System, apparatus, and method for calculating correction factors to correct the baseline of a Raman spectrum generated by waveguide-enhanced Raman spectroscopy

Abstract

One of the objectives of the present invention is to provide a method for correcting the baseline of a Raman spectrum by taking into account the phenomenon of baseline generation characteristic of waveguide-enhanced Raman spectroscopy. The solution of the present invention corrects the baseline of the Raman spectrum generated by physical elements constituting the device implementing waveguide-enhanced Raman spectroscopy. Subsequently, known baseline correction methods may be used before removing the baseline from the acquired Raman spectrum.

Description

Technology Field

[0001] The present invention relates to the field of processing Raman signals. In particular, it relates to a system, an integrated semiconductor device, and a method for calculating correction factors to correct a baseline of a Raman spectrum generated by waveguide-enhanced Raman spectroscopy. Background Technology

[0002] In the context of Raman spectroscopy, it is known that the performance of spectral analysis of Raman spectra can be severely degraded by an undesirable signal known as the 'baseline'.

[0003] As previously announced, in Raman spectroscopy, the baseline is considered to be due to Rayleigh scattering originating from the analyzed sample or fluorescence of specific organic molecules (i.e., the phenomenon in which a substance irradiated at one wavelength emits light at another wavelength).

[0004] Therefore, many methods for correcting the baseline of the Raman spectrum are known.

[0005] However, these methods do not account for the singularity of the baseline of the Raman spectrum acquired by sensors using waveguide-enhanced Raman spectroscopy (WERS).

[0006] In practice, in this technology, for example, the waveguide material through which light waves propagate itself also causes the Raman effect and thus contributes to the formation of a baseline. Examples of prior art are presented in the following literature: "A packaged, fiber-coupled waveguide-enhanced Raman spectroscopy sensor" (Kita Derek et al., Optics Express, May 11, 2020); "Waveguide-Enhanced Raman Spectroscopy (WERS): An Emerging Chip-Based Tool for Chemical and Biological Sensing" (Wang Pengyi et al., Sensors, November 22, 2022); "Waveguide Enhanced Raman Spectroscopy for Biosensing: A Review" (Ettabib et al., Sensors, American Chemical Society, June 25, 2021); "High index contrast photonic platforms for on-chip Raman spectroscopy" (Ali Raza et al., Optics Express, August 5, 2019); "Are slot and sub-wavelength grating waveguides better than strip waveguides for sensing?" (Kita et al., arXiv.org, May 9, 2018); "Are slot and sub-wavelength grating waveguides better than strip waveguides for sensing? Supplementary material" (Kita et al., Optica, September 20, 2018); and "Nanophotonic waveguides for chip-scale Raman spectroscopy: Theoretical considerations" (Stievater Todd H. et al., Proceedings of SPIE, May 12, 2016).

[0007] Therefore, a baseline correction method for Raman spectra that takes into account the specific characteristics of waveguide-enhanced Raman spectroscopy is required. The problem to be solved

[0008] The present invention aims to solve these needs at least partially. means of solving the problem

[0009] A first aspect of the present invention relates to a system for calculating a correction factor for correcting a reference line of a Raman spectrum acquired by at least one waveguide-enhanced Raman spectroscopy device (referred to as an on-chip Raman sensor), which is defined in claim 1.

[0010] In fact, the on-chip Raman sensor is designed to implement waveguide-enhanced Raman spectroscopy and is configured to acquire a first optical spectrum (referred to as a first Raman spectrum) comprising a plurality of discrete wavelengths representing the analysis medium by irradiating at least one excitation radiation onto a continuous fluid medium of a study subject having at least one first refractive index (referred to as an analysis medium).

[0011] In addition, the system includes at least one memory and at least one processor.

[0012] Additionally, the on-chip Raman sensor comprises a substrate defining at least one surface and at least one optical waveguide formed within an optical transmission material, wholly or partially disposed on or within the substrate, and configured to induce at least one light beam at at least one working wavelength.

[0013] Additionally, the memory is configured to store a database, and each record is configured to associate a correction factor with an analysis medium, a predetermined reference medium, a working wavelength, a first refractive index of the analysis medium, and a second refractive index of the predetermined reference medium. Furthermore, the memory is configured to store instructions executable by a processor. The instructions executable by a processor first implement a first calculation step for each wavelength of a first Raman spectrum, which calculates a first parameter referred to as a first Raman conversion efficiency parameter as a first parameter describing the Raman conversion efficiency of an on-chip Raman sensor within a predetermined reference medium. Next, the instructions executable by a processor implement a second calculation step for each wavelength of the first Raman spectrum, which calculates a second parameter referred to as a second Raman conversion efficiency parameter as a second parameter describing the Raman conversion efficiency of an on-chip Raman sensor within a medium to be analyzed. Finally, the instructions executable by a processor calculate a third correction factor corresponding to the ratio between the first Raman conversion efficiency parameter and the second Raman conversion efficiency parameter for each wavelength of the first Raman spectrum. A calculation step is implemented, and the correction coefficient is designed to correct the baseline of the second Raman spectrum.

[0014] In practice, each correction factor is designed to correct the baseline of the second optical spectrum (referred to as the second Raman spectrum), said baseline being generated during the process in which the second Raman spectrum is generated by the on-chip Raman sensor while at least one excitation radiation is irradiated onto a predetermined reference medium having at least one second refractive index different from the first refractive index. said second Raman spectrum includes a plurality of discrete wavelengths and represents a predetermined reference medium.

[0015] Finally, each correction factor corresponds to the ratio between the first Raman conversion efficiency parameter and the second Raman conversion efficiency parameter for each wavelength of the first Raman spectrum.

