Cars light source and measurement system

Abstract

To provide a light source for generating Stokes light, pump light, and probe light to be output for acquiring a CARS signal.SOLUTION: A light source includes: an oscillator 41a for generating a source laser pulse; a first fiber laser source module for outputting a first laser beam; a second fiber laser light source module for outputting a second laser beam; a first optical module for generating pump light from the first laser beam supplied from the first fiber laser light source module via a first compressor, and generating Stokes light in a first wavelength region from a part of the pump light via a photonic crystal fiber; and a second optical module for generating the probe light in a wavelength region shorter than a second wavelength region via a second harmonic generator, from a second laser beam supplied from the second fiber laser light source module via a second compressor.SELECTED DRAWING: Figure 6

Description

[Technical field]

[0001] The present invention relates to an emission source generating Stokes light, pump light and probe light for obtaining a CARS signal, and a system for measuring an object. [Background technology]

[0002] Patent Document 1 discloses a microscope. The microscope includes a first light splitting unit that splits a light beam from a light source into a first pump light beam and a second pump light beam, a Stokes light source that receives the second pump light beam as an input and outputs a Stokes light beam, a combining unit that combines the first pump light beam and the Stokes light beam to generate a combined light beam, a first focusing unit that focuses the combined light beam on a sample, a first detection device that detects the generated CARS light having a wavelength different from that of the combined light beam from the sample, a second light splitting unit that partially splits at least one of the second pump light beam and the Stokes light beam as a reference light beam, a second combining unit that combines the light beam from the sample and the reference light beam to generate interference light, and a second detection device that detects the interference light. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] International Publication No. WO2014 / 061147 Summary of the Invention [Problem to be solved by the invention]

[0004] A system is provided that has an emission source that generates Stokes light in a first wavelength region that is output to acquire a CARS signal, pump light in a second wavelength region that is shorter than the first wavelength region, and probe light in a wavelength region that is shorter than the second wavelength region.

[0005] An emission source according to one embodiment of the present invention includes an oscillator that generates a source laser pulse of a predetermined oscillation wavelength from light injected from a source laser diode, a first fiber laser light source module that generates a first laser light in a second wavelength region from a portion of the source laser pulse via a highly nonlinear fiber and outputs the amplified first laser light, a second fiber laser light source module that outputs a second laser light obtained by amplifying a portion of the source laser pulse, a first optical module that generates pump light from the first laser light supplied from the first fiber laser light source module via a first compressor, and generates Stokes light in the first wavelength region from a portion of the pump light via a photonic crystal fiber, and a second optical module that generates the probe light in a wavelength region shorter than the second wavelength region from the second laser supplied from the second fiber laser light source module via a second compressor via a second harmonic generator.

[0006] Another aspect of the present invention is a system having a core optical module including the above-mentioned light emission source, and an inspection interface module that outputs Stokes light, pump light, and probe light to an object and acquires CARS light generated in the object by the Stokes light, pump light, and probe light. The inspection interface module may be changeable for each application, and may be connected to the core optical module by an optical transmission unit, and configured to scan the object with light sent from the core optical module, receive light from the object, and send it to the core optical module. [Means for solving the problem]

[0007] In the system of the present invention, the core optical module can be shared by many types of test interface modules, and a system corresponding to many applications can be provided in a short time and at low cost. The test interface module may be a minimally invasive sampler, a non-invasive sampler, or a flow sampler. The test interface module may be a wearable test interface, a fingertip test interface, a urine sampler, or a dialysis effluent sampler for measuring glucose, hemoglobin A1c, creatinine, albumin, etc. [Brief description of the drawings]

[0008] In the following, the embodiments will be referred to in the drawings, which will be better understood from the following detailed description. [Figure 1] FIG. 1 illustrates one embodiment of the present invention. [Diagram 2] FIG. 2 illustrates several embodiments of a test interface module. [Diagram 3] FIG. 3 shows another embodiment of the system. [Figure 4] FIG. 4 shows the arrangement of the optical plates and fiber features of the core optical module. [Diagram 5] FIG. 5 shows a block diagram of the system. [Figure 6] FIG. 6 shows a block diagram of the fiber laser assembly. [Figure 7] FIG. 7 shows the wavelength plan of the fiber laser assembly. [Figure 8] FIG. 8 shows the wavelength plan of TD-CARS. [Figure 9] FIG. 9 shows the delay stage. [Figure 10] FIG. 10 shows a block diagram of the temperature control module. [Figure 11]FIG. 11 shows the conceptual configuration of the optical system of this system. [Figure 12] FIG. 12 shows an example of the arrangement of the optical plates. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0009] In the following, details of the embodiments and various features and advantages thereof will be more fully described with reference to the non-limiting embodiments illustrated in the accompanying drawings and described in detail in the following description. Descriptions of well-known components and processing techniques will be omitted so as not to unnecessarily obscure the embodiments herein. The examples used below are intended only to facilitate understanding that the embodiments below may be implemented, and to enable those skilled in the art to implement the embodiments below. Therefore, these examples should not be interpreted as limiting the scope of the present invention.

