Handheld probe for Raman spectroscopy system and Raman spectroscopy system

Abstract

In certain aspects, a handheld probe for a Raman spectroscopy system is provided. The handheld probe includes an excitation module configured to emit a light beam along an optical path; an optical splitter to directionally reflect the light beam along an observation axis; an objective lens module configured to receive and transmit the reflected light beam to an object so as to generate a scattered light beam by the object, and configured to receive and transmit the scattered light beam to the optical splitter; a focus lens configured to focus the refracted light beam from the optical splitter to a focus so as to generate a focused light beam; and a transmitting module disposed at the focal point and configured to receive the focused light beam, where the transmitting module and the excitation module are disposed on the same side with respect to the observation axis.

Description

Technical Field

[0001] The present disclosure generally relates to a handheld probe for a Raman spectroscopy system and a Raman spectroscopy system. Background Art

[0002] Due to their non-invasive nature and rich light-matter interactions, a variety of optical techniques have been investigated for various chemical and biomedical applications. For example, fluorescence spectroscopy is based on the absorption of photons and the subsequent emission of matter at different energy levels. Optical coherence tomography uses backscattered photons generated by different reflection patterns to obtain structural information of biological tissues. Visible / infrared spectroscopy relies on the optical absorption, transmission, or reflection of matter. Among these techniques, Raman spectroscopy, as a technique that measures the inelastic scattering of photons, has superior specificity than other optical techniques because the resulting spectral pattern is unique for different compounds. As a result, it has become a popular tool in biomedical applications such as drug design, DNA / RNA analysis, and disease diagnosis. Confocal Raman spectroscopy (CRS) provides additional spatial resolution in the micrometer range by combining confocal optics to suppress stray light and achieve deep profiling. Near-infrared lasers are often used as excitation sources to bring deeper penetration and less autofluorescence. The most commonly used spectrometers in Raman spectroscopy are silicon-based, featuring low noise, high sensitivity, and spectral resolution up to sub-nanometers. Its sensitive region covers 200-1100nm, corresponding to the fingerprint (FP) region (450 to 1750cm−1) of most organic chemicals, using 785nm excitation. In order to obtain the high wavenumber (HW) region (2800−3800cm−1) for water content analysis, some Raman spectroscopy systems adopt dual-wavelength excitation by adding a 671nm laser to broaden the spectral range. However, during the acquisition process, it is necessary to obtain FP and HW spectra separately by manually switching lasers and repeating measurements, which may lead to depth mismatch and extended acquisition time. This problem is more prominent in CRS system operation, especially in in vivo applications.

[0003] Therefore, there is a need for improved Raman spectroscopy systems. Summary of the invention

[0004] According to a first aspect of the present disclosure, a handheld probe for a Raman spectroscopy system is provided. The handheld probe may include an excitation module for emitting a light beam along an optical path that is not parallel to an observation axis; a beam splitter disposed in the optical path of the light beam emitted by the excitation module and directing the reflected light beam along the observation axis; an objective lens module disposed on the observation axis for receiving the reflected light beam and transmitting the reflected light beam to an object to be observed by the objective lens module so as to generate a scattered light beam by the object, and further for receiving the scattered light beam from the object and transmitting the scattered light beam to the beam splitter so as to generate a refracted light beam by the beam splitter; a focusing lens disposed on the observation axis for focusing the refracted light beam of the beam splitter to a focal point so as to generate a focused light beam; and a transmitting module disposed at the focal point for receiving the focused light beam from the focusing lens, wherein the transmitting module and the excitation module are disposed on the same side relative to the observation axis.

[0005] According to a second aspect of the present disclosure, a Raman spectroscopy system is provided. The Raman spectroscopy system may include: a handheld probe as described herein; and a six-axis robotic arm, wherein the handheld probe is mounted on the six-axis robotic arm, wherein the six-axis robotic arm includes a first joint arranged on a body of the Raman spectroscopy system, a second joint, a third joint arranged on the handheld probe, a first extension section movably connected to the first joint and the second joint, and a second extension section movably connected to the second joint and the third joint. BRIEF DESCRIPTION OF THE DRAWINGS

[0006] Figure 1 is a block diagram depicting a handheld probe head of an exemplary Raman spectroscopy system according to various embodiments of the present disclosure.

[0007] Figure 2 is a block diagram depicting a handheld probe head of an exemplary Raman spectroscopy system according to various embodiments of the present disclosure.

[0008] Figure 3 is a schematic diagram showing a Raman spectroscopy system with a handheld probe 300 according to various embodiments of the present disclosure.

