Method and device for measuring medical specimen through infrared femtosecond pulse laser

Abstract

The invention discloses a method and a device for measuring a medical specimen by using infrared femtosecond pulse laser, relates to a medical specimen detection technology and an infrared femtosecond pulse laser technology, and aims to solve the problems of large error and low detection accuracy of the existing medical specimen detection technology. The method comprises the following steps: irradiating a medical specimen by using wavelength-tunable long-wave infrared femtosecond pulse laser; transmitting light of the medical specimen is collected through a detector; and a measurement result of the medical specimen is given according to an output signal of the detector. The device comprises a sample pool used for placing a medical specimen, and a long-wave infrared femtosecond pulse laser used for outputting long-wave infrared femtosecond pulse laser with tunable wavelength and irradiating the long-wave infrared femtosecond pulse laser on the medical specimen; the detector is used for receiving an optical signal transmitted by the medical specimen; and the calculation module is used for processing the signal output by the detector so as to obtain a measurement result of the medical specimen. Compared with the prior art, the method is higher in detection precision.

Description

Technical Field

[0001] The invention relates to medical specimen detection technology and infrared femtosecond pulse laser technology. Background Art

[0002] At present, medical specimens are usually examined using a microscope equipped with a built-in light source, which is a visible light source or an ultraviolet light source. The medical specimen is placed under the microscope, and the light generated by the light source is irradiated on the medical specimen. The state of the specimen is observed through the microscope to determine the difference between the medical specimen and normal human tissue.

[0003] The above detection methods use microscopes to image the specimens, but the difference between normal human tissue and diseased human tissue under visible light or ultraviolet light is often not obvious. Therefore, judging the difference between the specimen and normal human tissue by imaging the specimen itself has large errors and low detection accuracy. Summary of the Invention

[0004] The purpose of the present invention is to solve the problems of large errors and low detection accuracy in existing medical specimen detection technologies, and to provide a method and device for measuring medical specimens using infrared femtosecond pulse laser.

[0005] A method for measuring medical specimens using an infrared femtosecond pulse laser of the present invention comprises:

[0006] Using wavelength-tunable long-wave infrared femtosecond pulse laser to irradiate medical specimens;

[0007] collecting the transmitted light of the medical specimen using a detector; and

[0008] The measurement result of the medical specimen is given according to the signal output by the detector.

[0009] Optionally, the long-wave infrared femtosecond pulse laser is obtained by:

[0010] The pulse width of a femtosecond pulse laser with a wavelength of 2 microns is widened to obtain a picosecond pulse laser with a wavelength of 2 microns;

[0011] Injecting the picosecond pulse laser with a wavelength of 2 microns as pump light into the resonant cavity of the optical parametric oscillator;

[0012] controlling the cavity mirrors of the resonant cavity to achieve synchronous pumping; and

[0013] The pulse width of the long-wave infrared picosecond pulse laser output by the resonant cavity is compressed to obtain a long-wave infrared femtosecond pulse laser.

[0014] Optionally, controlling the cavity mirror of the resonant cavity includes:

[0015] The cavity mirror of the resonant cavity is controlled by piezoelectric ceramics.

[0016] Optionally, the resonant cavity of the optical parametric oscillator is a ring cavity.

[0017] The present invention provides an infrared femtosecond pulse laser device for measuring medical specimens, comprising:

[0018] Long-wave infrared femtosecond pulse laser, used to output wavelength-tunable long-wave infrared femtosecond pulse laser;

[0019] A sample pool, used for placing a medical specimen, on which the long-wave infrared femtosecond pulse laser is irradiated;

[0020] a detector, configured to receive a light signal transmitted through the medical specimen;

[0021] A calculation module is used to process the signal output by the detector to obtain the measurement result of the medical specimen.