[0016] delete

[0017] delete

[0018] In an embodiment of the first aspect of the present invention, a processor-executable instruction further implements the step of correcting a reference line of a second Raman spectrum based on a correction factor to obtain a corrected second Raman spectrum representing a reference line of a first Raman spectrum, said reference line is generated by an on-chip Raman sensor during the acquisition of the first Raman spectrum.

[0019] Finally, the processor-executable instructions implement the step of subtracting the corrected second Raman spectrum from the first Raman spectrum.

[0020] delete

[0021] A second aspect of the present invention relates to an integrated semiconductor device for calculating a correction factor for correcting a reference line of a Raman spectrum obtained by the integrated semiconductor device, which is defined in claim 3.

[0022] In fact, the integrated semiconductor device is designed to implement waveguide-enhanced Raman spectroscopy and is configured to acquire a first optical spectrum (referred to as a first Raman spectrum) comprising a plurality of discrete wavelengths representing said analysis medium in response to irradiating at least one excitation radiation onto a continuous fluid medium of a study subject having at least one first refractive index.

[0023] Additionally, the integrated semiconductor device comprises a substrate defining at least one surface and at least one optical waveguide formed within an optical transmission material, wholly or partially disposed on or within the substrate, and configured to induce at least one light beam at at least one working wavelength.

[0024] Additionally, the integrated semiconductor device comprises at least one processor and at least one memory, wherein the memory is configured to store a database, and each record is configured to associate a correction factor with an analysis medium, a predetermined reference medium, a working wavelength, a first refractive index of the analysis medium, and a second refractive index of the predetermined reference medium. Additionally, the memory is configured to store instructions executable by the processor. Instructions executable by the processor first implement a first calculation step for each wavelength of a first Raman spectrum, wherein a first parameter referred to as a first Raman conversion efficiency parameter is calculated as a first parameter describing the Raman conversion efficiency of the integrated semiconductor device in a predetermined reference medium. Next, instructions executable by the processor implement a second calculation step for each wavelength of the first Raman spectrum, wherein a second parameter referred to as a second Raman conversion efficiency parameter is calculated as a second parameter describing the Raman conversion efficiency of the integrated semiconductor device in a medium to be analyzed. Finally, instructions executable by the processor for each wavelength of the first Raman spectrum, wherein between the first Raman conversion efficiency parameter and the second Raman conversion efficiency parameter A third calculation step is implemented to calculate a correction factor corresponding to the ratio, and said correction factor is designed to correct the baseline of the second Raman spectrum.

[0025] In practice, each correction factor is designed to correct a reference line of a second optical spectrum (referred to as the second Raman spectrum), said reference line is generated during the process in which the second Raman spectrum is generated by the integrated semiconductor device while irradiating at least one excitation radiation onto a predetermined reference medium having at least one second refractive index different from the first refractive index, said second Raman spectrum includes a plurality of discrete wavelengths and represents a predetermined reference medium.

[0026] Finally, each correction factor corresponds to the ratio between the first Raman transform efficiency parameter and the second Raman transform efficiency parameter for each wavelength of the first Raman spectrum. In an embodiment of the second aspect of the present invention, a processor is disclosed for an executable instruction.

[0027] delete

[0028] delete

[0029] In fact, the processor-executable instructions further implement a step of correcting the baseline of the second Raman spectrum based on a correction factor, thereby obtaining a corrected second Raman spectrum representing the baseline of the first Raman spectrum, wherein the baseline is generated by an integrated semiconductor device during the process of obtaining the first Raman spectrum.

[0030] Finally, the processor-executable instructions implement the step of subtracting the corrected second Raman spectrum from the first Raman spectrum.

[0031] delete

[0032] A third aspect of the present invention relates to a computer-implemented method for calculating a correction factor for correcting a reference line of a Raman spectrum obtained by at least one waveguide-enhanced Raman spectroscopic device called an on-chip Raman sensor, which is defined in claim 5.

[0033] In fact, the on-chip Raman sensor is designed to implement waveguide-enhanced Raman spectroscopy and is configured to acquire a first optical spectrum (referred to as the first Raman spectrum) comprising a plurality of discrete wavelengths representing the analysis medium in response to irradiating at least one excitation radiation onto a continuous fluid medium of a study subject having at least one first refractive index (referred to as the analysis medium).

[0034] In particular, the on-chip Raman sensor comprises a substrate defining at least one surface and at least one optical waveguide formed within an optical transmission material, wholly or partially disposed on or within the substrate, and configured to induce at least one light beam at at least one working wavelength.

[0035] Additionally, the method comprises the step of acquiring a second optical spectrum (referred to as the second Raman spectrum) by the on-chip Raman sensor (110), which is accomplished in response to irradiating at least one excitation radiation onto a predetermined reference medium having at least one second refractive index different from the first refractive index. The second Raman spectrum includes a plurality of discrete wavelengths and represents a predetermined reference medium, and the generation of the second Raman spectrum causes the formation of a baseline of the second Raman spectrum.

[0036] Next, the method also includes a first calculation step in which a processor calculates a first parameter (referred to as the first Raman conversion efficiency parameter) representing the Raman conversion efficiency of an on-chip Raman sensor in a predetermined reference medium for each wavelength of a first Raman spectrum.

[0037] Next, the method also includes a second calculation step in which a processor calculates a second parameter (referred to as the second Raman conversion efficiency parameter) representing the Raman conversion efficiency of the on-chip Raman sensor in the analysis medium for each wavelength of the first Raman spectrum.

[0038] Finally, the method also includes a third calculation step in which, for each wavelength of the first Raman spectrum, a processor calculates a correction factor corresponding to the ratio between a first Raman conversion efficiency parameter and a second Raman conversion efficiency parameter.

[0039] In the first embodiment of the third aspect of the present invention, the first calculation step and the second calculation step are performed based on an optical simulation of at least one optical mode of the optical waveguide of the on-chip Raman sensor.

