Spectroscopic device and spectroscopic method using time-resolved encoding
Through time-resolved coding analysis method and orthogonal code signal demodulation technology, the problem of noise signal removal in molecular diagnosis is solved, the signal-to-noise ratio and measurement efficiency are improved, and the accuracy and resolution of molecular diagnosis are improved.
Patent Information
- Application Number
- CN202080043871.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Priority Date
- 2019-10-29
- Filing Date
- 2020-07-14
- Publication Date
- 2024-12-17
- Estimated Expiration
- 2040-07-14
AI Technical Summary
Existing molecular diagnostic techniques are difficult to effectively remove noise signals when measuring biomolecules, resulting in low signal-to-noise ratio, long measurement time, insufficient accuracy, resolution and clarity.
The time-resolved encoding analysis method is used to irradiate the incident beam to the sample by generating a pulsed laser beam with a short pulse width, and demodulate the correlation between the orthogonal code signal and the detection signal to remove the noise signal to improve the Raman signal. signal-to-noise ratio.
It improves the signal-to-noise ratio of biomolecules, reduces the measurement time required for molecular diagnosis, and improves the accuracy, resolution and clarity of molecular diagnosis.
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Figure CN113994195B_ABST
Abstract
Description
Technical Field
[0001] The inventive concept relates to a spectroscopic device and a spectroscopic method, and more particularly, to a spectroscopic device and a spectroscopic method for analyzing biomolecules using time-resolved encoding. Background Art
[0002] Recently, the demand for personalized medicine has been increasing to diagnose diseases early and improve survival rates through appropriate treatment. In particular, there is a growing need for molecular diagnostic technologies that can accurately measure and analyze diseases at the molecular level, such as deoxyribonucleic acid (DNA) or ribonucleic acid (RNA).
[0003] As molecular diagnostic techniques, there are PCR (polymerase chain reaction) diagnostics and Raman spectroscopy. PCR diagnostics is a method of replicating and amplifying a desired portion of a nucleic acid by polymerase chain reaction, and measuring a signal emitted from a fluorescent marker attached to the amplified nucleic acid. Raman spectroscopy is a method of measuring and analyzing scattered light generated by vibration of nucleic acid molecules in a sample excited by light. Summary of the invention
[0004] [Technical issues]
[0005] The problem to be solved by the inventive concept is to provide a spectroscopic device and a spectroscopic method for analyzing biomolecules using time-resolved coding.
[0006] [Technical solution]
[0007] According to an embodiment of the present invention, a spectroscopic device includes: a laser irradiation device, which receives an orthogonal code including a bit sequence, each bit having a first value or a second value; generates a control signal having a pulse in a bit portion corresponding to a bit having a first value in the bit sequence, and the width of the pulse is shorter than the width of the above-mentioned bit portion; uses the pulse included in the control signal as a trigger to generate a pulse laser beam having a pulse width shorter than the above-mentioned bit portion; and irradiates an incident light beam including the generated pulse laser beam to a sample; and a detector, which receives a detection signal and an orthogonal code generated from the sample irradiated by the incident light beam; generates an orthogonal code signal having a waveform identical to that of the incident light beam based on the orthogonal code; and demodulates the Raman signal based on the correlation between the generated orthogonal code signal and the Raman signal included in the detection signal.
[0008] In an exemplary embodiment, the control signal has a first voltage or a second voltage greater than the first voltage, has the first voltage after having the second voltage in a bit portion corresponding to a bit having a first value in a bit sequence, and maintains the first voltage in another bit portion corresponding to a bit having a second value in the bit sequence.
[0009] In an exemplary embodiment, the laser irradiation device also generates a pulse laser beam using a rising edge of a pulse included in the control signal as a trigger.
[0010] In an exemplary embodiment, the laser irradiation device also generates a pulse laser beam using a falling edge of a pulse included in the control signal as a trigger.
[0011] In an exemplary embodiment, the laser irradiation apparatus includes: a master oscillator that receives an orthogonal code and outputs a time-resolved beam including a pulsed laser beam; and a power amplifier that receives the time-resolved beam and amplifies the time-resolved beam to irradiate an incident beam to a sample.
[0012] In an exemplary embodiment, the master oscillator includes: a control signal generator that receives an orthogonal code and outputs a control signal based on the received orthogonal code; a controller that receives the control signal and outputs a trigger signal for generating a pulsed laser beam based on the control signal; and a light source that receives the trigger signal, includes time-resolved width information for determining a pulse width of the pulsed laser beam, and outputs a time-resolved light beam based on the received trigger signal and the time-resolved width information.
[0013] In an exemplary embodiment, the power amplifier includes an isolator that receives the time-resolved light beam and blocks light reflected back to the light source.
[0014] In an exemplary embodiment, a power amplifier includes: a first pump laser that outputs a first pump laser beam for optically pumping a gain medium; and a coupler that couples the time-resolved optical beam and the first pump laser beam.
[0015] In an exemplary embodiment, the power amplifier further includes a second pump laser that outputs a second pump laser beam for optically pumping the gain medium, and the coupler is further configured to couple the time-resolved optical beam, the first pump laser beam, and the second pump laser beam.
[0016] In an exemplary embodiment, the power amplifier includes a filter that passes a laser beam corresponding to the wavelength of the time-resolved light beam and blocks noise.
[0017] In an exemplary embodiment, the power amplifier includes: a first amplification stage, which receives a time-resolved beam and amplifies the received time-resolved beam to output a first amplified time-resolved beam; a second amplification stage, which receives the first amplified time-resolved beam and outputs a second amplified time-resolved beam in which the first amplified time-resolved beam is further amplified; and a third amplification stage, which receives the second amplified time-resolved beam and irradiates the incident beam in which the second amplified time-resolved beam is further amplified to the sample.
[0018] The spectroscopic method according to an embodiment of the present invention includes: generating an orthogonal code including a bit sequence, each bit having a first value or a second value; generating a control signal having a pulse in a bit portion corresponding to a bit having a first value in the bit sequence, the width of the pulse being shorter than the width of the above-mentioned bit portion; using the pulse included in the control signal as a trigger, generating a pulse laser beam having a pulse width shorter than the bit portion, and irradiating an incident light beam including the generated pulse laser beam to a sample; receiving a detection signal output from the sample irradiated by the incident light beam; generating an orthogonal code signal having a waveform identical to that of the incident light beam based on the orthogonal code, and demodulating the Raman signal by calculating an autocorrelation coefficient based on the correlation between the orthogonal code signal and the Raman signal included in the detection signal.
[0019] In an exemplary embodiment, the detection signal includes: a Raman signal having a first intensity and received at a first time; and a noise signal having a second intensity greater than the first intensity and received at a second time later than the first time.
[0020] In an exemplary embodiment, the demodulation of the Raman signal further includes removing the noise signal based on a correlation between the orthogonal code signal and the noise signal, and the intensity of the demodulated Raman signal is greater than the intensity of the removed noise signal.
[0021] In an exemplary embodiment, the detection signal includes a Raman signal having a first lifetime and a noise signal having a second lifetime longer than the first lifetime, and a pulse width of the pulse laser beam is longer than the first lifetime and shorter than the second lifetime.