[0022] Optionally, the long-wave infrared femtosecond pulse laser comprises:

[0023] 2 micron femtosecond pulse laser, used to generate 2 micron femtosecond pulse laser;

[0024] A pulse width stretcher, used to stretch the pulse width of the 2 micron femtosecond pulse laser to obtain a 2 micron picosecond pulse laser;

[0025] An optical parametric oscillator, using the 2-micron picosecond pulse laser as pump light to achieve wavelength-tunable long-wave infrared picosecond pulse laser output; and

[0026] The pulse width compressor is used to compress the pulse width of the long-wave infrared picosecond pulse laser to obtain a wavelength-tunable long-wave infrared femtosecond pulse laser output.

[0027] Optionally, the resonant cavity of the optical parametric oscillator is a ring cavity.

[0028] Optionally, the optical parametric oscillator is equipped with a piezoelectric ceramic, and the piezoelectric ceramic is used to control a cavity mirror of the optical parametric oscillator to achieve synchronous pumping of the optical parametric oscillator.

[0029] Optionally, the wavelength tuning range of the long-wave infrared femtosecond pulse laser is 6-8 microns.

[0030] Optionally, the calculation module is further configured to compare the processing result corresponding to the normal tissue medical specimen with the processing result corresponding to the medical specimen to be tested.

[0031] The present invention utilizes a high-energy, extremely narrow pulse width, long-wavelength infrared laser to excite medical specimens, and measures the difference between medical specimen tissue and normal specimen tissue by detecting the nonlinear optical phenomenon generated by the excitation of the medical specimens. Compared with the conventional method of directly observing medical specimens with an optical microscope, the measurement accuracy of the embodiments of the present application is higher, and can provide a strong basis for detecting the degree of pathology in medical specimens. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 This is a schematic flow chart of a method for measuring medical specimens using an infrared femtosecond pulse laser according to an embodiment of the present application;

[0033] Figure 2 This is a schematic structural diagram of a device for measuring medical specimens using an infrared femtosecond pulse laser according to an embodiment of the present application. DETAILED DESCRIPTION

[0034] The following describes the embodiments of the present invention through specific examples. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments. The details in this specification can also be modified or changed based on different viewpoints and applications without departing from the spirit of the present invention. It should be noted that the following embodiments and features in the embodiments can be combined with each other unless they conflict.

[0035] As used herein, the singular forms "a", "an", and "the" are intended to include the plural forms as well, unless the context indicates otherwise. It should be further understood that the terms "comprise", "include" indicate the presence of the described features, operations, elements, components, items, kinds, and / or groups, but do not exclude the presence, occurrence, or addition of one or more other features, operations, elements, components, items, kinds, and / or groups. The terms "or" and "and / or" used herein are interpreted as inclusive, or mean any one or any combination. Thus, "A, B, or C" or "A, B, and / or C" means "any of the following: A; B; C; A and B; A and C; B and C; A, B, and C". Exceptions to this definition occur only when the combination of elements, functions, or operations is inherently mutually exclusive in some way.

[0036] Aiming at the problem that the existing technology uses microscopes to detect medical specimens and the measurement results have low accuracy, the present invention provides a method for measuring medical specimens using infrared femtosecond pulse laser, which can improve the measurement accuracy.

[0037] A method for measuring medical specimens using an infrared femtosecond pulse laser in an embodiment of the present application includes: irradiating the medical specimen with a wavelength-tunable long-wave infrared femtosecond pulse laser; collecting the transmitted light of the medical specimen with a detector; and providing a measurement result of the medical specimen based on an image output by the detector.

[0038] Figure 1 FIG. 1 is a schematic flow chart of a method for measuring medical specimens using an infrared femtosecond pulse laser according to an embodiment of the present application. Figure 1 As shown, a method for measuring medical specimens using an infrared femtosecond pulse laser according to an embodiment of the present application begins with step S100 .

[0039] In step S110 , a wavelength-tunable long-wave infrared femtosecond pulse laser is used to irradiate a medical specimen.

[0040] In the embodiments of this application, the medical specimen, typically a slice, is placed in a sample cell and illuminated by a long-wave infrared laser to stimulate the surface of the specimen to produce second- and third-order nonlinear optical phenomena. To induce nonlinear optical phenomena in the medical specimen, the peak power of the incident light must be sufficiently high. To this end, the embodiments of this application utilize a long-wave infrared laser with a pulse width on the order of femtoseconds.