[0040] In the second embodiment of the third aspect of the present invention, the third calculation step includes dividing the first Raman conversion efficiency parameter by the second Raman conversion efficiency parameter.

[0041] In a third embodiment of the third aspect of the present invention, the method also includes the step of storing a correction factor in a database by a processor, wherein each record is configured to associate the correction factor with an analysis medium, a predetermined reference medium, a working wavelength, a first refractive index of the analysis medium, and a second refractive index of the predetermined reference medium.

[0042] In the fourth embodiment of the third aspect of the present invention, a predetermined reference medium is a continuous fluid medium.

[0043] In the fifth embodiment of the third aspect of the present invention, the predetermined reference medium is a continuous solid medium.

[0044] In the sixth embodiment of the third aspect of the present invention, the method also includes the step of correcting a reference line of a second Raman spectrum based on a correction factor by a processor, thereby obtaining a corrected second Raman spectrum representing a reference line of a first Raman spectrum, wherein the reference line is generated by an integrated semiconductor device during the process of obtaining the first Raman spectrum.

[0045] Finally, the method also includes the step of subtracting a second Raman spectrum corrected by a processor from the second Raman spectrum.

[0046] In the first embodiment of the sixth embodiment of the third aspect of the present invention, the step of correcting the reference line of the second Raman spectrum includes the step of multiplying the second Raman spectrum by a correction factor corresponding to the wavelength of the first Raman spectrum.

[0047] In the second embodiment of the sixth embodiment of the third aspect of the present invention, the method also includes the step of selecting a correction factor from a database as a function of at least an analysis medium, a predetermined reference medium, a first refractive index of the analysis medium, a second refractive index of the predetermined reference medium, and a working wavelength by a processor. Brief explanation of the drawing

[0048] Other features and advantages of the present invention will be better understood by reading the following description with reference to the accompanying drawings, which is for illustrative purposes only and is not limiting in any way. Figure 1 illustrates a Raman spectrum and an associated baseline. FIG. 2 illustrates a system according to the present invention. FIG. 3 illustrates a plan view of a device according to the present invention. FIG. 4 illustrates a method for calculating a correction coefficient according to the present invention. For illustrative purposes, the drawings do not necessarily reflect the scale, particularly with respect to thickness. Specific details for implementing the invention

[0049] In order not to hinder the understanding of the teachings of the present invention or distract the reader's attention, the description herein does not exceed the scope deemed necessary for understanding and evaluating the basic concept of the invention. In fact, most of the embodiments illustrated in the description consist of elements known to those skilled in the art.

[0050] The context in which the present invention is implemented is waveguide-enhanced Raman spectroscopy (WERS).

[0051] In fact, Raman spectroscopic probes are commonly used in the fields of biochemical detection, research, or biochemical production.

[0052] For example, this applies when analyzing the chemical composition of a liquid mixture in industry.

[0053] Simply put, Raman spectroscopy involves irradiating a material to be analyzed to cause the molecular bonds constituting the material to vibrate. These vibrations take the form of secondary photon emission, and the wavelength shift of the excitation wave is called the Raman effect, which is expressed as a Raman spectrum representing the characteristic fingerprint of each bond.

[0054] The Raman spectrum obtained in this way ultimately represents a unique image of the molecules or molecules present within the field.

[0055] Therefore, this technique allows for the identification of molecules within a sample, as each peak in the Raman spectrum is associated with the vibrational mode of the molecule (and, in the case of gases, the rotational mode as well).

[0056] In other words, since each vibration frequency is unique to the chemical bonds and molecular symmetry, the intensity peaks of the Raman spectrum reveal qualitative and quantitative information regarding the properties of the sample's molecular vibrational dynamics (e.g., frequency, vibrational symmetry, etc.).

[0057] Figure 1 shows three examples of Raman spectra (a), (b), and (c).

[0058] In Fig. 1, the horizontal axis of this spectrum represents the Raman shift, which corresponds to the energy jump between fundamental vibration levels and cm -1 It is expressed in units (wavenumbers, which reflect the direct proportional relationship between the reciprocal of the wavelength of electromagnetic radiation and energy).

[0059] In Figure 1, the vertical axis of this spectrum corresponds to the Raman intensity for each wavenumber.

[0060] As shown in FIG. 1, spectra (a), (b) and (c) each include a baseline indicated by a dashed line.

[0061] In the context of waveguide-enhanced Raman spectroscopy, the inventors identified phenomena inherent or extrinsic to spectroscopic experiments and revealed that they contribute to the formation of a baseline.

[0062] In waveguide-enhanced Raman spectroscopy, an optical signal in the form of a monochromatic laser is induced within a waveguide. The attenuation field of the induced light (i.e., the portion of light physically existing outside the waveguide) excites sample molecules near the waveguide. In response to this excitation, these molecules emit Raman radiation. Finally, a portion of this Raman radiation is collected within the waveguide to form the Raman signal of interest.

[0063] Therefore, for example, the waveguide material itself through which the optical signal propagates also generates the Raman effect and thus contributes to the formation of a baseline.

[0064] This is also true for other physical elements constituting the device implementing waveguide-enhanced Raman spectroscopy.

[0065] However, known baseline correction methods for Raman spectra do not account for these phenomena unique to waveguide-enhanced Raman spectroscopy.

[0066] More specifically, in a known method called "calibration," the baseline of the Raman spectrum is removed by subtracting a reference measurement from the actual measurement.

[0067] However, this method can only operate when the baseline contribution of the device implementing conventional Raman spectroscopy is constant, regardless of the medium being analyzed. This is not the case with waveguide-enhanced Raman spectroscopy, where the baseline contribution of the device performing the spectroscopy varies depending on the refractive index of the medium being analyzed, because this changes the confinement of optical modes.

