Use of van der waals tellurium nanomaterial as near-infrared iia photoneuromodulation material

Abstract

Provided is a use of a van der Waals tellurium nanomaterial as a near-infrared IIa photoneuromodulation material. A preparation method for the van der Waals tellurium nanomaterial comprises the following steps: using selenium telluride as a raw material, performing chemical vapor deposition on the surface of a substrate, and then adjusting the temperature of the substrate to 200-400°C, so as to obtain the van der Waals tellurium nanomaterial, wherein the chemical vapor deposition is performed under a nitrogen atmosphere. The van der Waals nanomaterial enables photoneuromodulation across a broad spectral bandwidth (from visible light to near-infrared light), reaching a near-infrared IIa (1.3-1.4 μm) band, and can successfully induce, under irradiation of 1.31 μm near-infrared IIa light, action potentials in mouse cortical neurons.

Description

Application of a van der Waals tellurium nanomaterial in a near-infrared Ⅱa light neuroregulation material TECHNICAL FIELD

[0001] The present application relates to the technical field of optoelectronic materials, and particularly relates to application of a van der Waals tellurium nanomaterial in a near-infrared Ⅱa light neuroregulation material. BACKGROUND

[0002] Neuroregulation is an effective method for regulating brain function and treating brain diseases. Various forms of neuroregulation have been reported, mainly including electrical, optical and thermal methods. Among them, the most well-known electrical stimulation has been applied to deep brain electrical stimulation for Parkinson's disease and transcranial magnetic stimulation for mood regulation. However, the development of electrical stimulation for single neurons is hindered by many factors, such as the lack of spatial specificity of invasive and bulky electrodes, the possibility of damaging tissues, and the inability to target single nerve cells. Optical neuroregulation has great potential and can remotely stimulate neurons to achieve the regulation and treatment of neural tissues. Optical genetic neural stimulation combines optical and genetic technologies to provide precise control of neural cells and brain tissues with cell specificity. This technology mainly uses visible light (400-700 nm) for excitation. Optical genetics has revolutionized the study of neural circuits at the cellular level. However, most mature nerve cells lack photoreceptors and need to be implanted with optical genetic proteins (such as ChR2 or NpHR) to be regulated, which limits its further development and application.

[0003] Optoelectronic nanomaterials can convert light into electrical energy and induce cells to generate action potentials. Based on the unique photoelectric conversion of these nanomaterials, light regulation is divided into four types: p-n junction photovoltaic effect, spectral selective upconversion, photothermal effect, and photoacoustic effect. The p-n junction photovoltaic effect of coaxial silicon nanowires or organic semiconductors is currently mainly used for visible light (532 nm) for optical neuroregulation. Due to the limitation of the semiconductor band gap, the maximum wavelength of neural regulation can only reach 1.1 microns. Nanoparticles use spectral selective upconversion to convert near-infrared (800-980 nm) light into visible light and further stimulate nerve cells to generate action potentials. In addition, gold nanorods, mesoporous silicon, poly-benzothiadiazole-alternate-ethylene nanoparticles, etc. convert near-infrared 1.06 micron light into heat to induce neurons to generate action potentials. Photoacoustic effect is also found in nanoparticles, but the wavelength of light stimulation in neural regulation is limited to 1.03 microns. Therefore, the wavelength of light for optical neuroregulation has not yet reached the near-infrared Ⅱa (1.3-1.4 microns) band with deeper tissue penetration. How to develop new nanomaterials to achieve near-infrared Ⅱa light neuroregulation is a key problem to be solved. SUMMARY

[0004] The application aims to provide an application of van der Waals tellurium nanomaterial as a near-infrared IIa light nerve regulation material.

[0005] In order to achieve the above-mentioned application purposes, the application provides the following technical solutions.

[0006] The application provides a preparation method of van der Waals tellurium nanomaterial, which comprises the following steps.

[0007] The van der Waals tellurium nanomaterial is obtained by adjusting the temperature of the substrate to 200-400 DEG C after chemical vapor deposition on the surface of the substrate with tin telluride as raw material.