[0041] Long-wave infrared femtosecond pulse laser can be generated by an optical parametric oscillator (OPO). The optical parametric oscillator uses a pulsed laser with a wavelength of 2 microns as pump light. In order to avoid damage to the components of the optical parametric oscillator, the embodiment of the present application widens the pulse width of the femtosecond pulse laser with a wavelength of 2 microns to obtain a picosecond pulse laser with a wavelength of 2 microns, and uses the picosecond pulse laser with a wavelength of 2 microns as the pump light of the OPO. The pulse width of the long-wave infrared laser output by the OPO is in the picosecond order, and the pulse width of the long-wave infrared laser can be compressed to the femtosecond order to obtain a long-wave infrared femtosecond pulse laser. In the embodiment of the present application, the wavelength of the long-wave infrared femtosecond pulse laser can be tuned between 6 and 8 microns.

[0042] In addition to peak power, the incident light also requires good beam quality. To this end, the OPO in the embodiment of the present application adopts a ring cavity structure. Specifically, the resonant cavity consists of four optical lenses, including an input mirror for inputting pump light, an output mirror for outputting long-wave infrared femtosecond pulse laser light, and two reflectors. A nonlinear crystal is arranged in the cavity.

[0043] To generate ultrashort pulses, the present embodiment arranges a piezoelectric ceramic on one of the reflectors. The piezoelectric ceramic drives the reflector to vibrate, thereby adjusting the cavity length of the OPO resonant cavity. This matches the round-trip frequency of the laser in the resonant cavity with the pulse repetition frequency of the pump light, achieving synchronous pumping. Under synchronous pumping conditions, the pulses generated by the laser gradually reach a stable state during multiple round trips in the resonant cavity. The vibration of the piezoelectric ceramic will affect the stability of the OPO resonant cavity, and the long cavity structure of the ring cavity can minimize this effect.

[0044] In addition, in order to allow the long-wave infrared laser generated by the OPO to pass through in one direction, an isolator is set in the OPO resonant cavity in the embodiment of the present application. This isolator is different from the conventional medium-wave nanosecond isolator, but is an isolator suitable for long-wave femtosecond pulse laser.

[0045] In one implementation, a long-wave infrared femtosecond pulse laser is irradiated onto a medical specimen. During the irradiation process, the wavelength of the long-wave infrared femtosecond pulse laser is tuned so that the wavelength gradually changes within a range of 6 microns to 8 microns.

[0046] In another implementation, the wavelength of the long-wave infrared femtosecond pulse laser is adjusted to a specific wavelength band, and only the long-wave infrared femtosecond pulse laser in this wavelength band is used to irradiate the medical specimen.

[0047] Medical specimens of different tissues can sense different laser wavelengths. In actual operation, one of the above two implementation methods can be selected according to the actual situation.

[0048] Next, in step S120 , the transmitted light of the medical specimen is collected by using a detector.

[0049] Long-wave infrared femtosecond pulse laser is irradiated on medical specimens. Under the excitation of long-wave infrared femtosecond pulse laser, the medical specimens produce second-order and third-order nonlinear optical phenomena, generating lasers of new frequencies. These lasers are transmitted from the other side of the medical specimens and captured by detectors. The detectors can be implemented as CCDs, which convert the captured optical signals into electrical signals for output.

[0050] Next, in step S130 , a measurement result of the medical specimen is given according to the signal output by the detector.

[0051] The signal output by CCD can reflect the second-order and third-order nonlinear optical phenomena, and the nonlinear optical phenomena can reflect the conditions of one or certain indicators of medical specimens. Therefore, the numerical values ​​of one or certain indicators of medical specimens can be obtained by processing the CCD output signal, and the numerical values ​​of these indicators can be used as measurement results.

[0052] In this step, a computer can be used to process and calculate the signal output by the CCD to obtain the measurement result of the medical specimen.