[0010] FIG. 1 shows a system 1 according to one embodiment of the present invention. FIG. 1 shows a core optical module (core module, main body) 10 and multiple types of inspection interface modules (scan interface modules) 11, 12, and 13 for constituting the measurement system 1. In a certain application, the system 1 for measuring the state, composition, etc. of an object (measurement target, object) is configured by connecting the core optical module 10 and any type of scan modules 11 to 13 by an optical transmission unit 15. The optical transmission unit 15 may be an optical fiber 15a or a spatial coupling connector (free space coupling connector) 15b. By using the spatial coupling connector 15b, the inspection interface module of the type selected from the modules 11 to 13 can be stacked (stacked) on the core optical module 10. By using the optical fiber 15a, the measurement system 1 can be freely arranged, such as stacking the inspection interface module of the type selected from the modules 11 to 13 with the core optical module 10, side by side, or maintaining a distance between them.

[0011] One of the systems of the embodiment is a measurement system 1 including a core optical module 10 and a fingertip type inspection interface module (fingertip type scan interface) 11 connected to the core optical module 10 by an optical fiber 15a. As shown in FIG. 2(a), the fingertip type inspection interface module 11 includes an interface 18 for inserting a fingertip 19 as an object, and a button 18a for applying pressure to the fingertip to limit the movement at the scanning end. The core optical module 10 is configured to generate light 58 that generates a signal for analyzing the object 19 via the inspection interface module 11, and detect light 59 including a signal from the object 19 via the inspection interface module 11. The inspection interface module 11 can be changed according to each application, and is connected to the core optical module 10 by an optical transmission unit 15, and configured to scan the object (sample, target) 19 with the light 58 transmitted from the core optical module 10, receive the light 59 from the object 19, and transmit it to the core optical module 10.

[0012] 1 shows three different types of test interface modules 11, 12, and 13. Each test interface module 11, 12, and 13 is separate from the core optical module 10, but is connected to the core optical module 10 via an optical transmission unit 15, such as an optical fiber 15a. The type of test interface module can be changed or selected for different applications, such as invasive applications, non-invasive applications, and fluid measurement applications. The basic configuration of all types of test interface modules, including modules 12 and 13, is common to that of test interface module 11.

[0013] The fingertip test interface module 11 is an example of a non-invasive sampler. FIG. 2(b) shows another type of non-invasive sampler, module 11a. Module 11a includes a computer mouse-like dome 18b for ergonomically positioning the palm to obtain internal information of the living body through the palm using light from the core optical module 10. A blood glucose (blood glucose) monitoring system 1 may be provided by the core optical module 10 and the non-invasive sampler 11.

[0014] The test interface module 12 is an example of a minimally invasive sampler (minimally invasive sample collection device) and may include a micro-sampling tool such as a minimally invasive microneedle or microarray that does not cause a subject to feel pain when inserted to sample a body fluid such as subcutaneous tissue fluid. The minimally invasive micro-sampling tool is useful for sensing biological information by measuring the concentration of components in the body fluid and for transdermal administration of medicine. The medical monitoring system 1 may be provided by the core optical module 10 and the minimally invasive sampler 12.

[0015] The test interface module 13 is an example of a flow sampler and may include a flow path 13a through which a target fluid flows. The target fluid may be urine, dialysis drainage, blood, water, a solution, etc. A health care and / or monitoring system 1 may be provided by the core optical module 10 and a flow sampler 13, such as a urine sampler. A dialysis monitoring system 1 may be provided by the core optical module 10 and a flow sampler 13, such as a dialysis drainage sampler.

[0016] FIG. 3 shows a system according to a different embodiment of the present invention. The system 1 includes a wearable inspection interface 14, a portable core optical module 10, and an optical fiber 15a connecting the wearable inspection interface 14 and the portable core optical module 10. The wearable inspection interface 14 may be a wristwatch-type device, or may be a device integrated with a communication device such as a smart watch. In the wearable inspection interface 14, optical elements and / or optical paths for guiding and / or generating light for scanning an object may be provided as or integrated into a chip-type optical device having a size on the order of millimeters or less. The portable core optical module 10 may be the size of a mobile phone and may be integrated into a mobile phone or a smartphone. The portable core optical module 10 may include at least a laser light source device, a detector (spectrometer), a battery, etc., and other optical elements may be included in a chip-type optical device mounted on the wearable interface 14. The wearable test interface 14 may be paired with a glasses-type device such as smart glasses, a pendant-type device, an attachment-type device, or the like. The portable core optical module 10 may be common to each type of changeable test interface. The wearable test interface 14 may include a display 14a for outputting measurements and / or other information from the system 1. The portable core module 10 may include a display 10a for displaying measurements and / or monitoring results from the system 1, and / or other information.