[0008] The chemical vapor deposition is performed under the condition of nitrogen.

[0009] In some embodiments, the substrate comprises a silicon substrate, a glass substrate, a mica substrate or a sapphire substrate; and the thickness of the substrate is 500 nm-500 mu m.

[0010] In some embodiments, the flow rate of nitrogen is 30-80 sccm during the process of nitrogen.

[0011] In some embodiments, the chemical vapor deposition is performed under the condition of heating; the temperature of the heating is 550-700 DEG C, and the holding time is 20-60 min.

[0012] In some embodiments, the length of the van der Waals tellurium nanomaterial is 0.95-12.92 mu m, and the thickness is less than 200 nm.

[0013] The application further provides the van der Waals tellurium nanomaterial prepared by the preparation method, wherein the length of the van der Waals tellurium nanomaterial is 0.95-12.92 mu m, and the thickness is less than 200 nm.

[0014] The application further provides an application of the van der Waals tellurium nanomaterial as a near-infrared IIa light nerve regulation material.

[0015] The application provides application of a van der Waals tellurium nanomaterial in a near-infrared IIa light nerve regulation material, a preparation method of the van der Waals tellurium nanomaterial, and the method comprises the following steps: taking tin telluride as raw material, performing chemical vapor deposition on the surface of a substrate, adjusting the temperature of the substrate to 200-400 DEG C to obtain the van der Waals tellurium nanomaterial; the chemical vapor deposition is performed under the condition of nitrogen gas. The van der Waals tellurium nanomaterial prepared by the preparation method is a direct band gap semiconductor, the band gap is about 0.34 eV, the absorption coefficient of the van der Waals tellurium nanomaterial to visible light to near-infrared light is as high as 10 4 cm -1 , a large current can be generated under 637 nm, 940 nm and 1.31 mu m irradiation, and wide-spectrum nerve regulation is realized. BRIEF DESCRIPTION OF DRAWINGS

[0016] Fig. 1 is a statistical diagram of the average length of the van der Waals tellurium nanomaterial prepared in examples 1-7;

[0017] Fig. 2 is a flowchart of a cortical nerve cell culture medium and the van der Waals tellurium nanomaterial in the application example;

[0018] Fig. 3 is an immunohistochemical characterization diagram of the van der Waals tellurium nanomaterial in example 1;

[0019] Fig. 4 is a cell membrane patch clamp recording diagram of primary cortical neurons under wide-band light irradiation and a microscope photograph of neurons and the van der Waals tellurium nanomaterial in example 4;

[0020] Fig. 5 is a potential curve diagram of near-infrared IIa 1.31 mu m light irradiation under different light powers and different frequencies on the van der Waals tellurium nanomaterial in example 4;

[0021] Fig. 6 is a potential curve diagram of 637 nm and 940 nm light irradiation under different light powers and different frequencies on the van der Waals tellurium nanomaterial in example 4;

[0022] Fig. 7 is a potential curve diagram of near-infrared IIa 1.31 mu m light irradiation under different light powers without light irradiation on the van der Waals tellurium nanomaterial in example 4;

[0023] Fig. 8 is a light nerve regulation mechanism diagram of the van der Waals tellurium nanomaterial in example 4. DETAILED DESCRIPTION

[0024] The application provides application of a van der Waals tellurium nanomaterial in a near-infrared IIa light nerve regulation material, a preparation method of the van der Waals tellurium nanomaterial, and the method comprises the following steps:

[0025] The van der Waals tellurium nanomaterial is obtained by adjusting the temperature of the substrate to 200-400 ℃ after chemical vapor deposition on the surface of the substrate using tin telluride as raw material.

[0026] The chemical vapor deposition is carried out under nitrogen.

[0027] In the present application, all the raw materials are commercially available products or self-made products by using conventional methods in the art, unless otherwise specified.

[0028] In the present application, the van der Waals tellurium nanomaterial refers to a tellurium nanomaterial in which tellurium atoms form spiral chains and the chains are combined by van der Waals force.