[0053] In addition, a slice from normal human tissue (normal tissue medical specimen) can be placed in the sample pool, and the image output by the CCD can be obtained according to the above steps S110 and S120. This image is used as a reference image, and the image output by the CCD corresponding to the slice to be measured (medical specimen to be measured) is compared with the reference image, which can intuitively show the difference between the two.

[0054] The present application also provides an apparatus for measuring medical specimens using an infrared femtosecond pulse laser. The apparatus primarily comprises a long-wave infrared femtosecond pulse laser, a sample cell, a detector, and a computing module. The long-wave infrared femtosecond pulse laser generates wavelength-tunable long-wave infrared femtosecond pulse laser light; the sample cell is used to place a medical specimen, upon which the long-wave infrared femtosecond pulse laser light is irradiated; the detector receives light signals transmitted by the medical specimen; and the computing module processes the signals output by the detector to obtain measurement results for the medical specimen.

[0055] The long-wave infrared femtosecond pulse laser includes: a 2-micron femtosecond pulse laser for generating a femtosecond pulse laser with a wavelength of 2 microns; a pulse width stretcher for stretching the pulse width of the 2-micron femtosecond pulse laser to obtain a 2-micron picosecond pulse laser; an optical parametric oscillator for using the 2-micron picosecond pulse laser as pump light to achieve wavelength-tunable long-wave infrared picosecond pulse laser output; and a pulse width compressor for compressing the pulse width of the long-wave infrared picosecond pulse laser to obtain wavelength-tunable long-wave infrared femtosecond pulse laser output.

[0056] The resonant cavity of the optical parametric oscillator is preferably a ring cavity structure. The optical parametric oscillator is equipped with piezoelectric ceramics, and the piezoelectric ceramics are used to control a cavity mirror of the optical parametric oscillator to achieve synchronous pumping of the optical parametric oscillator.

[0057] The wavelength tuning range of the long-wave infrared femtosecond pulse laser is 6-8 microns.

[0058] The calculation module is further used to compare the processing result corresponding to the normal tissue medical specimen with the processing result corresponding to the medical specimen to be tested, and to provide the difference between the two indicators.

[0059] like Figure 2 As shown, in a specific implementation, the device for measuring medical specimens using infrared femtosecond pulse laser includes a long-wave infrared femtosecond pulse laser, a sample cell, a detector, and a computing module, wherein the computing module is embedded in a computer 14 .

[0060] The above-mentioned long-wave infrared femtosecond pulse laser includes a 2-micron femtosecond pulse laser 1, a pulse width stretcher 2, a dichroic mirror 3, a piezoelectric ceramic controlled by a controller 4, a first reflector 5, a nonlinear crystal 6, an optical isolator 7, an output mirror 8, a second reflector 9, and a pulse width compressor 10.

[0061] The dichroic mirror 3, the first reflector 5, the output mirror 8, and the second reflector 9 constitute the resonant cavity of the optical parametric oscillator, and the nonlinear crystal 6 and the optical isolator 7 are arranged in the resonant cavity. The piezoelectric ceramic is arranged on a reflector. Figure 2 In the embodiment, the piezoelectric ceramic is arranged on the first reflector 5, and the piezoelectric ceramic is controlled by the controller 4, thereby driving the first reflector 5 to vibrate, thereby realizing synchronous pumping.

[0062] The optical parametric oscillator uses a 2-micron femtosecond pulse laser as pump light and a laser with a wavelength of 2800-3100 nm as signal light. The 2-micron femtosecond pulse laser 1, serving as the pump light source for the optical parametric oscillator, can generate pulsed laser light with a wavelength of 2 microns and a pulse width on the femtosecond scale, i.e., a 2-micron femtosecond pulse laser. Specifically, the output laser light from the 2-micron femtosecond pulse laser 1 has a central wavelength of 2090 nm, a single pulse energy of 150 microjoules, and a pulse width of approximately 200 fs.

