Integrated optical fiber diagnosis and treatment integrated minimally invasive probe based on rare earth nano material

Abstract

The invention relates to an integrated optical fiber diagnosis and treatment integrated minimally invasive probe based on a rare earth nano material, and belongs to the technical field of medical minimally invasive machinery. The probe is composed of a flexible silica fiber, a rare earth doped nano core transfer material and a graphene composite photo-thermal layer. The temperature of the focus is monitored in real time through the fluorescence intensity ratio technology. In order to achieve the purpose of photo-thermal treatment, the graphene composite material is added, by means of the high thermal conductivity of the graphene composite material and the non-radiative relaxation effect of rare earth ions, the photo-thermal conversion efficiency is improved, and the thermal conductivity is further enhanced. The device has the advantages of miniaturization, high sensitivity, electromagnetic interference resistance and the like, and can be applied to scenes such as tumor ablation and vascular intervention.

Description

Technical Field

[0001] The present invention relates to an integrated optical fiber diagnosis and treatment integrated minimally invasive probe based on rare earth nanomaterials, belonging to the cross field of interventional radiology and nanomaterial technology. Background Art

[0002] In recent years, the photothermal diagnosis and treatment integrated technology based on rare earth nanomaterials has shown important application potential in the field of minimally invasive interventional surgery due to its non-invasive, high-sensitivity and multimodal functional characteristics. Traditional photothermal therapy probes mostly rely on external temperature monitoring devices, which have problems such as low spatial resolution, poor anti-electromagnetic interference ability, and inability to provide real-time feedback of local temperature, and are prone to cause damage to normal tissues due to heat diffusion. In addition, existing optical fiber sensing probes have a single function and it is difficult to simultaneously achieve high-precision temperature monitoring and targeted therapy. The research results of Zhao et al.'s paper show that lanthanide ions (such as Yb 3+ , Tm 3+ , Er 3+ ) doped upconversion luminescent materials have photoluminescence characteristics, and their temperature measurement sensitivity can reach 1.5% K -1 , but there is still insufficient coordination and optimization with the treatment function.

[0003] Graphene is used to enhance the photothermal conversion efficiency due to its ultra-high thermal conductivity (in-plane ≥ 4000 W / (m·K)) and photothermal synergy effect. Recent research shows that Yb 3+ / Tm 3+ / Er 3+ co-doped barium titanate (BaTiO3) can achieve high-sensitivity temperature measurement in a wide temperature range through non-thermal coupling energy levels. Therefore, developing an optical fiber probe with both high-sensitivity temperature measurement and efficient photothermal conversion has become a key technical breakthrough direction for precise minimally invasive diagnosis and treatment in the interventional department. Summary of the Invention

[0004] (1) Technical Problems to be Solved

[0005] Aiming at the technical bottlenecks of traditional interventional probes such as insufficient temperature measurement accuracy, low photothermal efficiency and single function, the present invention proposes an integrated optical fiber diagnosis and treatment integrated minimally invasive probe based on rare earth nanomaterials. Real-time and accurate temperature monitoring is achieved through the fluorescence intensity ratio technology of lanthanide ion co-doped barium titanate, and the relative sensitivity reaches 2.70% K -1 . And the energy conversion efficiency is improved by combining graphene to meet the requirements of interventional surgery.

[0006] (2) Technical Solutions

[0007] The purpose of the present invention is to provide an integrated optical fiber diagnosis and treatment integrated minimally invasive probe based on rare earth nanomaterials.

[0008] The technical solution adopted by the present invention to achieve the above purpose is as follows:

[0009] The present invention consists of two parts: an optical fiber body, which is composed of a single-mode optical fiber; and a rare-earth nano-graphene composite photothermal layer, which is composed of 8% Yb 3+ , 1.75% Tm 3+ , 0.1% Er 3+ , and a rare-earth nano-material prepared by a molten salt method with doped nano-particles and graphene are compounded in polydimethylsiloxane (hereinafter replaced by PDMS).

[0010] The present invention provides a preparation method of a rare-earth nano-material, and the specific scheme is as follows:

[0011] As a preferred scheme, in the integrated optical fiber diagnosis and treatment integrated minimally invasive probe based on a rare-earth nano-material, the rare-earth nano-material is a phosphor BaTiO3:8% Yb 3+ / 1.75% Tm 3+ / 0.1% Er 3+ prepared by a molten salt method. The raw materials used for the preparation are high-purity Yb2O3, Tm2O3, Er2O3, BaCO3 and TiO2, and the molten salt used is a mixture of NaCl and KCl with a molar ratio of 1:1.

