The invention generally relates to a system for measuring an object.
In the publication WO2014/061147, a microscope is disclosed. The microscope includes: a first light dividing part that divides a light flux of light from a light source into a first pump light flux and a second pump light flux; a Stokes light source that receives the second pump light flux as an input and outputs a Stokes light flux: a multiplexing part that multiplexes the first pump light flux and the Stokes light flux to generate a multiplexed light flux; a first light-collecting part that collects the multiplexed light flux in a sample; a first detector that detects a CARS light generated from the sample, the CARS light having a wavelength different from the multiplexed light flux; a second light dividing part that lets at least one of the second pump light flux and the Stokes light flux branch partially as a reference light flux; a second multiplexing part that multiplexes a light flux from the sample and the reference light flux to generate interfering light; and a second detector that detects the interfering light.
One of aspects of this invention is a system comprising a core optical module and a scanning interface module. The core optical module is configured to generate a light for generating signals for analysis by irradiating to an object through the scanning interface module and detect the light including the signals from the target through the scanning interface module. The scanning interface module is changeable for each application and configured to connect with the core optical module by a light transferring unit to scan the object with the transferred light from the core optical module and receive the light from the object to transfer to the core optical module.
In the system of this invention, since the core optical module can be shared by multiple types of scanning interface modules, it is possible to provide systems for multiple applications in a short period of time at low cost. The scanning interface module may be a minimum invasive sampler, a non-invasive sampler, or a flow sampler. The scanning interface module may be a wearable scanning interface, a fingertip scanning interface, a urine sampler, or a dialysis drainage sampler for measuring glucose, hemoglobin A1 c, creatinine, albumin and the like.
The embodiments herein will be better understood from the following detailed description with reference to the drawings, in which:
The embodiments herein and the various features and advantageous details thereof are explained more fully with reference to the non-limiting embodiments that are illustrated in the accompanying drawings and detailed in the following description. Descriptions of well-known components and processing techniques are omitted so as to not unnecessarily obscure the embodiments herein. The examples used herein are intended merely to facilitate an understanding of ways in which the embodiments herein may be practiced and to further enable those of skill in the art to practice the embodiments herein. Accordingly, the examples should not be construed as limiting the scope of the embodiments herein.
One of the systems of an embodiment is a measuring system 1 including the core optical module 10 and a fingertip scanning interface module 11 connected to the core module 10 by the optical fiber 15a. As illustrated in
In
The fingertip type scanning interface module 11 is one example of non-invasive samplers.
The scanning interface module 12 is one example of minimum invasive samplers that may include micro sampling tools such as minimally invasive microneedles and microarrays such that the subject does not feel pain at the time of insertion for sampling body fluids such as subcutaneous tissue fluid. The minimal invasive micro sampling tool is useful for sensing biological information by measuring the concentration of components in body fluids and transdermal administration of drugs. A medication monitoring system 1 may be supplied by the core optical module 10 and the minimum invasive sampler 12.
The scanning interface module 13 is one example of flow samplers that may include a flow path 13a through which a target fluid (object) flows. The target fluid may be urine, dialysis drainage, blood, water, solution, or others. A health management and/or monitoring system 1 may be supplied by the core optical module 10 and the flow sampler 13 as a urine sampler. A dialysis monitoring system 1 may be supplied by the core optical module 10 and the flow sampler 13 as a dialysis drainage sampler.
As illustrated in
One example of the light 58 for generating signals for analyzing the object 19 is a combination of Raman spectroscopy (RS) and optical coherence tomography (OCT). Both optical imaging and spectroscopy have been applied to the invasive and non-invasive characterization of an object (a target subject). Imaging techniques, such as OCT excel at relaying images of the target subject microstructure while spectroscopic methods, such as CARS (Coherent Anti-Stokes Raman Scattering), can probe the molecular composition of the target subject with excellent specificity.
OCT is a method of obtaining shape information, which reflects a change in the refractive index, using interference between a reflected light from an object (target) and a reference light that has not irradiated the object. CARS is based on a nonlinear optical phenomenon where, when two light beams with different wavelengths are incident on an object, a CARS light that has a wavelength corresponding to the vibration of molecules forming the object is obtained. A plurality of different methods, such as transmissive CARS and reflective CARS, can be arranged regarding the direction of detecting a CARS light to the incident direction of a pump light and a Stokes light.
