High-energy-efficiency coherent Raman spectroscopy system and method using a dual-comb laser

Abstract

A system and method for operating a dual comb laser, the method including generating pulsed laser light with a first laser source and a second laser source of the dual comb laser, at least one of the first laser source and the second laser source comprising a diode-pumped solid-state laser with tunable output intensity, and matching a phase repetition frequency of the pulsed laser light by selectively varying the output intensity of the diode-pumped solid-state laser.

Description

[Technical Field]

[0001] (Cross-reference of related applications) This application is based on U.S. Provisional Patent Application No. 63 / 071,3 filed on 28 August 2020. 77 Priority is claimed to be made to Japanese Patent Application No. 2020-153374, filed on September 11, 2020, the disclosures thereof being incorporated herein by reference.

[0002] This application relates to a spectroscopic measurement system. More specifically, this application relates to a high-energy-efficiency coherent Raman spectroscopy system and method using a dual-comb laser. [Background technology]

[0003] In recent years, the emergence of high-speed vibrational spectroscopy and imaging techniques has spurred various discoveries in biomedical science and materials science. These techniques are based on coherent Raman scattering processes (e.g., stimulated Raman scattering (SRS) and coherent anti-Stokes Raman scattering (CARS)) and are used in a wide range of applications (e.g., cancer detection, metabolic analysis, drug discovery, flow cytometry, and polymerization analysis). Furthermore, these techniques are extremely effective in studying high-speed dynamic events that were previously unattainable due to the difficulty or impossibility of regeneration with conventional pump-probe methods. Among the various high-speed vibrational spectroscopy methods, nonlinear dual-comb spectroscopy, more specifically dual-comb CARS (DC-CARS) spectroscopy, has attracted particular attention due to its unique ability to rapidly acquire high-resolution Raman spectra in the fingerprint region using a single-pixel photodetector. For example, state-of-the-art laser technology has a spectral range of 200-1400 cm⁻¹. -1 , spectral resolution is 3 cm -1The DC-CARS spectroscopy boasts high performance, with a spectral acquisition rate of 10,000 spectra per second. These excellent features of DC-CARS spectroscopy are realized based on a principle known as asynchronous optical sampling. In asynchronous optical sampling, a pair of optical frequency combs with slightly different fixed pulse repetition frequencies are used. In this method, the frequency difference between the two combs automatically and rapidly sweeps the group delay between the ultrashort pump pulse and the ultrashort probe pulse without requiring any mechanical movement, while the pump pulse excites molecular vibrations in the sample, and the probe pulse allows the time evolution of these molecular vibrations to be observed as a time-domain interferogram. The Raman spectrum of the sample is then obtained by taking the Fourier transform of the time-domain interferogram measured by a single-pixel photodetector.

[0004] However, DC-CARS spectroscopy is highly inefficient because over 99% of its laser energy is not used in the CARS process and is simply wasted. This is due to a mismatch between the laser pulse interval (>1 nm) and the coherence lifetime of molecular vibrations (~3 ps), resulting in a duty cycle of less than 1% for spectrum acquisition. This leads to a decrease in spectrum acquisition rate and a decrease in signal-to-noise ratio (SNR). The simplest approach to improving the duty cycle is to increase the laser repetition frequency by shortening the resonator length of each frequency comb laser. Mode-locked lasers with high repetition frequencies above 1 GHz have been developed and are commercially available, but a trade-off occurs between pulse repetition frequency and pulse energy, so mode-locked lasers sacrifice pulse energy and are therefore undesirable for nonlinear optical interactions that require high pulse peak intensity. Another approach to fast CARS spectroscopy is Fourier transform-type CARS (FT-CARS) spectroscopy, which uses a mechanically operated scanner to rapidly sweep the group delay between the pump pulse and the probe pulse. However, the inertia of the machine-operated scanner limits the spectral acquisition rate. [Overview of the project]

[0005] This application relates to a system and method for operating a dual-comb laser. The system generates pulsed laser light using a first laser source and a second laser source of a dual-comb laser, wherein at least one of the first and second laser sources comprises a diode-pumped solid-state laser with variable output intensity, and the system matches the phase repetition frequency of the pulsed laser light by selectively changing the output intensity of the diode-pumped solid-state laser (for example, by transitioning the diode-pumped solid-state laser from a first output intensity value to a different second output intensity value).

[0006] In one scenario, the first laser source comprises a diode-pumped solid-state laser with a fixed output intensity, and the second laser source comprises a diode-pumped solid-state laser with a variable output intensity. The output intensity of the diode-pumped solid-state laser can be selectively changed based on a group delay value determined using dichromatic interference and / or by changing the current supplied to the diode-pumped solid-state laser. The current can be changed according to the group delay value. By selectively changing the output intensity of the diode-pumped solid-state laser, the refractive index of the crystal can be changed. phase The repetition frequencies match.

[0007] In those or other scenarios, the method generates a feedback signal using one of the pulsed laser beams, and uses the feedback signal to control the position of the mirrors of the laser resonator of the first or second laser source, which is driven by a piezoelectric converter, and / or the first and second laser sources pulse This further includes rapidly modulating the difference in repetition frequencies.

[0008] This application further relates to a system and method for operating a laser light source. The method includes generating pulsed laser light using a crystal excited by excitation laser light output from a diode-pumped solid-state laser, and changing the refractive index of the crystal by selectively changing the intensity of the excitation laser light. The intensity of the excitation laser light can be selectively changed based on a group delay value determined using dichromatic interference and / or by adjusting the current supplied to the diode-pumped solid-state laser (for example, based on a group delay value determined using dichromatic interference).