[0009] Figure 4 is a schematic diagram showing a Raman spectroscopy system with a handheld probe 400 according to various embodiments of the present disclosure. DETAILED DESCRIPTION

[0010] The embodiments described below for the device, apparatus or system are also applicable to the corresponding methods, and vice versa. In addition, it should be understood that the embodiments described below may be combined, for example, a part of one embodiment may be combined with a part of another embodiment, and a part of one implementation may be combined with a part of another implementation.

[0011] It should be understood that the singular terms "a", "an", and "the" include plural references unless the context clearly indicates otherwise. Similarly, the term "or" shall include "and" unless the context clearly indicates otherwise.

[0012] In addition, it should be further understood that the terms "comprising" (and any form thereof, such as "comprising" and "including"), "having" (and any form thereof, such as "having" and "having"), "including" (and any form thereof, such as "including" and "including"), and "containing" (and any form thereof, such as "containing" and "containing") are open conjunctions. Therefore, a method or apparatus that "comprising", "having", "including" or "containing" one or more steps or elements possesses these one or more steps or elements, but is not limited to possessing only these one or more steps or elements. Similarly, a method step or apparatus element that "comprising", "having", "including" or "containing" one or more features possesses these one or more features, but is not limited to possessing only these one or more features. In addition, an apparatus or structure used in a specific manner is used in at least that manner, but may also be used in unlisted manners.

[0013] Approximating language, as used herein in the specification and claims, may be applied to modify any quantitative representation that may be permitted to vary without resulting in a change in the basic function to which it is related. Therefore, values ​​modified by one or more terms such as "about," "substantially," etc. are not limited to the precise values ​​specified, but are within acceptable tolerances for the application and operation of the embodiments. In some cases, approximating language may correspond to the instrumental precision of the measured values.

[0014] Various aspects described herein are intended to provide a handheld probe for a Raman spectroscopy system. The handheld probe may be based on a module design, including an excitation module, a beam splitter, an objective module, a focusing lens (e.g., an optical module with a focusing lens), and a launch module. The excitation module may be a fiber-coupled input light, which may consist of a laser beam of two wavelengths (e.g., 671nm and 785nm). A collimating lens may be used to collimate the laser beam from a single-mode optical fiber. In some embodiments, a short-pass filter may be arranged between the collimating lens and the beam splitter to allow a beam with a wavelength shorter than the cut-off transmission wavelength to pass. In other embodiments, a dual-passband laser cleaning filter (DPLCF) may be arranged between the collimating lens and the beam splitter to eliminate fluorescence or other unwanted wavelengths from the optical fiber. A beam splitter (e.g., a dichroic beam splitter) may be placed after the DPLCF to reflect the dual-wavelength beam to the objective module.

[0015] When the dual laser beams are irradiated on the object, both Rayleigh scattering and Raman scattering (e.g., two confocal Raman signals) may be collected by the objective lens module. Most (about 90%) of the Rayleigh scattering may be reflected by the beam splitter to the excitation module, while the remaining 10% will be blocked by a long-pass filter with an initial transmission wavelength (e.g., 809 nm) arranged between the beam splitter and the focusing mirror. By using a focusing mirror arranged behind the long-pass filter instead of a lens, the emitted Raman scattering may be reflected and focused into the multimode optical fiber. Advantageously, the emission module can be placed on the same side of the excitation module, which makes the probe more compact and convenient for handheld operation.

[0016] The proposed method according to various aspects may provide an advantageous design of a miniature handheld confocal Raman probe that achieves simultaneous dual-wavelength excitation through a compact wavelength synthesis multiplexer. The proposed probe may increase the signal collection efficiency by 30% and have a smaller size. By using a short-pass filter, a dichroic beam splitter, and a long-pass filter to replace the notch filter in the traditional Raman probe, it is possible to cascade two different wavelength laser beams into a multimode optical fiber. This may increase the energy collection efficiency while reducing the system size. The proposed fiber-based handheld design may increase the versatility of the probe, allowing it to be applied to different scenarios and different surfaces, such as face measurement. Dual-wavelength excitation may broaden the Raman spectral range, thereby simultaneously acquiring the fingerprint (FP) region and the high wavenumber (HW) region. The FP and HW spectra may be separated from the combined Raman spectrum, thereby reducing the sampling time by half.

[0017] The following examples relate to various aspects of the disclosure.