[0017] As shown in FIG. 1, the core optical module 10 includes an optical bench (optical stand) 20, an optical plate 21 on the upper side, and a fiber laser enclosure (fiber laser mechanism, fiber laser housing) 22 on the lower side. A plurality of optical elements are mounted on the optical plate 21 to form one or more optical paths for generating light 58. The fiber laser enclosure 22 is configured to accommodate at least one fiber laser for generating one or more lasers and supplying them to the optical plate 21. The core optical module 10 includes a stacked structure 20 in which the optical plate 21 and the fiber laser enclosure 22 are stacked. The core optical module 10 may have a multi-layer structure including a power supply board and an electric control board in addition to the optical bench 20. The control board may include a communication function, a system control function, a user interface function, and a power supply function for the electric module and the laser module.

[0018] One example of light 58 that generates a signal to analyze an object 19 is the combination of Raman spectroscopy (RS) and optical coherence tomography (OCT). Both optical imaging and spectroscopy have been applied to invasive and non-invasive characterization of objects. Imaging techniques such as OCT excel at conveying images of the target's microstructure, while spectroscopic techniques such as CARS (Coherent-Anti Stokes Raman Scattering) can probe the molecular composition of the object with great precision.

[0019] OCT is a method to obtain shape information that reflects changes in the refractive index by utilizing the interference between reflected light from an object (target) and a reference light that is not irradiated on the object. CARS is based on the nonlinear optical phenomenon, and when two light beams with different wavelengths are projected onto the object, CARS light with a wavelength corresponding to the vibration of the molecules that make up the object is obtained. Several different methods can be adopted for the detection direction of the CARS light relative to the projection direction of the pump light and Stokes light, such as transmission CARS and reflection CARS.

[0020] Time-resolved coherent anti-Stokes Raman scattering, or time-delayed coherent anti-Stokes Raman scattering (TD-CARS) microscopy, is also known as a technique that utilizes the different time responses of virtual electronic transitions and Raman transitions to suppress non-resonant background. Systems that can easily apply such measurement methods to a variety of applications are needed.

[0021] The fingertip inspection interface (fingertip scan interface) 11 may, for example, scan the skin of a finger 19 inserted into the interface 18 using light 58 generated in the core optical module 10 and supplied via the optical transmission unit 15, generate a TD-CARS signal and an OCT signal, and transmit light 59 including the TD-CARS and OCT signals (light) to the core optical module 10 through the optical transmission unit 15. The fingertip inspection interface 11 may be connected to the core module 10 by wire or wirelessly, and may communicate with the core module 10 or with the cloud via the core module 10.

[0022] 4(a) is a diagram showing the arrangement (configuration) of the optical plate 21, and FIG. 4(b) is a diagram showing the arrangement (configuration) of the fiber laser enclosure 22. On the optical plate 21, a mirror, a prism, a dichroic mirror, and other multiple optical elements 30 for configuring an optical path described below are mounted. The optical plate 21 may include a detector 24 for detecting a signal contained in the light 59 returned from the inspection interface module 11, and a control box 25 in which multiple modules are housed. On the fiber laser enclosure 22, a fiber laser assembly 40 and a probe delay stage 29 are mounted.

[0023] FIG. 5 shows a block diagram of the system 1. The inspection interface module 11 includes a fingertip scanning window 11x and an autofocus objective lens 11y, and may irradiate (radiate) light 58 from the core optical module 10 to an object and receive light 59 from the object and transmit it to the core optical module 10. The core optical module 10 may include an optical head module 26 and an optical base module 27. The optical head module 26 may be included in the inspection interface module 11, and the connection 16 between the optical head module 26 and the optical base module 27 may be an optical transmission unit. The optical base module 27 includes an emission (excitation) source module 28, a detector 24, a temperature control module 70, and control modules 25a to 25e. The control modules 25a to 25e are housed in a control box 25. The emission source module 28 includes a fiber laser assembly 40 and a plurality of optical paths that provide light for generating TD-CARS and OCT signals. The fiber laser assembly 40 includes a femtosecond fiber laser source module 41 for the Stokes light 51, the pump light 52, and the OCT light 53, a picosecond laser source module 42 for the probe light 54, and a temperature and power conditioning module 43 for controlling the power supply to the laser modules 41 and 42.