[0068] In addition, the disclosed algorithm processing method removes the baseline of the Raman spectrum by directly modeling the signal associated with the baseline for the actual measurement (e.g., through regression analysis) and then subtracting it from the actual measurement.

[0069] However, this method has two disadvantages.

[0070] First, this method requires assumptions about the signal associated with the actual measurement so that the contribution of the actual measured molecule and the contribution of the line can be separated.

[0071] Second, in this method, since the baseline changes when the medium being analyzed changes, the processing algorithm must be modified immediately. Therefore, algorithm-based processing may work under some conditions but may be ineffective under others.

[0072] The solution of the present invention can solve the problems identified in the "prior art" by having the ability to correct the baseline of the Raman spectrum caused by all or part of the physical elements constituting the device implementing waveguide-enhanced Raman spectroscopy.

[0073] Next, known baseline correction methods can be used before removing the baseline from the acquired Raman spectrum.

[0074] According to the solution of the present invention, the signal-to-noise ratio of the acquired Raman signal can be improved, and in particular, a better detection limit than that of the prior art can be provided.

[0075] First aspect of the invention: A system for calculating a correction factor for correcting a baseline of a Raman spectrum

[0076] As illustrated in FIG. 2, the present invention relates to a system (100) for correcting the baseline of a Raman spectrum.

[0077] Here, the term "system" refers to a set of interconnected elements that mutually influence one another.

[0078] In fact, the system (100) includes at least one waveguide-enhanced Raman spectrometer called an on-chip Raman sensor (110), at least one memory (120), and at least one processor (130).

[0079] Accordingly, the system (100) may include two or more first on-chip Raman sensors (110), two or more memories (120) and / or two or more processors (130).

[0080] In the present invention, the on-chip Raman sensor (110) is designed to implement waveguide-enhanced Raman spectroscopy technology as briefly described above.

[0081] In fact, in response to irradiating at least one excitation radiation onto a continuous fluid medium (referred to as the analysis medium) of the subject of study, the on-chip Raman sensor (110) is configured to acquire a first optical spectrum (referred to as the first Raman spectrum) representing the analysis medium.

[0082] In this way, the on-chip Raman sensor (110) can acquire a first Raman spectrum in response to irradiating two or more excitation radiations onto an analysis medium.

[0083] Actually, the radiation here is a photoelectric field (also called a photoelectric field).

[0084] In the present invention, the analysis medium has at least one first refractive index.

[0085] Therefore, the analysis medium may include two or more first refractive indices.

[0086] As a first example, the analysis medium comprises at least one liquid.

[0087] As a second example, the analysis medium includes at least one gas.

[0088] In addition, the first Raman spectrum in the present invention includes a plurality of discrete wavelengths.

[0089] A conventional on-chip Raman sensor (110) includes a substrate.

[0090] Here, the term "substrate" refers entirely to a semiconductor support (e.g., silicon), a stack of semiconductor layers, a support comprising a heterogeneous structure, or a support comprising an electronic component or a part of an electronic component at a somewhat advanced stage of the manufacturing process.

[0091] Additionally, the on-chip Raman sensor (110) includes at least one optical waveguide (not shown).

[0092] Accordingly, the on-chip Raman sensor (110) may include two or more optical waveguides.

[0093] Here, the term "optical waveguide" refers to an optical device (e.g., optical fiber) that has the characteristic of trapping light. In particular, its physical properties guide luminous flux passing through the visible or invisible spectrum, optimally focus it, and direct it toward a device capable of collecting it.

[0094] As a first example, the optical waveguide is a single-mode optical waveguide.

[0095] As a second example, the optical waveguide is a multimode optical waveguide.

[0096] In the present invention, the substrate defines at least one surface.

[0097] Therefore, the substrate may include two or more surfaces.

[0098] As a first example of a substrate surface, the surface is generally flat and generally oriented horizontally.

[0099] As a second example of a substrate surface, the surface is non-planar and generally oriented horizontally.

[0100] As a third example of a substrate surface, the surface is curved and is generally oriented vertically.

[0101] As a fourth example of a substrate surface, the surface is generally inclined with respect to the horizontal.

[0102] However, substrate surfaces of different shapes are also possible as needed without making essential changes to the invention.

[0103] In addition, the optical waveguide is formed of an optically transparent material.

[0104] As a first example of an optical waveguide material, the material comprises silicon dioxide (SiO2), chalcogen elements, and glass such as so-called chalcogenized glass fibers (e.g., sulfur, selenium, or tellurium).

[0105] As a second example of an optical waveguide material, the material includes plastics such as transparent polymers (e.g., polymethyl methacrylate (PMMA), polystyrene (PS), and polycarbonate (PC)).

[0106] As a third example of an optical waveguide material, the material comprises a semiconductor based on silicon (Si), gallium arsenide (GaAs) and / or gallium nitride (GaN).

[0107] However, optical waveguides can also be formed using other materials as needed without making essential changes to the invention.

[0108] In practice, the optical waveguide is placed entirely or partially on or within the substrate.

[0109] In a first embodiment of an optical waveguide, all or part thereof is placed on a substrate.

[0110] In a second embodiment of the optical waveguide, all or part thereof is disposed within a substrate.

[0111] In this second embodiment of the optical waveguide, the first part of the optical waveguide is outside the substrate, and the second part is inside the substrate.

[0112] As a first example, the ratio of the first part to the second part of the optical waveguide is 85 / 15.

[0113] As a second example, the ratio of the first part to the second part of the optical waveguide is 75 / 25.

[0114] As a third example, the ratio of the first part to the second part of the optical waveguide is 50 / 50.

[0115] However, other values ​​may be applied to the ratio of the first part and the second part as needed without making essential changes to the invention.

[0116] Additionally, the optical waveguide is configured to guide at least one light beam at at least one working wavelength in at least one specific optical propagation mode along at least one optical propagation direction.