[0018] Example 1 is a handheld probe for a Raman spectroscopy system, comprising: an excitation module, configured to emit a light beam along an optical path, which is not parallel to an observation axis; a beam splitter, disposed in the optical path of the light beam emitted by the excitation module, and directing a reflected light beam along the observation axis; an objective lens module, arranged on the observation axis, configured to receive the reflected light beam and transmit the reflected light beam to an object to be observed by the objective lens module so that a scattered light beam is generated by the object, and further configured to receive the scattered light beam from the object and transmit the scattered light beam to the beam splitter so that a refracted light beam is generated by the beam splitter; a focusing mirror, arranged on the observation axis, configured to focus the refracted light beam of the beam splitter to a focal point so as to generate a focused light beam; and an emission module, arranged at the focal point, configured to receive the focused light beam from the focusing mirror, wherein the emission module and the excitation module are arranged on the same side relative to the observation axis.

[0019] In Example 2, the subject matter of Example 1 optionally includes a collimating lens, wherein the collimating lens is disposed between the excitation module and the beam splitter and is configured to collimate the light beam emitted by the excitation module.

[0020] In Example 3, the subject matter of Example 2 optionally includes a short-pass filter having a cutoff transmission wavelength, wherein the short-pass filter is arranged between the collimating lens and the beam splitter so that the light beam emitted by the excitation module passes through the short-pass filter before being reflected by the beam splitter.

[0021] In Example 4, the subject matter of any of Examples 1 to 3 optionally includes a long pass filter having a starting transmission wavelength, wherein the long pass filter is arranged between the beam splitter and the focusing mirror so that the light beam refracted from the beam splitter passes through the long pass filter before being focused by the focusing mirror.

[0022] In Example 5, the subject matter of any of Examples 1 to 4 optionally includes an objective lens module comprising an objective lens assembly configured to focus the reflected light beam onto the object through a beam splitter and to collimate the scattered light beam received from the object.

[0023] In Example 6, the subject matter of any of Examples 1 to 5 optionally includes the light beam emitted by the excitation module being a combination of the first laser beam and the second laser beam via a wavelength division multiplexer (WDM).

[0024] In Example 7, the subject matter of Example 6 optionally includes that the wavelength of the first laser beam is in a range of 630 nm to 690 nm, and the wavelength of the second laser beam is in a range of 750 nm to 830 nm.

[0025] In Example 8, the subject matter of any of Examples 1 to 7 optionally includes that the light beam emitted by the excitation module is a first laser beam and a second laser beam combined by a fiber optic switch, the fiber optic switch being configured to switch between the first laser beam and the second laser beam.

[0026] In Example 9, the subject matter of Example 4 optionally includes that a portion of the Rayleigh scattered portion of the scattered light beam received by the objective lens module from the object is reflected by the beam splitter, and the rest of the Rayleigh scattered portion of the scattered light beam is blocked by the long pass filter.

[0027] In Example 10, the subject matter of any of Examples 1 to 9 optionally includes a housing having a cylindrical body and a protruding end extending from the cylindrical body, wherein the beam splitter, the objective lens module, and the focusing lens are arranged within the cylindrical body of the housing.

[0028] In Example 11, the subject matter of Example 10 optionally includes a protruding end of the shell, the protruding end including an annular structure having an opening, and a supporting structure extending from opposite ends of the annular structure of the protruding end to the cylindrical body of the shell, wherein a gap exists between the annular structure and the cylindrical body of the shell so that the annular opening can be accessed through the gap.

[0029] In Example 12, the subject matter of Example 11 optionally includes that the opening of the annular structure of the protruding end is aligned with the objective lens module.

[0030] In Example 13, the subject matter of Example 11 optionally includes that the annular structure of the protruding end is configured to conform to a surface of an object.

[0031] In Example 14, the subject matter of any of Examples 10 to 13 optionally includes the housing comprising a recess disposed on an outer surface of the housing and configured to accommodate a hand or at least one finger of a user.

[0032] In Example 15, the subject matter of any of Examples 1 to 14 optionally includes that the excitation module includes a single-mode optical fiber configured to emit a light beam and arranged along an excitation axis, and wherein the emission module includes a multimode optical fiber configured to receive a focused light beam from a focusing mirror and arranged along a receiving axis.

[0033] In Example 16, the subject matter of Example 15 optionally includes the excitation axis being parallel to the receiving axis.

[0034] In Example 17, the subject matter of Example 15 optionally includes that the excitation axis and the receiving axis are perpendicular to the observation axis.

[0035] In Example 18, the subject matter of Example 5 optionally includes that the objective lens module further includes a micro-motorized platform, and the objective lens assembly is mounted on the micro-motorized platform, wherein the micro-motorized platform is configured to drive the objective lens assembly to achieve confocal measurement.

