Method for selecting raman excitation wavelength in multi-source raman probe

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 comprises the steps of selecting a first excitation wavelength based on at least one characteristic of a target object; determining a range of first Raman signals associated with the first excitation wavelength; determining a peak quantum efficiency value within a determined range of a quantum efficiency curve associated with the spectrometer; determining a Raman shift peak of interest of the target object; and determining a second excitation wavelength based on the peak quantum efficiency value and the Raman shift peak of interest.

Description

Technical Field

[0001] This invention relates to the field of spectroscopy, and more specifically, to a compact Raman spectroscopy system and method for providing enhanced quantitative analysis for process control.

[0002] Related applications

[0003] The present invention disclosed herein relates to the subject matter described and taught in USP 10,359,313, the contents of which are incorporated herein by reference. Background Technology

[0004] Raman spectroscopy is a well-known technique used to observe vibrational, rotational, and other low-frequency modes in 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 the laser photons to shift upwards or downwards. Due to energy conservation, the energy gained or lost by the emitted photon equals the energy of the vibrational state.

[0005] Many Raman measurements are affected by fluorescence, which necessitates the use of longer wavelength (lower energy) excitation lasers to mitigate the fluorescence signal from overwhelming the Raman signal, making the latter impossible to extract. Using longer excitation wavelengths is advantageous for extracting Raman signals from fluorescent samples, but at the cost of reduced sensitivity of the silicon CCD detector that captures the spectrometer signal.

[0006] Capture coverage from 0 cm -1 Up to 4000 cm -1 Known Raman probes for Raman spectra across the entire wavenumber range can be obtained using the following:

[0007] (1) A single laser source with a large spectrometer that combines a long sensor to capture photons of all relevant wavenumbers with sufficient resolution;

[0008] (2) A single laser source with multiple spectrometers / detectors, each covering a different wavelength range (e.g., silicon and InGaAs).

[0009] (3) Multiple laser sources with a single spectrometer, or

[0010] (4) Multiple laser sources with individual spectrometers are configured to capture multiple Raman spectra, each Raman spectrum covering a small range of wavenumbers.

[0011] Examples of using various laser technologies are disclosed below:

[0012] “Novel Pressure-Induced Molecular Transformations Probed by In Situ Vibrational Spectroscopy”, Yang Song,

[0013] “Applications of Molecular Spectroscopy to Current Research in the Chemical and Biological Sciences”, Mark T. Stauffer (ed.), October 5, 2016, Chapter 8,

[0014] “Spatially Compressed Dual-Wavelength Excitation Raman Spectrometer”, J.B. Cooper, S. Marshall, R. Jones, M. Abdelkader, and K.L. Wise, Applied Optics, 53, 3333 (2014);

[0015] “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 / , published on October 16, 2018.

[0016] “Raman Fusion Spectroscopy: Multiwavelength Excitation for Compact Devices”, J. Kiefer, SciX 2019. (October 13 - 18, 2019).

[0017] "Apparatus and Method for Composite Raman MultispectralSpectrometry", BRUNEEL, Jean-Luc, BUFFETEAU, Thierry, DAUGEY, Nicolas, RODRIGUEZ, Vincent, WO 2019220047 (2019) and

[0018] U.S. Patent 10,359,313, which is assigned to the assignee of this application, the contents of which are incorporated herein by reference.

[0019] Each cited reference focuses on capturing multiple Raman spectra using a dual-laser configuration. However, these references do not disclose a method for selecting the wavelengths used in the spectral analysis based on the chosen material and the characteristics of the spectrometer employed. Therefore, there is a need in industry for a compact Raman probe and spectrometer system that provides improved quantitative analysis using two or more probe laser wavelengths, and a method for selecting laser probe wavelengths to enhance the quantitative analysis of the target material under study for different applications. Summary of the Invention

[0020] The Raman spectroscopy correlation concept described herein allows for the collection of fingerprint and stretched Raman spectra (i.e., the collected Raman wavelengths) using a single, relatively compact spectrometer, and provides a method for selecting laser source wavelengths to provide enhanced quantitative analysis of the target material under study. According to the principles of the invention, a single excitation wavelength is used to capture the fingerprint spectrum, while a second and first wavelength, selected based on the spectrometer's quantum efficiency, are used to capture the stretched spectrum. Selecting one or more laser source wavelengths in the manner disclosed herein provides an enhanced signal-to-noise ratio, thereby improving the performance of quantitative analysis of the target material under study.

[0021] This paper discloses a compact dual-wavelength Raman probe configured to provide two or more individual laser wavelengths selected in a manner that provides enhanced quantitative analysis of the material under study.

[0022] In the embodiments described herein, the two laser sources may be integrated within (or inside) the housing of the Raman probe and / or outside the housing of the Raman probe.

[0023] In the embodiments described herein, the light outputs emitted by two laser sources can be combined in a common optical path, wherein the emitted light can be combined using a combination of wavelength beams or a combination of geometric beams with dichroic mirrors.

[0024] This article describes an embodiment of a Raman probe that utilizes co-aligned excitation and collection beams with the same optical axis.

[0025] This article describes an embodiment of a Raman probe that spatially deflects excitation and collection light using a separate optical path.

[0026] This article describes an embodiment of a method for selecting the wavelength of light emitted by two laser sources in a Raman probe, wherein the wavelength of the laser source or probe is selected in a manner based in part on the quantum efficiency of a spectrometer used to analyze light reflected from a target material.

[0027] According to the principles 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 comprises a single detector array (silicon, InGaAs, or any other detector array) within the spectrometer. The quantum efficiency of the detector, a measure of the ratio of collected photons to incident photons relative to the wavelength, is a common characteristic of spectrometers supplied by manufacturers.

[0028] This document describes a method for determining a first excitation wavelength and a second excitation wavelength used in a dual-laser spectrometer system. Such a system may include a first laser source configured to emit the first excitation wavelength and a second laser source configured to emit the 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 includes:

[0029] - The first excitation wavelength is selected based on at least one characteristic of the target object, wherein the at least one characteristic is preferably associated with fluorescence generated by the interaction of the target object with the first excitation wavelength;

[0030] - Determine the range of the first Raman signal associated with the first excitation wavelength, preferably the fingerprint region;

[0031] - Within the defined range of the quantum efficiency curve QE(λ) associated with the spectrometer, the peak quantum efficiency value (λ) is preferably determined within the fingerprint region. QE Preferably, the wavelength (λ) is determined. QE At that wavelength, the quantum efficiency curve QE(λ) exhibits a peak value associated with the spectrometer within its range.

[0032] - Identify the Raman shift peaks (v) of interest for the target object. poi );as well as

[0033] - The second excitation wavelength is determined based on the peak quantum efficiency value and the Raman shift peak of interest.

[0034] This paper also describes a diagnostic system that optionally includes: a spectrometer having a known quantum efficiency; and a Raman probe device configured to provide the spectrometer with a Raman light wavelength generated in response to excitation light irradiating a target object.

[0035] The excitation light includes light having a first wavelength λ p 2 The first light and having a second wavelength λ p 1 At least one of the second light sources, wherein the first excitation wavelength is selected based on at least one characteristic of the target object, and the second excitation wavelength is determined based on the first excitation wavelength and a wavelength substantially associated with the peak of the known quantum efficiency.

[0036] The diagnostic system may include a control unit adapted to determine a second excitation wavelength, preferably adapted to perform the method substantially as described above.

[0037] This document describes a computer program that includes instructions to cause the system as described above to determine a second excitation wavelength, preferably by performing a method substantially as described above.

[0038] According to the principles of the present invention, the probe laser wavelength for different applications can be determined based on the quantum efficiency of the spectrometer and the material in the target object, so that the desired Raman spectrum is substantially consistent with the peak of the detector quantum efficiency, and thus a higher signal-to-noise ratio is achieved.

[0039] According to the principles of the present invention, selecting the Raman excitation wavelength based on the quantum efficiency of the spectrometer allows the fingerprint and stretching regions of the Raman spectrum to be moved to wavelengths where the silicon detector (or similar detector) has relatively high quantum efficiency.

[0040] In one aspect of the invention, the Raman spectra of each of the two laser sources can be captured individually and then cascaded or spliced ​​together to provide a single spectral scan encompassing the entire data range, including a fingerprint region and a stretched region, wherein the signal-to-noise ratio of the Raman signal in the stretched region is enhanced.

[0041] According to one aspect of the invention, it is also possible to analyze each dataset independently, while simultaneously collecting spectra from two excitation wavelengths.