[0009] This application further relates to a dual-comb laser. Each dual-comb laser comprises a first laser source and a second laser source that generate pulsed laser light. At least one of the first and second laser sources comprises a diode-pumped solid-state laser with variable output intensity. The dual-comb laser further comprises a circuit for selectively changing the output intensity of the diode-pumped solid-state laser to match the phase repetition frequency of the pulsed laser light.

[0010] In one scenario, the first laser source comprises a diode-pumped solid-state laser with a fixed output intensity, and the second laser source comprises a diode-pumped solid-state laser with a variable output intensity. The output intensity of the diode-pumped solid-state laser can be selectively changed by transitioning the diode-pumped solid-state laser from a first output intensity value to a different second output intensity value based on a group delay value determined using dichromatic interference, and / or by changing the current supplied to the diode-pumped solid-state laser. The current can change in accordance with the group delay value determined using dichromatic interference.

[0011] The dual-comb laser further comprises a crystal having a refractive index that changes when the output intensity of the diode-pumped solid-state laser is changed, and the change in refractive index phaseThe repetition frequencies match. The circuit further (i) generates a feedback signal using one of the pulsed laser lights, and (ii) controls the position of the mirror of the laser resonator of the first laser light source or the second laser light source, which is driven by a piezoelectric transducer, using the feedback signal.

[0012] This application further relates to a laser light source. The laser light source includes a diode-pumped solid-state laser, a crystal that generates pulsed laser light when excited by the excitation laser light output from the diode-pumped solid-state laser, and a circuit that changes the refractive index of the crystal by selectively changing the intensity of the excitation laser light. The intensity of the excitation laser light can be selectively changed based on the group delay value determined using two-color interference and / or by adjusting the current supplied to the diode-pumped solid-state laser. The current is adjusted based on the group delay value determined using two-color interference.

Brief Description of the Drawings

[0013] This disclosure is made with reference to the following drawings, and throughout the drawings, like reference numerals represent like features.

[0014] FIGS. 1 and 2 are graphs useful for understanding the conceptual differences between the conventional DC-CARS spectroscopy and Quasi-DC-CARS spectroscopy.

[0015] FIG. 3 is an explanatory diagram of a Quasi-DC-CARS spectrometer.

[0016] FIG. 4 is a block diagram of a circuit for a laser light source as an example.

[0017] FIGS. 5(a) to 5(e) (collectively referred to as "FIG. 5") are graphs useful for understanding the process of calculating the group delay from the two-color interferogram (TCI).

[0018] FIGS. 6(a) to 6(d) (collectively referred to as "FIG. 6") are graphs showing the results of a demonstration experiment of Quasi-DC-CARS spectroscopy.

[0019] Figures 7(a) to 7(c) (collectively referred to as "Figure 7") are graphs showing the analysis results of SNR in the Quasi-DC-CARS spectroscopy method.

[0020] Figure 8 is a flowchart of a method that is an example of the Quasi-DC-CARS spectroscopy method.

[0021] Figure 9 is a flowchart of a method that is an example for determining group delay measurement.

[0022] Figure 10 is an explanatory diagram of a computing device.

[0023] Figure 11 is a graph useful for understanding the modulation of the pulse repetition frequency by controlling the intensity of the pump laser for a crystal.

Best Mode for Carrying Out the Invention

[0024] It will be readily understood that the solution means described in this application and shown in the accompanying drawings may include a variety of different configurations. Therefore, the following more detailed description shown in the drawings is not intended to limit the scope of the present disclosure, but is merely a representative example of specific implementations in different scenarios. Although various aspects are shown, the drawings are not necessarily drawn to scale unless otherwise explicitly stated.

[0025] Throughout this specification, references to features, advantages, or similar language do not mean that all of the realizable features and advantages should be in any single embodiment of the invention. Rather, the language referring to features and advantages is to be understood as meaning that a particular feature, advantage, or characteristic described in connection with an embodiment is included in at least one embodiment of the invention. Therefore, discussions of features and advantages throughout this specification, and similar language, although not necessarily so, may refer to the same embodiment.

[0026] The term "spectroscopy" refers to the analysis of the interaction between matter and electromagnetic radiation as a function of the wavelength or frequency of the radiation. During this analysis, it is possible to measure the spectrum produced when matter interacts with or emits electromagnetic radiation.

[0027] The term "Raman spectroscopy" refers to a spectroscopic technique used to determine the vibrational modes of molecules. These vibrational modes give molecules a identifiable structural fingerprint. Raman spectroscopy relies on the inelastic scattering of photons, known as Raman scattering. When laser light interacts with molecular vibrations, the energy of the laser photons increases or decreases. This energy shift provides information that can be used to determine the vibrational modes of the molecule.

[0028] The term "dual-comb spectroscopy" refers to a spectroscopic technique that utilizes two coherent laser sources with different repetition frequencies to excite and probe a molecular sample.

[0029] The term "Dual-Comb Coherent Anti-Stokes Raman Spectroscopy" or "DC-CARS" refers to a spectroscopic technique that utilizes two coherent laser sources with different repetition frequencies to determine the vibrational modes of molecules. DC-CARS enables non-invasive measurements for the chemical analysis of objects. The DC-CARS system generates ultrashort laser pulses and automatically sweeps the group delay between the pump pulse and the probe pulse by superimposing a pair of laser pulses with slightly different pulse repetition frequencies. As the laser pulses pass through the sample, they excite the molecular vibrations of the sample. A time-domain interferogram is measured. By performing a Fourier transform on the time-domain interferogram, the Raman spectrum of the sample can be obtained.