[0036] Example 19 is a Raman spectroscopy system, comprising: the handheld probe of Example 1; and a six-axis robotic arm, wherein the handheld probe is mounted on the six-axis robotic arm, wherein the six-axis robotic arm comprises a first joint arranged on the body of the Raman spectroscopy system, a second joint, a third joint arranged on the handheld probe, a first extension section movably connected to the first joint and the second joint, and a second extension section movably connected to the second joint and the third joint.

[0037] In Example 20, the subject matter of Example 19 optionally includes a spectrometer connected to the emission module, wherein the light beam emitted by the excitation module is a combination of a first laser beam and a second laser beam through a wavelength division multiplexer (WDM), and the spectrometer is configured to record a combined Raman signal measured by the Raman spectroscopy system, which combined Raman signal is a Raman signal obtained by the Raman spectroscopy system when the light beam emitted by the excitation module is a combination of the first laser beam and the second laser beam.

[0038] In the following description, example configurations and systems / devices that may employ the techniques described herein are first described. Example details and methods are then described, which may be performed in the example configurations and by the systems / devices, and may also be performed in other configurations and by other systems / devices. Therefore, implementation of the example details and methods is not limited to the example configurations and systems / devices, and the example configurations and systems / devices are not limited to the example details and methods.

[0039] Figure 1 is a block diagram depicting a handheld probe 100 of an exemplary Raman spectroscopy system according to various embodiments of the present disclosure. The working principle of Raman spectroscopy may be based on the interaction of light with chemical bonds within a material. When a high-intensity laser beam is irradiated onto the surface of a material, the molecules may scatter the incident light into two modes: Rayleigh scattering at the same wavelength as the incident light, and Raman scattering at different wavelengths depending on the chemical structure of the analyte. The Raman scattered light may have some peaks that correspond to specific molecular bond vibrations within the wavelength range of the Raman spectrum. Therefore, Raman spectroscopy may determine the chemical structure of the material and provide useful information, including the nature of the chemical composition, intrinsic stress / strain, phase and polymorphism, as well as contamination and impurities.

[0040] According to various non-limiting embodiments, the handheld probe 100 may include an excitation module 102, a beam splitter 104, an objective lens module 106, a focusing lens 108, and an emission module 110. The beam splitter 104 and the focusing lens 108 may be combined into an optical module. The excitation module 102 may be configured to emit a light beam along an optical path that is not parallel to the observation axis 101. The excitation module 102 may include a single-mode optical fiber. The excitation module 102 may be further configured to emit a dual-wavelength laser beam. For example, the light beam emitted by the excitation module may be a combination of a first laser beam and a second laser beam through a wavelength division multiplexer (WDM). In another example, the light beam emitted by the excitation module may optionally be a combination of a first laser beam and a second laser beam through a fiber switch, and the fiber switch is configured to switch between the first laser beam and the second laser beam. Dual-wavelength excitation may broaden the Raman spectral range, thereby making it possible to simultaneously / quasi-simultaneously acquire the fingerprint (FP) region and the high wave number (HW) region. For example, the excitation module 102 may include a fiber-coupled input light, which consists of two laser beams of wavelengths (e.g., 671 nm and 785 nm). In various embodiments, the wavelength of the first laser beam may be in the range of 630 nm to 690 nm (e.g., 671 nm), and the wavelength of the second laser beam may be in the range of 750 nm to 830 nm (e.g., 785 nm). The difference between the two wavelengths may be in the range of 60 nm to 200 nm, preferably, in the range of 90 nm to 140 nm.

[0041] According to various non-limiting embodiments, the beam splitter 104 may be disposed in the optical path of the light beam emitted by the excitation module 102 and oriented to reflect the light beam along the observation axis 101. A beam splitter (or beamsplitter) is an optical element used to split light into two separate light beams, usually separated by wavelength or polarity. The beam splitter 104 may be configured to reflect the short wavelength light beam to the objective lens module 106. In various embodiments, the beam splitter 104 may include a dichroic beam splitter (or dichroic mirror). The dichroic beam splitter may transmit selected wavelengths while reflecting other wavelengths. It should be understood that the beam splitter 130 may include a plate beam splitter or a cubic beam splitter in configuration and may include a polarizing beam splitter or a non-polarizing beam splitter in function.

