak quantum efficiency value and the desired Raman shift peak.

8. The target Raman shift peak (ν ｐｏｉ ) is a stretch peak emitted by the target object (160) when irradiated with excitation light having a second excitation wavelength (210), and the stretch peak is related to the peak quantum efficiency value in the stretch region which is the range of Raman wavelengths related to the second excitation wavelength (210). The diagnostic system according to any one of claims 4 to 7.

9. A Raman probe device (100) for use in the system according to any one of claims 4 to 8, - A first lens (150), with a first excitation wavelength λ ｐ ２ (220) and second excitation wavelength λ ｐ １ Configured to receive at least one of (210), wherein the first excitation wavelength is determined based on at least one characteristic of the target object (160), and further configured to focus at least one of the first excitation wavelength (220) and the second excitation wavelength (210) onto the target object (160), The Raman wavelength is generated in response to the target object (160) being irradiated by at least one corresponding wavelength of the first excitation wavelength (220) and the second excitation wavelength (210) of the first lens (150), - A filter (171) configured to transmit a Raman light wavelength generated in response to the irradiation of the target object by at least one corresponding to the first excitation wavelength (220) and the second excitation wavelength (210) to a spectrometer (190) having a known quantum efficiency, The second excitation wavelength (220) is, [Math 3] It was determined that, in the formula, λ ＱＥ v is the wavelength relating to the substantial peak value of the quantum efficiency within the range defined by the first excitation wavelength, ｐｏｉ A Raman probe device (100) comprising a filter (171) which is the desired Raman shift peak of the target object.

10. The system includes a second lens (151) configured to collect the Raman light wavelength and present the collected Raman light wavelength to the filter (171), The Raman probe device according to claim 9.

11. A Raman probe device (100) according to claim 9 or 10, First excitation wavelength λ ｐ ２ (220) is a first laser source (110) for emitting the first laser light, Second excitation wavelength λ ｐ １ (210) is a second laser source (120) for emitting a second laser beam, wherein the second excitation wavelength λ ｐ １ This refers to the quantum efficiency of the spectrometer associated with the device and the first excitation wavelength λ. ｐ ２ A second laser source (120) is selected based on the following, The first dichroic mirror (135), Receiving the first excitation wavelength (220), A first dichroic mirror (135) configured to receive the second excitation wavelength (210), A second dichroic mirror (140), Receiving the first excitation wavelength light (220) and the second excitation wavelength (210), The first excitation wavelength (220) and the second excitation wavelength (210) are transmitted toward the target object (160). A second dichroic mirror (140) receives a first Raman light (225) associated with the transmitted first excitation wavelength (220) and a second Raman light (215) associated with the second excitation wavelength (210), and the first Raman light and the second Raman light represent the interaction between the first excitation wavelength and the target object (160), respectively. A focusing optical system (150), Receiving the first excitation wavelength (220) and the second excitation wavelength (210), The first excitation wavelength and the second excitation wavelength are focused onto the target object (160). The first Raman light (225) and the second Raman light (215) are collected. A focusing optical system (150) is configured to direct the collected first Raman light and the second Raman light towards the second dichroic mirror (140), Filter (170), The first Raman light (225) and the second Raman light (215) collected are received from the second dichroic mirror (140). A Raman probe device (100) comprising: a filter (170) configured to transmit wavelengths other than the first excitation wavelength (220) and the second excitation wavelength (210) from the collected first Raman light and the second Raman light to the spectrometer (190).

12. The Raman probe device according to claim 11, wherein at least one of the first laser source and the second laser source is located outside the Raman probe device.

13. The Raman probe device according to claim 11 or 12, wherein the first excitation wavelength and the second excitation wavelength are emitted in parallel.

14. The Raman probe device according to claim 11 or 12, wherein the first excitation wavelength and the second excitation wavelength are emitted continuously.

15. The first excitation wavelength λ ｐ ２ The wavelength is determined based on at least one characteristic of the target object, The second excitation wavelength is, [Math 4] It was determined that, in the formula, λ ＱＥ v is the peak quantum efficiency within the range defined by the first excitation wavelength, where v ｐｏｉ The Raman probe device according to any one of claims 11 to 14, wherein is the target Raman shift peak of the target object.

16. The Raman probe device according to claim 15, wherein the at least one property of the target object is related to fluorescence produced by the target object when irradiated with the first excitation wavelength.

17. The Raman probe device according to claim 16, wherein the first excitation wavelength is selected such that the fluorescence produced by the target object when irradiated with the first excitation wavelength does not obscure the first Raman wavelength.

18. The target object is a Raman probe device according to any one of claims 11 to 17, relating to medical diagnostics, petrochemical processing, or bioreactors.

