Application of Van der Waals tellurium nano material as near-infrared IIa light nerve regulation material

Abstract

The invention relates to the technical field of photoelectric materials, in particular to application of a Van der Waals tellurium nano material as a near-infrared IIa light nerve regulation material. The invention provides an application of a Van der Waals Te nanometer material as a near-infrared IIa light nerve regulation material, and a preparation method of the Van der Waals Te nanometer material comprises the following steps: taking selenium telluride as a raw material, carrying out chemical vapor deposition on the surface of a substrate, adjusting the temperature of the substrate to 200-400 DEG C, and carrying out heat preservation for 2-4 hours, so as to obtain the Van der Waals Te nanometer material. The Van der Waals tellurium nanometer material is obtained; the chemical vapor deposition is carried out under the condition of introducing nitrogen. The Van der Waals tellurium nano material has a wide spectrum (from visible light to near-infrared light) for optical nerve regulation, the wave band can reach the near-infrared IIa (1.3-1.4 microns) wave band, and under the irradiation of 1.31 microns of light of the near-infrared IIa, mouse cortical nerve cells can be successfully induced to generate action potential.

Description

Technical Field

[0001] The present invention relates to the technical field of optoelectronic materials, and in particular to the application of a van der Waals tellurium nanomaterial as a near-infrared IIa light neural regulation material. Background Art

[0002] Neuromodulation is an effective method for regulating brain function and treating brain diseases. Various forms of neuromodulation 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 emotion regulation. However, the development of electrical stimulation for single neurons has been hindered by many factors, such as invasive and bulky electrodes lacking spatial specificity, which may damage tissue and cannot target single neurons. Optical neuromodulation has great potential and can remotely stimulate neurons to achieve regulation and treatment of neural tissue. Optogenetic neurostimulation combines optical and genetic technologies to provide cell-specific and precise control of nerve cells and brain tissue. This technology mainly uses visible light (400-700nm) for excitation. Optogenetics has revolutionized the study of neural circuits at the cellular level. However, most mature neurons lack photoreceptors and need to be implanted with optogenetic proteins (such as ChR2 or NpHR) for regulation, which limits its further development and application.

[0003] Photoelectric nanomaterials have the ability to convert light into electrical energy and induce cells to produce action potentials. Based on the unique photoelectric conversion methods of these nanomaterials, photoregulation is divided into four types: pn junction photovoltaic effect, spectral selective upconversion, photothermal effect, and photoacoustic effect. The pn junction photovoltaic effect of coaxial silicon nanowires or organic semiconductors is used for optical neural regulation. Currently, visible light (532nm) is mainly used. Due to the limitation of the semiconductor band gap, the maximum wavelength of light for neural regulation can only reach 1.1 microns. Nanoparticles use the spectral selective upconversion effect to convert near-infrared (800-980nm) light into visible light and further stimulate nerve cells to produce action potentials. In addition, gold nanorods, mesoporous silicon, poly-benzothiadiazole-alternating-ethylene nanoparticles, etc. convert near-infrared 1.06 micron light into heat to induce neurons to produce 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 neural regulation 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 neural regulation is a key issue that needs to be addressed. Summary of the invention

[0004] The purpose of the present invention is to provide an application of van der Waals tellurium nanomaterials as near-infrared IIa optical neuromodulatory materials. The optical neuromodulatory properties of the van der Waals tellurium nanomaterials have a wide spectrum (from visible light to near-infrared light), and the wavelength can reach the near-infrared IIa (1.3-1.4 μm) band. Under the irradiation of 1.31 μm near-infrared IIa light, the action potentials of mouse cortical neurons can be successfully induced.

[0005] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0006] The present invention provides an application of a van der Waals tellurium nanomaterial as a near-infrared IIa light neural regulation material. The preparation method of the van der Waals tellurium nanomaterial comprises the following steps:

[0007] Using selenium telluride as a raw material, chemical vapor deposition is performed on the surface of a substrate, and then the temperature of the substrate is adjusted to 200-400° C. to obtain the van der Waals tellurium nanomaterial;

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

[0009] Preferably, the substrate includes a silicon substrate, a glass substrate, a mica substrate or a sapphire substrate;

[0010] The thickness of the substrate is 500nm-500μm.

[0011] Preferably, during the nitrogen flow process, the flow rate of nitrogen is 30-80 sccm.

[0012] Preferably, the chemical vapor deposition is carried out under heating conditions;

[0013] The heating temperature is 550-700° C., and the heat preservation time is 20-60 minutes.

[0014] Preferably, the van der Waals tellurium nanomaterial has a length of 0.95 to 12.92 μm and a thickness of less than 200 nm.