[0042] According to various non-limiting embodiments, the objective lens module 106 may be arranged along the observation axis 101 and configured to receive the reflected light beam from the beam splitter 104 and transmit the reflected light beam to an object (not shown) to be observed by the objective lens module 106 so as to generate a scattered light beam by the object. The objective lens module 106 may be further configured to receive the scattered light beam from the object and transmit the scattered light beam to the beam splitter 104 so as to generate a refracted light beam through the beam splitter 104. The light beam scattered from the object may include a Rayleigh scattered light beam and a Raman scattered light beam. Most (e.g., about 90%) of the Rayleigh scattered light beam may be reflected by the beam splitter 104 to the excitation module 102, while the remaining few (e.g., 10%) of the Rayleigh scattered light beam may be transmitted by the beam splitter 104 to the focusing lens 108. In other words, a portion of the Rayleigh scattered portion of the scattered light beam received by the objective lens module 106 from the object, such as about 90%, may be reflected by the beam splitter 104, and the remaining portion of the Rayleigh scattered portion of the scattered light beam, such as about 10%, may be transmitted by the beam splitter 104.

[0043] According to various non-limiting embodiments, the objective lens module 106 may include an objective lens assembly (e.g., see Figure 2 ), configured to focus the reflected light beam onto the object via a beam splitter 104 and to collimate the scattered light beam received from the object. The objective lens assembly may have a high magnification and numerical aperture (NA) for depth profiling. The objective lens module 106 may be equipped with a (high precision) micro linear motor that drives the objective lens assembly to achieve confocal measurements at various depths (e.g., movement along the observation axis 101). Advantageously, the synchronization of data collection and depth profiling may be automatically performed by a computing device.

[0044] According to various non-limiting embodiments, the focusing mirror 108 may be arranged in the observation axis 101 and configured to focus the refracted light beam from the beam splitter 104 to a focal point so as to produce a focused light beam. This may mean that the focusing mirror 108 may adjust the transmission direction of the light beam refracted from the beam splitter 104 by a specific angle (e.g., 45° or 90°). The focusing mirror 108 may adjust the transmission direction of the refracted light beam from the beam splitter 104 by reflecting the refracted light beam from the beam splitter 104 at a specific angle.

[0045] According to various non-limiting embodiments, the transmitting module 110 may be arranged at the focal point and configured to receive the focused light beam from the focusing lens 108. In various embodiments, the multimode optical fiber connected to the near infrared (NIR) spectrometer (i.e., the transmitting module) may be arranged at the focal point, so that the focusing lens 108 may be configured to focus the refracted light beam from the beam splitter 104 on the multimode optical fiber to the near infrared (NIR) spectrometer. The transmitting module 110 may be arranged on the same side of the observation axis 101 as the excitation module 102. Advantageously, the transmitting module 110 can be placed on the same side of the excitation module 102, which makes the handheld probe 100 more compact and convenient for handheld operation.

[0046] Figure 2 is a block diagram depicting a handheld probe 200 of an exemplary Raman spectroscopy system according to various embodiments of the present disclosure. The handheld probe 200 may include features of the handheld probe 100. In other words, the handheld probe 200 may include an excitation module 102, a beam splitter 104, an objective lens module 106, a focusing lens 108, and a transmitting module 110. The features described for the handheld probe 100 may be correspondingly applicable to the same or similar features in the handheld probe 200, and vice versa. In addition, the additional features and / or combinations and / or alternatives described for the features in the handheld probe 100 may be correspondingly applicable to the same or similar features in the handheld probe 200, and vice versa.

[0047] According to various non-limiting embodiments, the handheld probe 100 may further include a collimating lens 210. The collimating lens 210 may be disposed between the excitation module 102 and the beam splitter 104 and configured to collimate the light beam emitted by the excitation module 102.

[0048] According to various non-limiting embodiments, the handheld probe 200 may further include a short-pass filter 212 having a cut-off transmission wavelength. The short-pass filter 212 may be arranged between the collimating lens 210 and the beam splitter 104, so that the light beam emitted by the excitation module 102 passes through the short-pass filter before being reflected by the beam splitter 104. In other words, the wavelength of the light beam emitted by the excitation module 102 is longer than the cut-off transmission wavelength of the short-pass filter 212, and the short-pass filter 212 may not transmit the light beam.

[0049] According to various non-limiting embodiments, the handheld probe 200 may include a long pass filter 214 having a start transmission wavelength. The long pass filter 214 may be disposed between the beam splitter 104 and the focusing lens 108 such that the light beam refracted from the beam splitter 104 passes through the long pass filter 214 before being focused by the focusing lens 108. In other words, the refracted light beam from the beam splitter 104 having a wavelength shorter than the cut-off transmission wavelength of the long pass filter 214 may not be transmitted by the long pass filter 214. This may mean that a portion of the Rayleigh scattered portion of the scattered light beam received by the objective lens module 106 from the object, for example, about 90%, may be reflected by the beam splitter 104, and the remaining portion of the Rayleigh scattered portion of the scattered light beam, for example, about 10%, may be transmitted by the beam splitter 104 and blocked by the long pass filter 214.