[0042] The compact dual-wavelength Raman probe disclosed herein may include optics to configure the output beam of each laser source to have a circular, elliptical, or elongated cross-section, approximating the shape of a circular or elongated emission region in the near field of a laser.

[0043] In one aspect of the invention, light generated by a laser source can be emitted toward the target object or material under study, and the resulting scattered signal light is transmitted by a compact Raman probe via a beam that may also have a corresponding elliptical cross-section. The excitation and collection paths can be collinear (i.e., co-aligned) or separate (e.g., spatially offset (see USPPA20080076985) or transmission geometry (see USP 8085396)). An optical fiber comprising a core having dimensions approximating the size of the returned scattered beam transmits the returned scattered light to the incident aperture of the spectrometer.

[0044] Based on the inventive principles of the dual-wavelength Raman probe disclosed herein, the dual-wavelength Raman probe may include an external cavity laser (ECL), which can be integrated into the probe as a wavelength-stabilized laser source. See, for example, US 9,059,555, "Wavelength-Stabilized Diode Laser," the contents of which are incorporated herein by reference. Alternatively, the ECL may be located external to the Raman probe.

[0045] Based on the principle 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 may be integrally incorporated into the Raman probe or may be maintained outside the Raman probe.

[0046] Based on the principle of the compact dual-wavelength Raman probe disclosed in this paper, the light emitted by the laser can be used as a pump source for nonlinear optical (NLO) conversion to generate different wavelengths, such as through second harmonic generation (SHG), third harmonic generation (THG), or any other nonlinear optical process.

[0047] Based on the principle of the invention of the compact dual-wavelength Raman probe, the selection of the second wavelength is partly based on the first wavelength and the spectral efficiency of the spectrometer used to collect the Raman signal. Attached Figure Description

[0048] To better understand the exemplary embodiments and illustrate how to implement them, reference is made to the accompanying drawings. It should be emphasized that the specific embodiments shown are merely exemplary, intended to illustrate preferred embodiments of the invention, and are provided to offer a description of the principles and concepts of the invention that are considered most useful and readily understood. In this regard, no attempt is made to show the structural details of the invention in more detail than necessary for a basic understanding of the invention. The description taken in conjunction with the accompanying drawings will enable those skilled in the art to understand several forms of how the invention can be practiced. In the drawings:

[0049] Figure 1AA block diagram illustrating an exemplary embodiment of a dual-wavelength co-aligned / reflective Raman probe using an external laser source is shown.

[0050] Figure 1B A block diagram illustrating an exemplary embodiment of a dual-wavelength co-aligned / reflective Raman probe using an internal laser source is shown.

[0051] Figure 1C A block diagram illustrating an exemplary embodiment of a dual-wavelength co-aligned / transmitted Raman probe using an external laser source is shown.

[0052] Figure 1D A block diagram illustrating an exemplary embodiment of a dual-wavelength spatial offset / transmission Raman probe is shown.

[0053] Figure 2 A diagram illustrating the selection of laser wavelength in a dual-wavelength Raman probe according to the principles of the present invention is shown.

[0054] Figure 3A A flowchart illustrating an exemplary process for selecting a laser wavelength in a dual-wavelength Raman probe according to the principles of the present invention is shown.

[0055] Figure 3B A flowchart illustrating an exemplary process associated with a dual-wavelength Raman probe according to the principles of the present invention is shown.

[0056] Figure 4A and Figure 4B An exemplary quantum efficiency response is shown for a linear array of silicon detectors with 300 nm dispersion for two different Raman laser pump sources.

[0057] Figure 5A and Figure 5B The second exemplary quantum efficiency response of a linear array of silicon detectors with 300 nm dispersion for two different Raman laser pump sources is shown according to the principles of the present invention.

[0058] Figure 6A Exemplary spectroscopic analysis of target materials containing cyclohexane with and without selecting the excitation wavelength is shown according to the principles of the present invention.

[0059] Figure 6B It shows Figure 6A The expanded portion of the spectral analysis shown.

[0060] Figure 6C An exemplary spectral analysis of a target material containing urea is shown.

[0061] Figure 6D An exemplary spectral analysis of a target material containing water is shown.

[0062] Figure 7A block diagram illustrating an exemplary embodiment of a distance-based spatially offset Raman probe configuration is shown.

[0063] Figure 8 A block diagram of another embodiment of the spatially offset Raman probe is shown.

[0064] Figure 9A and Figure 9B Exemplary one-dimensional and two-dimensional linear arrays for transmitting excitation wavelengths and collecting Raman wavelengths are shown.

[0065] Figure 10A-10F An exemplary circular or ring configuration for transmitting excitation wavelengths and collecting Raman wavelengths is shown.

[0066] It should be understood that the accompanying drawings and descriptions of the invention described herein have been simplified to show elements relevant to a clear understanding of the invention, and many other elements have been omitted for clarity. However, because these omitted elements are well known in the art and because they would not facilitate a better understanding of the invention, a discussion of these elements is not provided herein. The disclosure herein also relates to variations and modifications known to those skilled in the art. Detailed Implementation

[0067] Figure 1A A block diagram illustrating an exemplary embodiment of a compact dual-wavelength co-aligned / reflective Raman probe configuration is shown, wherein the light output from the respective laser sources of the two laser sources shown is combined along the same optical path using wavelength beam combination with a dichroic mirror. This is similar to the configuration shown and disclosed in Figure 5 of USP 10,359,313, which discloses the use of a diode laser as a light source in the Raman spectrum.

[0068] 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 should be understood that light sources 110 and 120 may similarly be non-laser sources, such as superluminescent diodes). Lasers 110 and 120 may emit light in a single spatial mode or in multiple spatial modes. Optical couplers 111, 112, 121, and 122 are known devices for coupling optical fibers to a device or apparatus.

[0069] Laser sources 110 and 120 can be any laser device or system; preferably, laser sources 110 and 120 are wavelength-stable laser sources with narrow bandwidth.

[0070] One type of laser that can be used as a wavelength-stabilized laser source is an external cavity laser. For example, see US 9,059,555 and US 9,577,409, which are assigned to the assignee of this application and whose contents are incorporated herein by reference in their entirety, and which describe exemplary externally wavelength-stabilized diode lasers. Sources 110 and 120 can also be semiconductor lasers incorporating gratings in their structure, such as distributed feedback (DFB) or distributed Bragg reflection (DBR) lasers.

[0071] Laser sources 110 and 120 may also be DFB or DBR lasers coupled to nonlinear optical elements for generating second or third harmonics of shorter wavelength lasers, as is known in the art.

[0072] The compact dual-wavelength Raman probe 100 also includes optics 115 and 125 for configuring the output beams of the laser sources 110 and 120. Figure 1A Exemplary components shown are lenses 116, 117, and 118 (optics 115) for shaping the beam associated with laser 110 to form a beam cross-section, for example, suitable for exciting a Raman signal (or wavelength) by a target object 160 of interest, and corresponding components 126, 127, and 128 (optics 116) for shaping the beam associated with laser 120. Narrowband filters 119 and 129 suppress spontaneous emission from the outputs of lasers 110 and 120.

[0073] By using a first dichroic mirror 135 and a reflector 136, collimated beams 131 and 132 are combined into a single collimated beam 138, wherein the reflector 136 deflects beam 132 toward the first dichroic mirror 135. The first dichroic mirror 135 also allows beam 132 to pass through and deflects beam 131 to form the collimated beam 138.

[0074] In one aspect of the invention, a single short-pass filter (not shown) designed to allow wavelengths emitted by the first laser 110 and the second laser 120 to pass through but block wavelengths exceeding the longer of the two wavelengths (i.e., beams 131, 132) can be placed after beams 131, 132 are combined into collimated beam 138.

[0075] The probe (excitation, illumination) beam 138 passes through the second dichroic mirror 140 (its transmission characteristics are in...). Figure 1A (Schematally shown in illustration 141) is transmitted to lens 150, which focuses the combined light, including wavelengths emitted by the first laser 110 and the second laser 120 along optical path 145 onto the target object 160.

[0076] The light scattered from the target object 160 will include Raman, Rayleigh, and fluorescence components, which can be collected by lens 150 and guided back to the second dichroic mirror 140 via optical path 145. In the illustrated case, the second dichroic mirror 140 is configured to reflect longer Stokes-shifted Raman photons into a collimated beam 155. Light at wavelengths longer than the filter cutoff wavelength, including light at both excitation wavelengths, will largely pass through the second dichroic mirror 140 and be largely eliminated from the beam 155.