[0015] The present invention provides an application of a van der Waals tellurium nanomaterial as a near-infrared IIa light neuromodulatory material. The preparation method of 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, adjusting the temperature of the substrate to 200-400°C, and obtaining the van der Waals tellurium nanomaterial; the chemical vapor deposition is performed under nitrogen flow. The van der Waals tellurium nanomaterial prepared by the preparation method is a direct bandgap semiconductor with a bandgap of about 0.34 eV and a sensitivity of up to 10 to visible to near-infrared light. 4 cm -1The absorption coefficient can generate large current under 637nm, 940nm and 1.31μm irradiation, realizing wide-spectrum neural regulation. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 The average length statistics of the van der Waals tellurium nanomaterials prepared in Examples 1 to 7;

[0017] Figure 2 A schematic diagram of the process of preparing a culture medium for cortical neural cells and adding van der Waals tellurium nanomaterials in an application example;

[0018] Figure 3 This is an immunohistochemical characterization diagram of the van der Waals tellurium nanomaterial described in Example 1;

[0019] Figure 4 The images are patch clamp recordings of primary cortical neurons under broadband illumination and microscope images of neurons and the van der Waals tellurium nanomaterials described in Example 4;

[0020] Figure 5 is a graph of potential curves after irradiation with 1.31 μm near-infrared IIa light under different light powers and different frequencies on the van der Waals tellurium nanomaterial described in Example 4;

[0021] Figure 6 The potential curves of the van der Waals tellurium nanomaterials described in Example 4 after irradiation with 637nm and 940nm light at different light powers and different frequencies;

[0022] Figure 7 The potential curves are shown on the van der Waals tellurium nanomaterial described in Example 4 without light irradiation and after irradiation with 1.31 μm near-infrared IIa light under different light powers;

[0023] Figure 8 Schematic diagram of the optical neural regulation mechanism of the van der Waals tellurium nanomaterials described in Example 4. DETAILED DESCRIPTION

[0024] The present invention provides an application of a van der Waals tellurium nanomaterial as a near-infrared IIa light neural regulation material. The preparation method of the van der Waals tellurium nanomaterial comprises the following steps:

[0025] Using selenium telluride as a raw material, chemical vapor deposition is performed on the surface of a substrate, and then the temperature of the substrate is adjusted to 200-400° C. to obtain the van der Waals tellurium nanomaterial;

[0026] The chemical vapor deposition is performed under the condition of nitrogen flow.

[0027] In the present invention, unless otherwise specified, all preparation raw materials are commercially available products well known to those skilled in the art.

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

[0029] In the present invention, the substrate preferably includes a silicon substrate, a glass substrate, a mica substrate or a sapphire substrate, and more preferably a silicon substrate; the silicon substrate preferably includes a silicon substrate and a silicon dioxide layer on the surface of the silicon substrate. The thickness of the substrate is preferably 500nm to 500μm, more preferably 500nm to 100μm, and most preferably 500nm to 10μm.

[0030] In the present invention, the substrate is preferably placed downstream of the quartz tube, and the selenium telluride is preferably placed in a ceramic boat at the center of the quartz tube.

[0031] Before the chemical vapor deposition, the present invention preferably performs air exhaust. The present invention does not have any special limitation on the process of air exhaust, and the process well known to those skilled in the art can be used to ensure that the ambient pressure is reduced to below 20Pa.

[0032] In the present invention, during the nitrogen flow process, the flow rate of nitrogen is preferably 30 to 80 sccm, more preferably 40 to 60 sccm, and most preferably 50 sccm.

[0033] In the present invention, the chemical vapor deposition is preferably carried out under heating conditions; the heating temperature is preferably 550-700°C, more preferably 580-680°C, and most preferably 600-640°C; the heating holding time is preferably 20-60min, more preferably 30-50min, and most preferably 30-40min.

[0034] After the chemical vapor deposition is completed, the present invention also preferably includes cooling. The present invention does not have any special limitation on the cooling process, and the cooling process can be carried out using a process well known to those skilled in the art.

[0035] In the present invention, the temperature of the substrate is preferably adjusted to 235-370°C, more preferably to 270-335°C, and most preferably to 300°C.

[0036] The present invention also provides a van der Waals tellurium nanomaterial prepared by the preparation method described in the above technical solution. The van der Waals tellurium nanomaterial has a length of 0.95 to 12.92 μm and a thickness of less than 200 nm.

[0037] The application of the van der Waals tellurium nanomaterial provided by the present invention as a near-infrared IIa light neural regulation material is described in detail below in conjunction with the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0038] Example 1

[0039] Selenium telluride is placed as a raw material in a ceramic boat at the center of a quartz tube, a 0.5 mm thick silicon substrate (including a silicon dioxide layer on the surface) is placed downstream of the quartz tube, and then the air in the quartz tube is discharged until the pressure of the quartz tube drops below 20 Pa, and then nitrogen is introduced at a flow rate of 50 sccm. The tube is heated to 640°C and kept warm for 40 minutes. After natural cooling, the temperature of the silicon substrate is adjusted to 200°C to obtain van der Waals tellurium nanomaterials on the surface of the silicon substrate.