[0022] [Beneficial Effects]
[0023] According to an embodiment of the inventive concept, a spectroscopic apparatus and a spectroscopic method for improving a signal-to-noise ratio of a biomolecule by removing a noise signal are provided.
[0024] Furthermore, a spectroscopic apparatus and a spectroscopic method are provided which reduce the measurement time required for molecular diagnosis and improve the accuracy, resolution and clarity of molecular diagnosis. BRIEF DESCRIPTION OF THE DRAWINGS
[0025] Figure 1 is a diagram illustrating a light splitting device according to an embodiment of the inventive concept.
[0026] Figure 2 is a flowchart illustrating a PCR molecular diagnosis method according to an embodiment of the inventive concept.
[0027] Figure 3 is a flowchart illustrating a Raman spectroscopic method according to an embodiment of the inventive concept.
[0028] Figure 4a is a diagram exemplarily describing a Raman scattering signal generated from a sample.
[0029] Figure 4b It shows that according to Figure 4a A graph of the energy level diagram of the sample molecules generated by the Raman scattering signal.
[0030] Figure 5 is a block diagram illustrating a Raman spectroscopic apparatus using a spread spectrum code according to an embodiment of the inventive concept.
[0031] Figure 6 It is shown by Figure 5 A graph of the signal generated by the laser irradiation device.
[0032] Figure 7 It is shown by Figure 5 A graph of the signal processed by the detector.
[0033] Figure 8 is a block diagram exemplarily describing a Raman spectroscopic apparatus using time-resolved encoding according to an embodiment of the inventive concept.
[0034] Fig. 9 It is described exemplarily Figure 8 Block diagram of the master oscillator.
[0035] Fig.10 It is described exemplarily Figure 8 Block diagram of a power amplifier.
[0036] Fig.11a It is described exemplarily Fig.10 Block diagram of the first amplifier stage.
[0037] Fig.11b It is described exemplarily Fig.10 Block diagram of the third amplifier stage.
[0038] Fig.12 It is shown by Figure 8 A graph of the signal generated by the laser irradiation device.
[0039] Fig.13 It is shown by Figure 8 A graph of the signal processed by the detector.
[0040] Fig.14 It is shown that according to Figure 8 Plot of the correlation coefficient of the modulation frequency of the detector processed signal.
[0041] Fig.15 is a flowchart illustrating a spectroscopic method for restoring a Raman signal according to an embodiment of the inventive concept.
[0042] [Best Mode]
[0043] Fig.15 It is a diagram showing the best mode for carrying out the inventive concept. DETAILED DESCRIPTION
[0044] Hereinafter, embodiments of the present inventive concept will be described clearly and in detail so that those skilled in the art can easily implement the present inventive concept.
[0045] Figure 1 is a diagram showing a spectroscopic device according to an embodiment of the inventive concept. Figure 1 , the spectroscopic device 100 may include a laser irradiation device 110 and a detector 120. The spectroscopic device 100 may be a device for analyzing a sample SP. In this case, the sample SP may be a biological sample molecule to be analyzed. For example, the sample SP may be feces including nucleic acids such as DNA and RNA.
[0046] The laser irradiation device 110 may irradiate an incident light beam IB to the sample SP. The incident light beam IB may be a laser beam generated by the laser irradiation device 110. A detection signal DS may be output from the sample SP irradiated by the incident light beam IB. The detection signal DS may be a signal including molecular information of the sample SP. For example, the detection signal DS may be light emitted or scattered from the sample SP irradiated by the incident light beam IB.
[0047] The detector 120 may receive a detection signal DS generated from the sample SP. The detector 120 may analyze the sample SP based on the received detection signal DS. For example, the detector 120 may detect a signal including information of a virus that is contained in a stool sample and causes a disease.
[0048] As described above, according to an embodiment of the inventive concept, by irradiating an incident light beam to a sample SP, and by receiving and analyzing a detection signal DS generated from the sample SP, a spectroscopic apparatus 100 for analyzing a sample SP may be provided.
[0049] Figure 2 1 is a flow chart showing a PCR molecular diagnostic method according to an embodiment of the present invention. Figure 1 The spectroscopic device 100 is described according to Figure 2 Flow chart of the PCR molecular diagnostic method. Figure 1 and Figure 2 , a PCR molecular diagnostic method using polymerase chain reaction is shown as an example.
[0050] In step S110 , pre-processing may be performed on the sample SP. For example, step S110 may be a step of performing centrifugation, DNA binding, washing, elution, and plasmid DNA purification on the sample SP.
[0051] In step S111, the spectroscopic device may use PCR to amplify the DNA of the target molecule. For example, the pre-treated sample SP may be subjected to PCR amplification. PCR amplification may be a process of replicating and amplifying a desired portion of a nucleic acid based on a polymerase chain reaction. For example, step S111 may be a step of performing DNA denaturation, primer annealing, and DNA extension. In an exemplary embodiment, after performing step S111, a step of attaching a fluorescent marker to the sample SP subjected to PCR amplification may also be performed.
[0052] In step S120, the laser irradiation device 110 may irradiate the incident beam IB to the sample SP undergoing PCR amplification. A detection signal DS may be generated from the sample SP irradiated by the incident beam IB. In this case, the detection signal DS may include a fluorescent signal emitted from a fluorescent marker attached to the sample SP.
[0053] In step S130, the detector 120 may measure a fluorescent signal emitted from the sample SP. The detector 120 may analyze the sample SP based on the measured fluorescent signal. In an exemplary embodiment, by repeatedly performing the preprocessing step S110, a fluorescent signal with reduced noise and increased intensity may be measured.
[0054] Figure 3 FIG. 1 is a flow chart showing a Raman spectroscopic method according to an embodiment of the present invention. Figure 1 The spectroscopic device 100 is described according to Figure 3 Flow chart of the Raman spectroscopic method. Figure 1 and Figure 3 , a Raman spectroscopy method is shown as an example.
[0055] In step S210, non-destructive pre-processing may be performed on the sample SP. Figure 2 In contrast to the pretreatment step S110 and the PCR amplification step S111, in step S210, the treatment of destroying the cell wall and amplifying the nucleic acid can be omitted. In an exemplary embodiment, step S210 can be omitted. Therefore, a spectroscopic method that shortens the time required for diagnosis can be provided.
[0056] In step S220, the laser irradiation device 110 may irradiate the incident light beam IB to the sample SP. A detection signal DS may be generated from the sample SP irradiated by the incident light beam IB. In this case, the detection signal DS may include a Raman signal and a noise signal. For example, the noise signal may include a fluorescence noise signal.
[0057] In step S230, the detector 120 may measure the Raman signal scattered from the sample SP. The detector 120 may analyze the sample SP based on the measured Raman signal. In this case, the Raman signal may have a relative Figure 2 The fluorescence signal measured in step S130 has a narrower bandwidth, a shorter lifetime, and a weaker intensity signal. In an exemplary embodiment, when the detector 120 analyzes the sample SP using a signal having a narrow bandwidth, the measurement resolution of the sample SP may be high.