[0050] According to various non-limiting embodiments, the excitation module 102 may include a single-mode optical fiber configured to emit a light beam and arranged along an excitation axis 201. The transmitting module 110 may include a multimode optical fiber configured to receive a focused light beam from the focusing lens 108 and arranged along a receiving axis 203. The excitation axis 201 may be parallel to the receiving axis 110. The excitation axis 201 and the receiving axis 203 may be perpendicular to the observation axis. Advantageously, the transmitting module 110 can be placed on the same side of the excitation module 102, which makes the handheld probe 200 more compact and convenient for handheld operation.

[0051] According to various non-limiting embodiments, the objective lens module 106 may further include a micro-motorized stage, and the objective lens assembly may be mounted on the micro-motorized stage, wherein the micro-motorized stage is configured to drive the objective lens assembly to achieve confocal measurement.

[0052] According to various non-limiting embodiments, an exemplary assembly method of the handheld probe 200 is as described herein. The objective lens module 106 may first be assembled with an optical module including a beam splitter 104 and a focusing lens 108, and then the excitation module 102 may be installed on a five-axis alignment system, which can drive the excitation module 102 to move on the X, Y, and Z axes, rotate in the horizontal plane, and tilt in the vertical plane. The assembler may place an optical profiler after the objective lens and observe the shape and uniformity of the spot to adjust the position of the excitation module 102. When the excitation module 102 is in the correct position, it may be fixed by epoxy. After the excitation module 102 is fixed in the correct position, the emission module 110 may be aligned with the excitation module 102 by the same method. The emission module 110 may be installed on the FAAS and connected to the optical power meter. When the optical power meter obtains the maximum reading, the position of the emission module 110 may be locked and then may be fixed by epoxy.

[0053] Figure 3FIG. 1 is a schematic diagram illustrating a Raman spectroscopy system 30 having a handheld probe 300 according to various embodiments of the present disclosure. The handheld probe 300 may include features of the handheld probes 100 and 200 described herein, with reference to FIG. Figure 1 and 2 In other words, the handheld probe 300 may include an excitation module 302 (such as an excitation optical fiber), a beam splitter (not shown), an objective lens module 306 (such as an objective lens), a focusing lens (not shown), and a transmitting module 310 (such as a transmitting optical fiber). The features described for the handheld probes 100 and 200 may be correspondingly applicable to the same or similar features in the handheld probe 300, and vice versa. In addition, the additions and / or combinations and / or alternatives described for the features in the handheld probes 100 and 200 may be correspondingly applicable to the same or similar features in the handheld probe 300, and vice versa.

[0054] According to various non-limiting embodiments, the Raman spectroscopy system 30 may further include a spectrometer 31 (e.g., a near infrared (NIR) spectrometer), a wavelength division multiplexer (WDM) 35 configured to combine a first laser beam 32 (e.g., having a wavelength of 671 nm) and a second laser beam 34 (e.g., having a wavelength of 785 nm), and a computing device 36. In some embodiments, two continuous wave (CW) lasers with wavelengths of 671 and 785 nm may be simultaneously emitted through a 0.39NA single mode fiber (SMF) and combined into an excitation single mode fiber 302 through a 2-in-1 WDM (NR75A1, Thorlabs) with high transmission efficiency (greater than 90%). The output powers of the 671 nm and 785 nm lasers may be 5 mW and 20 mW, respectively. In some embodiments, a microscope objective (NIR Apo 60×1.0 W, Nikon) may be mounted on a micro linear motor 307 to achieve confocal measurement. The movement step of the motor 307 may be controlled by a computing device 36 (e.g., a laptop computer), and the position of the objective lens 306 may be automatically calibrated before each measurement to ensure the accuracy of the confocal depth. In some embodiments, the transmitting fiber 310 may be connected to a near-infrared spectrometer (Kymera193i) with a back-illuminated CCD camera (iDus416, Andor Technology). The spectral data may be acquired by the computing device 36 for further processing.

[0055] Advantageously, the transmitting module 310 can be placed on the same side of the excitation module 302 , which makes the handheld probe 300 more compact and convenient for handheld operation.