[0024] On the optical plate 21 of the optical bench 20, a light path 31 for supplying Stokes light 51 having a first wavelength region R1, a light path 32 for supplying pump light 52 having a second wavelength region R2 shorter than the first wavelength region R1, a light path 34 for supplying probe light 54 having a wavelength region R4, a light path 39 for coaxially outputting the Stokes light 51, the pump light 52, and the probe light 54 to the optical transmission unit 15, and a light path 35 for acquiring TD-CARS light 55 generated (created) in the object by the Stokes light 51, the pump light 52, and the probe light 54 from the optical transmission unit 15, using a plurality of optical elements 30 including mirrors, switching elements, reflectors, prisms, lenses, filters such as short wavelength pass filters (SP), and long wavelength pass filters (LP), and other elements. The TD-CARS light 55 has a wavelength region R5 shorter than the wavelength region of the CARS light generated only by the Stokes light 51 and the pump light 52. The optical path 34 includes an actuator-equipped probe delay stage 29 for controlling the emission of the probe light 54 in a time difference with respect to the emission of the pump light 52 .

[0025] On the optical plate 21, an optical path 33 for supplying OCT light 53 having a third wavelength region R3 shorter than the second wavelength region R2 and at least partially overlapping with the wavelength region R5 of the TD-CARS light 55 using a plurality of optical elements 30, an optical path 36 for acquiring the reflected OCT light 62 from the optical transmission unit 15, and an OCT engine 60 are provided. The path 36 includes a dichroic mirror 68 for outputting the OCT light 53 from the OCT engine 60 and receiving or returning the reflected light 62 to the OCT engine 60. The OCT engine 60 is configured to separate the reference light 61 from the OCT light 53 and generate an interference light 63 by the reference light 61 and the reflected OCT light 62 obtained from the object via the optical transmission unit 15. The optical path 39 outputs the OCT light 53 coaxially to the optical transmission unit 15 together with the Stokes light 51, the pump light 52, and the probe light 54. The optical path 39 may include a beam conditioning (adjustment) unit 39c, a beam alignment (position control) unit 39a, a beam steering (direction control) unit 39b, and a dichroic mirror device 39d. The dichroic mirror 39d combines the light 51, 52, 54 for generating the TD-CARS 55 with the OCT light 53 to generate light 58, and separates the return light 59 including the TD-CARS light 55 and the reflected light 62. Instead of or together with a plurality of optical elements, the optical paths may use a chip-type optical device, or may be provided using a chip-type optical device having the optical paths built therein. All or a part of the optical paths may be provided in an inspection module (scanning module) such as the wearable model 14, instead of being provided in the core optical module.

[0026] The core optical module 10 further includes a detector 24 for detecting the TD-CARS light 55 and the OCT interference light 63. The detector 24 includes a detection wavelength range at least partially shared by the TD-CARS light 55 and the interference light 63. The core optical module 10 further includes an analyzer 25a for acquiring and analyzing data from the detector 24. The analyzer 25a may include a high-speed data acquisition module 25b and a system control and communication interface module 25c. The communication interface module 25c may communicate with the laser assembly 40, the detector 24, the temperature control module 70, switching elements in the optical path, and other control elements in the core optical module 10 via an embedded switching platform 25d. The core optical module 10 may include a cloud-based UI (user interface) platform 25e and communicate with external devices such as a personal computer 80 or a server via the Internet. The system 1 including the core optical module 10 and the inspection interface module 11 may communicate with an application 81 installed on a computer 80 to provide certain services to a user using the system 1 .

[0027] FIG. 6 shows one embodiment of the fiber laser assembly 40. FIG. 7 shows the wavelength plan of the fiber laser assembly 40. The assembly may be a MOPA (Master Oscillator Power Amplifier) ​​fiber laser, and may include a source laser diode LD0 41a to inject into the oscillator and generate a source laser pulse 50 at 1560 nm. A photodetector PD0 provides a feedback signal to ensure that the 1560 nm pulse is generated stably against environmental changes. The source laser 50 is split into a port of the probe generation precursor 42a of the picosecond laser source module 42 and a port of the generation stage 41b of the femtosecond fiber laser source module 41. In the generation stage 41b, the laser LD1 is pumped into an Er (Erbium doped) preamplifier spliced ​​into a highly nonlinear fiber (HNLF) to generate 1040 nm, which is fed into the Stokes generation precursor 41c. In the precursor device 41c, the laser LD2 is injected (pumped) into a Yb (ytterbium-doped) preamplifier to amplify the 1040 nm pulse, and the laser LD3 is injected (pumped) into a Yb high-power amplifier to generate a 1040 nm pulse with an average output of 600 mW. The laser output from the Stokes generation precursor device 41c is supplied to a compressor 41d via a parabolic collimator to generate Stokes light 51 having a broadband supercontinuum (SC) generated by a photonic crystal fiber (PCF) 41e. The laser output from the compressor 41d is split to generate pump light 52.