[0077] In one aspect of the invention, additional optical elements (not shown) may be included in the optical path of the beam 138 to shape the beam 138. For example, the beam 138 may be shaped into a circular beam, such that the beam 138 (i.e., the combined first and second excitation wavelengths) forms an annular region on the target object 160. In another aspect, the optical elements may be configured to adjust the diameter of the annular region projected onto the target object. According to another aspect of the invention, additional optical elements (not shown) may be included in the optical path of the beam 138 to shape the beam 138 into an elliptical or elongated shape.

[0078] The spatial extent of the excitation light on the target object 160 can be long enough to generate off-axis scattered light, which may cause the second dichroic mirror 140 to reflect a range of wavelengths (including those wavelengths that will be preferentially excluded) into the beam 155. The second dichroic mirror 140 is preferably designed to eliminate as much unwanted light as possible.

[0079] The second dichroic mirror 140 may be an edge filter, which is designed to guide the wavelength of the Raman scattered light along a single fiber or axis (i.e., co-aligned) to the spectrometer 190 and substantially remove other light near the pump wavelength.

[0080] In the disclosed embodiments of the invention, wherein the Stokes signal wavelength is to be detected, the second dichroic mirror 140 is a short-pass filter that reflects wavelengths longer than the pump wavelength and substantially removes wavelengths at and shorter than the pump wavelength from the beam 155, as shown.

[0081] In the disclosed embodiments of the invention, wherein the anti-Stokes signal is to be detected, the second dichroic mirror 140 is a long-pass filter that reflects wavelengths shorter than the pump wavelength and substantially removes wavelengths at and longer than the pump wavelength from the beam 155.

[0082] The second dichroic mirror 140 is typically used at a 45° angle of incidence, and... Figure 1AIn the illustrated embodiment, the second dichroic mirror 140 directs light from laser sources 110 and 120 toward the target object 160 under study. An exemplary dichroic mirror is Semrock's RAZOREDGE beam splitter. RAZOREDGE is a registered trademark of IDEX Health & Science LLC (Rornette Campus, California).

[0083] To detect Stokes signals, the long-pass dichroic filter 170 is designed to transmit wavelengths longer than its cutoff wavelength, such as... Figure 1A As shown in illustration 171, lens 180 focuses the filtered light onto the incident surface of optical fiber 185, which then transmits the light to slit 191 of compact spectrometer 190.

[0084] Filter 170 can be one of the following: a dichroic filter, a volume holographic grating filter, and a fiber Bragg grating filter, used in combination with focusing and collecting optics or any filter that provides the required wavelength-dependent blocking and transmission capabilities. Exemplary filters include the STOPLINE® single notch filter and the RAZOREDGE® ultra-steep long-pass edge filter for Stokes detection, and the ultra-steep short-pass edge filter for anti-Stokes detection. STOPLINE and RAZOREDGE are registered trademarks of IDEX Health & Science LLC (Rornette Campus, California).

[0085] Spectrometer 190 is designed to diffract light input through slit 191 onto a linear silicon detector array (not shown). The range of light diffracted onto the array is limited by the design of the spectrometer diffraction grating and the linear range of the detector array, as is well known in the art. Therefore, the spectrometer grating and detector can be configured such that the detector receives a limited range of wavelengths, for example, approximately 791 nm to 934 nm for a Stokes signal. If detected alone, the exemplary 2048 element linear detector can have approximately 1 cm² in both the fingerprint and stretch regions of the spectrum. -1 The resolution (i.e., 1 wavenumber, where wavenumber is a technical term in the field of optics).

[0086] In another embodiment of the invention, from Figure 1A The light from lasers 110 and 120 can be combined onto a single optical fiber (not shown) before being provided to the second dichroic mirror 140. The elements that generate and combine the light from lasers 110 and 120 do not need to be contained within the body 105, but can be combined outside the body 105 in a geometric or dichroic manner, and then combined onto a single optical fiber before being provided to the second dichroic mirror 140.

[0087] Figure 1BAn exemplary embodiment of the dual-laser co-aligned / reflection Raman probe is shown, wherein laser sources 110 and 120 are incorporated within the Raman probe housing 105. In a second exemplary embodiment of this dual-laser Raman probe, Figure 1B The components (parts) and operation of the Raman probe shown are similar to those described above. Figure 1A The dual-wavelength Raman probe shown is discussed in terms of its components and operation. Due to... Figure 1B The components and operation of the configuration shown are similar to Figure 1A The components and operation of the dual-laser Raman probe shown are similar, therefore those skilled in the art can understand them by reading... Figure 1A The components and operations within will be understood Figure 1B The details of the components and operation shown are so specific that further discussion is not required. Figure 1B .

[0088] Figure 1C An exemplary embodiment of a dual-laser co-aligned Raman / transmission probe with a Raman probe is shown, wherein, as previously described, light output from external laser sources 110 and 120 is combined into a single beam 138 using a wavelength beam combination utilizing a first dichroic mirror 135 and a reflector 136. In this third exemplary embodiment, a second dichroic mirror 140 is used to guide the excitation light from the laser source onto the target object 160 via a lens 150. The lens 150 further collects the Raman wavelength generated in response to the interaction of the excitation wavelength and transmits it to the second dichroic mirror 140. The second dichroic mirror 140 then transmits the collected Raman light as beam 155 to a filter 170. In this case, the filter 170 is used to remove light from laser sources 110 and 120, preventing it from being provided to the slit 191 of the spectrometer 190.

[0089] In a third exemplary embodiment of the dual-laser Raman probe, Figure 1C The remaining components (parts) and operations shown are similar to those described above. Figure 1A The dual-wavelength Raman probe shown is discussed in terms of its components and operation. Due to... Figure 1C The components and operation shown are consistent with Figure 1A The components and operation of the dual-laser Raman probe shown are similar, and those skilled in the art can understand them by reading... Figure 1A The components and operation can be understood Figure 1C The details of the components and operation shown are so specific that further discussion is not required. Figure 1C .

[0090] Figure 1DAn exemplary embodiment of a dual-laser spatially offset / transmitted Raman probe is shown, wherein, as previously described, light output from two external laser sources 110, 120 is combined along the same optical path using a wavelength beam combination utilizing a first dichroic mirror 135 and a reflector 136. The combined light 138 is then guided by a reflector 152 through a focusing lens 150 onto a target object 160. A collecting lens 151 collects the Raman light generated in response to irradiation of the target object 160 with the combined excitation (or illumination) light 138, and guides the collected Raman light, i.e., beam 155, to a filter 170, as previously described, for removing the excitation wavelength from the collected Raman light.

[0091] In the fourth exemplary embodiment of the dual-laser Raman probe, Figure 1D The remaining components (parts) and operations shown are similar to those described above. Figure 1A The dual-wavelength Raman probe shown is discussed for its components and operation. Due to... Figure 1D The remaining components and operations of the configuration shown are the same as those in the diagram. Figure 1A The remaining components and operation of the dual-laser Raman probe shown are similar, as can be understood by those skilled in the art through reading... Figure 1A The components and operation can be understood Figure 1D The details of the remaining components and operation of the configuration shown are therefore assumed to require no further discussion. Figure 1D .

[0092] The present invention also relates to a diagnostic system comprising: a spectrometer having a known quantum efficiency; and a Raman probe device configured to provide a Raman light wavelength to the spectrometer, the Raman light wavelength being generated in response to excitation light irradiating a target object, wherein the excitation light comprises having a first wavelength λ. p 2 The first light and having a second wavelength λ p 1 At least one of the second light, wherein the first excitation wavelength is selected based on at least one characteristic of the target object, and the second excitation wavelength is determined based on the first excitation wavelength and a wavelength substantially associated with the peak of the known quantum efficiency.

[0093] In a preferred embodiment, in the above system, the second excitation wavelength is determined as:

[0094] λ p 1 = 1 / [ν poi + 1 / λ QE ] ;

[0095] Where λ QEThe wavelength that is substantially associated with the peak of the quantum efficiency within the range defined by the first excitation wavelength; ν poi These are the Raman shift peaks of interest for the target object. More precisely, ν poi The wavenumber of the Raman shift peak of interest is related to 1 / λ. QE The dimensions are the same. Preferably, the Raman shift peak of interest (ν) poi The stretching peak emitted by the target object when irradiated with a second laser at the second excitation wavelength is the stretching peak emitted by the target object.