Time-resolved coherent anti-Stokes Raman scattering or Time-delayed coherent anti-Stokes Rama scattering (TD-CARS) microscopy is also known as a technique for suppressing non-resonant background by utilizing the different temporal responses of virtual electronic transitions and Raman transitions. There is a need for a system that can easily apply such measurement methods to various applications.
The fingertip scanning interface 11, for example, may scan skin of a finger 19 inserted in the interface 18 with the light 58 generated in the optical core module 10 and supplied through the light transferring unit 15, for generating TD-CARS signals and OCT signals, and send the light 59 including signals (lights) of TD-CARS and OCT to the core optical module 10 through the light transferring unit 15. The fingertip scanning interface 11 may be connected by wired or wireless with the core module 10 to communicate with the core module 10 or the cloud through the core module 10.
On the optics plate 21 of the optical bench 20, by using the plurality of optical elements 30 including mirrors, switching elements, reflectors, prisms, lenses, filters such as short wavelength pass filter (SP) and long wavelength pass filter (LP), and others, an optical path 31 for supplying the Stokes light 51 with a first range R1 of wavelengths; an optical path 32 for supplying the pump light 52 with a second range R2 of wavelengths shorter than the first range R1 of wavelengths; an optical path 34 for supplying the probe light 54 with a range of wavelength R4; an optical path 39 for coaxially outputting the Stokes light 51, the pump light 52, and the probe light 54 to the light transmitting unit 15; and an optical path 35 for acquiring the TD-CARS light 55 generated by the Stokes light 51, the pump light 52, and the probe light 54 at the object from the light transmitting unit 15. The TD-CARS light 55 has a range R5 of wavelengths shorter than a range of wavelengths of a CARS light only generated by the Stokes light 51 and the pump light 52. The optical path 34 includes a probe delay stage 29 with an actuator for controlling the emitting of the probe light 54 with the time difference from the emission of the pump light 52.
On the optical plate 21, by using the plurality of optical elements 30, an optical path 33 for supplying the OCT light 53 with a third range R3 of wavelengths shorter than the second wavelength range R2 range of wavelength and at least partly overlapping the wavelength range R5 of the TD-CARS light 55, an optical path 36 for acquiring a reflected OCT light 62 from the light transmitting unit 15, and an OCT engine 60 are also provided. The path 36 includes a dichroic mirror 68 for outputting the OCT light 53 and receiving or returning the reflected light 62 to the OCT engine 60. The OCT engine 60 is configured to split off a reference light 61 from the OCT light 53 and generate an interference light 63 by the reference light 61 and a reflected OCT light 62 through the light transmitting unit 15 from the object. The optical path 39 outputs the OCT light 53 coaxially with the Stokes light 51, the pump light 52, and the probe light 54 to the light transmitting unit 15. The optical path 39 may include a beam conditioning unit 39c, a beam alignment unit 39a, a beam steering unit 39b, and a dichroic mirror device 39d. The dichroic mirror 39d makes the light 58 by combining the light 51, 52, and 54 for generating TD-CARS 55, and the OCT light 53, and separates the returned light 59 that includes TD-CARS light 55 and the reflected light 62. Instead of using the optical elements, or with the use of the optical elements, those optical paths may be provided in or using a chip type optical device. All or a part of those optical paths, instead of providing in the optical core module, may be provided in the scanning module such as wearable model 14.
The core optical module 10 further includes the detector 24 for detecting the TD-CARS light 55 and the interference light 63 of OCT. The detector 24 includes a range of detection wavelengths at least a partially shared with the TD-CARS light 55 and the interference light 63. The core optical module 10 further includes an analyzer 25a for acquiring and analyzing the data from the detector 24. The analyzer 25a may include a high-speed data acquisition module 25b and a system controller and communications interface module 25c. The communications interface module 25c may communicate with the laser assembly 40, the detector 24, the temperature control module 70, switching elements in the optical paths, 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 platform 25e to communicate with the external devices such as a personal computer 80 or server via the Internet. The system 1 including the optical core module 10 and the scanning interface module 11 may communicate with an application 81 installed in the computer 80 to provide a service to a user or users using the system 1.