19. A Raman probe device (100) according to any one of claims 9 to 18, - Spectrometer (190), - First excitation wavelength λ ｐ ２ (220) is a first laser source (110) for emitting the first laser light, - Second excitation wavelength λ ｐ １ (210) is a second laser source (120) for emitting a second laser beam, wherein the second excitation wavelength λ ｐ １ (210) is a second laser source (120) selected based on the quantum efficiency of the spectrometer (190) in a range defined by the first excitation wavelength (220) and the desired Raman shift peak of the target object (160), preferably within the fingerprint region (223), - A focusing optical system (150), The first laser beam and the second laser beam are focused onto the target object (160). A focusing optical system (150) is configured to collect a corresponding one of the first Raman light (225) and the second Raman light (215) reflected from the target object (160), - Filter (170), Receiving the collected light, A Raman probe device (100) comprising: a filter (170) configured to transmit light having wavelengths other than the first laser light and the second light from the collected light to the spectrometer (190).

20. The wavelength of the second laser light is, [Math 5] It was determined that in the formula, λQE is λ ｐ ２ ~λ ｓ １１ -λ ｓ ２２ The peak quantum efficiency within the aforementioned range is v ｐｏｉ The Raman probe device according to claim 19, wherein is the target Raman shift peak of the target object.

21. The first excitation wavelength λ ｐ ２ The wavelength is determined based on at least one characteristic of the target object, The second excitation wavelength is, [Math 6] It was determined that, in the formula, λ ＱＥ This is the peak quantum efficiency within the range defined by the first excitation wavelength, δ is the region near the peak quantum efficiency value, and v ｐｏｉ This is the target Raman shift peak of the target object. A Raman probe device according to any one of claims 9 to 20.

22. Use of the Raman probe device according to any one of claims 9 to 21 in medical diagnostics or in analysis related to petrochemical processing or bioreactors.

23. The aforementioned Raman probe device is The first lens, A first lens configured to focus the first light and the second light onto the target object, It is a filter, The aforementioned Raman light wavelength is passed through, A diagnostic system according to any one of claims 4 to 8, comprising: a filter configured to prevent the first wavelength and the second wavelength from passing through the spectrometer.

24. The first lens is, The Raman light wavelengths are collected, The diagnostic system according to claim 23, configured to provide the collected Raman light wavelength to the filter.

25. The second lens, The Raman light wavelengths are collected, The system includes a second lens configured to provide the aforementioned Raman light wavelength to the filter, The diagnostic system according to claim 23 or 24.

26. It is an optical device, At least one optical fiber, Upon receiving the aforementioned excitation light, An optical fiber configured to direct the received excitation light toward the target object, Multiple optical fibers, Receiving the aforementioned Raman light wavelength, The optical device comprises a plurality of optical fibers configured to direct the received Raman light wavelength toward the second lens, A diagnostic system according to any one of claims 23 to 25.

27. The system includes a mask that prevents a selected optical fiber from receiving the Raman light wavelength among the plurality of optical fibers that receive the Raman light wavelength. The diagnostic system according to claim 26.

28. The optical device is The diagnostic system according to claim 26 or 27, comprising a plurality of optical fibers arranged in one of a one-dimensional array of optical fibers and a two-dimensional array of optical fibers.

29. The optical device is A diagnostic system according to any one of claims 25 to 28, comprising a plurality of optical fibers arranged in a ring around a central optical fiber, wherein the central cable is one of a transmissive optical device and a receptive optical device.

30. The diagnostic system according to any one of claims 4 to 8, wherein the at least one property of the target object is related to fluorescence produced by the target object when irradiated with the first excitation wavelength.

31. The first laser, A first laser configured to generate the first light, which is located either inside or outside the Raman probe device, The second laser, A second laser configured to generate the second light, which is located either inside or outside the Raman probe device, A diagnostic system according to any one of claims 4 to 8.

32. The first excitation wavelength is emitted by the following: The first laser source, A second laser source configured to emit the second excitation wavelength, At least one first laser source and the second laser source are located outside the Raman probe device and inside the Raman probe device. A Raman probe device according to any one of claims 9 to 10.

33. The Raman probe device according to any one of claims 9 to 10 or 32, wherein the first excitation wavelength and the second excitation wavelength are emitted either simultaneously or sequentially.

34. It is an optical device, The system comprises multiple optical fibers, and a selected optical fiber receives the first excitation wavelength and the second excitation wavelength. A selected optical fiber from the aforementioned optical fibers is equipped with an optical device that receives the Raman light wavelength. A Raman probe device according to any one of claims 9 to 10 or 32 to 33.

35. The Raman probe device according to claim 34, wherein the plurality of optical fibers are arranged in one of a matrix configuration and an annular configuration.

36. A computer program comprising an instruction for the system according to any one of claims 4 to 8 to determine the second excitation wavelength (210) by performing the method according to any one of claims 1 to 3.

Images