[0096] In a preferred embodiment, in the above system, the Raman probe includes: a first lens configured to focus the first light and the second light onto the target object; and a filter configured to allow the Raman light wavelength to pass through and block the first wavelength and the second wavelength from passing through the spectrometer.

[0097] In a preferred embodiment, in the above system, the first lens is configured to collect the Raman light wavelength and provide the collected Raman light wavelength to the filter.

[0098] In a preferred embodiment, the system includes a second lens configured to collect the Raman light wavelength and provide the Raman light wavelength to the filter.

[0099] In a preferred embodiment, the system includes an optical device comprising: at least one optical fiber configured to receive the excitation light and guide the received excitation light to the target object; and a plurality of optical fibers configured to receive the Raman light wavelength and guide the received Raman light wavelength to the second lens.

[0100] In a preferred embodiment, the system includes a mask, wherein the mask prevents a selected fiber among the plurality of optical fibers that receive the Raman light wavelength from receiving the Raman light wavelength.

[0101] In a preferred embodiment, within the above system, the optical device includes: a plurality of optical fibers arranged in one of the following configurations: a one-dimensional fiber array and a two-dimensional fiber array.

[0102] In a preferred embodiment, within the above system, the optical device includes multiple optical fibers arranged in a ring around a central optical fiber, wherein the central optical fiber is one of the following: the transmitting optical device and the receiving optical device.

[0103] In a preferred embodiment, within the system described above, the at least one characteristic of the target object is associated with the fluorescence generated when the target object is irradiated by the first excitation wavelength. Preferably, the first excitation wavelength is selected such that the influence of fluorescence on the Raman spectral signal is minimized.

[0104] The first light and the second light can be emitted concurrently. The first excitation wavelength and the second excitation wavelength can be emitted sequentially.

[0105] In a preferred embodiment, the system described above includes a first laser configured to generate the first light, wherein the first laser is one of the following: inside the Raman probe and outside the Raman probe device; and / or a second laser configured to generate the second light, wherein the second laser is one of the following: inside the Raman probe and outside the Raman probe device.

[0106] The present invention also relates to a Raman probe device including a first lens, the first lens being configured to receive at least one of the following: a first excitation wavelength λ p 2 Second excitation wavelength λ p 1 The first excitation wavelength is determined based on at least one characteristic of the target object; and the first lens is configured to focus at least one of the first excitation wavelength and the second excitation wavelength onto the target object, wherein a Raman wavelength is generated in response to the target object being irradiated by a corresponding wavelength of at least one of the first excitation wavelength and the second excitation wavelength; and wherein the Raman probe device further includes a filter configured to transmit the Raman wavelength generated in response to the target object being irradiated by a corresponding excitation wavelength of at least one of the first excitation wavelength and the second excitation wavelength to a spectrometer; and wherein the spectrometer has a known quantum efficiency, and the second excitation wavelength is determined to be: λ p 1 = 1 / [v poi + 1 / λ QE ] ; where λ QE It is the wavelength associated with the peak of the quantum efficiency within the range defined by the first excitation wavelength; v poi These are the Raman shift peaks of interest for the target object.

[0107] In a preferred embodiment of the Raman probe as described above, the first lens is configured to collect the Raman wavelength and provide the collected Raman wavelength to the filter.

[0108] In a preferred embodiment, the Raman probe as described above includes a second lens configured to collect the Raman wavelength and provide the collected Raman wavelength to the filter.

[0109] In a preferred embodiment, the Raman probe as described above includes: 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 laser source and the second laser source is external to the Raman probe. Alternatively, at least one of the first laser source and the second laser source may be internal to the Raman probe.

[0110] In a preferred embodiment of the Raman probe as described above, the first excitation wavelength and the second excitation wavelength can be emitted in one of the following ways: concurrently and sequentially.

[0111] In a preferred embodiment, the Raman probe described above includes an optical device comprising a plurality of optical fibers, wherein a selected optical fiber receives the first excitation wavelength and the second excitation wavelength; and the selected optical fiber receives the Raman light wavelength.

[0112] In a preferred embodiment of the Raman probe as described above, the plurality of optical fibers are arranged in either a matrix configuration or a ring configuration.

[0113] Figure 7 A block diagram illustrating an exemplary embodiment of a distance-based spatially offset Raman probe configuration is shown, wherein a spatial interval (or distance) 710 between an excitation wavelength 702 and a collection wavelength 704 allows detection of a region beneath the surface of a target object 160. Hereinafter, a combined light 138 comprising a first excitation wavelength 220 and a second excitation wavelength 210 will be referred to as the excitation light 702, and the Raman light wavelength will be referred to as the collection wavelength 704. By increasing the distance 710 between the excitation wavelength 702 and the collection wavelength 704, the region beneath the surface of the target object 160 can be observed.

[0114] Figure 8 A block diagram of a second embodiment of a distance-based spatially oriented Raman probe according to the principles of the present invention is shown. Similar to... Figure 1D In this illustrative embodiment of the shown example, an optical device 810 is further included, which is optically connected to lenses 150 and 151. In this second embodiment, light (or excitation wavelength) emitted by lens 150 is guided to optical device 810 through an optically transparent material (e.g., optical fiber), and Raman light 704 generated in response to excitation light 702 irradiating target object 160 can be collected by optical device 810 and provided to collecting lens 151 through a second set of optically transparent materials (e.g., optical fiber).

[0115] For example, the optical device 810 may include an optical probe that can be used to scan the target object 160 while emitting an excitation wavelength 702 and collecting a Raman wavelength 704. The tip of the optical probe may include an optically transparent material (e.g., multiple optical fibers) that receives the excitation wavelength from the lens 150, and a second, separate, optically transparent material (e.g., optical fiber) that collects the Raman wavelength and provides the collected Raman wavelength to the collecting lens 151. Alternatively, the optical device 810 may be a mounting device including a platform on which the target object can be placed or contained. In one aspect of the invention, the optical device 810 may include, for example, multiple optical fibers that receive the excitation wavelength 702, and, for example, a second set of multiple optical fibers that collect the Raman wavelength 704 and provide the collected Raman wavelength to the collecting lens 151. Furthermore, the first and second sets of optical fibers may, for example, be as follows: Figure 7 The orientation is shown. In another aspect, the first set of optical fibers can be oriented such that the excitation wavelength 702 is projected at an angle onto the target object 160, and the second set of optical fibers can be oriented at an angle relative to the target object 160. In yet another aspect of the invention, the first set of optical fibers (or a transparent material) can be positioned on one side of the target object 160, while the second set of optical fibers can be positioned on a second side of the target object 160.

[0116] Although the optical device 810 is shown outside the housing 105, it should be understood that the optical device 810 may be inside the housing 105.

[0117] Figure 9A A first exemplary embodiment of the optical device 810 is shown, wherein a first set of multiple optical fibers (or other optically transparent materials) 910 and a second set of optical fibers 920 are arranged in a one-dimensional array. In this exemplary embodiment, optical fiber 910 represents a transmission device that can be used to provide an excitation wavelength or light 702 to a target object 160, while optical fiber 920 represents 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 [link to documentation]). Figure 8 ).

[0118] The spatial distance 710 between the excitation wavelength 702 and the Raman wavelength 704 can be varied, for example, by using different fibers in the collection fiber 920.

[0119] Figure 9B A second example of an optical device 810 is shown, which includes a two-dimensional array comprising first and second sets of optical fibers 910, 920 arranged in a matrix.

[0120] and Figure 9A As shown in the diagram, the excitation wavelength or light 702 can be provided to the target object 160 via optical fiber 910, while the Raman light 704 can be collected via optical fiber 920.

[0121] In the illustrated embodiment, the spatial distance 710 can be measured horizontally, vertically, or diagonally relative to the transmitting and receiving optical fibers.

[0122] In one aspect of the 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 spacing (or maximum spacing distance). Return Figure 9A A mask (not shown) can be positioned between the second and fifth rows of the receiving fiber optic cable 920 to establish a minimum spacing between the transmitting fiber optic cable 910 and the receiving fiber optic cable 920. Therefore, the spacing can be made variable.

[0123] Figure 10A-10F An exemplary embodiment of the optical device 810 is shown, wherein the optical fibers 910, 920 are arranged in a circular or annular configuration.

[0124] Figure 10A An example is shown of a central transmission fiber 910 surrounded by multiple collection fibers 920.