[0028] In the probe generation precursor 42a, a laser LD4 is pumped into an Er high-power amplifier to generate pulses at 1560 nm with an average power of 150 mW. The laser output from the probe generation precursor 42a is supplied to a compressor 42b via a parabolic collimator, and the high-power 1560 nm pulses are frequency-doubled to 780 nm via a PPLN (Periodically Poled Lithium Niobate nonlinear crystal) acting as an SHG (Second Harmonic Generation) to generate a probe light 54. The Stokes light 51, the pump light 52, and the OCT light 53 may include multiple pulses on the order of 1 to hundreds of fS (femtoseconds) with tens to hundreds of mW. The probe light 54 may include multiple pulses on the order of 1 to tens of pS (picoseconds) with tens to hundreds of mW.

[0029] FIG. 7 shows one wavelength plan for the core optical module 10. It is desirable for the core optical module 10 to meet the requirements of several operating modes with minimal hardware and cost. One requirement for the core optical module 10 may be that the CARS radiation does not overlap with the TD-CARS radiation. Another requirement for the core optical module 10 may be that the TD-CARS radiation overlaps with the OCT excitation and the range of the spectrometer overlaps. Yet another requirement for the core optical module 10 may be that efficient excitation (generation of scattered light) is obtained through tissue. That is, the Stokes light 51 in the first region R1, the pump light 52 in the second region R2, the probe light 54 in the fourth region R4, and the OCT light 53 and TD-CARS light 55 in the third regions R3 and R5 are desirably prepared (positioned) in an optical window region between 600 nm and 1300 nm, where the absorbance of major parts of the living body, such as water, melanin, reduced hemoglobin (Hb), and oxygenated hemoglobin (HbO2), is substantially low.

[0030] In the plan shown in Figure 8, the Stokes light 51 has a first region R1 of wavelengths from 1085 to 1230 nm (400 cm-1 to 1500 cm-1), the pump light 52 has a second region R2 of wavelengths from 1040 nm, the probe light 54 has a fourth region R4 of wavelengths from 780 nm, the OCT light 53 (interference light 63) has a third region R3 of wavelengths from 620 to 780 nm, and the TD-CARS light 55 has a fifth region R5 of wavelengths from 680 to 760 nm. All of the regions R1, R2, R3, R4, and R5 are included in the wavelength region from 600 nm to 1300 nm. The second region R2 is shorter than the first region R1, the third region R3 is shorter than the second region R2, the fourth region R4 is shorter than the second region R2 and is larger than or included in the third region R3, and the region R5 of the TD-CARS 55 is shorter than the fourth region R4 and at least partially overlaps the third region R3. The detection wavelength region DR of the detector 24 may be 620 to 780 nm and shared between the TD-CARS 55 and the interference light 63 of the OCT. In this plan, only one detector 24 having a detection wavelength region DR shared between the TD-CARS 55 and the OCT light 53 (63) is required. By applying a single and common detector 24 that shares the detection wavelength region DR between the CARS detection and the OCT detection, the system configuration is simplified and the spectral resolution of the CARS detector and the imaging depth of the OCT are improved. In this core optical module 10, time-shared scanning may be required because the CARS light 55 and the OCT light 53 (63) use the same spectral region of the single detector 24. The optical switching elements 38a and 38b of the core optical module 10 may be used for time-share control.

[0031] In this plan (design), by using a probe light 54 having a wavelength region R4, for example 780 nm, shorter than the region R2 of the pump light 52, a TD-CARS 55 having a wavelength region R5 shorter than the region R4 of the probe light 54 is generated. That is, by using a probe light 54 having a wavelength region R4 shorter than the wavelength region R6 of the CARS light 55x generated only by the Stokes light 51 and the pump light 52 and having a time difference with the emission of the pump light 52, a TD-CARS 55 having a wavelength region R5 shorter than the wavelength region R6 of the CARS light 55x is generated. Therefore, no interference occurs between the TD-CARS light 55 and the CARS light 55x, and clear TD-CARS light 55 can be detected without the interference of the CARS light 55x. A probe light 54 having a wavelength region shorter than the wavelength region R6 of the CARS light 55x generated by only the Stokes light 51 and the pump light 52 may be required to detect time difference CARS (TD-CARS) 55 generated by the Stokes light 51, the pump light 52, and the probe light 54.

[0032] It should be noted that the above description does not mean that CARS light cannot be used as the scanned light 59 generated at the object via the inspection module 11, and that the scanning light 58 and the resulting scanning light 59 may be CARS light, SRS (Stimulated Raman Scattering), infrared light, or any light that can capture the state of the object as a signal and / or spectrum. The core optical module 10 may be a hybrid optical system including two detectors, one for TD-CARS and one for OCT, or may detect CARS signals and OCT having different spectral regions by splitting the detector in half and using one half for CARS and the other half for OCT.