[0117] Accordingly, an optical waveguide can guide two or more light rays at two or more working wavelengths along two or more directions of optical propagation in at least one specific optical propagation mode.

[0118] As a first example of an optical waveguide, the light is a laser beam emitted in the visible spectrum.

[0119] As a second example of an optical waveguide, the light is a laser beam emitted in the non-visible spectrum (e.g., ultraviolet or near-infrared).

[0120] In the present invention, the memory (120) is of a known type (e.g., RAM, ROM, or EEPROM) and is configured to store a database (121), and in a specific embodiment, is configured to store processor-executable instructions (122).

[0121] In the database (121), each record is configured to associate a correction factor with an analysis medium, a predetermined reference medium, a working wavelength, a first refractive index of the analysis medium, and a second refractive index of the predetermined reference medium.

[0122] In the present invention, each correction factor is designed to correct the reference line of a second optical spectrum (referred to as the second Raman spectrum) representing a predetermined reference medium.

[0123] In fact, the baseline to be corrected is generated by the on-chip Raman sensor (110) while a second Raman spectrum is generated in response to irradiating at least one excitation radiation onto a given reference medium.

[0124] Accordingly, a given reference medium may include two or more second refractive indices.

[0125] In a specific embodiment, the baseline to be corrected is generated by an on-chip Raman sensor similar to or identical to the on-chip Raman sensor (110).

[0126] In the present invention, a predetermined reference medium has at least one second refractive index different from the first refractive index.

[0127] In a first embodiment of a given reference medium, this medium substantially does not generate a Raman response.

[0128] As a first example, a specified standard medium is water.

[0129] As a second example, a specified standard medium is air.

[0130] However, if necessary, other specified standard media may be used without making essential changes to the invention.

[0131] In a second embodiment of a predetermined reference medium, this medium produces a known Raman response.

[0132] In addition, the second Raman spectrum includes multiple discrete wavelengths.

[0133] In the present invention, the correction factor corresponds to the ratio between a first parameter (referred to as the first Raman conversion efficiency parameter) representing the Raman conversion efficiency of the on-chip Raman sensor (110) in a predetermined reference medium on one side, and a second parameter (referred to as the second Raman conversion efficiency parameter) representing the Raman conversion efficiency of the on-chip Raman sensor (110) in an analysis medium on the other side, for each wavelength of the first Raman spectrum.

[0134] As previously announced, Raman conversion efficiency is a measure of the strength of the Raman signal generated by a specific material.

[0135] Formulas for calculating Raman transform efficiency can be found particularly in the literature, and are described in, for example, the following papers.

[0136] - Equation (8) of Ali Raza, Stephane Clemmen, Pieter Wuytens, Michiel de Goede, Amy SK Tong, Nicolas Le Thomas, Chengyu Liu, Jin Suntivich, Andre G. Skirtach, Sonia M. Garcia-Blanco, Daniel J. Blumenthal, James S. Wilkinson, and Roel Baets, “High index contrast photonic platforms for on-chip Raman spectroscopy” Opt. Express 27, 23067-23079 (2019),

[0137] - Equation (S22) of Derek M. Kita, Jerome Michon, Steven G. Johnson, and Juejun Hu, “Are slot and sub-wavelength grating waveguides better than strip waveguides for sensing?” Optica 5, 1046-1054 (2018).

[0138] - Equation (13) of Todd H. Stievater, Jacob B. Khurgin, Scott A. Holmstrom, Dmitry A. Kozak, Marcel W. Pruessner, William S. Rabinovich, R. Andrew McGill, "Nanophotonic waveguides for chip-scale raman spectroscopy: Theoretical considerations" Proc. SPIE 9824, Chemical, Biological, Radiological, Nuclear, and Explosives (CBRNE) Sensing XVII, 982404 (May 12, 2016),

[0139] - Y. Li, H. Zhao, A. Raza, S. Clemmen and R. Baets, "Surface-Enhanced Raman Spectroscopy Based on Plasmonic Slot Waveguides With Free-Space Oblique Illumination" IEEE Journal of Quantum Electronics, Vol. 56, No. 1, pp. 1-8, February 2020, Art no. 7200108, doi: 10.1109 / JQE.2019.2946839, Section 111.B.

[0140] In fact, Raman conversion efficiency is defined as the ratio between the intensity of the emitted Raman signal and the intensity of the incident laser light.

[0141] As mentioned earlier, the Raman signal is scattered light emitted when incident laser light interacts with molecular vibrations within a material.

[0142] In particular, Raman conversion efficiency depends not only on the properties of the material but also on experimental parameters such as the wavelength of the laser, the polarization of the light, and temperature.

[0143] In a specific embodiment of the correction factor, the correction factor corresponds to dividing the first Raman transform efficiency parameter by the second Raman transform efficiency parameter.

[0144] Additionally, in the present invention, a processor-executable instruction (122) implements a step of correcting a reference line of a second Raman spectrum based on at least one correction coefficient, thereby obtaining a corrected second Raman spectrum representing a reference line of a first Raman spectrum, wherein the reference line is generated by an on-chip Raman sensor (110) during the process of obtaining the first Raman spectrum.

[0145] Accordingly, the processor-executable instruction (122) can implement the step of correcting the baseline of the second Raman spectrum based on two or more correction factors.

[0146] In a specific embodiment of the step of correcting the baseline of the second Raman spectrum, the step includes multiplying the second Raman spectrum by at least one correction factor corresponding to the wavelength of the first Raman spectrum.

[0147] Accordingly, this particular embodiment of the step of correcting the baseline of the second Raman spectrum may include the step of multiplying the second Raman spectrum by two or more correction factors, each corresponding to the wavelength of the first Raman spectrum.