[0012] As a preferred scheme, in the integrated optical fiber diagnosis and treatment integrated minimally invasive probe based on a rare-earth nano-material, during the preparation process, the raw materials and the molten salt are mixed at a molar ratio of 1:4. Then, it is carefully ground in a mortar for 20 minutes to ensure uniform dispersion of each component. Next, the ground mixture is transferred to a covered alumina crucible. Finally, the crucible is placed in a muffle furnace and calcined at 900 °C for 2.5 hours in an air atmosphere.

[0013] As a preferred scheme, in the integrated optical fiber diagnosis and treatment integrated minimally invasive probe based on a rare-earth nano-material, after the preparation step, after the product is cooled to room temperature, it is washed with deionized water and centrifuged several times to remove water-soluble ions such as Na+ and K+. Then, it is rinsed twice with ethanol and dried at 60 °C for 8 hours to obtain a white powder.

[0014] As a preferred scheme, in the integrated optical fiber diagnosis and treatment integrated minimally invasive probe based on a rare-earth nano-material, the probe combination scheme includes but is not limited to hydrothermal synthesis method, chemical reduction method, plasma-assisted modification method, covalent bonding method, in-situ growth method, surface modification and dispersion method, sol-gel method. In this scheme, the PDMS base glue and the curing agent are mixed at a mass ratio of 10:1, and 5 wt% of an ultraviolet light initiator is added to form a PDMS prepolymer. The rare-earth nano-particles and graphene are dispersed in the PDMS prepolymer and ultrasonicated for 30 minutes.

[0015] As a preferred solution, in the integrated optical fiber diagnosis and treatment integrated minimally invasive probe based on rare earth nanomaterials, in the probe combination solution, rare earth nano-graphene and optical fiber are combined by ultraviolet light curing to form a probe. The surface of the probe is polished to improve the smoothness and biocompatibility of the probe. Sandpaper is used for polishing.

[0016] As a preferred solution, in the integrated optical fiber diagnosis and treatment integrated minimally invasive probe based on rare earth nanomaterials, its diagnostic function is to excite the upconversion luminescence of rare earth nanomaterials by 980nm laser, and use the non-thermal coupling energy level fluorescence intensity ratio of Tm 3+ and Er 3+ to establish a temperature function relationship. The formula is: (a, b are calibration parameters), and the accurate value of the measured temperature in real time is deduced inversely according to the value of FIR.

[0017] As a preferred solution, in the integrated optical fiber diagnosis and treatment integrated minimally invasive probe based on rare earth nanomaterials, the diameter of the optical fiber core is 105±2μm, the core layer material is pure quartz, the working wavelength range is 200 - 1200nm, and the working temperature is -45 - 85°C.

[0018] As a preferred solution, the integrated optical fiber diagnosis and treatment integrated minimally invasive probe based on rare earth nanomaterials adapts to the real-time positioning requirements of image guidance in interventional surgery, and can transmit temperature data through an external spectrometer.

[0019] (III) Beneficial Effects

[0020] The integrated optical fiber diagnosis and treatment integrated minimally invasive probe based on rare earth nanomaterials involved in the present invention has the following advantages:

[0021] 1) The relative temperature measurement sensitivity of rare earth nanomaterials reaches 2.70%K -1 , with an error of ±0.5K. It has high sensitivity and can achieve real-time and accurate temperature measurement.

[0022] 2) Preparing rare earth nanomaterials and graphene into a composite material is beneficial to heat conduction. At the same time, the non-radiative relaxation of rare earth ions converts light into heat, increasing the photothermal conversion efficiency. The photothermal efficiency breaks through 90%. Targeted therapy can be achieved.

[0023] 3) The preparation method of the proposed rare earth nanomaterials is simple and can be mass-produced.

[0024] 4) The probe described in the present invention has low assembly difficulty and low requirements for equipment. Description of the Drawings

[0025] Figure 1 It is the scanning electron microscope photo of the BaTiO3 rare earth nanomaterials prepared by the present invention;

[0026] Figure 2 For the temperature-dependent upconversion spectrum of rare-earth nanomaterials with 8% Yb 3+ / 1.75% Tm 3+ / 0.1% Er 3+ under 980 nm excitation;

[0027] Figure 3 This is the temperature-dependent change curve of the absolute sensitivity and relative sensitivity of the rare-earth nanomaterials in the present invention; Detailed implementation mode

[0028] Example 1: Probe preparation and application

[0029] The preparation method of the rare-earth nanomaterials of the present invention uses the molten salt method to prepare BaTiO3:Yb 3+ / Tm 3+ / Er 3+ phosphor. The raw materials are high-purity Yb2O3, Tm2O3, Er2O3, BaCO3 and TiO2, and the molten salt is a mixture of NaCl-KCl with a molar ratio of 1:1. Weigh and mix according to the molar ratio of raw materials to molten salt of 1:4, grind evenly, transfer to an alumina crucible, and calcine at 900 °C for 2.5 hours in an air atmosphere. The cooled product is centrifuged and washed with deionized water multiple times to remove Na + / K + ions, rinse twice with ethanol and dry at 60 °C for 8 hours to finally obtain nanoparticles. Mix the PDMS base gum (such as Sylgard 184) and the curing agent in a mass ratio of 10:1, and add 5 wt% of an ultraviolet light initiator (such as benzophenone) to form a PDMS prepolymer.