[0030] DC-CARS is a powerful technique for rapidly probing the vibrational characteristics of molecules in the fingerprint region. However, due to a mismatch between the laser pulse interval (>1 nm) and the coherence lifetime of molecular vibrations (~3 ps), the duty cycle for spectrum acquisition is less than 1%, resulting in over 99% of the incident laser energy being wasted. This application describes a 100% energy-efficient DC-CARS using a "quasi" dual-comb laser. A RS will be explained. DC-C of this application A RS is a conventional low-speed DC-C A It has even higher sensitivity than RS and can provide a relatively high spectral acquisition rate of 100,000 spectra / second.

[0031] The solution of this application includes a 100% energy-efficient DC-CARS spectroscopy method using a pseudo-dual-comb laser. The concept of this solution originates from THz time-domain spectroscopy using electrically controlled optical sampling, but is not directly applicable to fast vibrational spectroscopy methods (e.g., DC-CARS spectroscopy). This is because the operation is relatively slow (~1 kHz) due to the slow response of the piezoelectric transducer that modulates the laser resonator length, and the measurement accuracy of the group delay is far from what is required in fast vibrational spectroscopy methods. To overcome this limitation, the resonator length of one frequency comb is rapidly modulated via the modulation of the Kerr lens effect in the laser gain medium (this is called the pseudo-comb state), and the group delay between the pump pulse and the probe pulse is accurately measured by dichromatic interference to calibrate the phase of each Raman active mode in the sample. Specifically, by sweeping the group delay from 0.0 ps to 0.7 ps at a sweep rate of up to 100,000 times / second with a duty cycle of nearly 100%, DC-CARS spectroscopy with a relatively high spectral acquisition rate of 100,000 spectra / second is achieved. Thanks to the high duty cycle, the detection sensitivity of this solution is also increased by more than 100 times compared to conventional DC-CARS spectroscopy with a fixed comb frequency difference. In other words, this solution (called Quasi-DC-CARS spectroscopy) has a product of spectral acquisition rate and spectral power density that is more than 100 times higher than conventional DC-CARS spectroscopy. Quasi-DC-CARS spectroscopy can be used in a wide range of applications, where high speed and high sensitivity are required for vibrational spectroscopy. Such applications include, but are not limited to, particle analysis, flow cytometry, high-throughput screening, real-time large tissue imaging, and / or polymerization analysis.

[0032] Theory of Quasi-DC-CARS spectroscopy

[0033] Referring to FIGS. 1 and 2, the conceptual differences between the conventional DC-CARS spectroscopy and the Quasi-DC-CARS spectroscopy can be understood. As shown in FIG. 1, the conventional DC-CARS spectroscopy uses a pair of frequency combs with fixed values whose repetition frequencies are slightly different. Let the pulse repetition frequencies of frequency comb 1 and frequency comb 2 be f1 and f2, respectively, and f1 < f2. Then, the group delay between the pump pulse and the probe pulse is Δt = f1 -1 - f2 -1 and thus the group delay is swept from zero to 1 / f1. Based on the highest pulse repetition frequency of commercially available lasers, if f1 ≈ f2 ≈ 1 GHz, the group delay will exceed the coherence lifetime of molecular vibrations (~3 ps) for more than 99% of the spectrum acquisition time, so the duty cycle is 1% less than which is a very small value. Also, the spectrum acquisition rate of the conventional DC-CARS spectroscopy is limited by the Nyquist frequency. To cover the entire fingerprint region (200 - 1600 cm -1 ) with a 1 GHz dual-comb laser, the difference in repetition frequencies Δf = |f2 - f1| must be less than 10.4 kHz.

[0034] Referring to FIG. 2, the strategy of the solution means to achieve a duty cycle of almost 100% can be understood. By rapidly modulating the repetition frequency of one of the frequency combs at the modulation frequency f mod (i.e., by rapidly modulating the difference in the repetition frequencies of the two frequency combs), the group delay is swept from zero to about 3 picoseconds (close to the coherence lifetime of molecular vibrations). Thus, almost all pump pulses and probe pulses contribute to the generation of the CARS signal. Therefore, the spectrum acquisition rate of the Quasi-DC-CARS spectroscopy is determined by twice the modulation frequency of the frequency difference. Due to the high energy efficiency, the Quasi-DC-CARS spectroscopy can achieve not only a much higher spectrum acquisition rate but also much higher sensitivity than the conventional DC-CARS spectroscopy.

[0035] Example of a Quasi-DC-CARS spectrometer

[0036] Referring to Figure 3, a diagram of the Quasi-DC-CARS spectrometer 300 is shown. A pair of laser sources 302 and 304 are used as a dual-comb laser source 306. Laser sources 302 and 304 are equipped with lasers based on oscillating-electron state titanium-doped sapphire crystals (Ti:sapphire crystals). These lasers are called Ti:sapphire lasers. Examples of Ti:sapphire lasers include, but are not limited to, the taccor power laser available from Cambridge Technology, Inc. in Bedford, Massachusetts. Ti:sapphire lasers operate at a repetition frequency of approximately 1 GHz, are mode-locked, and can output ultrashort pulses with widths ranging from a few picoseconds (ps) to tens of attoseconds (as) (e.g., tens of femtoseconds (fs)). Each Ti:sapphire laser emits laser light generated by exciting a Ti:sapphire crystal with an excitation laser beam at a shorter wavelength. The excitation laser beam is generated by a diode-pumped solid-state (DPSS) laser. The intensity of the DPSS laser can be rapidly controlled by adjusting the strength of the current applied to it. This allows the refractive index of the Ti:sapphire crystal to change in response to the excitation power due to the nonlinear optical Kerr effect, thereby modulating the optical path length of the Ti:sapphire crystal. The pulse repetition frequency of the laser light source 302 is, at maximum f mod It can be modulated at 50kHz.