[0056] Figure 4FIG. 4 is a schematic diagram illustrating a Raman spectroscopy system 40 having a handheld probe 400 according to various embodiments of the present disclosure. The handheld probe 400 may include features of the handheld probes 100, 200, and 300 described herein, with reference to FIG. Figure 1 , 2 and 3. In other words, the handheld probe 400 may include an excitation module (not shown), a beam splitter (not shown), an objective lens module (not shown), a focusing lens (not shown), and a transmitting module (not shown). The features described for the handheld probes 100, 200, and 300 may be correspondingly applicable to the same or similar features in the handheld probe 400, and vice versa. In addition, the additions and / or combinations and / or alternatives described for the features of the handheld probes 100, 200, and 300 may be correspondingly applicable to the same or similar features in the handheld probe 400, and vice versa.

[0057] According to various non-limiting embodiments, the handheld probe 400 may further include a housing 420 having a cylindrical body 422 and a protruding end shui extending from the cylindrical body 422. A beam splitter, an objective lens module, and a focusing lens may be arranged in the cylindrical body of the housing 420. The protruding end 424 of the housing 422 may include an annular structure with an opening, and a support structure extending from opposite ends of the annular structure of the protruding end 424 to the cylindrical body 422 of the housing 420. There may be a gap between the annular structure and the cylindrical body 422 of the housing 420, so that the annular opening can be contacted through the gap. The annular structure of the protruding end 424 may be configured to fit on the surface of an object. In some embodiments, the annular structure opening of the protruding end 422 may be aligned with the objective lens module. In some embodiments, the housing 420 may include a groove 426, which is arranged on the outer surface of the housing 420 and is configured to accommodate a user's hand or at least one finger.

[0058] According to various non-limiting embodiments, the handheld probe 400 may be mounted on a six-axis robotic arm 47, which is connected to a portable base 43, and the remaining components of the system may be housed by the portable base 43. The arm 47 and base 43 may allow the probe 400 to be placed in any position and angle, so that depth profile data can be obtained from any part of the body. This also minimizes movement during the measurement process.

[0059] According to various non-limiting embodiments, the objective lens module of the handheld probe 400 may include an objective lens with high magnification and numerical aperture (NA), and in particular, a water immersion objective lens may be used to increase the throughput of the system.

[0060] According to various non-limiting embodiments, the six-axis robotic arm 47 may include three joints. The three joints of the robotic arm 47 may be unlocked, and the protruding end 424 of the probe 400 may be placed on the surface of the object to be measured (for example, on the protruding reservoir of the skin adhesive of the object to be measured). This configuration may allow the user to easily place the probe 400 in the desired position without any effort. Once completed, the three joints of the robotic arm 47 may be locked. The objective lens assembly may then be moved to a position closer to the reservoir so as to maintain the surface tension of the water. The water may then be injected into the opening 424 of the probe 400 by a syringe and needle. This configuration and workflow may make the probe 400 extremely stable and sturdy, resulting in a fast, high-quality imaging and data acquisition process.

[0061] Although this specification contains many details, these should not be construed as limitations on the scope of possible claims, but rather as descriptions of features of specific examples. Certain specific features described in this specification or shown in the drawings may also be combined with respect to a single embodiment. Conversely, various features described or shown in a single embodiment may also be implemented separately or in any suitable sub-combination with respect to multiple embodiments.

[0062] Likewise, although the operations are depicted in a particular order in the figures, this should not be understood as requiring that the operations be performed in the particular order shown or in sequence, or that all of the operations shown be performed to achieve the desired result. In certain circumstances, multitasking and parallel processing may be advantageous. In addition, the separation of various system components in the above-described embodiments should not be understood as requiring such separation in all embodiments, and it should be understood that the described program components and systems can generally be integrated into a single product or packaged into multiple products.

[0063] A few implementations have been described. However, it will be appreciated that various modifications may be made. Accordingly, other implementations are within the scope of the following claims.

Claims

1. A handheld probe for a Raman spectroscopy system, comprising: an excitation module configured to emit a light beam along an optical path, the optical path being non-parallel to an observation axis; A beam splitter, disposed in the optical path of the light beam emitted by the excitation module and directed to reflect the light beam along the observation axis; an objective lens module arranged along the observation axis and configured to receive the reflected light beam and transmit the reflected light beam to an object observed by the objective lens module so as to cause the object to generate a scattered light beam, and further configured to receive the scattered light beam from the object and transmit the scattered light beam to the beam splitter so as to cause the beam splitter to generate a refracted light beam; a focusing mirror disposed on the observation axis and configured to focus the refracted light beam from the beam splitter to a focal point so as to produce a focused light beam; and A transmitting module is arranged at the focal point and configured to receive the focused light beam from the focusing mirror, wherein the transmitting module and the excitation module are arranged on the same side relative to the observation axis.