In the probe generation precursor 42a, a laser LD4 pumps an Er high power amplifier to generate 150 mW average power at 1560 nm. A laser outputted from the probe generation precursor 42a is supplied to a compressor 42b through a parabolic collimator and high power 1560 nm pulses are frequency doubled to 780 nm pulses via PPLN (Periodically Poled Lithium Niobate nonlinear crystal) that acts as SHG (Second Harmonic Generation) to generate the probe light 54. The Stokes light 51, the pump light 52, and the OCT light 53 may include one to several hundred fS (femto second)-order pulses with tens to hundreds of mW. The probe light 54 may include one to several tens pS (pico second)-order pulses with tens to hundreds of mW.
In the plan shown in
In this plan, by using the probe light 54 having the shorter wavelength range R4, for example 780 nm, than the range R2 of the pump light 12, the TD-CARS 55 having the wavelength range R5 shorter than the range R4 of the probe light 54 is generated. That is, by using the probe light 54 with the range R4 of wavelengths shorter than the range R6 of wavelengths of the CARS light 55x only generated by the Stokes light 51 and the pump light 52 with a time difference from the emission of the pump light 52, the TD-CARS 55 having the wavelength range R5 shorter than the wavelength range R6 of the CARS light 55x is generated. Accordingly, no interference is made between the TD-CARS 55 and the CARS 55x, and distinct TD-CARS 55 can be detected without interference with the CARS light 55x. The probe light 54 with the range of wavelength shorter than the range R6 of wavelengths of a CARS light 55x only generated by the Stokes light 51 and the pump light 52 may be required to detect a time difference CARS (TD-CARS) 55 that is generated by the Stokes light 51, the pump light 52, and the probe light 54.
Note that the above description does not mean that the CARS light cannot be used as the scanned light 59 to be generated at the object via the scanning module 11, and the scanning light 58 and the scanned light 59 may be for CARS light, SRS (Stimulated Raman Scattering), an infrared light, or any light that may be used as long as it can capture the state of the object as signals and/or spectra. The optical core modules 10 may be a hybrid optical system that includes two detectors for TD-CARS and OCT, or one detector splitting into one half to be used for CARS and the other half used for OCT for detecting the CARS signal and OCT having different spectral ranges.
One example of the temperature control unit 70 includes a heater controller module 71. The heater controller module 71 detects the temperature of the optics plate 21 and/or the environment of the optics plate 21 by a thermistor 79 attached to the optics plate 21, via ADC 73, and control the temperature of the optics plate 21 using a heater 78 via the FETs 72. The heater controller 71 controls the temperature of the optics plate 21 above the ambient temperature to maintain the temperature of the plate 21 at the constant value. The heater 78 may have the heating capacity to maintain the temperature of the plate 21 up to 20C above the averaged ambient temperature such as 25C when the ambient temperature is the lowest such as 15C. The temperature control unit 70 may include a cooling unit such as a Peltier cooling unit. If the optics plate includes an auto tuning unit for compensating the deviations and/or distance changing, the temperature control unit may have a function that avoids the sudden change of the temperature and keeps the temperature gradient in a predetermined range.
In the optical core module 10, the OCT light 53 is generated in time division manner for the Stokes light 51, the pump light 52, and the probe light 54 and delivered to the scanning module 11 using the same route of the lights 51, 52, and 54. That is, the OCT light 53 is delivered to the scanning module 11 as the scan light 58 via the light transferring unit 15 (optical fiber 15a or frees pace coupling 15b). In the scanning module 11, the OCT light 53 (scan light 58) shares the same galvanometer 11g and objective lens module 11i and emits to the object (target, sample) 19. The reflected light 62 from the object 19 is returned as the scanned light 59 through the same route as the scanning light 58 to the optical core module 10.