[0037] The two laser beams output from the dual-comb laser light source 306 are combined by a polarizing beam splitter (PBS) 308 and directed along two paths 310 and 312. Path 310 is used for CARS signal measurement, while path 312 is used for group delay measurement using dichromatic interference.

[0038] For CARS signal measurement along path 310, the laser beam is chirp-compensated by a chirp mirror pair 314 and then focused onto the sample 320 via an achromatic lens 318. The CARS signal generated from the sample is extracted from the incident light by an optical long-pass filter 316 located in front of the sample 320 and an optical short-pass filter 324 located behind the sample 320. The CARS signal is detected by a photodetector 326. The photodetector 326 is a high-sensitivity avalanche photodetector, part number APD210, available from Menlo Systems GmbH in Germany, but is not limited to this.

[0039] For dichromatic interferometry along path 312, the laser beam is spatially dispersed by the diffraction grating 328 into two laser beams 330 and 332 with nearly equal intensity but different frequencies (e.g., red and blue). The laser beams 330 and 332 pass through one or more achromatic lenses 334. The achromatic lenses 334 focus the laser beams toward the photodetectors 336 and 338. The light intensity of laser beam 330 is detected and measured by photodetector 336. The light intensity of laser beam 332 is detected and measured by photodetector 338. The measured light intensities are then provided from photodetectors 336 and 338 to the computing device 340 for storage and / or processing.

[0040] The computing device 340 determines the group delay value 360 ​​using the measured light intensity. Both the group delay value and the method for determining the group delay value based on intensity measurement are well known. The group delay value 360 ​​is passed from the computing device 340 to the dual-comb laser source 306 for use in selective control of the output intensity of one or both of the DPSS lasers of the laser sources 302 and 304. The output intensity can be selectively changed between high and low intensity values. For example, when the group delay has a value of zero picoseconds, the DPSS laser is controlled to have a high intensity value, and when the group delay has a value between 1 / 2 picosecond and several picoseconds, the DPSS laser is controlled to have a low intensity value. The solutions of this application are not limited to the details of this example.

[0041] By selectively changing the output intensity of the DPSS laser, the refractive index of the Ti:sapphire crystal can be changed relatively quickly, allowing the pulse repetition frequency of the pulsed laser light to be changed at least several orders of magnitude faster than when adjusting the laser resonator mirror (i.e., mirror 408 in Figure 4) via a piezoelectric transducer (i.e., piezoelectric transducer 406 in Figure 4). In one or both of the laser sources 302 and 304, the output intensity of the DPSS laser is selectively changed. In addition to selectively changing the output intensity of the DPSS laser, the position of the laser resonator mirror may also be selectively changed arbitrarily in one or both of the laser sources 302 and 304.

[0042] In this configuration, a diffraction grating 328 with a groove density of 12,000 grooves per millimeter, an achromatic lens 334 with a focal length of 200 mm, and an effective area of ​​0.126 mm² are used. 2 Using photodetectors 336 and 338, the maximum measurable group delay is estimated to be 18.7 ps. The measured CARS signal and dichromatic interference signal are electrically filtered by low-pass filters (not shown) with cutoff frequencies of 530 MHz and 600 MHz, respectively, and digitized at 5 gigasamples / second using a high-speed oscilloscope (not shown). The high-speed oscilloscope could be, but is not limited to, the digital oscilloscope part number RTOl 004 available from Rohde & Schwarz USA, Inc. in Columbia, Maryland.

[0043] Referring to Figure 4, a detailed block diagram of the laser light source 400 is shown. The laser light sources 302 and 304 in Figure 3 may be identical or similar to the laser light source 400. Therefore, the discussion concerning the laser light source 400 is sufficient to understand the laser light sources 302 and 304 in Figure 3. The laser light source 400 comprises various electronic circuit elements 402 to 430 that control the pulse repetition frequency of the output pulsed laser light 450. The operation of these elements will be explained first with respect to the laser light source 302 in Figure 3, and then with respect to the laser light source 304 in Figure 3.

[0044] figure 3 The pulse repetition frequency of the laser light source 302 is controlled by the servo controller 402 using feedback information to maintain a constant frequency. f Stabilization is performed at 1. The servo controller 402 receives feedback signals 432 output from feedback branches 422-426 and uses the content of the feedback signals to control the position of the laser resonator mirror 408 driven by the piezoelectric transducer 406. The piezoelectric transducer 406 is provided to modulate the length of the laser resonator, which consists of a set of mirrors 408, 410, 412, and 414. The laser resonators 408-414 (i) ensure that the generated light follows a closed path and (ii) control the frequency at which the laser light source 400 generates optical pulses. This optical pulse frequency is referred to in this application as the pulse repetition frequency. Mirror 414 also functions as an output coupler, providing a repeating train or sequence of pulses as pulsed light 440 by transmitting a portion of the incident light.

[0045] The pulsed laser beam 440 propagates to the beam splitter 420. The beam splitter 420 includes an optical device that separates the pulsed laser beam 440 into two pulsed laser beams 450 and 452. The pulsed laser beam 450 is output from the laser light source 400. Meanwhile, the pulsed laser beam 452 is supplied to feedback branches 422-426.

[0046] The feedback branches 422-426 each comprise a photodiode 422, a mixer 424, and a low-pass filter 426. The photodiode 422 is a semiconductor diode that converts pulsed laser light 452 into a current 454. The current 454 flows to the mixer 424 and mixes with the waveform 434 from the signal generator 428. The signal generator 428 is not limited to, but could be the SMA 100A signal generator available from Rohde & Schwarz USA, Inc. in Columbia, Maryland. This signal mixing is minimized by proportional-integral (PI) control. The signal 456 output from the mixer 424 is filtered by the low-pass filter 426 to generate the feedback signal 432. The feedback signal 432 is used by the servo controller 402 to maintain a constant pulse repetition frequency of the laser light source. f It stabilizes at 1.