[0029] In some embodiments, the substrate comprises a silicon substrate, a glass substrate, a mica substrate or a sapphire substrate; in some embodiments, the substrate is a silicon substrate; in some embodiments, the silicon substrate comprises a silicon substrate and a silicon dioxide layer on the surface of the silicon substrate. In some embodiments, the thickness of the substrate is 500 nm-500 μm; in some embodiments, the thickness of the substrate is 500 nm-100 μm; in some embodiments, the thickness of the substrate is 500 nm-10 μm.

[0030] In some embodiments, the substrate is placed downstream of a quartz tube; in some embodiments, the tin telluride is placed in a ceramic boat at the center of the quartz tube.

[0031] In some embodiments, the present application is evacuated before the chemical vapor deposition. The process of the evacuation is not particularly limited in the present application, and any process known to those skilled in the art can be used as long as the environmental pressure is reduced to below 20 Pa.

[0032] In some embodiments, the flow rate of nitrogen is 30-80 sccm during the nitrogen flow; in some embodiments, the flow rate of nitrogen is 40-60 sccm; in some embodiments, the flow rate of nitrogen is 50 sccm.

[0033] In some embodiments, the chemical vapor deposition is carried out under heating. In some embodiments, the temperature of the heating is 550-700 ℃; in some embodiments, the temperature is 580-680 ℃; in some embodiments, the temperature is 600-640 ℃; in some embodiments, the holding time of the heating is 20-60 min; in some embodiments, the holding time is 30-50 min; in some embodiments, the holding time is 30-40 min.

[0034] In some embodiments, after the chemical vapor deposition is completed, the present application further comprises cooling (i.e., cooling (e.g., to room temperature) after the temperature of the substrate is adjusted to 200-400°C, the surface of the substrate is subjected to chemical vapor deposition using tin telluride as the raw material, to obtain the van der Waals tellurium nanomaterial). The present application does not have any special limitation on the process of cooling, which can be performed using a process well known to those skilled in the art (additional cooling means can be used, or it can be left to cool naturally). When the temperature of the substrate reaches the range of 200-400°C, Te begins to grow, and after the growth of Te is completed, the temperature is lowered (e.g., to room temperature).

[0035] In some embodiments, the temperature of the substrate is adjusted to 235-370°C; in some embodiments, the temperature of the substrate is adjusted to 270-335°C; and in some embodiments, the temperature of the substrate is adjusted to 300°C.

[0036] The present application also provides a van der Waals tellurium nanomaterial prepared by the preparation method described in the above technical solution, wherein the length of the van der Waals tellurium nanomaterial is 0.95-12.92 μm, and the thickness is <200 nm.

[0037] The present application also provides a neural regulation method using the van der Waals tellurium nanomaterial described in the present application, which comprises the following steps: (1) preparing the van der Waals tellurium nanomaterial by the preparation method described in the present application; (2) contacting the van der Waals tellurium nanomaterial with target nerve cells or nerve tissues; and (3) irradiating the van der Waals tellurium nanomaterial in contact with the nerve cells or nerve tissues with near-infrared IIa light to induce the nerve cells or nerve tissues to generate action potentials.

[0038] There is no limitation on the order of the steps (2) and (3).

[0039] In a broad sense, the near-infrared IIa light described in the present application refers to light with a wavelength of 1.0-1.7 μm. In some embodiments, the wavelength of the near-infrared IIa light is 1.0-1.4 μm. In some embodiments, the wavelength of the near-infrared IIa light is 1.3-1.4 μm. In some embodiments, the wavelength of the near-infrared IIa light is 1.31 μm.

[0040] The application of the van der Waals tellurium nanomaterial provided by the present application as a near-infrared IIa light neural regulation material will be described in detail below in conjunction with examples, but they should not be understood as limiting the scope of protection of the present application.