2. The handheld probe according to claim 1, further comprising: Collimating lens, in, The collimating lens is arranged between the excitation module and the beam splitter, and is configured to collimate the light beam emitted by the excitation module.

3. The handheld probe according to claim 2, further comprising: A short-pass filter with a cut-off transmission wavelength, in, The short-pass filter is arranged between the collimating lens and the beam splitter, so that the light beam emitted by the excitation module passes through the short-pass filter before being reflected by the beam splitter.

4. The handheld probe according to any one of claims 1 to 3, further comprising: Long pass filter with a starting transmission wavelength, in, The long pass filter is arranged between the beam splitter and the focusing mirror, so that the refracted light beam from the beam splitter passes through the long pass filter before being focused by the focusing mirror.

5. The handheld probe according to any one of claims 1 to 4, wherein: The objective lens module includes an objective lens assembly configured to focus the light beam reflected by the beam splitter onto the object and collimate the scattered light beam received from the object.

6. The handheld probe according to any one of claims 1 to 5, wherein: The light beam emitted by the excitation module is a combination of a first laser beam and a second laser beam through a wavelength division multiplexer (WDM).

7. The handheld probe according to claim 6, wherein: The wavelength of the first laser beam is in the range of 630 mm to 690 mm, and the wavelength of the second laser beam is in the range of 750 mm to 830 mm.

8. The handheld probe according to any one of claims 1 to 7, wherein: The light beam emitted by the excitation module is a combination of a first laser beam and a second laser beam passed through a fiber optic switch, and the fiber optic switch is configured to switch between the first laser beam and the second laser beam.

9. The handheld probe according to claim 4, wherein: A portion of the Rayleigh scattered portion of the scattered light beam received by the objective lens module from the object is reflected by the beam splitter, and the remaining portion of the Rayleigh scattered portion of the scattered light beam is blocked by the long pass filter.

10. The handheld probe according to any one of claims 1 to 9, further comprising: a housing having a cylindrical body and a protruding end extending from the cylindrical body, in, The beam splitter, the objective lens module and the focusing lens are arranged within the cylindrical body of the housing.

11. The handheld probe according to claim 10, in, The protruding end of the housing includes an annular structure having an opening, and a support structure extending from opposite ends of the annular structure of the protruding end to the cylindrical body of the housing, There is a gap between the annular structure and the cylindrical body of the housing, so that the annular opening is contacted through the gap.

12. The handheld probe according to claim 11, wherein: The opening of the annular structure of the protruding end is aligned with the objective lens module.

13. The handheld probe according to claim 11, wherein: The annular structure of the protruding end is configured to fit onto a surface of the object.

14. The handheld probe according to any one of claims 10 to 13, wherein: The housing includes a recess disposed on an outer surface of the housing and configured to accommodate a hand or at least one finger of a user.

15. The handheld probe according to any one of claims 1 to 14, wherein: The excitation module includes a single-mode optical fiber, which is configured to emit the light beam and is arranged along an excitation axis; and wherein the emission module includes a multi-mode optical fiber, which is used to receive the focused light beam from the focusing mirror and is arranged along a receiving axis.

16. The handheld probe according to claim 15, wherein: The excitation axis is parallel to the receiving axis.

17. The handheld probe according to claim 15, wherein: The excitation axis and the receiving axis are perpendicular to the observation axis.

18. The handheld probe according to claim 5, wherein: The objective lens module further comprises a micro-electric platform, the objective lens assembly is mounted on the micro-electric platform, and the micro-electric platform is configured to drive the objective lens assembly to achieve confocal measurement.

19. A Raman spectroscopy system comprising: The handheld probe as claimed in claim 1; and Six-axis robotic arm, in, The handheld probe is mounted on the six-axis robotic arm. The six-axis robotic arm includes a first joint and a second joint arranged on the main body of the Raman spectroscopy system, a third joint arranged on the handheld probe, a first extension section movably connected to the first joint and the second joint, and a second extension section movably connected to the second joint and the third joint.

20. The Raman spectroscopy system of claim 19, further comprising: a spectrometer connected to the emission module, in, The light beam emitted by the excitation module is a combination of a first laser beam and a second laser beam through a wavelength division multiplexer (WDM), and The spectrometer is configured to record a combined Raman signal measured by the Raman spectroscopy system, wherein the combined Raman signal is a Raman signal obtained by the Raman spectroscopy system when the light beam emitted by the excitation module is a combination of the first laser beam and the second laser beam.

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