[0058] As described above, according to an embodiment of the inventive concept, a Raman spectroscopic method with improved measurement resolution can be provided by analyzing a sample based on a Raman signal having a bandwidth narrower than a fluorescent signal. Figure 2 S111 in the figure) can provide a Raman spectroscopy method that shortens the time required for diagnosis.
[0059] Figure 4a is a diagram exemplarily describing a Raman scattering signal generated from a sample. Figure 4a , scattering signals S1 to S3 generated from a sample SP irradiated by an incident light beam IB are shown as examples. The incident light beam IB may be a laser beam having an incident frequency v0. The energy of the incident light beam IB may be "hv0". In this case, "h" may be the Boltzmann constant. The vibration energy of the sample SP irradiated by the incident light beam IB may be increased, maintained, or decreased.
[0060] In an exemplary embodiment, the first scattered signal S1 may be generated from the sample SP irradiated by the incident light beam IB. The first scattered signal S1 may be a Stokes scattering signal. In this case, the energy of the sample SP after being irradiated by the incident light beam IB may be greater than the energy of the sample SP before being irradiated by the incident light beam IB. The energy h(v0-v v ) can be smaller than the energy hv0 of the incident light beam IB.
[0061] In an exemplary embodiment, the second scattered signal S2 may be generated from the sample SP irradiated by the incident light beam IB. The second scattered signal S2 may be a Rayleigh scattering signal. In this case, the energy of the sample SP after being irradiated by the incident light beam IB may be the same as the energy of the sample SP before being irradiated by the incident light beam IB. The energy hv0 of the second scattered signal S2 may be the same as the energy hv0 of the incident light beam IB.
[0062] In an exemplary embodiment, the third scattered signal S3 may be generated from the sample SP irradiated by the incident light beam IB. The third scattered signal S3 may be an anti-Stokes scattering signal. In this case, the energy of the sample SP after being irradiated by the incident light beam IB may be less than the energy of the sample SP (e.g., sample molecules) before being irradiated by the incident light beam IB. The energy h(v0+v v ) can be greater than the energy hv0 of the incident light beam IB.
[0063] As described above, according to an embodiment of the inventive concept, the Raman scattering signal generated from the sample molecules irradiated by the incident light beam IB may include a first scattering signal S1 as a Stokes scattering signal, a second scattering signal S2 as a Rayleigh scattering signal, and a third scattering signal S3 as an anti-Stokes scattering signal.
[0064] Figure 4b It is shown that according to Figure 4a A graph showing the process of generating Raman scattering signals by the vibration energy of sample molecules caused by the incident light beam. Figure 4b , a process of generating each of the scattered signals S1 to S3 according to the vibration energy of the sample molecules is shown as an example.
[0065] In addition, a process of generating a first resonant Raman scattering signal RRS1 according to the energy change of the sample molecules caused by the incident light beam is shown. The first resonant Raman scattering signal RRS1 may be a Stokes scattering signal generated based on the resonant Raman effect. The resonant Raman effect may be when the irradiation has a resonant energy E R The resonance energy E significantly increases the intensity of the Raman scattering signal when the incident beam is R It can represent the interval between the possible energies of electrons of a particular material. For example, the resonance energy E R It can be the band gap of the sample.
[0066] Referring to the process of generating the first scattering signal S1 according to the vibration energy of the sample caused by the incident light beam, the sample before being irradiated by the incident light beam may have energy at the ground state level ES0. The spectroscopic device may irradiate the sample with the incident light beam having energy "hv0". The sample excited by the incident light beam may have energy at the first virtual state level EVT1. A scattering signal having energy "h(v0-v v )”. The sample generating the first scattered signal S1 may have an energy of a vibrational state level EVB. That is, the energy of the sample irradiated by the incident light beam may increase “hv v ”.
[0067] Referring to the process of generating the second scattering signal S2 according to the vibration energy of the sample caused by the incident light beam, the sample before being irradiated by the incident light beam may have energy at the ground state level ES0. The spectroscopic device may irradiate the sample with an incident light beam having energy "hv0". The sample excited by the incident light beam may have energy at the first virtual state level EVT1. A second scattering signal S2 having energy "hv0" may be generated from the excited sample. The sample generating the second scattering signal S2 may have energy at the ground state level ES0. That is, the energy of the sample after being irradiated by the incident light beam may be the same as the energy of the sample before being irradiated by the incident light beam.
[0068] In an exemplary embodiment, the second scattered signal S2 may be a signal that is not suitable for reflecting the characteristics of the sample. In more detail, the second scattered signal S2 may have the same energy as the incident light beam. The second scattered signal S2 may not reflect the energy change caused by the molecular vibration of the sample. In other words, the second scattered signal S2 may be a signal that does not reflect the characteristics of the sample.
[0069] Referring to the process of generating the third scattered signal S3 according to the vibration energy of the sample caused by the incident light beam, the sample before being irradiated by the incident light beam may have energy at the vibration state level EVB. The spectroscopic device may irradiate the sample with the incident light beam having energy "hv0". The sample excited by the incident light beam may have energy at the second virtual state level EVT2. A signal having energy "h(v0+v v )”. The sample generating the third scattered signal S3 may have an energy of the ground state level ES0. That is, the energy of the sample irradiated by the incident light beam may be reduced by “hv v ”.
[0070] Referring to the process of generating the first resonant Raman scattering signal RRS1 according to the vibration energy caused by the incident light beam, the sample before being irradiated by the incident light beam may have energy at the ground state level ES0. R Equal energy "hv r The incident light beam of " is irradiated to the sample. The sample excited by the incident light beam may have energy of the first energy state level ES1. A light having energy "h(v r -v v )”. The sample generating the first resonant Raman scattering signal RRS1 may have an energy of a vibrational state level EVB. That is, the energy of the sample irradiated by the incident light beam may increase “hv v ”.
[0071] In an exemplary embodiment, the resonance energy E RThe incident light beam is irradiated onto the sample to provide a spectroscopic device for measuring a resonant Raman scattering signal having a stronger intensity than a typical Raman scattering signal. R The energy h(v r -v v ) can be greater than the resonance energy E R The energy h(v0-v v ).
[0072] As described above, according to an embodiment of the inventive concept, a spectroscopic device can be provided, which reflects the characteristics of a sample and analyzes the characteristics of the sample based on the third scattered signal S3 or the first scattered signal S1. R The incident light beam is irradiated onto the sample, and a spectroscopic device for measuring a first resonant Raman scattering signal RRS1 having an intensity stronger than that of the first scattering signal S1 can be provided.
[0073] Figure 5 is a block diagram showing a spectroscopic device according to an embodiment of the present inventive concept. Figure 5 , the spectroscopic apparatus 200 may include a laser irradiation device 210, a detector 220, and a code generator 230. The spectroscopic apparatus 200 may be a spectroscopic apparatus that analyzes a Raman signal included in a first detection signal DS1 generated from a sample SP.
[0074] The code generator 230 may generate an orthogonal code OC. The orthogonal code OC may be a code having mathematical orthogonality with other codes. The orthogonal code OC may include a plurality of bits corresponding to a digital sequence. The code generator 230 may output the generated orthogonal code OC to the laser irradiation device 210 and the detector 220.