[0125] Figure 10B An example is shown of a central transmission fiber 910 surrounded by two rows of multiple collection fibers 920.

[0126] Figure 10C An example of multiple transmission optical fibers 910 centered on a central collection optical fiber 920 is shown.

[0127] Figure 10D An example of a center-based transmission fiber 910 surrounded by a ring of optically transparent material 1020 is shown, which is used to collect Raman light 704.

[0128] Figure 10E An example of a center-based transmission fiber 910 surrounded by multiple collection fibers 920 is shown.

[0129] Figure 10F An example of a center-based collecting optical fiber 920 surrounded by an optically transparent material 1010 is shown.

[0130] In one aspect of the invention, the physical spacing 710 between the excitation wavelength 702 and the collection wavelength 704 can be achieved by using a central irradiation (excitation) region and a ring-shaped collection region. In another aspect of the invention, the physical spacing 710 between the excitation wavelength 702 and the collection wavelength 704 can be achieved by using a ring-shaped irradiation (excitation) region and a central collection region. In another aspect, the collection wavelength region can be physically moved or masked from the excitation wavelength region to allow for a variable distance between the excitation wavelength irradiation region and the collection wavelength region.

[0131] In another aspect of the invention, the excitation wavelength region and the collection wavelength region may be oriented on opposite sides of the target object 160 in a so-called transmission configuration.

[0132] In another embodiment of the invention, the excitation wavelength 702 may be directed at an angle to the target object 160. Similarly, the collection wavelength 704 may be collected at an angle relative to the target object 160.

[0133] Although dual-wavelength co-aligned / reflection Raman probes with external lasers have been discussed ( Figure 1A ), dual-wavelength co-aligned / reflected n-Raman probe with internal laser ( Figure 1B Dual-wavelength co-aligned / transmission Raman probe with external laser ( Figure 1C ), and a dual-wavelength spatial orientation / reflection Raman probe with an external laser ( Figure 1D The exemplary embodiments described herein are provided, but it should be understood that the methods for selecting the excitation wavelength given herein can be applied to other types of dual-wavelength Raman probes (e.g., spatially oriented / reflective Raman probes with external or internal lasers) and are considered to be within the scope of the claims of this invention.

[0134] Furthermore, those skilled in the art will understand that the combination of excitation wavelengths discussed can be performed by any of the known number of known wavelength combination methods (e.g., wavelength beam combination or geometric beam combination using a dichroic mirror, see USP 7,420,996).

[0135] According to the principles of the present invention, the excitation lasers 110 and 120 disclosed herein can operate simultaneously, concurrently, or sequentially. Sequential operation eliminates spurious signals, such as fluorescence that may be generated when two laser sources operate simultaneously. However, it should be understood that simultaneous or concurrent operation has been considered, and both simultaneous and concurrent operation of the laser sources are considered to be within the scope of the invention. Thus, when the light sources operate concurrently, the lasers from the two sources can be combined to form a single beam consisting of two wavelengths. However, when (e.g., wavelength beams, geometric beam combinations (e.g., see US 7420,996)...)

[0136] In the case of sequential operation of light sources, the laser from one light source is considered to be "combined" with the light from a second, non-existent laser source, thereby forming a single beam of a single wavelength.

[0137] Currently used exemplary Raman pump wavelengths are 532 nm, 638 nm, 785 nm, 830 nm, and 1064 nm. As is known in the art, shorter pump wavelengths produce higher Raman scattering signals because the Raman intensity is related to λ. -4Proportional. However, shorter pump wavelengths are more likely to generate fluorescence, which suppresses Raman spectral features. Since fluorescence is wavelength-dependent, and the Raman signal is proportional to λ... -4 The fluorescence intensity is proportional to and shifted relative to the excitation wavelength, thus the Raman cascading method offers the possibility of mitigating the negative effects of fluorescence by using a shorter wavelength excitation source. This allows for the quantization of the Raman signal in the stretched band when high levels of fluorescence make it impossible to quantify the Raman signal in the fingerprint region. Finally, specific wavelengths of either short or long wavelength laser sources can be selected to mitigate any fluorescence resonance effects.

[0138] Furthermore, Stokes spectra are generally stronger than anti-Stokes spectra. As is well known in the art, the Stokes shift v (measured in wavenumber, i.e., cm⁻¹) will generate a Raman signal wavelength λ. s Its relationship with probe wavelength λ p Related:

[0139] 1 / λ s = 1 / λ p + v (1)

[0140] Generally, the "fingerprint" region of the spectrum includes areas smaller than approximately 2000 cm⁻¹. -1 The wave number, and the "stretched" region includes approximately 2000 cm. -1 Up to 4000 cm -1 The wave number.

[0141] Figure 2 An example of determining the fingerprint and stretching region of a spectrum is shown, which can be excited by two separate wavelengths, allowing the detection of two resulting Stokes signal spectra using a single detector array in a compact spectrometer.

[0142] According to the principles of the present invention, it is designated as λ p 1 210 and λ p 2 Two probe wavelengths of 220 nm are used to excite the stretched region and fingerprint region of the Raman spectrum, respectively. In the case shown, the second excitation wavelength λ... p 1 The wavelength is greater than the first excitation wavelength λ p 2 220 nm has a short wavelength.

[0143] An exemplary wavelength range Δv2 223 associated with the fingerprint region is also shown, expressed in wavenumber. The illustrated fingerprint region 213 is shown as ranging from the Raman signal wavelength λ s 21 225 extends to λ s 22 227, which is the same as the first excitation wavelength λ.p 2 220 is associated with. Wavelength λ s 21 225 and λ s 22 227 is derived from wavelength λ p 2 220 respectively through displacement value V 21 and V 22 Determined, where the displacement value V 21 and V 22 It can be determined by Equation 1 above.

[0144] In the example shown, the Raman signal wavelength λ s 21 225 is typically obtained from the first excitation wavelength λ p 2 The 220 nm wavelength was shifted by 1-2 nm to avoid saturation of the spectrometer by backscattered pump light, while the Raman signal wavelength λ was... s 22 227 is determined by calculating the wavelength associated with the fingerprint wavenumber range Δv2 223:

[0145] 1 / λ s 22 = 1 / λ s 21 +Δv2. (2)

[0146] The wavelength range Δv1 213 associated with the stretched region of the Raman signal is also shown, expressed in wavenumber. The stretched region shown is depicted as extending from the Raman signal wavelength λ. s 11 215 extends to λs 12 217, the Raman signal wavelength λ s 11 215 and λ s 12 217 and the second excitation wavelength λ p 1 210 is associated with this. Wavelength λ s 11 215 and λs 12 217 are respectively composed of wavelength λ p 1 210 via displacement value V 11 and V 12 Determine, where the value V is... 11 and V 12 It can be determined by Equation 1 above.

[0147] Therefore, the Raman signal wavelength λ s 11 215 was chosen as essentially the same as λs 21 225 is consistent, so that the detector element of the spectrometer can be used for two pump lasers, while the Raman signal wavelength λ s 12 217 is determined by calculating the wavelength associated with the stretched wavenumber range Δv1213, where λ s 11 and λ s 12 The difference between them defines the stretching area.

[0148] 1 / λ s 12 = 1 / λ s 11 + Δv1 (3)

[0149] An exemplary quantum efficiency curve QE(λ)230 of a spectrometer is also shown for collecting and analyzing Raman signals generated by the first and second excitation wavelengths.

[0150] Therefore, by appropriately selecting the second excitation wavelength λ p 1 210 and the first excitation wavelength λ p 2 220, the Raman signal generated in the stretch region and fingerprint region can be captured by the detector element of a single spectrometer.

[0151] To describe the subject matter of the invention to those skilled in the art, the wavenumber range of the fingerprint region and the wavenumber range of the stretched region are approximately equal, i.e., Δv1≈Δv2, resulting in λ s 11 ≈λ s 21 , and λ s 21 ≈λ s 22 .

[0152] Furthermore, although a second excitation wavelength λ can be selected p 1 210 and the first excitation wavelength λ p 2 220 uses the same detector array to provide capture of fingerprints and stretched areas, but with a wavelength λ according to the principles of the present invention. p 1 210 and λ p 2 The 220 option provides enhanced analytical performance for the spectrometer.

[0153] Figure 3AA flowchart of an exemplary process 300 for determining the wavelength of a dual-wavelength Raman probe according to the principles of the present invention is shown.