[0040] Example 2

[0041] Referring to Example 1, the only difference is that the temperature of the silicon substrate is adjusted to 235°C.

[0042] Example 3

[0043] Referring to Example 1, the only difference is that the temperature of the silicon substrate is adjusted to 270°C.

[0044] Example 4

[0045] Referring to Example 1, the only difference is that the temperature of the silicon substrate is adjusted to 300°C.

[0046] Example 5

[0047] Referring to Example 1, the only difference is that the temperature of the silicon substrate is adjusted to 335°C.

[0048] Example 6

[0049] Refer to Example 1, the only difference is that the temperature of the silicon substrate is adjusted to 370°C.

[0050] Example 7

[0051] Referring to Example 1, the only difference is that the temperature of the silicon substrate is adjusted to 400°C.

[0052] Figure 1 is a statistical diagram of the average length of the van der Waals tellurium nanomaterials prepared in Examples 1 to 7, Figure 1It can be seen that the average length of the van der Waals tellurium nanomaterials corresponding to a substrate temperature of 200°C is 0.95μm, the average length of the van der Waals tellurium nanomaterials corresponding to a substrate temperature of 235°C is 1.76μm, the average length of the van der Waals tellurium nanomaterials corresponding to a substrate temperature of 270°C is 2.97μm, the average length of the van der Waals tellurium nanomaterials corresponding to a substrate temperature of 300°C is 5.19μm, the average length of the van der Waals tellurium nanomaterials corresponding to a substrate temperature of 335°C is 7.76μm, the average length of the van der Waals tellurium nanomaterials corresponding to a substrate temperature of 370°C is 10.22μm, and the average length of the van der Waals tellurium nanomaterials corresponding to a substrate temperature of 400°C is 12.92μm.

[0053] Application Examples

[0054] All mice were housed under standard housing conditions of 22 ± 1 °C, 50 ± 10% relative humidity, and a 12-hour light-dark cycle with food and book. Primary cortical neurons were randomly taken from the cerebral cortex of embryonic day 18 ICR mice. First, the cerebral cortex tissue was isolated and digested with a mixture of 0.5% deoxyribonuclease and 0.25% papain at 37 °C for 30 min. The solution was transferred to a 15 mL centrifuge tube. Then, the cortical tissue was collected using centrifugation at 1000 rpm for 4 minutes. The cortical tissue blocks were blown and transformed 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 strainer and centrifuged at 0.5 × 10 6 The cells were plated at a density of 10 cells / mL on 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 1% penicillin / streptomycin mixture. Half of the medium was replaced with fresh feeding medium every 3 days. On the 10th day of culture, the van der Waals tellurium nanomaterial described in Example 1 was added to the cortical neuron culture medium (eg, Figure 2 As shown), wherein the concentration of the van der Waals tellurium nanomaterial added to the culture medium containing cortical neurons is 5 μg / mL;

[0055] The control group without the van der Waals tellurium nanomaterial was used for immunohistochemical characterization; neurons were fixed with 4% (w / v) paraformaldehyde at 4°C for 4 hours. After fixation, neurons were washed three times with 0.1M PBS (pH=7.4) at room temperature. Subsequently, neurons were blocked with a 0.1% (w / v) PBS solution containing 10% (w / v) serum, 3% (w / v) BSA and 0.3% (w / v) Triton X-100 at room temperature for 2 hours. Neurons were then incubated with the antibody solution at 4°C overnight. After incubation, neurons were washed three times with PBS containing 0.1% (w / v) TritonX-100 and stained with Alexa488 and Alexa 546 at room temperature for 2 hours. DAPI was added for counterstaining, and neurons were fixed on slides. Images were acquired using a Zeiss 980 confocal microscope and processed using ImageJ. The test results are shown in the figure. Figure 3 As shown by Figure 3 It can be seen that after 48 hours of co-incubation with van der Waals tellurium nanomaterials, there was no expression of apoptosis markers such as cleaved caspase-3 (CAPS-3) in neurons, indicating that less than 5 μg / mL van der Waals tellurium nanomaterials did not induce neuronal apoptosis;