[0075] In an exemplary embodiment, the laser irradiation device 210 and the detector 220 may be synchronized based on the orthogonal code OC output from the code generator 230. In more detail, the orthogonal code OC may allow the laser irradiation device 210 to modulate the continuous wave signal CW. The orthogonal code OC may allow the detector 220 to demodulate the first detection signal DS1.
[0076] The laser irradiation device 210 may include a continuous wave laser 211 and a modulator 212. The continuous wave laser 211 may generate a continuous wave signal CW. The continuous wave signal CW may be a laser beam having a uniform intensity. The modulator 212 may receive the continuous wave signal CW from the continuous wave laser 211. The modulator 212 may receive an orthogonal code OC from the code generator 230. The modulator 212 may irradiate the sample SP with a first incident light beam IB1 obtained by modulating the continuous wave signal CW into an orthogonal code OC pattern.
[0077] The detector 220 may include a sensor 221, a code signal processor 222, a demodulator 223, and a processor 224. The sensor 221 may receive a first detection signal DS1 from the sample SP. The sensor 221 may sense the received first detection signal DS1. The sensor 221 may output the sensed first detection signal DS1 to the demodulator 223. That is, the sensor 221 may be a module that senses the first detection signal DS1 output from the sample SP, converts the sensed first detection signal DS1 into an electrical signal that can be processed by the demodulator 223, and then transmits the electrical signal.
[0078] The code signal processor 222 may receive the orthogonal code OC from the code generator 230. The code signal processor 222 may output a first orthogonal code signal OCS1 based on the received orthogonal code OC. The first orthogonal code signal OCS1 may be an electrical signal having the same waveform as the first incident light beam IB1. For example, the timing of the first orthogonal code signal OCS1 corresponding to a specific bit of the orthogonal code OC may be the same as the timing of the first incident light beam IB1.
[0079] The demodulator 223 may receive the first detection signal DS1 from the sensor 221. The demodulator 223 may receive the first orthogonal code signal OCS1 from the code signal processor 222. The demodulator 223 may output a first demodulated detection signal DDS1.
[0080] The first demodulated detection signal DDS1 may be a signal obtained by demodulating the first detection signal DS1 by calculating an autocorrelation coefficient based on the correlation between the first detection signal DS1 and the first orthogonal code signal OCS1. That is, the demodulator 223 may be a module that restores the first detection signal DS1 based on the first orthogonal code signal OCS1.
[0081] The processor 224 may receive the first demodulated detection signal DDS1 from the demodulator 223. The processor 224 may analyze molecular information of the sample SP through a combination of Raman frequencies corresponding to peaks of the Raman signal appearing in the Raman spectrum based on the Raman signal included in the first demodulated detection signal DDS1.
[0082] In an exemplary embodiment, due to the noise reduction effect of the delta function-like autocorrelation property of the orthogonal code, the signal-to-noise ratio of the first demodulated detection signal DDS1 obtained based on the orthogonal code OC can be greater than the signal-to-noise ratio of the detection signal that is not modulated and demodulated by the code and the signal-to-noise ratio of the detection signal demodulated based on an arbitrary code (e.g., a universal code with poor autocorrelation property). The signal-to-noise ratio may refer to the intensity of the Raman signal divided by the intensity of the noise signal. In this case, the arbitrary code may refer to a code that does not have mathematical orthogonality with other codes.
[0083] As described above, according to an embodiment of the inventive concept, a spectroscopic device may be provided that irradiates a first incident beam IB1 obtained by modulating a continuous wave signal CW based on an orthogonal code OC to a sample SP and demodulates a first detection signal DS1 output from the sample SP to analyze the sample SP.
[0084] Figure 6 It is shown by Figure 5 A graph of the signal generated by the laser irradiation device. Figure 5 and Figure 6 , a bit sequence included in the orthogonal code OC, a waveform of the continuous wave signal CW, and a waveform of the first incident light beam IB1 are shown as examples. The modulator 212 may output the first incident light beam IB1 obtained by modulating the continuous wave signal CW based on the orthogonal code OC to the sample SP.
[0085] The orthogonal code OC may be a code including a bit sequence. The bit sequence may be a code having mathematical orthogonality with the bits of other codes. The value of each bit may be "1" or "0". For example, the value of the bit sequence included in the orthogonal code OC may be "10011100".
[0086] In an exemplary embodiment, the first incident light beam IB1 may irradiate the sample in a portion corresponding to a bit having a value of "1" among the bits included in the orthogonal code OC. The first incident light beam IB1 may not irradiate the sample in a portion corresponding to a bit having a value of "0" among the bits included in the orthogonal code OC.
[0087] In an exemplary embodiment, the modulator 212 may modulate the continuous wave signal CW so that the length of a portion corresponding to each of the bits included in the orthogonal code OC becomes the first time T1.
[0088] Figure 7 It is shown by Figure 5 A graph of the signal processed by the detector. Figure 5 and Figure 7, shows the first Raman signal RS1 and the first noise signal NS1 included in the first detection signal DS1. In addition, the first demodulated Raman signal DRS1 and the first noise-removed signal DNS1 included in the first demodulated detection signal DDS1 are shown.
[0089] In an exemplary embodiment, the demodulator 223 may receive the first detection signal DS1 including the first Raman signal RS1 and the first noise signal NS1. The demodulator 223 may receive the first orthogonal code signal OCS1 from the code signal processor 222. In this case, the waveform of the first orthogonal code signal OCS1 may be the same as Figure 6 That is, the first orthogonal code signal OCS1 may be a signal synchronized with the first incident light beam IB1.
[0090] The first Raman signal RS1 may have a lower intensity than the first noise signal NS1. The first Raman signal RS1 may have a shorter lifetime than the first noise signal NS1. The first Raman signal RS1 may be a signal measured prior to the first noise signal NS1 in time. For example, the first noise signal NS1 may be a fluorescence noise signal.
[0091] In an exemplary embodiment, the demodulator 223 can obtain the first demodulated Raman signal DRS1 by restoring the first Raman signal RS1 based on the correlation between the first orthogonal code signal OCS1 and the first Raman signal RS1. The demodulator 223 can obtain the first noise-removed signal DNS1 by canceling the first noise signal NS1 based on the correlation between the first orthogonal code signal OCS1 and the first noise signal NS1.
[0092] In this case, the signal-to-noise ratios of the first demodulated Raman signal DRS1 processed by the autocorrelation coefficient and the first noise-removed signal DNS1 processed by the cross-correlation coefficient may be greater than those of the first Raman signal RS1 and the first noise signal NS1.
[0093] The processor 224 can analyze the molecular information of the sample SP based on the intensity, center frequency, and bandwidth of the first demodulated Raman signal DRS1 included in the first demodulated detection signal DDS1. In this case, since the intensity of the first demodulated Raman signal DRS1 is greater than the intensity of the first noise removal signal DNS1, the processor 224 can obtain molecular information with higher accuracy and resolution.