[0041] Example 1

[0042] Put tin telluride as raw material in the center of the quartz tube ceramic boat, 0.5mm thick silicon substrate (surface including silicon dioxide layer) is placed downstream of the quartz tube, then the air in the quartz tube is discharged, the pressure of the quartz tube is reduced to below 20Pa, nitrogen is introduced at a flow rate of 50sccm, heated to 640℃ and kept for 40min, after natural cooling, the temperature of the silicon substrate is adjusted to 200℃, and the van der Waals tellurium nanomaterial is obtained on the surface of the silicon substrate.

[0043] Example 2

[0044] Reference Example 1, the difference is only that the temperature of the silicon substrate is adjusted to 235℃.

[0045] Example 3

[0046] Reference Example 1, the difference is only that the temperature of the silicon substrate is adjusted to 270℃.

[0047] Example 4

[0048] Reference Example 1, the difference is only that the temperature of the silicon substrate is adjusted to 300℃.

[0049] Example 5

[0050] Reference Example 1, the difference is only that the temperature of the silicon substrate is adjusted to 335℃.

[0051] Example 6

[0052] Reference Example 1, the difference is only that the temperature of the silicon substrate is adjusted to 370℃.

[0053] Example 7

[0054] Reference Example 1, the difference is only that the temperature of the silicon substrate is adjusted to 400℃.

[0055] Figure 1 is a statistical diagram of the average length of the van der Waals tellurium nanomaterial prepared in Examples 1-7, as shown in Figure 1, the average length of the van der Waals tellurium nanomaterial corresponding to the substrate temperature of 200℃ is 0.95μm, the average length of the van der Waals tellurium nanomaterial corresponding to the substrate temperature of 235℃ is 1.70μm, the average length of the van der Waals tellurium nanomaterial corresponding to the substrate temperature of 270℃ is 2.97μm, the average length of the van der Waals tellurium nanomaterial corresponding to the substrate temperature of 300℃ is 5.19μm, the average length of the van der Waals tellurium nanomaterial corresponding to the substrate temperature of 335℃ is 7.76μm, the average length of the van der Waals tellurium nanomaterial corresponding to the substrate temperature of 370℃ is 10.22μm, and the average length of the van der Waals tellurium nanomaterial corresponding to the substrate temperature of 400℃ is 12.92μm. The thickness of the van der Waals tellurium nanomaterial prepared in Examples 1-7 is less than 200nm.

[0056] Application examples

[0057] All mice were housed under standard feeding conditions of 22±1℃, 50±10% relative humidity, and a 12-hour food and water IDE light-dark cycle. Primary cortical neurons were randomly obtained from the cerebral cortex of 18-day-old ICR mice. First, the cerebral cortex tissue was isolated and digested at 37℃ for 30 minutes with a mixture of 0.5% deoxyribonuclease and 0.25% papain. The solution was transferred to 15 mL centrifuge tubes. Cortical tissue was then collected by centrifugation at 1000 rpm for 4 minutes. The cortical tissue blocks were blown up and converted into single cells in neurobasal medium containing 10% fetal bovine serum, 2 mM glutamine, and 1% penicillin / streptomycin. The single-cell solution was filtered through a 40 microcell filter and concentrated at 0.5 × 10⁻⁶ micrograms per cell. 6 Cells were seeded at a density of 10 cells / mL in 24-well plates treated with polylysine (0.2 mg / mL) in Neurobasic medium. After approximately 5 hours, the cells were cultured in serum-free Neurobasic medium containing 2% B27, 2 mM glutamine, and a 1% penicillin / streptomycin mixture. Half of the medium was replaced with freshly fed medium every 3 days. On day 10, the van der Waals tellurium nanomaterials described in Example 1 were added to the cortical neuron culture medium (as shown in Figure 2), wherein the van der Waals tellurium nanomaterials added to the cortical neuron culture medium were 5 μg / mL.