[0063] The dichroic mirror 3 is a flat mirror coated on both sides with a 2090nm high-transmittance film and on one side with a 2800-3100nm and 5900-8100nm high-reflection film. The side coated with the 2800-3100nm and 5900-8100nm high-reflection films faces the cavity. The first reflector 5 is a flat mirror coated on one side with a 2800-3100nm high-reflection film to reflect laser light with a wavelength of 2800-3100nm. The uncoated side of the first reflector 5 is affixed with a piezoelectric ceramic connected to a controller 4 to control the resonant cavity frequency of the optical parametric oscillator, thereby achieving synchronous pumping. The nonlinear crystal 6 is a zinc germanium phosphide crystal, with both ends coated with high-transmittance films of 2090nm, 2800-3100nm, and 5900-8100nm to achieve nonlinear frequency conversion. The optical isolator 7 is used to achieve one-way passage of laser light with a wavelength of 5900-8100nm. The second reflector 9 is a flat mirror with a 2800-3100nm high-reflection film coated on one side. It is used to reflect laser light with a wavelength of 2800-3100nm, with the side coated with the 2800-3100nm high-reflection film facing the cavity. The output mirror 8 is a flat mirror with a 2090nm and 5900-8100nm high-transmittance film coated on both sides and a 2800-3100nm high-reflection film coated on one side. The output mirror 8 is used to output laser light with a wavelength of 5900-8100nm.

[0064] In the above-mentioned device, the high-transmittance film of each optical component has a transmittance exceeding 99.9% at the corresponding wavelength. This ultra-high transmittance significantly improves the output efficiency of the laser. In addition to high transmittance, the film layer of each optical component also has strong water-repellent properties. This embodiment of the application selects a laser in the 6-8 micron wavelength range, which is easily absorbed by human tissue, for measuring medical specimens. The 6-8 micron wavelength range is the absorption peak of water, and the peak power of femtosecond lasers is extremely high. The film layer's strong water-repellent properties prevent the film from being damaged by the high-power laser.

[0065] In the above device, the pump light is incident on the dichroic mirror 3 at a 45-degree angle, enters the resonant cavity of the optical parametric oscillator through the dichroic mirror 3, passes through the zinc germanium phosphide crystal, and is incident on the output mirror 8 at a 45-degree angle. After passing through the output mirror 8, it is output outside the cavity. After the pump light undergoes parametric transformation in the resonant cavity of the optical parametric oscillator, it generates a long-wave infrared picosecond pulse laser with a pulse width of approximately 300 ps and a wavelength of 5900-8100 nm, as well as signal light with a wavelength of 2800-3100 nm. The signal light serves as the resonant light of the OPO, and the long-wave infrared picosecond pulse laser is output outside the resonant cavity through the output mirror 8. The pulse width compressor 10 is used for dispersion compensation and can narrow the pulse width of the 5900-8100 nm laser, ultimately obtaining a long-wave infrared laser output with a wavelength of 5900-8100 nm and a pulse width of 300-500 fs.

[0066] The sample pool 12 is a sealed cubic box. The upper and lower surfaces of the sample pool 12 are windows made of CaF2. Both the upper and lower surfaces of the windows are flat. The two windows can be removed or installed as needed. A bracket that can carry medical specimens is installed in the middle of the box.

[0067] A femtosecond pulse laser of 5900-8100nm is irradiated on the medical specimen. The light signal generated by the medical specimen excited by the long-wave infrared femtosecond pulse laser passes through the window at the bottom of the sample pool 12 and is received by the detector 13. After the light signal received by the detector 13 undergoes photoelectric conversion, the image and processing results are displayed in the computer module 14 (processing software) embedded in the computer.

[0068] In order to save space occupied by the device, a third reflector 11 may be arranged between the pulse width compressor 10 and the sample pool 12 , and the long-wave infrared femtosecond pulse laser is reflected by the third reflector 11 onto the medical specimen in the sample pool 12 .

[0069] The above-mentioned device is arranged on an optical platform. The adjustment step of a conventional optical platform is 5nm, which cannot meet the high precision and high stability requirements of the above-mentioned device. The embodiment of the present application uses an optical platform with an adjustment step of 1nm to ensure the accuracy and stability of the device.

[0070] It should be noted that the optical platform of the embodiment of the present application is placed in a vibration-free environment, which makes the stability of the OPO resonant cavity extremely high.