[0033] FIG. 9(a) shows an example of a manual delay stage 29, and FIG. 9(b) shows an example of a motorized delay stage 29. The temporal overlap between the probe light 54 and the pump / Stokes light 51 and 52 may be controlled by a manual delay stage (±2.5 mm) and / or a motorized delay stage (±2.5 mm). In the manual delay stage 29, a 1560 nm collimator 29a is mounted on a manual delay table 29b. The motorized delay stage 29 includes a pair of collimating devices (collimators) 29c and 29d each connected to an optical fiber, a delay table 29e, and a motor 29f. In the motorized optical delay stage 29, the probe light 54 moves in the following path: fiber in → collimator → spatial coupling → collimator → fiber out. The total movement range may be 10 mm (33 ps).

[0034] 10 shows a temperature control module 70. In the optical plate 21, a plurality of optical elements 30 are mounted on the optical plate 21, and since a slight displacement of the positions of the elements and / or a slight change in the distance between them significantly affects the optical performance of the optical plate 21, the optical plate 21 and the optical bench 20 are made rigid, and the temperature of the optical plate 21 is made constant to avoid the effect of thermal expansion. Therefore, the core optical module 10 includes a temperature control unit 70 configured to control the temperature of the optical plate 21 and / or the optical bench 20.

[0035] An example of the temperature control unit 70 includes a heater control module 71. The heater control module 71 detects the temperature of the optical plate 21 and / or the surroundings by a thermistor 79 attached to the optical plate 21 via an ADC 73, and controls the temperature of the optical plate 21 using a heater 78 via a number of FETs 72. The heater control device 71 controls the temperature of the optical plate 21 to be equal to or higher than the surrounding temperature (air temperature, room temperature, atmospheric temperature) and maintains the temperature of the optical plate 21 at a constant value. The heater 78 may have a heating capacity to maintain the temperature of the plate 21 at a value 20°C higher than the average surrounding temperature, such as 25°C, even when the surrounding temperature is the lowest, such as 15°C. The temperature control unit 70 may include a cooling unit, such as a Peltier cooling unit. If the optical plate includes an auto-tuning unit that compensates for displacement and / or distance changes, the temperature control unit may have a function to avoid sudden changes in temperature and keep the temperature gradient within a predetermined range.

[0036] FIG. 11 shows a schematic configuration between the core optical module 10 and the non-invasive scanning module 11. In the core optical module (optical core module, optical body module) 10, the Stokes light 51, the pump light 52, and the probe light 54 are bundled and sent to the scan module 11 as the scan light 58 via the optical transmission unit 15 (optical fiber 15a or spatial coupling 15b). In the scan module 11, the scan light (scanning light, detection light) 58 is irradiated to the object (target, sample) 19 via the galvanometer scanner (galvanometer) 11g and the objective lens module 11i. The Stokes light 51, the pump light 52, and the probe light 54 generate TD-CARS light 55 in the object 19, and the backward (Epi) TD-CARS light 55 is returned to the optical core module 10 as the scanned light 59 through the same path as the scan light 58. The scanning module 11 may include a second objective lens module 11f disposed on the opposite side of the object 19 and may focus the forward TD-CARS light 55f. The forward TD-CARS light 55f may be returned as scanned light 59 via the optical transmission path 15 using the same path as the scanning light 58.

[0037] In the optical core module 10, the OCT light 53 is generated in a time-division manner with respect to the Stokes light 51, the pump light 52, and the probe light 54, and is sent to the scan module 11 using the same path as the lights 51, 52, and 54. That is, the OCT light 53 is sent to the scan module 11 as the scan light 58 via the optical transmission unit 15 (optical fiber 15a or spatial coupling 15b). In the scan module 11, the OCT light 53 (scan light 58) is emitted toward the object (target, sample) 19 using the same galvano scanner 11g and objective lens module 11i. The reflected light 62 from the object 19 is returned to the optical core module 10 as the scanned light 59 through the same path as the scan light 58.

[0038] FIG. 12 shows one embodiment of the arrangement of the optical elements 30 on the optical plate 21. The path from the OCT engine 60 through the lens L1, the mirror M2, the lenses L6 and L7, and the mirrors M7 and M8 to the mirror M1 is the optical path 36 for outputting the OCT light 53 to the object. In this example, the mirrors M7 and M8 are mirrors for selecting the OCT light 53 and the returned TD-CARS light 55. When the OCT light 53 is selected, the mirrors M7 and M8 are moved to a preset position by a motorized moving stage. The lenses L6 and L7 are beam expanders that adjust the beam width of the OCT collection arm so that a suitable numerical aperture (NA) is obtained to be sent onto the object. The OCT light 53 passes through a galvanometer scanner and a customized multi-element objective lens to be sent to the object.