[0058] Immunohistochemical characterization was performed using a control group without the aforementioned van der Waals tellurium nanomaterials. Neurons were fixed with 4% (w / v) paraformaldehyde at 4°C for 4 h. After fixation, the neurons were washed three times with 0.1M PBS (pH=7.4) at room temperature. Subsequently, the neurons were blocked for 2 h at room temperature with 0.1% (w / v) PBS solution containing 10% (w / v) serum, 3% (w / v) BSA, and 0.3% (w / v) Triton X-100. The neurons were then incubated with antibody solution overnight at 4°C. After incubation, the neurons were washed three times with PBS containing 0.1% (w / v) Triton X-100 and stained with Alexa488 and Alexa 546 at room temperature for 2 h. DAPI was added for counterstaining, and the neurons were fixed on glass slides. Images were acquired using a Zeiss 980 confocal microscope and processed using ImageJ. The test results are shown in Figure 3. As can be seen from Figure 3, after co-incubating with van der Waals tellurium nanomaterials for 48 hours, no expression of apoptosis markers such as caspase-3 (CAPS-3) was observed in neurons, indicating that van der Waals tellurium nanomaterials at concentrations of 5 μg / mL or less did not induce neuronal apoptosis.

[0059] Electrophysiological recording of van der Waals tellurium nanomaterials and neurons: Whole-cell patch-clamp recordings of primary cortical neurons from DIV11 mice were performed using an internal solution (136 mM potassium gluconate, 6 mM KCl, 1 mM EGTA, 2.5 mM Na2ATP, 10 mM HEPES (280 mOsm, pH 7.2, KOH)) and an extracellular solution ACSF (126 mM NaCl, 4.9 mM KCl, 1.2 mM KH2PO4, 2.4 mM MgSO4, 2.5 mM CaCl2, 26 mM NaHCO3, 20 mM glucose). The resistance of the recording pipette was 10–12 MΩ. Near-infrared IIa 1.31 μm laser light, approximately 12 μm in length, was focused onto the van der Waals tellurium nanomaterials adhered to the neurons using a 60x objective lens. The diameter of the 1.31 μm light beam was 74.6 μm. Action potential data were collected using a 2kHz low-pass filter (Multiclamp 700B and Digidata 1322 A / D converter) and sampled at 10kHz. Action potential characteristics were analyzed using CLAMPFIT 10.7 software. Figure 4 shows patch-clamp recordings of primary cortical neurons under broadband illumination and microscopic images of neurons with the van der Waals tellurium nanomaterial described in Example 4. Figure 4 shows that the van der Waals tellurium nanomaterial has a length of approximately 10.4 μm and a width of approximately 3.65 μm. The van der Waals tellurium nanomaterial is in contact with the cell body of the neuron. Figure 5 shows the potential curves after irradiation with 1.31 μm near-infrared IIa light at different power and frequency conditions on the van der Waals tellurium nanomaterial described in Example 4. Figure 5 shows that when 1.31 μm near-infrared IIa light irradiates the van der Waals tellurium nanomaterial for 5 ms, the action potential voltage generated by the mouse cortical neurons gradually increases with increasing light power density. When the power density reaches 0.38mW / mm -2 When the light intensity is increased, a complete action potential is generated, mainly consisting of the peak potentials of the rapid depolarization rising phase and the rapid repolarization falling phase, as well as a slow afterpotential. Further changing the irradiation frequency of the 1.31 μm light, when the light frequency is 10 Hz or 20 Hz, the neuron can generate a corresponding complete action potential. When the light frequency reaches 40 Hz, the neuron can only generate a partial action potential.

[0060] Figure 6 shows the potential curves of the van der Waals tellurium nanomaterial described in Example 4 after irradiation with 637 nm and 940 nm light under different optical powers and frequencies. As can be seen from Figure 6, when the power density of 637 nm light reaches 26.5 mW / mm², the potential is significantly higher than that of 940 nm light. -2 At this time, the nerve cell generates a complete action potential. For 940nm light, the power density is relatively low, reaching 1.09mW / mm². -2When the frequency of 637nm and 940nm light is 10Hz, the nerve cell can generate a corresponding complete action potential;