[0071] The method and device for measuring medical specimens using infrared femtosecond pulse laser in the embodiments of the present application utilize a wavelength-tunable long-wave infrared femtosecond pulse laser to excite the medical specimens, and obtain numerical values ​​of medical specimen-related indicators based on the nonlinear optical phenomena generated by the medical specimens. For medical specimens of different tissues, the specific indicators measured are different, and the indicators to be measured can be selected according to actual conditions.

[0072] Some of the techniques described herein may be implemented in conjunction with hardware or software, or a combination thereof. Thus, the methods and apparatus of the present invention, or certain aspects or portions of the methods and apparatus of the present invention, may be implemented in the form of program codes (i.e., instructions) embedded in a tangible medium, such as a removable hard disk, a USB flash drive, a floppy disk, a CD-ROM, or any other machine-readable storage medium, wherein when the program is loaded into a machine such as a computer and executed by the machine, the machine becomes an apparatus for practicing the present invention.

Claims

1. A method for measuring medical specimens using infrared femtosecond pulse laser, characterized in that: include: Using wavelength-tunable long-wave infrared femtosecond pulse laser to irradiate medical specimens; collecting the transmitted light of the medical specimen using a detector; as well as The measurement result of the medical specimen is given according to the signal output by the detector.

2. The method according to claim 1, wherein The long-wave infrared femtosecond pulse laser is obtained by the following method: The pulse width of a femtosecond pulse laser with a wavelength of 2 microns is widened to obtain a picosecond pulse laser with a wavelength of 2 microns; Injecting the picosecond pulse laser with a wavelength of 2 microns as pump light into the resonant cavity of the optical parametric oscillator; controlling the cavity mirrors of the resonant cavity to achieve synchronous pumping; as well as The pulse width of the long-wave infrared picosecond pulse laser output by the resonant cavity is compressed to obtain a long-wave infrared femtosecond pulse laser.

3. The method according to claim 2, wherein The controlling of the cavity mirror of the resonant cavity comprises: The cavity mirror of the resonant cavity is controlled by piezoelectric ceramics.

4. The method according to claim 2 or 3, wherein: The resonant cavity of the optical parametric oscillator is a ring cavity.

5. An infrared femtosecond pulse laser device for measuring medical specimens, characterized in that: include: Long-wave infrared femtosecond pulse laser, used to output wavelength-tunable long-wave infrared femtosecond pulse laser; A sample pool, used for placing a medical specimen, on which the long-wave infrared femtosecond pulse laser is irradiated; a detector, configured to receive a light signal transmitted through the medical specimen; A calculation module is used to process the signal output by the detector to obtain the measurement result of the medical specimen.

6. The device according to claim 5, characterized in that The long-wave infrared femtosecond pulse laser comprises: 2 micron femtosecond pulse laser, used to generate 2 micron femtosecond pulse laser; A pulse width stretcher, used to stretch the pulse width of the 2 micron femtosecond pulse laser to obtain a 2 micron picosecond pulse laser; An optical parametric oscillator, using the 2-micron picosecond pulse laser as pump light to achieve wavelength-tunable long-wave infrared picosecond pulse laser output; and The pulse width compressor is used to compress the pulse width of the long-wave infrared picosecond pulse laser to obtain a wavelength-tunable long-wave infrared femtosecond pulse laser output.

7. The device according to claim 6, characterized in that The resonant cavity of the optical parametric oscillator is a ring cavity.

8. The device according to claim 7, characterized in that The optical parametric oscillator is equipped with piezoelectric ceramics, and the piezoelectric ceramics are used to control a cavity mirror of the optical parametric oscillator to achieve synchronous pumping of the optical parametric oscillator.

9. The device according to any one of claims 5 to 8, characterized in that The wavelength tuning range of the long-wave infrared femtosecond pulse laser is 6-8 microns.

10. The device according to any one of claims 5 to 8, characterized in that The calculation module is further used to compare the processing result corresponding to the normal tissue medical specimen with the processing result corresponding to the medical specimen to be tested.

Images