[0094] As described above, according to an embodiment of the inventive concept, the detector 220 including the demodulator 223 that improves the SNR of the first demodulated Raman signal DRS1 may be provided by restoring the first Raman signal RS1 based on correlation with the first orthogonal code signal OCS1 and removing the first noise signal NS1.
[0095] Figure 8 2 is a block diagram exemplarily describing a light splitting device according to an embodiment of the inventive concept. Figure 8 , the spectroscopic device 300 may include a laser irradiation device 310, a detector 320, and a code generator 330. Since the operations of the sensor 321, the demodulator 323, the processor 324, and the code generator 330 are similar to Figure 5 The operations of the sensor 221, the demodulator 223, the processor 224, and the code generator 230 are similar, and thus a detailed description thereof will be omitted.
[0096] The laser irradiation device 310 may include a master oscillator 311 and a power amplifier 313. The laser irradiation device 310 may be a laser device having a master oscillator power amplifier (MOPA) structure including a master oscillator that oscillates pulses and a power amplifier that amplifies the pulses.
[0097] The master oscillator 311 may receive the orthogonal code OC from the code generator 330. The master oscillator 311 may output the time-resolved light beam TRB based on the received orthogonal code OC. In this case, the time-resolved light beam TRB may include bit information of the orthogonal code OC and have a width corresponding to the bit narrower than Figure 5 That is, the second incident beam IB2 may have a laser beam having a Figure 5 The first incident light beam IB1 has a high modulation frequency.
[0098] The power amplifier 313 may receive the time-resolved beam TRB from the master oscillator 311. The power amplifier 313 may irradiate the second incident beam IB2 obtained by amplifying the time-resolved beam TRB to the sample SP. That is, the power amplifier 313 may be a module that amplifies the intensity of the time-resolved beam TRB.
[0099] The code signal processor 322 may receive the orthogonal code OC from the code generator 330. The code signal processor 322 may output a second orthogonal code signal OCS2 based on the received orthogonal code OC. The second orthogonal code signal OCS2 may be an electrical signal having the same waveform as the second incident light beam IB2. That is, the second orthogonal code signal OCS2 may be an electrical signal having a waveform greater than Figure 5 The first orthogonal code signal OCS1 is a signal of a high modulation frequency.
[0100] As described above, according to an embodiment of the inventive concept, a light splitting device 300 can be provided, which generates a time-resolved light beam TRB having a high modulation frequency by using a master oscillator 311, and modulates the time-resolved light beam TRB having a modulation frequency higher than the modulation frequency TRB. Figure 5The second incident light beam IB2 of the first incident light beam IB1 is irradiated to the sample SP, and the modulation frequency is higher than Figure 5 Demodulation is performed on the first orthogonal code signal OCS1 and the second orthogonal code signal OCS2.
[0101] Fig. 9 It is described exemplarily Figure 8 Block diagram of the master oscillator. Fig. 9 , the master oscillator 311 may include a control signal generator 311 - 1 , a controller 311 - 2 , and a light source 311 - 3 .
[0102] The control signal generator 311-1 may receive an orthogonal code OC from the code generator 330. The control signal generator 311-1 may output a control signal CS based on the received orthogonal code OC. The control signal CS may be a pulse signal having an arbitrary duty cycle.
[0103] For example, in a portion corresponding to a bit having a value of "1" among bits included in the orthogonal code OC, the control signal CS may have a pulse. In a portion corresponding to a bit having a value of "0" among bits included in the orthogonal code OC, the control signal CS may maintain a constant value.
[0104] The controller 311-2 may receive a control signal CS from the control signal generator 311-1. The controller 311-2 may output a trigger signal TG based on the received control signal CS. The trigger signal TG may be a signal that allows the light source 311-3 to output a pulsed laser beam in response to a pulse included in the control signal CS. That is, the trigger signal TG may be a signal that controls the generation time of the pulsed laser beam based on the voltage fluctuation of the control signal CS. In this case, the pulsed laser beam may be a laser beam included in the time-resolved beam TRB.
[0105] In an exemplary embodiment, the controller 311 - 2 may detect a rising edge of the control signal CS. The controller 311 - 2 may allow the light source 311 - 3 to output a pulse laser beam when the rising edge occurs.
[0106] In an exemplary embodiment, the controller 311 - 2 may detect a falling edge of the control signal CS. The controller 311 - 2 may allow the light source 311 - 3 to output a pulse laser beam when the falling edge occurs.
[0107] The light source 311-3 may receive a trigger signal TG from the controller 311-2. The light source 311-3 may have time-resolved width information TRW. The light source 311-3 may output a time-resolved light beam TRB including a pulsed laser beam generated based on the trigger signal TG and the time-resolved width information TRW to the power amplifier 313.
[0108] In this case, the time-resolved width information TRW may be information indicating the pulse width of the pulsed laser beam included in the time-resolved beam TRB. The time-resolved beam TRB may include a pulsed laser beam generated according to the trigger signal TG. The pulse width of each generated pulsed laser beam may be determined based on the time-resolved width information TRW.
[0109] In an exemplary embodiment, the light source 311 - 3 may be a module that outputs a pulse laser beam having a short pulse width. For example, the light source 311 - 3 may include a distributed feedback (DFB) laser diode.
[0110] In an exemplary embodiment, by controlling the timing of the light source 311-3 outputting a pulsed laser beam based on the orthogonal code OC, a light source 311-3 that outputs a pulsed laser beam identical to high frequency modulation without a separate modulator can be provided. In this case, the time-resolved beam TRB output from the light source 311-3 may include bit information of the orthogonal code OC.
[0111] In an exemplary embodiment, the pulsed laser beam included in the time-resolved light beam TRB output from the light source 311-3 may have a narrow pulse width and a strong intensity. For example, the pulse width of the pulsed laser beam may be 1 [ns]. The peak power output of the master oscillator 311 that outputs the time-resolved light beam TRB may be 1 [W].
[0112] Fig.10 It is described exemplarily Figure 8 The block diagram of the power amplifier. Fig.10 , the power amplifier 313 may include a first amplification stage 313-1, a second amplification stage 313-2, and a third amplification stage 313-3. That is, the power amplifier 313 may be an amplifier including a plurality of amplifier stages. Fig.10 The power amplifier 313 in FIG. 3 is illustrated as including “3” amplification stages, but the scope of the inventive concept is not limited thereto, and the number of amplification stages included in the power amplifier 313 may be increased or decreased.
[0113] The first amplifier stage 313-1 may receive the time-resolved beam TRB from the master oscillator 311. The first amplifier stage 313-1 may output a first amplified time-resolved beam ATRB1 obtained by amplifying the received time-resolved beam TRB. For example, the output power of the first amplifier stage 313-1 may be about 0.1 to 1 [mW].
[0114] The first amplifying stage 313 - 1 may have a core pumping structure. In an exemplary embodiment, the first amplifying stage 313 - 1 may have a cladding pumping structure instead of a core pumping structure.
[0115] The second amplifying stage 313-2 may receive the first amplified time-resolved optical beam ATRB1 from the first amplifying stage 313-1. The second amplifying stage 313-2 may output a second amplified time-resolved optical beam ATRB2 obtained by further amplifying the first amplified time-resolved optical beam ATRB1. For example, the output power of the second amplifying stage 313-2 may be about 100 to 200 [mW]. The second amplifying stage 313-2 may have a cladding pumping structure.