[0047] The pulse repetition frequency of the laser light source 304 in Figure 3 is modulated at high speed as f2 = f1 + g(t). Here, g(t) is a symmetric modulation function that satisfies the following equation.

number

[0048] Since the modulation g(t) does not necessarily follow the input drive function due to the time variation of the pump intensity, the role of the two-color interferometer is to accurately measure the group delay in conjunction with the CARS signal measurement and calibrate the phase of each Raman active mode in the sample 320 using the group delay. Specifically, the group delay can be calculated from the TCI at wavelengths w1 and w2 according to the known process shown in FIG. 5. FIG. 5(a) shows an example of the measured TCI. As indicated by arrow 502, the measured TCI is Fourier-transformed to give a spectrum having three peaks as shown in FIG. 5(b). Next, as indicated by arrow 504, by applying a mask function, the necessary frequency components of the spectrum are extracted near 21 kHz and the unnecessary frequency components are removed. Then, the masked spectrum is inverse Fourier-transformed to reconstruct the complex TCI as shown in FIG. 5(c). As shown in FIG. 5(d), the phase delay at w1 and w2 can be calculated from the complex TCI as its argument. The group delay τ between the two pulses is obtained as τ = (φ1 - φ2) / (w1 - w2). Here, φ1 and φ2 are the phase delays at w1 and w2, respectively (see FIG. 5(e)). When evaluating the accuracy of the TCI-based group delay measurement under the condition that the pulse repetition frequencies of the two laser light sources 302 and 304 are fixed at 1000.200 MHz and 1000.190 MHz, respectively, the error was 17.5 fs, which was found to correspond to an error of 0.146 cm -1 in the Raman spectrum region.

[0049] Demonstration experiment of Quasi-DC-CARS spectroscopy

[0050] Using liquid toluene as a sample, a proof-of-principle of Quasi-DC-CARS spectroscopy was performed at a modulation frequency of 50 kHz. FIG. 6(a) shows the TCI obtained at 767 nm and 816 nm. According to the process described above in relation to FIG. 5, the group delay was calculated from this TCI as shown in FIG. 6(b). The CARS signal recorded simultaneously with the TCI was accurately calibrated using the calculated group delay as shown in FIG. 6 (c). By Fourier-transforming the calibrated CARS signal, FIG. 6A series of CARS spectra were obtained as shown in (d). The obtained CARS spectrum was 532 cm⁻¹. -1 , 786cm -1 , 1004cm -1 , and 1210cm -1 The Raman peak is shown. The spectral acquisition rate of the Quasi-DC-CARS spectrometer is 100,000 spectra / second, which is 10 times higher than the highest value reported by conventional DC-CARS spectroscopy and 2 times higher than the highest value reported by FT-CARS spectroscopy, which uses high-speed mechanical delayed sweeping. At 100,000 spectra / second, the group delayed sweep range is calculated to be 0.71 ps, which corresponds to 23.4 cm². -1 This corresponds to a spectral resolution of 532 cm². Although spectral resolution degrades because it is determined by the group delay sweep range which is inversely proportional to the modulation frequency, thanks to the highly energy-efficient Quasi-DC-CARS scheme, it is 532 cm². -1 , 1210cm -1 This allows for the recognition of spectral characteristics that were previously obscured by noise, including Raman peaks. A recently proposed method can improve spectral resolution without sacrificing spectral acquisition rate. This method improves the spectral resolution of Raman spectra obtained from time-domain interferograms measured in a limited time domain by assuming that the time-domain interferogram consists of multiple exponentially decaying synusoid functions.

[0051] Further quantitative analysis of SNR as a function of modulation frequency and sample concentration is described below. Approximately 1004 cm⁻¹ -1 It peaked at approximately 1780 cm. -1 The SNR of measured CARS spectra of toluene with an intensity standard deviation was evaluated at various spectral acquisition rates. As shown in Figure 7(a), by fitting, the SNR in conventional DC-CARS spectroscopy is (spectral acquisition rate) -0.489 It is proportional to and close to what is theoretically predicted when the noise floor is occupied by photon shot noise. On the other hand, the SNR in Quasi-DC-CARS spectroscopy is (spectral acquisition rate) -0.104It is proportional to this. The reason why the slope is smaller in this way is presumed to be because the origin of the noise is different from that of the conventional DC-CARS method, such as time fluctuations of the laser intensity where the repetition frequency is modulated at high speed. Specifically, through fitting, at a spectral acquisition rate of 100,000 spectra / second, the Quasi-DC-CARS spectroscopy method has an SNR that is about 20 times higher than that of the conventional DC-CARS spectroscopy method (assuming that 100,000 spectra / second is possible). In other words, thanks to the high energy efficiency, the Quasi-DC-CARS spectroscopy method at 100,000 spectra / second achieves the same SNR as the conventional DC-CARS spectroscopy method at 200 spectra / second. Furthermore, as shown in Figure 7(b), the sample concentration dependence of the SNR was analyzed using a toluene solution in ethanol. The SNR shows a quadratic dependence on the sample concentration, which can be explained by considering the interference between the CARS electric field and the local oscillator and the CARS signal originating from the square of the absolute value of the CARS electric field. The relationship between sample concentration and SNR demonstrates that Quasi-DC-CARS spectroscopy is effective for quantitative chemical analysis. Furthermore, as shown in Figure 7(c), a spectral acquisition rate of 100,000 spectra / second yields a sufficient SNR even at a low sample concentration of 0.4 mol / L.