[0154] According to the principle of the present invention, in step 310, a first excitation wavelength (i.e., λ) is selected. p 2 The first excitation wavelength is associated with the fingerprint region of the Raman signal reflected or scattered by the target object under the illumination of the first excitation wavelength.

[0155] First excitation wavelength λ p 2 The wavelength was chosen to be as short as possible to mitigate the fluorescence in the Raman spectrum generated by inelastic scattering of the target object at the first excitation wavelength. Therefore, the first excitation wavelength λ... p 2 The determination is based on the Raman target 160 studied and its specific fluorescence characteristics when irradiated with the excitation wavelength.

[0156] For example, it is known in the art that for target categories such as heavy petroleum (oil), biomaterials, pharmaceutical materials, and transparent liquids, the first excitation wavelength λ p 2 The available wavelengths are 1064nm, 830nm, 785nm, and 532nm.

[0157] In order to teach the claimed invention, a wavelength such as 785 nm (nanometer) may be selected as the first excitation wavelength, wherein 785 nm is selected to minimize the fluorescence generated when the target object is irradiated by the first excitation wavelength.

[0158] In step 320, based on the spectrometer's desired spectral range and resolution (e.g., 2000 cm⁻¹), -1 Select the desired range of fingerprint region wavenumber (Δv2).

[0159] First excitation wavelength λ p 2 The choice of Δv2 will determine the longest measurement wavelength (λs) of the spectrometer. 22 (Step 330) is limited to

[0160] λ s 22 = 1 / [Δv2 + 1 / λ p 2 (4)

[0161] Using a first excitation wavelength of 785nm λ p 2 In this exemplary instance, the longest measurement wavelength λ s 22 It can be determined to be 931nm by Equation 4 above.

[0162] Then, an examination of the quantum efficiency spectrum associated with the spectrometer used in the collection and analysis of the Raman signal can be performed to determine the fingerprint region (i.e., at wavelength λ). p 2 (It is approximately equal to λ) s 21 ) and λ s 22 (between) determine the peak wavelength QE(λ) of the quantum efficiency response of the spectrometer (step 340).

[0163] The quantum efficiency curve QE(λ) provides a measurement of the efficiency of a spectrometer in collecting Raman signals over a known wavelength band. For example, and for the purpose of describing the claimed invention, the quantum efficiency response curve (λ) over the defined fingerprint region is used. QE It can be determined based on the current or previous measurement of the spectrometer's response characteristics.

[0164] For example, and for the purpose of describing the invention claimed by those skilled in the art, and with reference to Figure 2 The peak (maximum) quantum efficiency (λ) of the quantum efficiency response curve 230 within the determined fingerprint region 223 can be determined. QE 235. For the purpose of teaching the claimed invention, the peak quantum efficiency in the example shown can be determined to be 800 nm.

[0165] Then, in step 350, the Raman shift peaks of interest (vo) of the specific compound under study (i.e., the target) can be determined. poi For example, and in order to describe the claimed invention to those skilled in the art, the Raman shift peak of interest for a particular target object can be determined with respect to 3000 cm⁻¹. -1 The wavenumber is related.

[0166] Then, in step 360, a second excitation wavelength (λ) for quantitative analysis in the tensile region can be determined. p 1 )for:

[0167] λ p 1 = 1 / [v poi + 1 / λ QE (5)

[0168] Therefore, the second excitation wavelength (λ) p 1 The peak quantum efficiency of the spectrometer in the Raman shift peak of interest associated with a specific target object and the fingerprint region is determined by the selection of a first excitation wavelength.

[0169] From the selection of the first excitation wavelength (λ) p 2 ) 220 exemplary wavelength, for example 3000 cm -1 Interesting Raman shift peak (v) poi ) and peak quantum efficiency (λ) QE 235, second excitation wavelength (λ) p 1 )210 can be determined to be 645nm.

[0170] It is understandable that the second excitation wavelength is selected in the manner disclosed in Equation 5 so that the Raman peak of the wavelength of interest coincides with the peak wavelength of the spectrometer quantum efficiency in the fingerprint region (λ). QE (Consistent)

[0171] Therefore, the analysis of the Raman signal associated with the second excitation wavelength is performed at or near the peak quantum efficiency of the spectrometer, which gives the target object better analytical performance.

[0172] As expressed in Equation 5, although the selection of the second excitation wavelength is determined based on the peak quantum efficiency, and the most significant spectral performance can be achieved when the determined second excitation wavelength coincides with the peak quantum efficiency, it should be recognized that non-peak quantum efficiency values ​​can be similarly used to determine the second excitation wavelength. However, it is preferable to determine the wavelength λ. QE The quantum efficiency within the range of the quantum efficiency curve QE(λ) at that wavelength exhibits a peak associated with the spectrometer. That is, according to the principles of the invention, the term "peak" used in connection with the term "peak quantum efficiency" does not need to be "peak" or a maximum value in the ordinary and conventional sense. Rather, the term "peak" as used herein is considered to be a range near the maximum (or peak) value of the spectral quantum efficiency. For example, this range can be defined by + / - 10% of the number of wavelengths at which the maximum spectral quantum efficiency is achieved. Similarly, this range can be defined as + / - 15% of the number of wavelengths at which the maximum spectral quantum efficiency is achieved. In another example, this range can be defined as the number of wavelengths within 3 dB of the maximum spectral quantum efficiency. See, for example, [link to relevant documentation]. Figure 2 Points 240a and 240b represent points at 3 dB (or half-power) relative to the peak quantum efficiency of 235. According to another aspect of the invention, a specific range can be determined by the expected increase in the signal-to-noise ratio of the received Raman spectrum.

[0173] Therefore, the determination of the second excitation wavelength based on Equation 5 can be expressed more generally as follows:

[0174] λ p 1 = 1 / [v poi+ 1 / (λ QE +(+ / -δ))] (6)

[0175] Where δ represents the range near the maximum (peak) quantum efficiency value.

[0176] Therefore, according to the principles of the present invention, the term "peak" is considered to be one of the following: the maximum value of the response spectrum of the spectrometer and the range near the maximum value of the response spectrum of the spectrometer.

[0177] Figure 3B An exemplary process for operating a dual-wavelength Raman probe according to the principles of the present invention is shown.

[0178] According to the principles of the present invention, as shown in steps 310, 365, 368, 371, and 374 respectively, the first spectral Raman component generated by exciting the target object with the first excitation wavelength is captured, filtered, received, processed, and stored. More specifically, the target object is excited by the first excitation wavelength (i.e., λ). p 2 Irradiation is performed on the target object, with the first excitation wavelength selected to minimize fluorescence generated when the target object is irradiated with the first excitation wavelength. In step 365, Raman scattered light reflected or scattered by the target object is captured. Then, in step 368, the Raman scattered light is filtered and provided to a spectrometer in step 371. In step 374, spectral analysis is performed on the reflected or scattered signal provided to the spectrometer, and then the data is stored.

[0179] In step 360, the second excitation wavelength (i.e., λ) p 1 The value 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, as described above.

[0180] According to the principles of the present invention, after determining the second excitation wavelength based on Equation 5 above, the determined second excitation wavelength can be evaluated against the wavelength performance of a conventional laser device in order to determine the suitability of using a conventional laser with a known wavelength output.

[0181] That is, the wavelength of one or more selected conventional lasers can be evaluated based on Equation 6 to determine which of the multiple or multiple selected conventional lasers can be used to replace the specially designed laser based on the output wavelength of Equation 5.

[0182] As shown in steps 377, 381, 384, 387, and 390, the second Raman component generated by exciting the target object 160 with the determined second excitation wavelength is captured, filtered, received, processed, and stored, respectively. Specifically, in step 377, the target object 160 is irradiated with the second excitation wavelength. The scattered or reflected Raman wavelength associated with the second excitation wavelength is captured (step 381) and filtered in step 384. 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, wherein the first Raman spectral component can be used to determine the identification of compounds of target object 160, while the second Raman spectral component can be used to determine the concentration of compounds of the target object. Alternatively, the first and second Raman spectra can be processed independently to provide a more detailed analysis of the target object. The selection of the first and second excitation wavelengths according to the principles of the invention provides enhanced quantitative analysis because the Raman spectra coincide (or substantially coincide) with the peak of the quantum efficiency of the spectrometer within the fingerprint region. The increase in the signal-to-noise ratio of the received Raman signal caused by the coincidence of the Raman signal with the peak of the quantum efficiency of the spectrometer provides an increase in the distinguishing characteristics of the target object (or the analyte within the target object).