[0116] The third amplifying stage 313-3 may receive the second amplified time-resolved optical beam ATRB2 from the second amplifying stage 313-2. The third amplifying stage 313-3 may output the second incident optical beam IB2 obtained by further amplifying the second amplified time-resolved optical beam ATRB2 to the sample SP. For example, the output power of the third amplifying stage 313-3 may be about 1 to 3 [W]. The third amplifying stage 313-3 may have a cladding pumping structure.
[0117] Fig.11a It is described exemplarily Fig.10 The block diagram of the first amplifier stage is shown in Figure 1. Fig.11a , the first amplification stage 313 - 1 may include a first isolator 313 - 1 a , a first pump laser 313 - 1 b , a first coupler 313 - 1 c , a first optical fiber 313 - 1 d , and a first filter 313 - 1 e .
[0118] The first isolator 313-1a may be an optical isolator that increases the output of the time-resolved optical beam TRB by blocking light reflected back to the light source. The first pump laser 313-1b may be a light source that outputs a pump laser beam for optically pumping the gain medium. The first coupler 313-1c may be a device that couples the time-resolved optical beam TRB and the pump laser beam. The first optical fiber 313-1d may be an optical fiber doped with a rare earth. The first filter 313-1e may be a filter that passes a laser beam corresponding to the wavelength of the time-resolved optical beam TRB and blocks noise of other wavelengths.
[0119] According to an embodiment of the inventive concept, a first amplification stage 313-1 may be provided which amplifies the time-resolved beam TRB based on the pump laser beam output from the first pump laser 313-1b to output a first amplified time-resolved beam ATRB1. The first amplified time-resolved beam ATRB1 may be a laser beam having a higher intensity than the time-resolved beam TRB.
[0120] In an exemplary embodiment, the second amplifier stage 313-2 may have a similar structure to the first amplifier stage 313-1. For example, the second amplifier stage 313-2 may include a second isolator, a second pump laser, a second coupler, a second optical fiber, and a second filter. In this case, the second coupler may couple the first amplified time-resolved optical beam ATRB1 and the pump laser beam so that the pump laser output from the second pump laser is emitted to the cladding of the optical fiber.
[0121] In an exemplary embodiment, the second amplification stage 313-2 may also amplify the first amplified time-resolved beam ATRB1 based on the pump laser beam output from the second pump laser to output a second amplified time-resolved beam ATRB2. The second amplified time-resolved beam ATRB2 may be a laser beam having a higher intensity than the first amplified time-resolved beam ATRB1.
[0122] Fig.11b It is described exemplarily Fig.10 The block diagram of the third amplifier stage. Fig.11b , the third amplifier stage 313-3 may include a third isolator 313-3a, a third pump laser 313-3b, a third coupler 313-3c, a third optical fiber 313-3d, a third filter 313-3e, an end cap 313-3f and a fourth pump laser 313-3g. Fig.11a Some components 313 - 1 a to 313 - 1 e of the first amplifying stage 313 - 1 are similar, and thus a detailed description thereof will be omitted.
[0123] The fourth pump laser 313-3g may be a light source that outputs a pump laser beam for optically pumping the gain medium. The third coupler 313-3c may be a device that couples the second amplified time-resolved light beam ATRB2, the pump laser beam output from the third pump laser 313-3b, and the pump laser beam output from the fourth pump laser 313-3g. That is, the third amplifier stage 313-3 may include a plurality of pump lasers 313-3b and 313-3g. Therefore, the third amplifier stage 313-3 may have a high amplification gain.
[0124] The end cap 313 - 3f may be a device that emits the laser beam output from the third filter 313 - 3e The second incident beam IB2 output from the end cap 313 - 3f may be irradiated to the sample SP.
[0125] According to an embodiment of the inventive concept, based on the pump laser beam output from the third pump laser 313-3b and the pump laser beam output from the fourth pump laser 313-3g, a second incident beam IB2 obtained by further amplifying the second amplified time-resolved beam ATRB2 may be output. The second incident beam IB2 may be a laser beam having a higher intensity than the second amplified time-resolved beam ATRB2.
[0126] Fig.12 It is shown by Figure 8 A graph of the signal generated by the laser irradiation device. Fig.12 , shows the bit sequence included in the orthogonal code OC, the waveform of the control signal CS, the waveform of the time-resolved beam TRB and the waveform of the second incident beam IB2.
[0127] In addition, in order to clearly describe the characteristics of the second incident light beam IB2, the Figure 5 The waveform of the first incident light beam IB1 generated by the laser irradiation device. Since the characteristics of the orthogonal code OC and the first incident light beam IB1 are the same as Figure 6 The orthogonal code OC described in and the characteristics of the first incident light beam IB1 are similar, so their detailed description will be omitted.
[0128] The control signal CS may be a return-to-zero signal generated based on an orthogonal code. The control signal CS may be an electrical signal. Fig. 9 The control signal generator 311-1 may include information about the width and duty cycle "D" of the portion corresponding to the specific bit included in the orthogonal code. For example, in the control signal CS, the width of the portion corresponding to the specific bit included in the orthogonal code may be the first time T1. The duty cycle D of the control signal CS may be "0.5".
[0129] In an exemplary embodiment, the control signal CS may have a pulse in a portion corresponding to a bit having a value of "1" among bits included in the orthogonal code OC. For example, the control signal CS may have a second voltage V2 for 0.5T1 [ns] in a portion corresponding to a bit having a value of "1", and then may have a first voltage V1 for 0.5T1 [ns]. The second voltage V2 may be greater than the first voltage V1. That is, the control signal CS may be a return-to-zero signal having the first voltage V1 after having the second voltage V2 for a specific time.
[0130] In an exemplary embodiment, the control signal CS may maintain a constant value in a portion corresponding to a bit having a value of “0” among bits included in the orthogonal code OC. For example, the control signal CS may maintain a first voltage V1 in a portion corresponding to a bit having a value of “0”.
[0131] In an exemplary embodiment, the control signal CS may be a signal having a voltage that varies based on the value of a bit included in the orthogonal code OC. In more detail, the control signal CS may maintain a first voltage V1 in a portion corresponding to a bit having a value of "0" among the bit sequence of the orthogonal code OC. The control signal CS may have a first voltage V1 after having a second voltage V2 higher than the first voltage V1 in a portion corresponding to a bit having a value of "1" among the bit sequence of the orthogonal code OC.
[0132] The time-resolved beam TRB may consist of Figure 8 The master oscillator 311 generates a pulsed laser beam based on the control signal CS. The light source of the master oscillator may have time-resolved width information. For example, the time-resolved light beam TRB may include a pulsed laser beam generated in response to the rising edge of the pulse included in the control signal CS. The width of the pulse may be determined as the second time T2 based on the time-resolved width information.
[0133] That is, the time-resolved light beam TRB may include a pulsed laser beam in a portion corresponding to a bit having a value of "1" among the bits included in the orthogonal code OC. The time-resolved light beam TRB may not include a pulsed laser beam in a portion corresponding to a bit having a value of "0" among the bits included in the orthogonal code OC.