[0061] Figure 7 is a potential curve diagram of the near-infrared IIa 1.31μm light irradiation under different light power conditions without light irradiation on the van der Waals tellurium nanomaterial described in Example 4. As can be seen from Figure 7, the mouse cortical nerve cells cannot generate an action potential when there is no light irradiation on the tellurium nanomaterial. When the near-infrared IIa 1.31μm light is irradiated onto the tellurium nanomaterial, a potential is generated. The light power is 15.5, 13.4, 9.82, 6.84, 11.4, 10.2 and 7.32mWmm -2 respectively. The dotted curve is without light irradiation, and the solid line is the near-infrared IIa 1.31μm light irradiation;

[0062] Figure 8 is a schematic diagram of the optical nerve regulation mechanism of the van der Waals tellurium nanomaterial described in Example 4. As can be seen from Figure 7, the principle of the optical nerve regulation of the van der Waals tellurium nanomaterial is that when the van der Waals tellurium nanomaterial is placed in a solution and in contact with neurons, the energy band of tellurium is bent downward. Under light irradiation, the electrons in the valence band are excited to the conduction band, and holes are generated in the valence band. Due to the bending of the energy band, the photo-generated electrons move to the Te surface. The electrons accumulated on the surface then diffuse into the electrolyte solution and diffuse to the extracellular side of the neuron membrane. These electrons diffuse to the extracellular side and react with positive ions such as K + , Na + and Ca 2+ in the solution, resulting in a change in transmembrane voltage and subsequent depolarization of the nerve, generating an action potential. On the other hand, the photo-generated holes are recombined in the tellurium nanomaterial or the solution.

[0063] The above only describes the preferred embodiments of the present application, and it should be noted that for those skilled in the art, without departing from the principles of the present application, a number of improvements and refinements can be made, and these improvements and refinements should also be considered within the scope of protection of the present application.

Claims

1. A method for preparing a van der Waals tellurium nanomaterial, characterized in that, The method comprises the following steps: The van der Waals tellurium nanomaterial is obtained by chemical vapor deposition on the surface of a substrate using tin telluride as raw material, and adjusting the temperature of the substrate to 200-400 DEG C. The chemical vapor deposition is carried out under the condition of nitrogen.

2. The production method according to claim 1, wherein The substrate comprises a silicon substrate, a glass substrate, a mica substrate or a sapphire substrate. The thickness of the substrate is 500 nm-500 microns.

3. The production method according to claim 1, wherein The flow rate of nitrogen is 30-80 sccm during the nitrogen passing process.

4. The production method according to claim 1, wherein The chemical vapor deposition is carried out under the condition of heating. The temperature of the heating is 550-700 DEG C, and the holding time is 20-60 min.

5. The van der Waals tellurium nanomaterial prepared by the method of any one of claims 1 to 4, characterized in that, The length of the van der Waals tellurium nanomaterial is 0.95-12.92 microns, and the thickness is less than 200 nm.

6. Application of a van der Waals tellurium nanomaterial as a near-infrared IIa light neuromodulation material, characterized in that, The method for preparing the van der Waals tellurium nanomaterial comprises the following steps: The van der Waals tellurium nanomaterial is obtained by chemical vapor deposition on the surface of a substrate using tin telluride as raw material, and adjusting the temperature of the substrate to 200-400 DEG C. The chemical vapor deposition is carried out under the condition of nitrogen.

7. Use according to claim 6, wherein The substrate comprises a silicon substrate, a glass substrate, a mica substrate or a sapphire substrate. The thickness of the substrate is 500 nm-500 microns.

8. The use according to claim 6, wherein The flow rate of nitrogen is 30-80 sccm during the nitrogen passing process.

9. The use according to claim 6, wherein The chemical vapor deposition is carried out under the condition of heating. The temperature of the heating is 550-700 DEG C, and the holding time is 20-60 min.

10. Use according to any one of claims 6 to 9, characterized in that, The length of the van der Waals tellurium nanomaterial is 0.95-12.92 microns, and the thickness is less than 200 nm.

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