[0184] Therefore, the dual-laser Raman probe described herein provides an opportunity to monitor, for example, drug bioreactors (i.e., sealed containers in which bacteria grow in an aqueous liquid). On the other hand, the H stretching band can be used as a calibration standard, against which the CH and NH stretching bands can be monitored. For example, the CH and NH stretching bands can be used to determine changes in protein levels within a drug bioreactor, as bacteria produce proteins and consume food (carbohydrates). According to another application of the dual-laser Raman probe disclosed herein, the concentration of an additive can be determined by calibration using the Raman signal from pure water.

[0185] Figure 4A and 4B A typical quantum efficiency curve for a silicon detector is shown. Figure 4A ) and the corresponding table ( Figure 4B This figure shows the relationship between the expected quantum efficiency and wavenumber for a first Raman-pumped laser source with a wavelength dispersion range of 300 nm.

[0186] refer to Figure 4A It illustrates an exemplary relationship between quantum efficiency and wavenumber, and the efficiency associated with the wavelength shift of a 785 nm pump laser source, compared to 200 cm⁻¹. -1 A wavenumber-correlated wavelength shift of the 785 nm excitation wavelength provides 96% quantum efficiency, compared to 3600 cm⁻¹. -1Wavenumber-dependent wavelength shift provides 1% efficiency. Therefore, at 200 cm⁻¹... -1 The analysis of the Raman shift wavelength associated with the 785 nm excitation wavelength was significantly better than that at 3600 cm⁻¹. -1 Analysis of the Raman shift wavelength associated with the 785 nm excitation wavelength, because for 200 cm⁻¹... -1 At the Raman shift wavelength, the spectrometer's performance is significantly better.

[0187] Figure 4B The quantum efficiency of the spectrometer, associated with the 785 nm excitation wavelength, is listed for different wavelength shifts.

[0188] Figure 5A and 5B Efficiency improvements according to the principles of the invention are shown, along with corresponding tables for the selection of excitation wavelengths.

[0189] According to the principles of the present invention, based on the selection of the second excitation wavelength (e.g., 680 nm) based on the first wavelength and the spectral efficiency of the spectrometer, at 200 cm⁻¹ -1 It provides 90% quantum efficiency, while at 3600 cm⁻¹... -1 Wavenumber-dependent wavelength shift provides a quantum efficiency of 82%. Therefore, the selection of the second excitation wavelength according to the principles of the invention provides a significant improvement in the analysis of Raman signals.

[0190] Therefore, according to the principle of the present invention, the signal processing capability of the spectrometer is enhanced by selecting the dual excitation wavelength by matching the peak of the quantum efficiency curve with the specific wavenumber band of interest.

[0191] Examples of the selection of the first and second excitation wavelengths can be determined as follows:

[0192]

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

[0194] Furthermore, by utilizing the enhanced stretch band signal, the entire enhanced stretch band can be used as additional data as input to chemometric algorithms or as orthogonal data to verify data from the fingerprint region.

[0195] For example, the Raman probe excitation wavelength selection method described in this article can be used for medical diagnosis because fats and proteins can be monitored using the CH and NH bands, while water can be monitored using the OH band.

[0196] Analyzing the CH and NH bands using the improved or enhanced signal analysis performance described in this article can help diagnose inflammation or other pathological conditions.

[0197] The Raman probe excitation wavelength selection method described in this article can be used for pharmaceutical process analysis of compounds grown in water (H2O), because the analysis of such compounds using near-infrared (NIR) spectroscopy is ineffective.

[0198] The Raman probe excitation wavelength selection method described in this article can be used for petrochemical analysis because the CH band is important and water is often a contaminant.

[0199] Generally, the present invention includes the use of the apparatus described herein in medical diagnostics and analyses associated with petrochemical processing or bioreactors.

[0200] Figure 6A and 6B An example of enhancing Raman signal processing of cyclohexane using a wavelength laser pump source in the stretching band region according to the principles of the present invention is shown.

[0201] Specifically, Figure 6A Spectral analysis is shown in association with the fingerprint region and the stretched region associated with the target object including cyclohexane. Figure 6B It shows Figure 6A The extended version of the stretched region shown.

[0202] Figure 6A Two Raman spectra, 610 and 615, are shown, wherein spectrum 610 was obtained using a laser excitation signal with a wavelength of 785 nm, and spectrum 615 was obtained using a first excitation wavelength of 785 nm and a second excitation wavelength of 680 nm, wherein the 680 nm wavelength was selected in accordance with the principles of the invention disclosed herein.

[0203] According to the principles of this invention, the dual-wavelength Raman probe technology disclosed herein can enable new applications in the process automation market. For example, by utilizing the relationship between the -H stretching region and the fingerprint region, improved quantitative measurement of concentration changes or predictive quantification of concentration can be provided. For example, a dual-wavelength Raman probe with wavelength selection as described herein can be directly applied to enhance the analysis of:

[0204] • Percentage of petroleum products in water

[0205] • Percentage of pollutants in water

[0206] • Percentage of sugar in water

[0207] • Percentage of protein in water

[0208] • Percentage of sugar / protein over time in biopharmaceutical process reactions

[0209] • Identification of bacterial byproducts (e.g., Did you produce the product you wanted?)

[0210] • The intensity ratio of one set of peaks to another set of peaks (e.g., reducing the complexity of system calibration).

[0211] • Monitor the intensity of one or more peaks over time.

[0212] • Higher sensitivity due to reduced noise floor (increased S / N)

[0213] • Optimize the quantum efficiency of the Raman band of interest and the detector (e.g., amplify the alkyne band signal).

[0214] • Pass / fail analysis (e.g., identifying the presence or absence of a specific band).

[0215] In summary, a dual-wavelength Raman probe system, comprising first and second excitation wavelengths, impinges on a target object, and the wavelengths reflected or scattered by the target object are collected and analyzed by a spectrometer. According to the principles of the invention, the excitation wavelength is selected based on the quantum efficiency (or within a known range) of the target object and the spectrometer, in order to improve the signal-to-noise ratio (SNR) of the Raman signal by making the Raman signal substantially consistent with the peak quantum efficiency of the spectrometer. The collection of a Raman signal substantially consistent with the peak quantum efficiency of the spectrometer provides an improved SNR for the Raman signal.

[0216] Although the invention has been described with respect to “wavelength” emitted by a laser source or operated by Raman and Rayleigh scattering, it should be understood that the term “wavelength” is a term used in the art and refers to a wavelength or wavelength band around the nominal desired wavelength.

[0217] The invention has been described with reference to specific embodiments. However, those skilled in the art will understand that various modifications and changes can be made without departing from the scope of the invention as set forth in the claims. Therefore, the specification should be considered illustrative rather than restrictive, and all such modifications should be included within the scope of the invention. Benefits, other advantages, and solutions to problems have been described above with reference to specific embodiments. The benefits, advantages, and solutions to problems, as well as any elements that may cause any benefit, advantage, or solution to appear or become more significant, should not be construed as key, essential, or necessary features or elements of any or all claims.

[0218] For the purposes of this invention, the term "wavelength" is sometimes used as an abbreviation to express "light of (a specific) wavelength". Those skilled in the art will recognize that in these cases, the expressions are interchangeable.

[0219] Those skilled in the art will understand that, for the purposes of this invention, wavenumber (ν, typically expressed in cm⁻¹) is used. -1 The wavelength (λ, usually given in nm) and the wavelength (given) must be converted to the same dimensions for easy calculation.

[0220] As used herein, the terms “comprising,” “including,” “containing,” “having,” “having,” “containing,” or any other variations thereof are intended to cover non-exclusive inclusion. For example, a process, method, article, or apparatus that comprises a list of elements is not necessarily limited to those elements, but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. Furthermore, unless expressly stated to the contrary, the term “or” refers to inclusive “or” rather than exclusive “or.” For example, condition A or B satisfies any of the following conditions: 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); and both A and B are true (or exist).

[0221] The terms “a” or “an” as used herein are used to describe elements and components of the invention. This is done for the reader's convenience and to give the reader a general understanding of the invention. The use of these terms in the description herein should be read and understood to include one or at least one. Furthermore, the singular also includes the plural, unless otherwise indicated. For example, references to compositions containing “compound” include one or more compounds. As used in this specification and the appended claims, the term “or” is generally used to mean “and / or” unless the context clearly indicates otherwise.