[0134] The second incident beam IB2 may be a laser beam obtained by amplifying the time-resolved beam TRB. For example, the time-resolved beam TRB may have a first intensity X1. The second incident beam IB2 may have a second intensity X2. The second intensity X2 may be greater than the first intensity X1. That is, the second incident beam IB2 may be a laser beam having the same pulse width as the time-resolved beam TRB and having a higher intensity than the time-resolved beam TRB.
[0135] In an exemplary embodiment, the second incident light beam IB2 may be a laser beam having a narrower pulse width than the first incident light beam IB1. In more detail, the light source outputting the time-resolved light beam TRB may output a laser beam including a pulsed laser beam having a higher frequency than the modulator outputting the first incident light beam IB1. Therefore, the second time T2, which is the pulse width per bit of the second incident light beam IB2, may be less than the first time T1, which is the pulse width per bit of the first incident light beam IB1.
[0136] Fig.13 It is shown by Figure 8 A graph of the signal processed by the detector. Figure 8 and Fig.13, shows the second Raman signal RS2 and the second noise signal NS2 included in the second detection signal DS2. In addition, shows the second demodulated Raman signal DRS2 and the second noise removal signal DNS2 included in the second demodulated detection signal DDS2.
[0137] In addition, in order to clearly describe the characteristics of the second demodulated Raman signal DRS2 and the second noise-removed signal DNS2, Figure 7 The first demodulated Raman signal DRS1 and the first noise-removed signal DNS1 are obtained. Since the characteristics of the second Raman signal RS2 and the second noise signal NS2 are the same as Figure 7 The characteristics of the first Raman signal RS1 and the first noise signal NS1 are similar, and thus a detailed description thereof will be omitted.
[0138] In an exemplary embodiment, the demodulator 323 can restore the second Raman signal RS2 by calculating the autocorrelation relationship based on the correlation between the second orthogonal code signal OCS2 and the second Raman signal RS2, and can obtain the second demodulated Raman signal DRS2. The demodulator 323 can obtain the second noise-removed signal DNS2 by reducing the second noise signal NS2 based on the correlation between the second orthogonal code signal OCS2 and the second noise signal NS2.
[0139] In an exemplary embodiment, as the frequency of the laser beam irradiated to the sample SP and the frequency of the signal for demodulation increase, a Raman signal with high intensity can be obtained. For example, the second time T2 as the pulse width of the second orthogonal code signal OCS2 may be smaller than Figure 7 The second demodulated Raman signal DRS2 may be a signal with a higher intensity than the first demodulated Raman signal DRS1.
[0140] In an exemplary embodiment, as the frequency of the laser beam irradiated to the sample SP and the frequency of the signal for demodulation increase, a noise signal with low intensity can be obtained. For example, the second time T2 as the pulse width of the second orthogonal code signal OCS2 can be less than Figure 7 The second noise removal signal DNS2 may be a signal with a lower strength than the first noise removal signal DNS1.
[0141] In an exemplary embodiment, the second time T2 which is the pulse width of the second orthogonal code signal OCS2 may be longer than the lifetime of the second Raman signal RS2 and shorter than the lifetime of the second noise signal NS2.
[0142] As described above, according to an embodiment of the present invention, by irradiating a second incident light beam IB2 including a pulsed laser beam having a high modulation frequency onto a sample SP, and by demodulating a second Raman signal RS2 and a second detection signal DS2 using a second orthogonal code signal OCS2 having a high modulation frequency, a spectroscopic device 300 having an improved signal-to-noise ratio of a second demodulated Raman signal DRS2 and a second noise-removed signal DNS2 can be provided.
[0143] Fig.14 It is shown that according to Figure 8 A graph showing the correlation coefficient of the modulation frequency of the signal processed by the detector. Fig.14 , which exemplarily shows the correlation coefficient of the Raman signal and the fluorescence noise signal recovered by the demodulator according to the modulation frequency.
[0144] For example, the modulation frequency on the horizontal axis can be expressed as Figure 5 The continuous wave signal CW is modulated by the modulator 212 or from Fig. 9 The correlation coefficient on the vertical axis can be expressed as the inverse of the pulse width of the time-resolved light beam TRB output by the light source 311-3. Figure 7 The correlation coefficient of each of the first Raman signal RS1 and the first noise signal NS1 associated with the first orthogonal code signal OCS1 or the correlation coefficient of each of the first Raman signal RS1 and the first noise signal NS1 associated with the first orthogonal code signal OCS1 Fig.13 The correlation coefficient of each of the second Raman signal RS2 and the second noise signal NS2 associated with the second orthogonal code signal OCS2 may refer to a value obtained by dividing the covariance between variables by each standard deviation.
[0145] In an exemplary embodiment, as the modulation frequency of the spectroscopic device increases, the signal-to-noise ratio of the Raman signal and the fluorescence noise signal restored by the demodulator can be improved. The molecular information of the sample analyzed based on the Raman signal with the improved signal-to-noise ratio can have high accuracy and resolution.
[0146] For example, the correlation coefficient of the Raman signal with a modulation frequency of 1000 [MHz] may be greater than the correlation coefficient of the Raman signal with a modulation frequency of 250 [MHz]. The correlation coefficient of the fluorescence noise signal with a modulation frequency of 1000 [MHz] may be less than the correlation coefficient of the fluorescence noise signal with a modulation frequency of 250 [MHz]. In other words, the signal-to-noise ratio of the Raman signal with a modulation frequency of 1000 [MHz] and the fluorescence noise signal may be greater than the signal-to-noise ratio of the Raman signal with a modulation frequency of 250 [MHz].
[0147] Fig.15 is a flow chart showing a spectroscopic method for recovering a Raman signal according to an embodiment of the inventive concept. Fig.15, a spectroscopic method for analyzing a sample according to a Raman spectroscopic method is shown as an example. A spectroscopic device used in the spectroscopic method may include a laser irradiation device and a detector.
[0148] In step S310, an orthogonal code may be generated. An orthogonal code may be a code including a bit sequence that is mathematically orthogonal to other codes. The orthogonal code may synchronize a laser irradiation device and a detector.
[0149] In step S320, a control signal may be generated based on the orthogonal code. The control signal may have a portion corresponding to the bit included in the orthogonal code. A pulse may be obtained based on the value of the bit in the corresponding portion. In an exemplary embodiment, in a portion corresponding to a bit having a value of "1", the control signal may have a pulse waveform. In a portion corresponding to a bit having a value of "0", the control signal may maintain a constant value.
[0150] In step S330, a time-resolved laser beam generated based on the control signal may be output. In an exemplary embodiment, the time-resolved laser beam may include a pulsed laser beam generated using a rising edge of a pulse included in the control signal as a trigger. In an exemplary embodiment, the time-resolved laser beam may include a pulsed laser beam generated using a falling edge of a pulse included in the control signal as a trigger. The pulse width of the time-resolved laser beam may be determined based on time-resolved width information included in a light source that outputs the time-resolved laser beam.