[0148] Additionally, in the present invention, the processor-executable instruction (122) implements the step of subtracting the corrected second Raman spectrum from the first Raman spectrum.

[0149] Finally, in the present invention, the processor (130) is of a known type (e.g., state machine, microprocessor or microcontroller) and is configured to execute executable instructions (122).

[0150] Now that the features of the system (100) have been described, an integrated semiconductor device for calculating a correction factor to correct the baseline of the Raman spectrum is described.

[0151] Second aspect of the invention: an integrated semiconductor device for calculating a correction factor for correcting a baseline of a Raman spectrum obtained by the integrated semiconductor device.

[0152] As illustrated in FIG. 3, the present invention also relates to a single integrated semiconductor device (200) designed to implement waveguide-enhanced Raman spectroscopy technology and integrating all features of the system (100).

[0153] In fact, the integrated semiconductor device is configured to acquire a first optical spectrum (referred to as a first Raman spectrum) comprising a plurality of discrete wavelengths representing the analysis medium in response to irradiating at least one excitation radiation onto a continuous fluid medium (referred to as an analysis medium) having at least one first refractive index.

[0154] Additionally, the integrated semiconductor device (200) includes a substrate (210), at least one optical waveguide (220), at least one memory (230), and at least one processor (240) as described above.

[0155] In particular, the substrate (210) defines at least one surface.

[0156] Additionally, the optical waveguide (220) is formed within the optical transmission material, and all or part thereof is disposed on or within the substrate (210) and configured to guide at least one light beam at at least one working wavelength.

[0157] The memory (230) is configured to store a database, and each record is configured to associate a correction factor with an analysis medium, a predetermined reference medium, a working wavelength, a first refractive index of the analysis medium, and a second refractive index of the predetermined reference medium.

[0158] In practice, each correction factor is designed to correct a reference line of a second optical spectrum (referred to as the second Raman spectrum), said reference line is generated by an integrated semiconductor device (200) while the second Raman spectrum is generated in response to irradiating at least one excitation radiation onto a predetermined reference medium having at least one second refractive index different from the first refractive index. The second Raman spectrum includes a plurality of discrete wavelengths and represents a predetermined reference medium.

[0159] Additionally, for each wavelength of the first Raman spectrum, each correction factor corresponds to the ratio between a first parameter (referred to as the first Raman conversion efficiency parameter) representing the Raman conversion efficiency of the integrated semiconductor device (200) in a predetermined reference medium on one side, and a second parameter (referred to as the second Raman conversion efficiency parameter) representing the Raman conversion efficiency of the integrated semiconductor device (200) in an analysis medium on the other side.

[0160] In one embodiment of the above integrated semiconductor device (200), the device also includes at least one processor (240).

[0161] Additionally, the memory (230) is configured to store processor-executable instructions (232), which implement a step of correcting the baseline of the second Raman spectrum based on at least one correction factor to obtain a corrected second Raman spectrum representing the baseline of the first Raman spectrum. The baseline is generated by the integrated semiconductor device (200) during the process of obtaining the first Raman spectrum.

[0162] Additionally, the processor executable instruction (232) implements the step of subtracting the corrected second Raman spectrum from the first Raman spectrum.

[0163] Finally, the processor (240) is configured to execute an executable instruction (232).

[0164] Now that the features of the integrated semiconductor device (200) have been described, a computer implementation method for calculating a correction factor to correct the reference line of the Raman spectrum is described.

[0165] Third aspect of the invention: A computer-implemented method for calculating a correction factor to correct a baseline of a Raman spectrum.

[0166] As illustrated in FIG. 4, the present invention also relates to a computer-implemented method (300) for calculating a correction factor for correcting a baseline of a Raman spectrum obtained by an on-chip Raman sensor (110), which is performed in response to irradiating at least one excitation radiation onto an analysis medium having at least one first refractive index.

[0167] In fact, as previously described in relation to the first aspect of the invention, the on-chip Raman sensor (110) is configured to acquire a first optical spectrum (referred to as the first Raman spectrum) comprising a plurality of discrete wavelengths representing the analysis medium.

[0168] In the present invention, a computer implementation method (300) for calculating a correction factor includes the step (310) of acquiring a second Raman spectrum by an on-chip Raman sensor (110), which is performed in response to irradiating at least one excitation radiation onto a predetermined reference medium having at least one second refractive index different from the first refractive index.

[0169] In the first embodiment, the predetermined reference medium is a continuous fluid medium (e.g., water, air, acetone, methanol, chloroform, toluene, or glycerol).

[0170] In the second embodiment, the predetermined reference medium is a continuous solid medium (e.g., graphite, silicon, corundum, diamond, or quartz).

[0171] Next, the computer implementation method (300) for calculating a correction factor further includes a first calculation step (320) for calculating, by a processor, a first parameter (referred to as the first Raman conversion efficiency parameter) representing the Raman conversion efficiency of the on-chip Raman sensor (110) in a predetermined reference medium for each wavelength of the first Raman spectrum.

[0172] Next, the computer implementation method (300) further includes a second calculation step (330) in which a processor calculates a second parameter (referred to as the second Raman conversion efficiency parameter) representing the Raman conversion efficiency of the on-chip Raman sensor (110) in the analysis medium for each wavelength of the first Raman spectrum.

[0173] In one embodiment of a computer implementation method (300) for calculating a correction factor, the first calculation step (320) and the second calculation step (330) are performed based on an optical simulation of at least one optical mode (e.g., TE0 or TM0) of the optical waveguide of the on-chip Raman sensor (110).

[0174] Accordingly, the first calculation step (320) and the second calculation step (330) can be performed based on two or more optical modes of the optical waveguide of the on-chip Raman sensor (110).

[0175] For example, optical simulation software such as Zemax®, COMSOL Multiphysics®, FRED®, OpticStudio®, or Lumerical® can be used.