[0039] The path from the OCT engine 60 through the lens L2, the dichroic beam splitter (dichroic mirror) BS1, the lens L3, and the mirror M9 to the detector (spectrometer) 24 is the path 37 for OCT detection. The return (reflected) OCT light 62 from the target (object) is combined or superimposed (combined) with the reference light 61 to form an interference signal 63, which is brought to the spectrometer 24 through the two lenses L2 and L3. In this example, the OCT interference signal 63 and the CARS light 55 share the same spectrometer 24, and OCT and CARS may be acquired simultaneously. However, if the wavelengths of OCT and CARS overlap, it is necessary to obtain OCT and CARS in a time-division manner. The dichroic beam splitter BS1 transmits the wavelength of OCT.

[0040] Optical paths 31, 32, and 34 are optical paths for sending pump light 52, Stokes light 51, and probe light 54 to the target (object sample). In this example, dichroic beam splitter BS4 combines pump light 52 and Stokes light 51, and dichroic beam splitter BS3 combines pump light 52 and Stokes light 51 with probe light 54. A short-pass filter (SP filter, short wavelength pass filter) along probe path 34 filters the rest of the 1560 nm signal, and a long-pass filter (LP filter, long wavelength pass filter) along Stokes path 31 filters lower wavelengths outside the region of interest. After mirror M1, these beams are combined and sent via transmission unit 15.

[0041] The optical path 35 is for detecting the backward CARS (backscattered CARS, TD-CARS) 55. In this example, the mirror M6 for selecting the collection of the forward scattered CARS light 55 and the mirrors M7 and M8 for selecting the OCT light 53 and 63 are removed via a motorized stage. The dichroic beam splitters BS1, BS2, and BS3 reflect and collect the detected CARS signal 55. The dichroic beam splitter BS1 is used to enable detection of both CARS and OCT with a single spectrometer. The lenses L4 and L5 form a beam expander to obtain an appropriate collection numerical aperture (NA) for the spectrometer 24. The short pass filter (SP filter) on this path 35 ensures that only the wavelength of interest is collected by the spectrometer 24.

[0042] The optical path 35a, which is a part of the optical path 35, is a path for detecting forward CARS (forward scattered CARS) 55f. In this example, a mirror M6 for selecting the collection of the forward CARS light 55f is moved to a predetermined position via a motorized stage. A dichroic beam splitter BS1 reflects and collects the detected CARS signal 55 or 55f. Lenses L4 and L5 constitute a beam expander for obtaining an appropriate collection numerical aperture (NA) of the spectrometer 24. A short pass filter (SP filter) ensures that only wavelengths of interest are collected by the spectrometer 24.

[0043] In the present system 1, the core optical module 10 and one of the inspection interface modules 11-14 may be prepared separately, stacked, or even arranged in parallel, so long as the optical fiber is within a distance that allows the core optical module 10 and the scanning interface modules 11-14 to be connected to each other. By providing the core optical module 10 that is versatile, common, and versatile, it is possible to easily develop an optimal inspection interface module for each application, and it is possible to provide a system 1 that is easily customizable, low-cost, and suitable for measurement, research, monitoring, and / or self-treatment (self-care) in various fields.

[0044] Disclosed herein is a system comprising a core optical module and an inspection interface module. The core optical module is configured to generate light for generating a signal for target locating and further to detect a signal from the target. The inspection interface module (scanning interface) is separate from the core optical module but connected to the core optical module via optical fiber or spatial coupling. The inspection interface module can be modified depending on the application. The inspection interface module is configured to inspect (scan) the target with light sent from the core optical module via optical fiber or spatial coupling to create a signal, receive a signal from the target, and send the signal to the core optical module via optical fiber or spatial coupling. The inspection interface module can be a minimally invasive sampler, a non-invasive sampler, or a flow sampler. The inspection interface module can be modified depending on the application, such as fingertip detection or urine detection to measure glucose, hemoglobin A1c, creatinine, albumin, etc.

[0045] The above discloses a system comprising a core optical module and an inspection interface module, wherein the core optical module is configured to generate light for generating a signal for analyzing an object via the inspection interface module, and to detect light including the signal from the object via the inspection interface module, and the inspection interface module is replaceable for each application, is connected to the core optical module by an optical transmission unit, and is configured to scan the object with the light sent from the core optical module, receive the light from the object and send it to the core optical module.

[0046] The inspection interface module may be separated from the core optical module and connected to the core optical module by the optical transmission unit. The core optical module may include an optical plate on which a plurality of optical elements constituting an optical path for generating the light are mounted, and a fiber laser mechanism configured to accommodate at least one fiber laser that generates a laser to be supplied to the optical plate. The core optical module may include a stacked structure in which the optical plate and the fiber laser mechanism are stacked. The core optical module may further include a temperature control unit configured to control a temperature of the optical plate. The temperature control unit may control the temperature of the optical plate to be equal to or higher than an ambient temperature.