[0151] In step S340, an incident light beam obtained by amplifying the time-resolved laser beam may be irradiated to the sample. In an exemplary embodiment, the time-resolved laser beam may include a pulsed laser beam having a narrow pulse width and high intensity. The time-resolved laser beam may be amplified by a power amplifier. The amplified time-resolved laser beam may be irradiated to the sample.
[0152] In step S350, a detection signal may be received from the sample. The detection signal may be a signal generated from the sample irradiated by the incident light beam. The detection signal may include a Raman signal and a noise signal. The Raman signal may include molecular information of the sample. The Raman signal may have a lower intensity than the noise signal. The Raman signal may be measured in time prior to the noise signal.
[0153] In step S360, the Raman signal may be demodulated based on the correlation with the orthogonal code. In more detail, an orthogonal code signal synchronized with the incident light beam may be generated based on the orthogonal code. The orthogonal code signal may be an electrical signal having the same waveform as the incident light beam.
[0154] In an exemplary embodiment, based on the correlation between the orthogonal code signal and the detection signal, the Raman signal can be restored and the noise signal can be removed. In this case, as the Raman signal strength increases and the noise signal strength decreases, the signal-to-noise ratio of the demodulated Raman signal can be significantly improved.
[0155] As described above, according to an embodiment of the inventive concept, a spectroscopic method can be provided that uses a pulse of a control signal generated based on an orthogonal code as a trigger to irradiate an incident light beam including a pulsed laser beam of a high modulation frequency. In addition, a spectroscopic method can be provided that demodulates a Raman signal based on a correlation with an orthogonal code signal having the same waveform as the incident light beam.
[0156] The above content is a specific embodiment for realizing the concept of the present invention. The concept of the present invention may include not only the above-mentioned embodiments, but also embodiments that can simply or easily change the design. In addition, the concept of the present invention may also include technologies that are easily changed to be implemented using the embodiments. Therefore, the scope of the concept of the present invention is not limited to the described embodiments, but should be limited by the equivalents of the claims and the appended claims.
[0157] [Industrial Applicability]
[0158] The inventive concept relates to a spectroscopic device and a spectroscopic method. In more detail, the inventive concept can be used in a spectroscopic device and a spectroscopic method for analyzing a biological signal using time-resolved coding.
Claims
1. A spectroscopic device, comprising: A laser irradiation device receives an orthogonal code including a sequence of bits, each bit having a first value or a second value; generating a control signal, wherein the control signal has a pulse in a first bit portion, the width of the pulse being shorter than the width of the first bit portion, the first bit portion corresponding to the bit having the first value in the bit sequence; generating a pulse laser beam having a pulse width shorter than the first bit portion using a pulse included in the control signal as a trigger; and irradiating an incident light beam including the generated pulsed laser beam to the sample; as well as a detector that receives a detection signal generated from the sample irradiated by the incident light beam and the orthogonal code; and generates an orthogonal code signal having the same waveform as that of the incident light beam based on the orthogonal code; and demodulating the Raman signal based on a correlation between the generated orthogonal code signal and the Raman signal included in the detection signal.
2. The spectroscopic device according to claim 1, wherein: The control signal has a first voltage or a second voltage greater than the first voltage, has the first voltage in the first bit portion after having the second voltage, and maintains the first voltage in a second bit portion, and the second bit portion corresponds to a bit having the second value in the bit sequence.
3. The spectroscopic device according to claim 1, wherein: The laser irradiation device also generates the pulse laser beam using a rising edge of a pulse included in the control signal as a trigger.
4. The spectroscopic device according to claim 1, wherein: The laser irradiation device also generates the pulse laser beam using a falling edge of a pulse included in the control signal as a trigger.
5. The spectroscopic device according to claim 1, wherein: The laser irradiation equipment comprises: a master oscillator that receives the orthogonal code and outputs a time-resolved light beam including the pulsed laser beam; and A power amplifier receives the time-resolved light beam and amplifies the time-resolved light beam to irradiate the incident light beam to the sample.
6. The spectroscopic device according to claim 5, wherein: The master oscillator comprises: a control signal generator, receiving the orthogonal code and outputting the control signal based on the received orthogonal code; a controller that receives the control signal and outputs a trigger signal for generating the pulse laser beam based on the control signal; and A light source receives the trigger signal, includes time-resolved width information for determining a pulse width of the pulse laser beam, and outputs the time-resolved light beam based on the received trigger signal and the time-resolved width information.
7. The spectroscopic device according to claim 5, wherein: The power amplifier includes an isolator that receives the time-resolved light beam and blocks light reflected back to the light source.
8. The spectroscopic device according to claim 5, wherein: The power amplifier comprises: a first pump laser that outputs a first pump laser beam for optically pumping the gain medium; and A coupler is used to couple the time-resolved light beam and the first pump laser beam.
9. The spectroscopic device according to claim 8, wherein: The power amplifier further comprises a second pump laser, the second pump laser outputting a second pump laser beam for optically pumping the gain medium, and The coupler further couples the time-resolved light beam, the first pump laser beam and the second pump laser beam.
10. The spectroscopic device according to claim 5, wherein: The power amplifier includes a filter that passes a laser beam corresponding to a wavelength of the time-resolved light beam and blocks noise.
11. The spectroscopic device according to claim 5, wherein: The power amplifier comprises: a first amplification stage, receiving the time-resolved light beam, and amplifying the received time-resolved light beam to output a first amplified time-resolved light beam; a second amplification stage, receiving the first amplified time-resolved light beam, and outputting a second amplified time-resolved light beam in which the first amplified time-resolved light beam is further amplified; and The third amplification stage receives the second amplified time-resolved light beam and irradiates the incident light beam in which the second amplified time-resolved light beam is further amplified to the sample.
12. A spectroscopic method, comprising: generating an orthogonal code comprising a sequence of bits, each bit having a first value or a second value; generating a control signal having a pulse in a bit portion corresponding to a bit having the first value in the bit sequence, the width of the pulse being shorter than a width of the bit portion; generating a pulse laser beam having a pulse width shorter than the bit portion using a pulse included in the control signal as a trigger, and irradiating an incident light beam including the generated pulse laser beam to a sample; receiving a detection signal output from the sample illuminated by the incident light beam; An orthogonal code signal having the same waveform as that of the incident light beam is generated based on the orthogonal code, and the Raman signal included in the detection signal is demodulated by calculating an autocorrelation coefficient based on a correlation between the orthogonal code signal and the Raman signal.
13. The spectroscopic method according to claim 12, wherein: The detection signal includes: a Raman signal having a first intensity and received at a first time; and A noise signal has a second intensity greater than the first intensity and is received at a second time later than the first time.
14. The spectroscopic method according to claim 13, wherein: The demodulation of the Raman signal further includes removing the noise signal based on the correlation between the orthogonal code signal and the noise signal, and The intensity of the demodulated Raman signal is greater than the intensity of the removed noise signal.
15. The spectroscopic method according to claim 12, wherein: The detection signal includes the Raman signal having a first lifetime and a noise signal having a second lifetime longer than the first lifetime, and The pulse width of the pulse laser beam is longer than the first lifetime and shorter than the second lifetime.
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