A route from the OCT engine 60 to the detector (spectrometer) 24 through a lens L2, a dichroic beam splitter (dichroic mirror) BS1, a lens L3 and a mirror M9 is a path 37 for the OCT detection. The returned (reflected) OCT light 62 from the target (object) is combined or multiplexed with the reference light 61 to form the interference signal 63 and coupled into the spectrometer 24 through two lenses L2 and L3. In this example, OCT interference signal 63 and CARS light 55 share the same spectrometer 24, which provides the potential to acquire OCT and CARS simultaneously. Time-division between OCT and CARS is however needed if OCT and CARS have overlaps in wavelength. The dichroic beam splitter BS1 is transmissive at the OCT wavelength.
The optical paths 31, 32, and 34 are the paths for delivering the pump light 52, the Stokes light 51, and the probe light 54 onto the target (object sample). In this example, a dichroic beam splitter BS4 combines the pump light 52 and the Stokes light 51, and a dichroic beam splitter BS3 combines the probe light 54 with the pump light 52 and the Stokes light 51. The short pass filter (SP filter) along the probe path 34 filters out the remaining of 1560 nm signal, and the long pass filter (LP filter) along the Stokes path 31 removes the lower wavelength that is out of the region of interest. After the mirror M1, these beams are combined and delivered through the transferring unit 15.
The optical path 35 is the path for the detection of backward CARS (TD-CARS) 55. In this example, a mirror M6 for selecting the forward CARS light 55 collection and the mirrors M7 and M8 for selecting the OCT lights 53 and 63 are moved out of the way through motorized stages. The dichroic beam splitters BS1, BS2 and BS3 reflect the detected CARS signal 55 for collection. The use of the dichroic beam splitter BS1 enables the single spectrometer for both CARS and OCT detection. Lenses L4 and L5 consist of a beam expander to ensure a proper collection NA for spectrometer 24. The short pass filter (SP filter) on this path 35 ensures that only the interested wavelengths are collected by the spectrometer 24.
An optical path 35a that is a part of the path 35 is a route for the detection of forward CARS 55f. In this example, a mirror M6 is moved in place for selecting the forward CARS light 55f collection through a motorized stage. The dichroic beam splitter BS1 reflects the detected CARS signal 55 or 55f for collection. The lenses L4 and L5 consist of a beam expander to ensure a proper collection NA for spectrometer 24. The short pass filter (SP filter) ensures that only the interested wavelengths are collected by the spectrometer 24.
In this system 1, the core optical module 10 and the one kind of the scanning interface module 11 to 14 may be arranged separately, may be stacked, may be arranged in parallel within the distance where the optical fiber can connect the core optical module 10 and the scanning interface module 11 to 14. By providing the highly versatile, common and general purpose core optical module 10, it is possible to easily develop an optimum scanning interface module for each application, that is easy to customize, low in cost, and capable of supplying a system 1 suitable for measurement, research, monitoring and/or self-care in various filed.
In this specification, a system comprising a core optical module and a scanning interface module is disclosed. The core optical module is configured to generate lights for making signals for searching a target and detect the signals from the target. The scanning interface module is separated from the core optical module but connected with the core optical module via an optical fiber or a free space coupling. The scanning interface module is changeable for each application. The scanning interface module is configured to scan the target with the transferred lights from the core optical module for making the signals and to receive the signals from the target to transfer the signals to the core optical module via the optical fiber or the free space coupling. The scanning interface module may be a minimum invasive sampler, a non-invasive sampler, or a flow sampler. The scanning interface module can change for each application such as fingertip scanning and urine scanning for measuring glucose, hemoglobin A1c, creatinine, albumin and the like.
The foregoing description of the specific embodiments will so fully reveal the general nature of the embodiments herein that others can, by applying current knowledge, readily modify and/or adapt for various applications such specific embodiments without departing from the generic concept, and, therefore, such adaptations and modifications should and are intended to be comprehended within the meaning and range of equivalents of the disclosed embodiments. It is to be understood that the phraseology or terminology employed herein is for the purpose of description and not of limitation. Therefore, while the embodiments herein have been described in terms of preferred embodiments, those skilled in the art will recognize that the embodiments herein can be practiced with modification within the spirit and scope of the appended claims.
Filing Document | Filing Date | Country | Kind |
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PCT/JP2020/017886 | 4/27/2020 | WO | 00 |
Number | Date | Country | |
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62840704 | Apr 2019 | US |