[0176] In fact, such software must be able to model the geometry and materials (i.e., all its components), the analysis medium, and a predetermined reference medium of the on-chip Raman sensor (110).

[0177] In addition, this software enables the refractive index of the analysis medium and a predetermined reference medium to be changed independently or in combination.

[0178] Finally, the computer implementation method (300) for calculating the correction factor includes a third calculation step (340) in which, for each wavelength of the first Raman spectrum, a correction factor corresponding to the ratio between the first Raman conversion efficiency parameter and the second Raman conversion efficiency parameter is calculated by a processor.

[0179] In a first embodiment of a computer implementation method (300) for calculating correction coefficients, a third calculation step (340) includes calculating a predetermined number of correction coefficients that is smaller than the total number of wavelengths of the first Raman spectrum. Subsequently, the third calculation step (340) includes a step of interpolating missing correction coefficients from all or part of the previously calculated predetermined number of correction coefficients.

[0180] In a second embodiment of a computer implementation method (300) for calculating a correction factor, the third calculation step (340) includes dividing a first Raman transform efficiency parameter by a second Raman transform efficiency parameter.

[0181] In a specific embodiment of a computer implementation method (300) for calculating a correction factor, the method also includes the step (350) of storing the correction factor in a database (121), wherein each record is configured to associate the correction factor with an analysis medium, a predetermined reference medium, a working wavelength, a first refractive index and a second refractive index of the analysis medium.

[0182] In a variation of a specific embodiment of a computer implementation method (300) for calculating a correction factor, the database (121) may be filled by repeating all steps of the method while varying the following parameters, namely the analysis medium, a predetermined reference medium, a working wavelength, a first refractive index, and a second refractive index, independently or in combination.

[0183] In an alternative version of a specific embodiment of the computer implementation method (300) for calculating a correction factor, the following parameters may be added to the database (121): the polarization and geometry of the on-chip Raman sensor (110) (i.e., all its components), the analysis medium, and a predetermined reference medium.

[0184] In a third embodiment of a computer implementation method (300) for calculating a correction factor, the method also includes a step (360) of correcting a reference line of a second Raman spectrum based on at least one correction factor by a processor, thereby obtaining a corrected second Raman spectrum representing a reference line of a first Raman spectrum. The reference line is generated by an on-chip Raman sensor (110) during the process of acquiring the first Raman spectrum.

[0185] In one embodiment of a computer implementation method (300) for calculating a correction factor, the step (360) of correcting the second Raman spectrum includes the step of multiplying the second Raman spectrum by at least one correction factor corresponding to the wavelength of the first Raman spectrum.

[0186] In an alternative to a specific embodiment of the computer implementation method (300) for calculating a correction factor, the method also includes the step (361) of selecting a correction factor from a database (121) by a processor, which is a function of at least an analysis medium, a predetermined reference medium, a first refractive index of the analysis medium, a second refractive index of the predetermined reference medium, and a working wavelength.

[0187] Finally, a computer implementation method (300) for calculating a correction factor includes a known step (370) of subtracting the corrected second Raman spectrum from the first Raman spectrum.

[0188] Although the invention has been described and illustrated, it is not limited to the embodiments presented. In practice, numerous variations, alternatives, embodiments, and combinations of examples are possible without making any essential changes to the invention. Those skilled in the art can derive other variations, alternatives, embodiments, and examples by referring to the description in this specification and the accompanying drawings, depending on the economic, ergonomic, and dimensional constraints to be satisfied.

[0189] The present invention may include numerous alternatives and applications in addition to those described above. In particular, unless otherwise specified, the various structural and functional features of each specific embodiment described above should not be considered as combined, closely or inseparably related to one another, but should be understood as simply juxtapositions. Furthermore, all or part of the structural and / or functional features of the various embodiments described above may be subject to different juxtapositions or different combinations.

[0190] Furthermore, when it is said in the present invention that an element is "designed" to perform a specific function, this means that the element is specially manufactured for the purpose of performing a specific function.

[0191] However, depending on the needs and available resources, this specific function can be performed by modifying or adapting existing elements without making essential changes to the invention.