[0052] Referring to Figure 8, a flowchart of Method 800, an example of Quasi-DC-CARS spectroscopy using a pseudo-dual-comb laser as the light source, is shown. Method 800 of this solution provides an unprecedentedly high CARS spectrum acquisition rate of 100,000 spectra / second, and is even more sensitive than conventional slow DC-CARS spectroscopy. Due to the significantly improved spectrum acquisition rate and sensitivity, Quasi-DC-CARS spectroscopy can be used in a wide range of applications, such as biomedical applications and materials science applications.

[0053] Firstly, video-rate imaging of living cells with vibrational fingerprints using laser-swept Quasi-DC-CARS spectroscopy not only provides an approach for intraoperative tissue diagnosis but also an approach for visualizing rapid intracellular dynamics such as signal transduction and substance transport. The high-frequency range (2700 cm²) covers CH / OH stretching. -1 ~3000cm -1 Compared to SRS imaging in the fingerprint region, Raman imaging in the fingerprint region provides more molecular information (approximately 10 times more bio-information than in the high-frequency region), which will help to gain deeper insights into the mechanisms of biological function.

[0054] Secondly, large-scale single-cell analysis based on coherent Raman spectroscopy is a novel method for characterizing cellular diversity and identifying rare cell subpopulations without the need for fluorescent labeling that could interfere with metabolic or other functions. While its application has been limited to microorganisms (e.g., microalgae) due to its low sensitivity, Quasi-DC-CARS spectroscopy opens the way to high-precision Raman flow cytometry of mammalian cells, which requires several orders of magnitude higher precision than in the case of microorganisms.

[0055] Thirdly, Quasi-DC-CARS spectroscopy will be useful for observing fast and non-repeating events such as phase transitions, polymerization, non-photochemical reactions, and blinking of surface-enhanced Raman scattering. Despite their importance in basic science and industry, the underlying mechanisms of these phenomena remain unclear due to the lack of methods that can observe them in real time. Quasi-DC-CARS spectroscopy will help elucidate these mechanisms.

[0056] As shown in Figure 8, method 800 begins in 802, and in the subsequent 804, a current (e.g., current 448 in Figure 4) is supplied from a function generator (e.g., function generator 416 in Figure 4) to the DPSS laser (e.g., DPSS laser 418 in Figure 4) of at least one of the laser sources (e.g., laser sources 302 and / or 304 in Figure 3) of a dual-comb laser source (e.g., dual-comb laser source 306 in Figure 3). In 806, the output intensity of the DPSS laser of the first laser source (e.g., laser source 302 in Figure 3) is fixed. Meanwhile, in 808, the output intensity of the DPSS laser of the second laser source (e.g., laser source 304 in Figure 3) is controlled by adjusting the strength of the current supplied from the function generator (e.g., current 448 in Figure 4). The output intensity of the DPSS laser is controlled to have a high or low intensity value based on a predetermined initial output intensity or a previously determined group delay value. The group delay value is well known, and the methods for determining the group delay value are also well known.

[0057] In step 810, the Ti:sapphire crystal (e.g., crystal 470 in Figure 4) of each laser light source (e.g., laser light sources 302 and 304 in Figure 3) is excited by the excitation laser light output from each DPSS laser. In step 812, each laser light source uses a laser resonator (e.g., laser resonator 472 in Figure 4) to control the frequency at which optical pulses are generated by the Ti:sapphire crystal. The frequency at which optical pulses are generated is also referred to in this application as the pulse repetition frequency or pulse frequency. In step 814, the first mirror of the laser resonator of each laser light source (e.g., mirror 414 in Figure 4) is used to generate pulsed laser light (e.g., laser light 440 in Figure 4). The first mirror transmits a portion of the incident light along the output path of the dual-comb laser light source. The pulsed laser light generated by the first laser light source (e.g., laser light source 302 in Figure 3) is referred to in this application as the first pulsed laser light, and the second laser light source (e.g., Figure 4) 3 In this application, the pulsed laser light generated by the laser light source 304) is referred to as the second pulsed laser light. The first pulsed laser light and the second pulsed laser light differ in their pulse repetition frequency or pulse frequency.

[0058] The first pulsed laser beam and the second pulsed laser beam are each separated into an output pulsed laser beam (e.g., pulsed laser beam 450 in Figure 4) and a feedback pulsed laser beam (e.g., feedback pulsed laser beam 452 in Figure 4). In 818, the output pulsed laser beam is emitted from a dual-comb laser light source.

[0059] In 820, each feedback pulse laser beam is converted into a feedback signal (e.g., feedback signal 432 in Figure 4). In 822, the feedback signal is used to control the position of the second mirror (e.g., mirror 408 in Figure 4) of the laser resonator, which is driven by a piezoelectric converter (e.g., piezoelectric converter 406 in Figure 4), thereby stabilizing the pulse repetition frequency of the output pulse laser beam.

[0060] In 824, the output intensity of the DPSS laser of at least the second laser source (e.g., laser source 304 in Figure 3) is arbitrarily adjusted. This adjustment may include transitioning the output intensity of the DPSS laser from a high intensity value to a low intensity value, or vice versa. By performing this intensity adjustment, it is possible to promote high-speed modulation of the difference in pulse repetition frequencies between the first and second laser sources (e.g., laser sources 302 and 304 in Figure 3). The graph shown in Figure 11 is useful for understanding that modulation of pulse repetition frequencies can be achieved by controlling the intensity of the DPSS laser of at least the second laser source.