[0056] Electrophysiological recordings of van der Waals tellurium nanomaterials and neurons: Whole-cell patch clamp recordings of primary cortical neurons of DIV11 mice were recorded through internal solution (136mM potassium gluconate, 6mM KCl, 1mM EGTA, 2.5Na2ATP, 10mM HEPES (280mOsm, pH=7.2, KOH)) and extracellular solution ACSF (126mMNaCl, 4.9mM KCl, 1.2mM KH2PO4, 2.4mM MgSO4, 2.5mM CaCl2, 26mM NaHCO3, 20mM glucose). The resistance of the recording pipette was 10-12MΩ. The 1.31μm laser of near-infrared IIa was focused through a 60x objective lens and irradiated on the van der Waals tellurium nanomaterials adhered to the neurons, with a length of about 12μm. The diameter of 1.31μm light is 74.6μm. Action potential data were collected using a 2 kHz low-pass filter (Multiclamp 700B and Digidata 1322 A / D converter) and sampled at 10 kHz. Action potential characteristics were analyzed using CLAMPFIT10.7 software; Figure 4 The cell patch clamp recording image of primary cortical neurons under broadband illumination and the microscope image of neurons and the van der Waals tellurium nanomaterial described in Example 4 are shown in FIG. Figure 4 It can be seen that the length of the van der Waals tellurium nanomaterial is about 10.4μm and the width is about 3.65μm. The van der Waals tellurium nanomaterial is in contact with the cell body of the neuron; Figure 5is a potential curve diagram of the van der Waals tellurium nanomaterial described in Example 4 after irradiation with near infrared IIa 1.31 μm light under different light powers and different frequencies, Figure 5 It can be seen that when the 1.31μm near-infrared IIa light is irradiated on the van der Waals tellurium nanomaterial, the duration of light irradiation is 5ms. As the light power density gradually increases, the action potential voltage generated by the mouse cortical nerve cells gradually increases. When the power density reaches 0.38mWmm -2 When the irradiation frequency of 1.31μm light is further changed, when the frequency of light is 10Hz or 20Hz, the neuron can generate a corresponding complete action potential. When the frequency of light reaches 40Hz, the neuron can only generate a partial action potential;

[0057] Figure 6 is a potential curve diagram of the van der Waals tellurium nanomaterial described in Example 4 after irradiation with 637nm and 940nm light at different light powers and different frequencies, Figure 6 It can be seen that when the power density of 637nm light reaches 26.5mWmm -2 When the nerve cell generates a complete action potential, the power density is relatively small for 940nm light, reaching 1.09mWmm -2 When the frequency of 637nm and 940nm light is 10Hz, nerve cells can generate corresponding complete action potentials;

[0058] Figure 7 is a potential curve diagram of the van der Waals tellurium nanomaterial described in Example 4 without light irradiation and after irradiation with near-infrared IIa 1.31 μm light under different light powers, Figure 7 It can be seen that when there is no light irradiating the tellurium nanomaterial, the mouse cortical nerve cells cannot generate action potentials. When the near-infrared Ⅱa 1.31μm light is irradiated on the tellurium nanomaterial, a potential will be generated. The light powers are 15.5, 13.4, 9.82, 6.84, 11.4, 10.2 and 7.32mWmm -2 The dashed curve is without light irradiation, and the solid curve is irradiation with 1.31 μm near-infrared IIa light;

[0059] Figure 8 Schematic diagram of the optical nerve regulation mechanism of van der Waals tellurium nanomaterials described in Example 4, Figure 7It can be seen that the principle of optical neural regulation of van der Waals tellurium nanomaterials is that when van der Waals tellurium nanomaterials are placed in a solution and in contact with neurons, the energy band of tellurium bends downward. Under light, electrons in the valence band are excited to the conduction band, respectively, and holes are generated in the valence band. Due to the bending of the energy band, the photogenerated electrons move toward the Te surface. The electrons accumulated on the surface then diffuse into the electrolyte solution and diffuse to the extracellular side of the neuronal membrane. These electrons diffuse to the extracellular side and interact with positive ions in the solution such as K + 、Na + and Ca 2+ The photogenerated holes are then recombined in the tellurium nanoparticles or solutions.

[0060] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. Application of a van der Waals tellurium nanomaterial as a near-infrared IIa light neural regulation material, characterized in that: The method for preparing the van der Waals tellurium nanomaterial comprises the following steps: Using selenium telluride as a raw material, chemical vapor deposition is performed on the surface of a substrate, and then the temperature of the substrate is adjusted to 200-400° C. to obtain the van der Waals tellurium nanomaterial; The chemical vapor deposition is performed under the condition of nitrogen flow.

2. The use according to claim 1, characterized in that The substrate includes a silicon substrate, a glass substrate, a mica substrate or a sapphire substrate; The thickness of the substrate is 500nm-500μm.

3. The use according to claim 1, characterized in that During the nitrogen flow, the flow rate of nitrogen is 30-80 sccm.

4. The use according to claim 1, characterized in that The chemical vapor deposition is carried out under heating conditions; The heating temperature is 550-700° C., and the heat preservation time is 20-60 minutes.

5. The use according to any one of claims 1 to 4, characterized in that: The length of the van der Waals tellurium nanomaterial is 0.95-12.92 μm, and the thickness is less than 200 nm.

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