Claims

Claim 1 A system (100) for calculating a correction factor for correcting a baseline of a Raman spectrum, wherein the system (100) is for correcting a Raman spectrum obtained by at least one waveguide-enhanced Raman spectroscopic device referred to as an on-chip Raman sensor (110), and the system (100) comprises: - the on-chip Raman sensor (110), which is designed to implement waveguide-enhanced Raman spectroscopic technology and is configured to obtain a first optical spectrum referred to as a first Raman spectrum comprising a plurality of discrete wavelengths representing said analysis medium in response to irradiating at least one excitation radiation onto a continuous fluid medium of a subject of study referred to as an analysis medium having at least one first refractive index; and - at least one memory (120); and - at least one processor (130), wherein, - the on-chip Raman sensor (110) is formed in a substrate defining at least one surface and - in an optical transmission material, wholly or partially on or within the substrate. The memory (120) comprises at least one optical waveguide that is positioned and configured to guide at least one light beam at at least one working wavelength, and the memory (120) is configured to store a database (121), each record being configured to associate a correction factor with an analysis medium, a predetermined reference medium, a working wavelength, a first refractive index of the analysis medium, and a second refractive index of the predetermined reference medium, and is configured to store a command (122) executable by a processor (130), said command (122) being configured to implement the following steps: a first calculation step: for each wavelength of the first Raman spectrum, a first parameter referred to as a first Raman conversion efficiency parameter representing the Raman conversion efficiency of the on-chip Raman sensor (110) in a predetermined reference medium, a second calculation step: for each wavelength of the first Raman spectrum,A step of calculating a second parameter, referred to as a second Raman conversion efficiency parameter, which represents the Raman conversion efficiency of the on-chip Raman sensor (110) in the analysis medium; and a third calculation step: for each wavelength of the first Raman spectrum, a step of calculating a correction factor corresponding to the ratio between the first Raman conversion efficiency parameter and the second Raman conversion efficiency parameter, wherein the correction factor is designed to correct a reference line of the second Raman spectrum, and each correction factor is designed to correct a reference line of the second optical spectrum referred to as the second Raman spectrum, wherein the reference line is generated by the on-chip Raman sensor (110) while the second Raman spectrum is generated in response to irradiating at least one excitation radiation onto a predetermined reference medium having at least one second refractive index different from the first refractive index, and the second Raman spectrum includes a plurality of discrete wavelengths and represents a predetermined reference medium, and, for each wavelength of the first Raman spectrum, corresponds to the ratio between the first Raman conversion efficiency parameter and the second Raman conversion efficiency parameter, and The above processor (130) is a system (100) configured to execute the above executable command (122). Claim 2 In claim 1, the executable command (122) further comprises: - a step of correcting a reference line of a second Raman spectrum based on the correction coefficient, thereby obtaining a corrected second Raman spectrum representing a reference line of the first Raman spectrum, wherein the reference line is generated by an on-chip Raman sensor (110) during the process of obtaining the first Raman spectrum, and - a step of subtracting the corrected second Raman spectrum from the first Raman spectrum, the system (100). Claim 3 In claim 1 or 2, the system (100) is manufactured in the form of an integrated semiconductor device (200), and comprises: an on-chip Raman sensor (110) integrated in the integrated semiconductor device (200); a memory (120) manufactured in the form of an integrated memory (230); and a processor (130) manufactured in the form of an integrated processor (240). Claim 4 A computer-implemented method (300) for calculating a correction factor for correcting a reference line of a Raman spectrum obtained by at least one waveguide-enhanced Raman spectroscopic device referred to as an on-chip Raman sensor (110), wherein the on-chip Raman sensor (110) is designed to implement waveguide-enhanced Raman spectroscopic technology and is configured to obtain a first optical spectrum referred to as a first Raman spectrum comprising a plurality of discrete wavelengths representing said analysis medium in response to irradiating at least one excitation radiation onto a continuous fluid medium of a subject of study referred to as an analysis medium having at least one first refractive index, said analysis medium having at least one first refractive index, said on-chip Raman sensor (110) comprises: - a substrate defining at least one surface, and - at least one optical waveguide formed within an optical transmission material and wholly or partially disposed on or within said substrate and configured to induce at least one light beam at at least one working wavelength, said method (300) comprises: - step (310): irradiating at least one excitation radiation onto a predetermined reference medium having at least one second refractive index different from the first refractive index. In response to this, a step of acquiring a second optical spectrum referred to as a second Raman spectrum by an on-chip Raman sensor (110), wherein the second Raman spectrum comprises a plurality of discrete wavelengths and represents a predetermined reference medium, and the generation of the second Raman spectrum causes the formation of a baseline of the second Raman spectrum, - a first calculation step (320): a step of calculating, by a processor, for each wavelength of the first Raman spectrum, a first parameter referred to as a first Raman conversion efficiency parameter representing the Raman conversion efficiency of the on-chip Raman sensor (110) in a predetermined reference medium, - a second calculation step (330): a step of calculating, by a processor, a second parameter referred to as a second Raman conversion efficiency parameter representing the Raman conversion efficiency of the on-chip Raman sensor (110) in an analysis medium for each wavelength of the first Raman spectrum, and - a third calculation step (340): by a processor,A computer-implemented method (300) comprising, for each wavelength of a first Raman spectrum, a step of calculating a correction factor corresponding to the ratio between the first Raman conversion efficiency parameter and the second Raman conversion efficiency parameter, wherein the correction factor is designed to correct the baseline of the second Raman spectrum. Claim 5 In paragraph 4, the first calculation step (320) and the second calculation step (330) are performed based on an optical simulation of at least one optical mode of the optical waveguide of the on-chip Raman sensor (110), in a computer-implemented method (300). Claim 6 In paragraph 4, the computer implementation method (300) wherein the third calculation step (340) includes the step of dividing the first Raman transform efficiency parameter by the second Raman transform efficiency parameter. Claim 7 A computer-implemented method (300) according to claim 4, further comprising the step (350) of storing a correction coefficient in a database (121) by a processor, wherein each record of the database (121) is configured to associate the correction coefficient with an analysis medium, a predetermined reference medium, a working wavelength, a first refractive index of the analysis medium, and a second refractive index of the predetermined reference medium. Claim 8 In paragraph 4, the computer implementation method (300) wherein the predetermined reference medium is a continuous fluid medium. Claim 9 In paragraph 4, the computer implementation method (300) wherein the predetermined reference medium is a continuous solid medium. Claim 10 In any one of claims 4 to 9, the method further comprises: a step (360) of correcting a reference line of a second Raman spectrum based on the correction coefficient by a processor, thereby obtaining a corrected second Raman spectrum representing a reference line of a first Raman spectrum, wherein the reference line is generated by an on-chip Raman sensor (110) during the process of obtaining the first Raman spectrum, and a step (370) of subtracting the corrected second Raman spectrum from the first Raman spectrum by a processor, a computer-implemented method (300). Claim 11 In claim 10, the step (360) of correcting the reference line of the second Raman spectrum includes the step of multiplying the second Raman spectrum by a correction factor corresponding to the wavelength of the first Raman spectrum, in a computer-implemented method (300). Claim 12 In claim 10, the above method further comprises the step (361) of selecting a correction factor from a database (121) by a processor, wherein the correction factor is a function of at least an analysis medium, a predetermined reference medium, a first refractive index of the analysis medium, a second refractive index of the predetermined reference medium, and a working wavelength, computer implementation method (300). Claim 13 delete

Images