[0061] As shown in 826, the dual-comb laser light source continues to emit two output pulsed laser beams. In 828, the two output pulsed laser beams combine with each other to generate a combined laser beam. In 830, the combined laser beam is directed along a first path where CARS signal measurements are performed (e.g., the path defined by branch 310 in Figure 3) and a second path where group delay measurements are performed by dichromatic interference (e.g., the path defined by branch 312 in Figure 3). CARS signal measurements and group delay measurements are well known, and the methods for determining them are also well known. In 832, the group delay measurements are optionally used to match the phase repetition frequencies of the first pulsed laser beam and the second pulsed laser beam, and / or to calibrate the phase of each Raman active mode in the sample in the first path (e.g., sample 320 in Figure 3). Then, in 834, method 800 is terminated, at least part of method 800 is repeated, or other operations are performed.

[0062] Referring to Figure 9, a flowchart of Method 900, which is an example of a method for measuring or determining a group delay based on TCI, is shown. Method 900 can be performed in block 830 of Figure 8 to perform a group delay measurement.

[0063] Method 900 begins in 902, and continues in 904, using a diffraction grating (e.g., diffraction grating 328 in Figure 3) to spatially disperse the combined laser beam into two laser beams of approximately equal intensity but different frequencies (e.g., laser beams 330 and 332 in Figure 3). These laser beams are then made to travel along different optical paths, as shown in 906. In 908, a photodetector (e.g., photodetector 336 or 338 in Figure 3) is used to detect and measure the intensity of each laser beam over a period of time. In 906, a Fourier transform is used to convert each photodetector measurement from the time domain to the frequency domain, generating a spectrum with multiple peaks. In 908, a masked spectrum is generated using a mask function to remove unwanted frequency components from each spectrum. As shown in 910, the complex dichromatic interference signal is reconstructed by performing an inverse Fourier transform on each of the masked spectra. In 912, the phase delay between the two laser beams is calculated based on the reconstructed complex dichromatic interference signal. Such phase delay calculations are well known. Based on the phase delay, a group delay measurement between two pulses is determined. Such group delay measurement determinations are well known. Then, in 916, method 900 is terminated, at least part of method 900 is repeated, or other operations are performed.

[0064] Referring to Figure 10, a hardware block diagram is shown of an exemplary computer system 1000 that can be used to implement all or some of the components 340 of Figure 3 and / or components 402, 416, and 428 of Figure 4. The machine may have a set of instructions used to cause the circuit / computer system to perform any one or more of the methods discussed in this application. Although only a single machine is shown in Figure 10, it should be understood that in other scenarios, the system may include any collection of multiple machines that perform one or more sets of instructions individually or together, as described in this application.

[0065] The computer system 1000 comprises a processor 1002 (e.g., a central processing unit (CPU)), main memory 1004, static memory 1006, a drive unit 1008 for large-capacity data storage having a machine-readable medium 1020, an input / output device 1010, a display unit 1012 (e.g., a liquid crystal display (LCD)) or a solid-state display, and one or more interface devices 1014. Communication between these various components can be facilitated by a data bus 1018. One or more sets of instructions 1024 can be stored in whole or in part in one or more of the main memory 1004, static memory 1006, and drive unit 1008. While the computer system is executing an instruction, the instruction may also reside in the processor 1002. The input / output device 1010 may include a keyboard, a multi-touch surface (e.g., a touchscreen), etc. The interface device 1014 may include hardware components and software or firmware to facilitate interfacing with external circuits. For example, in one scenario, the interface device 1014 may have one or more analog-to-digital (A / D) converters, digital-to-analog (D / A) converters, input voltage buffers, output voltage buffers, voltage drivers, and / or comparators. By connecting these components to a communication line, a computer system can decode signal inputs received from an external circuit and generate control signals necessary for the specific operations described in this application.

[0066] The drive unit 1008 has a machine-readable medium 1020 storing one or more sets of instructions 1024 (e.g., software) used to trigger one or more of the methods and functions described in this application. The term “machine-readable medium” will be understood to include any tangible medium capable of storing instructions or data structures that trigger any one or more of the methods of this disclosure. Examples of machine-readable mediums include solid memory, Electrically Erasable Programmable Read-Only Memory (EEPROM), and flash memory devices. The tangible mediums described in this application are non-transient mediums insofar as they do not contain propagated signals.

[0067] It should be understood that computer system 1000 is a possible example of a computer system that can be adopted in connection with the various implementations disclosed in this application. However, the systems and methods disclosed in this application are not limited, and other suitable computer system architectures can also be adopted without limitation. Similarly, dedicated hardware implementations, including but not limited to application-specific integrated circuits, programmable logic arrays, and other hardware devices, can also be configured to implement the methods described in this application. Applications that may include the devices and systems encompass a wide range of electronic and computer systems. Thus, examples of systems are applicable to software, firmware, and hardware implementations.

[0068] Furthermore, it should be understood that this embodiment may take the form of a computer program product on a tangible computer-usable storage medium (e.g., a hard disk or CD-ROM). A computer-usable storage medium may have computer-usable program code embodied within the medium. As used in this application, the term "computer program product" refers to a device comprising all features capable of carrying out the method described in this application. Computer program, software application, computer software routine, and / or other variations of these terms mean, in the present context, any expression of a set of instructions intended to cause a system having information processing capabilities to perform a particular function, either directly or after either or both of the following: a) conversion to another language, code, or notation, or b) reproduction in a different material form.

[0069] The features, advantages, and characteristics disclosed and described in this application can be combined in appropriate ways. Those skilled in the art will recognize, in light of the description in this application, that the disclosed systems and / or methods can be implemented without one or more specific features. In other examples, additional features and advantages may be recognized in specific scenarios not presented in all examples.

[0070] In this application, the singular forms "a," "an," and "the" include plural references unless otherwise specified in the context. Unless otherwise defined, all technical and scientific terms used in this application have the same meaning as generally understood by those skilled in the art. In this application, the term "comprising" means "including, but not limited to."