[0047] The plurality of optical elements may include an optical element for supplying Stokes light in a first wavelength region and pump light in a second wavelength region shorter than the first wavelength region, an optical element for supplying probe light in a wavelength region shorter than the wavelength region of the CARS light generated by the Stokes light and the pump light so as to be emitted with a time difference from the emission of the pump light, an optical element for coaxially outputting the Stokes light, the pump light, and the probe light to the optical transmission unit, and an optical element for acquiring the TD-CARS light generated in the object by the Stokes light, the pump light, and the probe light from the optical transmission unit. The core optical module may further include a probe delay stage with an actuator for controlling the time difference. The plurality of optical elements may further include an optical element for supplying OCT light in a third wavelength region shorter than the second wavelength region and at least partially overlapping with the wavelength region of the TD-CARS light, an optical element for outputting the OCT light to the optical transmission unit coaxially with the Stokes light, the pump light, and the probe light, and an optical element for acquiring reflected OCT light from the optical transmission unit, and the core optical module may further include an OCT engine configured to split a reference light from the OCT light and generate interference light from the reference light and the reflected OCT light from the optical transmission unit. The core optical module may further include a detector for detecting the TD-CARS light. The core optical module may further include a detector having a detection wavelength region including at least a portion of a detection wavelength region shared by the TD-CARS light and the interference light.

[0048] The optical transmission unit may include an optical fiber or a free space coupling. The test interface module may include any of a minimally invasive sample collection device, a non-invasive sample collection device, and a flow sample collection device. The test interface module may include any of a wearable test interface, a fingertip test interface, a urine sample collection device, and a dialysis effluent sample collection device.

[0049] The above description of specific embodiments fully reveals the general content of those embodiments, and others can easily modify and / or adapt such specific embodiments for various applications by applying current knowledge without departing from the above concept, and such adaptations and modifications should be understood and are intended to be within the equivalent means and scope of the disclosed embodiments. The expressions or terms employed in this specification should be understood as being for the purpose of description and not for the purpose of limitation. Thus, although the embodiments herein have been described in terms of preferred embodiments, those skilled in the art will recognize that these embodiments can be practiced with modification within the spirit and scope of the appended claims. [Explanation of symbols]

[0050] 1. Measurement system 10 Core Optical Module 11 Inspection Interface Module

Claims

1. A light source that generates Stokes light in a first wavelength region, pump light in a second wavelength region shorter than the first wavelength region, and probe light in a wavelength region shorter than the second wavelength region, the Stokes light being outputted in order to acquire a CARS signal, an oscillator that generates a source laser pulse having a predetermined oscillation wavelength by light injected from a source laser diode; a first fiber laser light source module that generates a first laser light in the second wavelength region from a portion of the source laser pulse through a highly nonlinear fiber and outputs the amplified first laser light; a second fiber laser light source module that outputs a second laser light obtained by amplifying a portion of the source laser pulse; a first optical module that generates the pump light from the first laser light supplied from the first fiber laser light source module via a first compressor, and generates the Stokes light in the first wavelength region from a portion of the pump light via a photonic crystal fiber; a second optical module that generates the probe light in a wavelength range shorter than the second wavelength range via a second harmonic generator from a second laser supplied from the second fiber laser light source module via a second compressor.

2. In claim 1, The oscillator provides the source laser pulse having an oscillation wavelength centered at 1560 nm; The first fiber laser light source module supplies the second laser having a central wavelength of 1040 nm in the second wavelength range; The second fiber laser source module provides the second laser having a central wavelength of 1560 nm; The first optical module provides pump light having a central wavelength of 1040 nm in the second wavelength range and the Stokes light in the first wavelength range including 1085 to 1230 nm; The second optical module is a light source that provides the probe light having a central wavelength of 780 nm.

3. A core optical module including the light source according to claim 1 or 2; and an inspection interface module that outputs the Stokes light, the pump light, and the probe light to an object, and acquires CARS light generated in the object by the Stokes light, the pump light, and the probe light.

4. In claim 3, The core optical module includes: an optical element for supplying Stokes light in the first wavelength region and pump light in a second wavelength region shorter than the first wavelength region; an optical element for providing the probe light such that the probe light is emitted at a time offset from the emission of the pump light.

5. In claim 3, A system in which the inspection interface module is replaceable for each application, connected to the core optical module by an optical transmission unit, and configured to scan the object using light sent from the core optical module, and to receive the light from the object and send it to the core optical module.

6. In claim 5, The system, wherein the inspection interface module is separate from the core optical module and connected to the core optical module by the optical transmission unit.

7. In claim 3, The system, wherein the test interface module includes one of a minimally invasive sample collection device, a non-invasive sample collection device, and a flow sample collection device.

8. In claim 3, The system, wherein the test interface module includes any of a wearable test interface, a fingertip test interface, a urine sample collection device, and a dialysis effluent sample collection device.

Images