[0030] Disperse 1.5 wt% rare-earth nanoparticles and 0.5 wt% graphene evenly in the PDMS prepolymer, and ultrasonically treat for 30 minutes (power 200 W) to avoid agglomeration. Inject the mixture into the mold, carefully insert the pretreated optical fiber into the PDMS composite material in the mold, ensure that the optical fiber is located at the center of the mold, and the end of the optical fiber is kept at an appropriate distance from the bottom of the mold (for example, 0.5 - 1 mm). The insertion position of the optical fiber can be observed with the assistance of a microscope.

[0031] Ultraviolet light curing (wavelength 365 nm, intensity 20 mW / cm 2 , time 10 minutes) to form a probe with the sensing unit combined with the optical fiber. Polish the surface of the probe to improve the smoothness and biocompatibility of the probe. Sandpaper or polishing liquid can be used for polishing.

Claims

1. An integrated optical fiber diagnosis and treatment integrated minimally invasive probe based on rare earth nanomaterials, characterized in that: The probe consists of two parts, namely: an optical fiber body composed of a single-mode optical fiber; and a rare-earth nano-graphene composite photothermal layer coated on the end of the optical fiber and composed of a composite of lanthanide ion-doped nanoparticles and graphene material.

2. A preparation method of a rare earth nanomaterial, characterized in that: The rare-earth nano-material is prepared by a molten salt method, which specifically includes the following steps: (1) Mix and grind the raw materials and the molten salt according to a suitable ratio. (2) Transfer the ground mixture to a covered alumina crucible and place the crucible in a muffle furnace for calcination. (3) After the product is cooled to room temperature, wash it with deionized water and centrifuge it several times, then rinse it twice with ethanol, and dry it to obtain a white powdery material.

3. According to the preparation method described in claim 2, it is characterized in that: The preparation raw materials are high-purity Yb2O3, Tm2O3, Er2O3, BaCO3 and TiO2, and the molten salt is a mixture of NaCl and KCl with a molar ratio of 1:

1.

4. According to the preparation method described in claim 2, wherein: The molar ratio of the raw materials to the molten salt is 1:

4.

5. According to the preparation method described in claim 2, characterized in that: The calcination process should be carried out in an air atmosphere at 900 °C for 2.5 hours.

6. The preparation method according to claim 2, characterized in that: In the preparation process, after washing with deionized water and centrifuging several times, it should be rinsed twice with ethanol and dried in an environment of 60 °C for 8 hours.

7. An integrated optical fiber diagnosis and treatment integrated minimally invasive probe based on rare earth nanomaterials according to claim 1, characterized in that: The combination methods of the rare-earth nano-material and graphene include, but are not limited to, hydrothermal synthesis method, chemical reduction method, plasma-assisted modification method, covalent bond binding method, in-situ growth method, surface modification dispersion method, sol-gel method.

8. An integrated optical fiber diagnosis and treatment integrated minimally invasive probe based on rare earth nanomaterials according to claim 1, characterized in that: The probe is assembled by pouring the rare-earth nano-material into a mold and inserting the optical fiber into the mold for combination. After the combination is completed, the surface of the probe is polished with sandpaper.

9. An integrated optical fiber diagnosis and treatment integrated minimally invasive probe based on rare earth nanomaterials according to claim 1, characterized in that: The diagnostic function excites the upconversion luminescence of rare earth nanomaterials through 980nm laser, and establishes a temperature function relationship by using the fluorescence intensity ratio of the non-thermally coupled energy levels of Tm 3+ and Er 3+ . The formula is: (a and b are calibration parameters), and the exact value of the measured temperature in real time is deduced inversely according to the value of FIR.

10. An integrated optical fiber diagnosis and treatment integrated minimally invasive probe based on rare earth nanomaterials according to claim 1, characterized in that: The core diameter of the optical fiber is 105 ± 2 μm, the material is pure quartz, the working wavelength range is 200 - 1200 nm, and the working temperature is -45 - 85 °C.

11. An integrated optical fiber diagnosis and treatment integrated minimally invasive probe based on rare earth nanomaterials according to claim 1, characterized in that: The probe is adapted to the real-time positioning requirements of image guidance in interventional surgery and can transmit temperature data through an external spectrometer.

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