[0222] Whether explicitly stated or not, all numerical values ​​herein are assumed to be modified by the term "about". The term "about" generally refers to a range of numerical values ​​that a person skilled in the art would consider equivalent to the stated value (i.e., having the same function or result). In any case, the term "about" may include numbers rounded (or reduced) to the nearest significant figure.

[0223] Clearly, all combinations of those elements that perform substantially the same function in substantially the same manner to achieve the same result are within the scope of this invention. Substitution of elements from one described embodiment to another is also entirely in accordance with expectation and exemplary principles.

Claims

1. A method for determining light with a first excitation wavelength and light with a second excitation wavelength to be used in a dual-laser spectrometer system, the dual-laser spectrometer system comprising: - A first laser source (110) configured to emit light of the first excitation wavelength, and a second laser source (120) configured to emit light of the second excitation wavelength; as well as - 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 and the second Raman signal is associated with a second excitation wavelength. The method includes: - The first excitation wavelength is selected based on at least one characteristic of the target object (160), said at least one characteristic being associated with fluorescence generated by the interaction of light passing through the first excitation wavelength with the target object (160); - Determine the fingerprint region of the first Raman signal associated with the first excitation wavelength; - Within the defined fingerprint region of the quantum efficiency curve associated with the spectrometer, determine the peak quantum efficiency value, i.e., determine the wavelength λ. QE At that wavelength, the quantum efficiency curve exhibits a peak value associated with the spectrometer within its range. - Determine the Raman shift peak of interest for the target object; and - The second excitation wavelength is determined based on the peak quantum efficiency value and the Raman shift peak of interest, wherein the second excitation wavelength λ p 1 It was identified as: l p 1 = 1 / [ n poi + 1 / λ QE ]; Where λ QE The wavelength is the wavelength associated with the peak value of the quantum efficiency within the range defined by the first excitation wavelength; and ν poi It is the wavenumber of the Raman shift peak of interest for the target object.

2. The method according to claim 1, wherein, The Raman shift peak of interest is the stretching peak emitted by the target object when irradiated with a second laser at the second excitation wavelength.

3. A diagnostic system, comprising - A spectrometer (190) having a known quantum efficiency; and - A Raman probe device (100) is configured to provide light of a Raman wavelength to a spectrometer (190) having a known quantum efficiency, the light of which is generated in response to excitation light irradiating a target object (160). The excitation light comprises a first light having a first excitation wavelength and a second light having a second excitation wavelength, the first excitation wavelength being selected based on at least one characteristic of the target object (160), the at least one characteristic being associated with fluorescence generated by the interaction of the light of the first excitation wavelength with the target object (160), and the second excitation wavelength being determined based on the first excitation wavelength and a wavelength associated with a peak value of the known quantum efficiency, wherein the second excitation wavelength λ p 1 It was identified as: l p 1 = 1 / [ n poi + 1 / λ QE ]; Where λ QE It is the wavelength associated with the peak value of the quantum efficiency within the fingerprint region determined based on the first excitation wavelength; and ν poi It is the wavenumber of the Raman shift peak of interest for the target object.

4. The diagnostic system according to claim 3, wherein, The system includes - A control unit adapted to determine the second excitation wavelength by performing the method according to any one of claims 1 to 2.

5. The diagnostic system according to claim 4, wherein, The Raman shift peak of interest is a stretching peak emitted by the target object (160) when irradiated with light including a second excitation wavelength.

6. The diagnostic system according to claim 3, wherein, The Raman probe device includes: The first lens is configured as follows: Focus the first light and the second light onto the target object; and The filter is configured as follows: Allow light of the specified Raman wavelength to pass through; and The light of the first excitation wavelength and the light of the second excitation wavelength are blocked from passing through the spectrometer.

7. The diagnostic system according to claim 6, wherein, The first lens is configured as follows: Collect the light of the Raman wavelength, and The collected Raman wavelength light is provided to the filter.

8. The diagnostic system according to claim 6, comprising: The second lens is configured as follows: Collect the light of the Raman wavelength, and The light of the Raman wavelength is provided to the filter.

9. The diagnostic system according to claim 8, comprising: Optical device, comprising: At least one optical fiber is configured as follows: Receive the excitation light; and The received excitation light is directed to the target object; and Multiple optical fibers are configured as follows: Light receiving the Raman wavelength; and The received Raman wavelength light is guided to the second lens.

10. The diagnostic system according to claim 9, comprising: A mask, wherein the mask prevents a selected fiber among the plurality of optical fibers that receive light of the Raman wavelength from receiving light of the Raman wavelength.

11. The diagnostic system according to claim 9, wherein, The optical device includes: Multiple optical fibers are arranged in one of the following ways: a one-dimensional fiber array and a two-dimensional fiber array.

12. The diagnostic system according to any one of claims 9 to 11, wherein, The optical device includes: Multiple optical fibers are arranged in a ring around a central optical fiber, wherein the central optical fiber is one of the following: a transmission optical device and a receiving optical device.

13. The diagnostic system according to claim 3, comprising: The first laser is configured as follows: The first light is generated, wherein the first laser is one of the following: inside the Raman probe device and outside the Raman probe device; The second laser is configured as follows: The second light is generated, wherein the second laser is one of the following: inside the Raman probe device and outside the Raman probe device.

14. A computer program comprising instructions that determine the second excitation wavelength (210) by executing the method according to any one of claims 1 to 2.

15. A Raman probe device (100), comprising: A first laser source (110) is used to emit a first laser at a first excitation wavelength; A second laser source (120) is used to emit a second laser at a second excitation wavelength; wherein the second excitation wavelength is selected based on the quantum efficiency of the spectrometer associated with the Raman probe device and the first excitation wavelength; The first dichroic mirror (135) is configured as follows: Receive light of the first excitation wavelength; as well as Receive light of the second excitation wavelength; The second dichroic mirror (140) is configured as follows: Receive light of the first excitation wavelength and light of the second excitation wavelength. Transmit light of the first excitation wavelength and light of the second excitation wavelength to the target object (160); as well as Receive a first Raman light (225) associated with the transmitted first excitation wavelength light, and receive a second Raman light (215) associated with the second excitation wavelength light, wherein the first Raman light and the second Raman light represent light generated by the interaction of the first excitation wavelength light and the second excitation wavelength light with the target object (160), respectively; Focusing optics, which are configured as follows: Receive light of the first excitation wavelength and light of the second excitation wavelength; The light of the first excitation wavelength and the light of the second excitation wavelength are focused onto the target object (160); Collect the first Raman beam (225) and the second Raman beam (215); and The collected first Raman light and second Raman light are directed to the second dichroic mirror (140). The filter is configured as follows: The first Raman light (225) and the second Raman light (215) are received from the second dichroic mirror (140). The collected first Raman light and second Raman light of wavelengths other than the first excitation wavelength and the second excitation wavelength are transmitted to the spectrometer (190). The first excitation wavelength is determined based on at least one characteristic of the target object, which is associated with fluorescence generated by the interaction of light passing through the first excitation wavelength with the target object (160); and The second excitation wavelength λ p 1 It was identified as: l p 1 = 1 / [ n poi + 1 / λ QE ]; Where λ QE The wavelength is the wavelength associated with the peak of the quantum efficiency within the fingerprint region determined based on the first excitation wavelength; and ν poi It is the wavenumber of the Raman shift peak of interest for the target object.

16. The Raman probe device according to claim 15, wherein, At least one of the first laser source and the second laser source is located outside the housing of the Raman probe device.

17. The Raman probe device according to claim 15, wherein, The light of the first excitation wavelength and the light of the second excitation wavelength are emitted concurrently.

18. The Raman probe device according to claim 15, wherein, The light of the first excitation wavelength and the light of the second excitation wavelength are emitted sequentially.

19. The Raman probe device according to claim 15, wherein, The first excitation wavelength is selected such that the fluorescence generated by the target object when irradiated with light of the first excitation wavelength does not block the light of the first Raman wavelength.

20. The Raman probe device according to claim 15, wherein, The target objects are related to medical diagnostics, petrochemical processing, or bioreactors.

21. The Raman probe device according to claim 15, wherein, The first excitation wavelength is determined based on at least one characteristic of the target object; and The second excitation wavelength λ p 1 It was identified as: l p 1 = 1 / [v poi + 1 / (λ) QE +(+ / -δ))] Where λ QE It is the peak quantum efficiency within the range defined by the first excitation wavelength; δ represents the region near the peak quantum efficiency value; and v poi It is the wavenumber of the Raman shift peak of interest for the target object.

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