[0071] While systems and methods have been illustrated and described in relation to one or more embodiments, equivalent modifications and variations will be conceivable to those skilled in the art by reading and understanding this specification and the accompanying drawings. Furthermore, certain features may be disclosed in relation to only one of several embodiments, but such features may be combined with one or more other features of other embodiments so as to be desirable and advantageous for any or particular application. Accordingly, the breadth and scope of this disclosure should not be limited by any of the foregoing description. Rather, the scope of the invention should be defined according to the following claims and their equivalents.

Claims

1. A method for operating a dual-comb laser, The dual-comb laser generates a first pulse laser beam and a second pulse laser beam, respectively, with the first pulse laser beam and the second pulse laser beam having different pulse repetition frequencies, and at least one of the first and second laser light sources comprises a diode-pumped solid-state laser whose excitation laser beam output intensity can be changed, and a crystal as a laser gain medium excited by the excitation laser beam output from the diode-pumped solid-state laser. By selectively changing the output intensity of the diode-pumped solid-state laser, the refractive index of the crystal is changed in accordance with the excitation power due to the nonlinear optical Kerr effect, thereby matching the phase repetition frequencies of the first pulse laser beam and the second pulse laser beam. including, method.

2. The first laser light source comprises a diode-pumped solid-state laser having a fixed output intensity, The method according to claim 1, wherein the second laser light source comprises the diode-pumped solid laser whose output intensity can be changed.

3. The first optical device generates a laser beam consisting of a pump pulse and a probe pulse by combining the first pulsed laser beam and the second pulsed laser beam. The computing device further includes determining the group delay value between the pump pulse and the probe pulse using two-color interference, Based on the group delay value, the output intensity of the diode-pumped solid laser is selectively changed. The method according to claim 1, wherein the two-color interference includes dispersing the laser light into two lights of different optical frequencies using a second optical device, measuring the light intensity of the two lights using a photodetector, and determining the group delay value using the measured light intensity with the computing device.

4. The method according to claim 1, wherein the output intensity of the diode-pumped solid-state laser is selectively changed by transitioning the diode-pumped solid-state laser from a first output intensity value to a different second output intensity value.

5. The method according to claim 1, wherein the output intensity of the diode-pumped solid-state laser is selectively changed by changing the current supplied to the diode-pumped solid-state laser.

6. The first optical device generates a laser beam consisting of a pump pulse and a probe pulse by combining the first pulsed laser beam and the second pulsed laser beam. The computing device further includes determining the group delay value between the pump pulse and the probe pulse using two-color interference, The current changes according to the group delay value. The method according to claim 5, wherein the two-color interference includes dispersing the laser light into two lights of different optical frequencies using a second optical device, measuring the light intensity of the two lights using a photodetector, and determining the group delay value using the measured light intensity with the computing device.

7. A feedback signal is generated using one of the first pulsed laser beam and the second pulsed laser beam. Using the aforementioned feedback signal, the position of the mirror of the laser resonator of the first laser light source or the second laser light source, which is driven by a piezoelectric converter, The method according to claim 1, further comprising:

8. The method according to claim 1, further comprising modulating the difference in pulse repetition frequencies of the first laser light source and the second laser light source.

9. A first laser light source that generates a first pulse laser beam and a second laser light source that generates a second pulse laser beam, wherein the first pulse laser beam and the second pulse laser beam have different pulse repetition frequencies, and at least one of the first laser light source and the second laser light source comprises a diode-pumped solid-state laser whose output intensity of the excitation laser beam can be changed, and a crystal as a laser gain medium excited by the excitation laser beam output from the diode-pumped solid-state laser, A circuit for selectively changing the output intensity of the diode-pumped solid laser in order to match the phase repetition frequencies of the first pulse laser beam and the second pulse laser beam, Equipped with, A dual-comb laser in which the phase repetition frequencies of the first pulse laser beam and the second pulse laser beam are matched by changing the output intensity of the diode-pumped solid-state laser, thereby changing the refractive index of the crystal in accordance with the excitation power due to the nonlinear optical Kerr effect.

10. The first laser light source comprises a diode-pumped solid-state laser having a fixed output intensity, The dual-comb laser according to claim 9, wherein the second laser light source comprises the diode-pumped solid-state laser whose output intensity can be changed.

11. Based on the group delay value between the pump pulse and probe pulse of the laser light generated by combining the first pulsed laser light and the second pulsed laser light, which is determined using dichromatic interference, the output intensity of the diode-pumped solid-state laser is selectively changed. The dual-comb laser according to claim 9, wherein the two-color interference comprises dispersing the laser light into two lights of different optical frequencies, measuring the light intensity of the two lights, and determining the group delay value using the measured light intensities.

12. The dual-comb laser according to claim 9, wherein the output intensity of the diode-pumped solid-state laser is selectively changed by transitioning the diode-pumped solid-state laser from a first output intensity value to a different second output intensity value.

13. The dual-comb laser according to claim 9, wherein the output intensity of the diode-pumped solid-state laser is selectively changed by changing the current supplied to the diode-pumped solid-state laser.

14. The current changes according to the group delay value between the pump pulse and probe pulse of the laser light generated by combining the first pulsed laser light and the second pulsed laser light, which is determined using dichromatic interference. The dual-comb laser according to claim 13, wherein the two-color interference includes dispersing the laser light into two lights of different optical frequencies, measuring the light intensity of the two lights, and determining the group delay value using the measured light intensities.

15. The circuit further, (i) A feedback signal is generated using one of the first pulsed laser beam and the second pulsed laser beam. (ii) The dual-comb laser according to claim 9, wherein the position of the mirror of the laser resonator of the first laser light source or the second laser light source, which is driven by a piezoelectric converter, is controlled using the feedback signal.

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