A nanoelectrode probe based on pre-pulled hollow capillary in-situ growth of conductive core and a preparation method thereof

Abstract

This invention relates to the field of nanoprobe technology, and more particularly to an in-situ growth method for conductive material nanoelectrode probes based on pre-stretched hollow capillaries. The invention first constructs a nano-tipped hollow tube with a conical hollow tip, and then, depending on the type of nanoelectrode probe to be prepared, uses different methods to grow conductive material in situ within the tube. This not only avoids the interface adhesion and leakage problems encountered in preparing metal nanoelectrode probes, but also provides universal preparation parameters for different metals. Furthermore, it can also prepare nanoscale carbon electrode probes and their hollow conductive probe bodies as needed.

Description

Technical Field

[0001] This invention relates to the field of nanoprobe technology, and in particular to a nanoelectrode probe based on an in-situ grown conductive core using a pre-stretched hollow capillary and its preparation method. Background Technology

[0002] Nanoelectrode probes are extremely fine electrodes with tips ranging from tens to hundreds of nanometers. They are widely used in cutting-edge analytical techniques such as SECM (scanning electrochemical microscopy), SECCM (scanning electrochemical cell microscopy), SICM (scanning ion conductivity microscopy), FSCV (fast scanning cyclic voltammetry), and single-cell / single-vesicle electrochemical detection. In practical applications, nanoelectrode probes have high requirements, such as small tips, high outer wall insulation, and stable conductive components.

[0003] Current nanoelectrode probes are mainly prepared using a co-drawing method, which involves pre-placing conductive materials such as metal wires or carbon fibers inside a glass tube and then heating and drawing them together. However, this preparation method has the following problems: 1) In the preparation of metal nanoelectrode probes, a thin metal wire (such as platinum wire or gold wire) is inserted into a glass capillary tube, and then heated on a drawing instrument to draw the glass and metal wire together into a thin and pointed shape. After cooling, a probe with a glass-encased metal core is formed.

[0004] ① However, during the preparation process, due to the different coefficients of thermal expansion of metal and glass, they deform and contract at different rates during heating and drawing. After cooling, tiny gaps often appear between the metal wire and the glass wall. The metal wire and the glass wall cannot fit tightly together, which can lead to leakage of the solution into the tube cavity during use. This can easily cause insulation failure, background current spikes, and signal instability. Furthermore, because the leakage causes the solution to come into contact with the side of the metal wire behind the tip, the actual electrode area is larger than expected. Moreover, the degree of leakage varies for each probe, resulting in poor batch repeatability and non-repeatable testing. In addition, the parasitic ion current caused by the gap will be superimposed on the Faraday current, making the electrochemical performance unstable and affecting the test results. The accuracy of the results is significantly affected, especially at low concentrations; ② Furthermore, when preparing nanoelectrode probes of different metals, the melting points and softening behaviors of different metals vary greatly. Platinum has a melting point of about 1768°C, gold about 1064°C, and silver about 962°C. Therefore, when preparing nanoelectrode probes of different metals, it is necessary to explore and find matching parameters (such as heating temperature, tension, speed, etc.) based on the selected metal to meet the requirement of synchronous deformation of the metal wire and glass during heating and drawing. When changing different metals, it is necessary to explore and establish a complete set of drawing parameters again. The process has poor versatility and high adaptation costs. Moreover, some metals (such as iridium, niobium, and rhodium) have extremely high melting points, which are too different from the softening temperature of conventional glass, making it difficult to process them using the co-drawing method.

[0005] 2) When preparing carbon electrode probes using carbon fibers as raw materials, the carbon fibers are pre-formed solid fibers, and their thermal behavior differs fundamentally from that of glass: glass softens and can be drawn thinner under heating conditions, while carbon fibers do not undergo plastic deformation after heating and cannot be drawn thinner. When carbon fibers are pre-placed in a glass capillary for co-drawing, the glass tube wall can be drawn to the nanoscale, while the diameter of the carbon fibers remains essentially unchanged. Therefore, the core diameter of the carbon probe is entirely determined by the diameter of the pre-formed carbon fibers themselves and cannot shrink synchronously with the glass tube. Conventional carbon fiber diameters are typically 5–10 μm, and the traditional co-drawing method can only prepare micron-sized carbon probes, making it difficult to stably obtain nanoscale carbon electrodes, which severely limits the application of carbon electrodes in high-resolution electrochemical detection.

[0006] 3) Probes obtained by traditional co-drawing of metal wires and carbon fibers are all solid-tipped structures, which cannot form a through-channel. However, in scenarios such as single-cell puncture simultaneous electrochemical detection, intracellular drug delivery, and electrochemical impedance pulsation (ERP) detection of single liposomes / exosomes, hollow conductive nanoprobes are required: the tip has a hollow channel that allows liquid or microparticles to flow through, while the tube wall has good conductivity. However, existing co-drawing processes are difficult to fabricate tubular nanoprobe structures that integrate a conductive outer wall and a hollow channel.

[0007] Given the problems of interface bonding and leakage, poor process versatility, and difficulty in nano-sizing carbon fibers and fabricating hollow conductive probes in the co-drawing method for preparing metal nanoelectrode probes, there is an urgent need to develop a preparation method that is highly versatile, has tight interface bonding, and can integrate nanoscale carbon probes with hollow conductive probes. Summary of the Invention

[0008] Therefore, based on the background technology, the present invention provides a nano-electrode probe with an in-situ grown conductive core based on a pre-stretched hollow capillary and its preparation method. This not only avoids the problems of interface bonding and leakage in the preparation of metal nano-electrode probes, but also has universal preparation parameters for different metals. Furthermore, it can also prepare nano-sized carbon electrode probes and their hollow conductive probe bodies as needed.

[0009] The technical solution provided by this invention is as follows: A method for preparing a nanoelectrode probe with an in-situ grown conductive core based on a pre-stretched hollow capillary includes the following steps: 1) Select hollow capillaries of different glass materials according to the type of nanoelectrode probe to be prepared: If the nanoelectrode probe to be prepared is a metal nanoelectrode probe, borosilicate glass should be selected. If the nanoelectrode probe to be prepared is a carbon nanoelectrode probe or a single-channel metal-carbon composite probe, quartz glass should be selected. If the nanoelectrode probe to be prepared is a theta-type dual-channel probe, and both channels of the theta-type dual-channel probe are metal nanoelectrodes, borosilicate glass or quartz glass shall be selected; if at least one channel of the theta-type dual-channel probe is a carbon nanoelectrode, quartz glass shall be selected. 2) The hollow capillary tube is drawn into two nano-tipped hollow tubes with a conical hollow tip at one end; 3) Depending on the type of nanoelectrode probe to be prepared, conductive material is generated in situ within the hollow cavity of the nano-tip hollow tube; If metal nanoelectrode probes are to be prepared, a metal conductive core can be generated in situ within the hollow cavity of a nano-tip hollow tube by means of wet chemical reduction or in-situ electrodeposition using metal salt solution and reducing solution. If carbon nanotube electrode probes are to be prepared, carbon conductive cores can be generated in situ within the hollow cavity of a nanotube using a carbon source through high-temperature gas-phase pyrolysis. To prepare a single-channel metal-carbon composite probe, a carbon conductive material layer is first generated in situ in the hollow cavity of a nano-tip hollow tube by high-temperature gas phase pyrolysis, and then a metal conductive material layer is deposited on the carbon conductive material layer by wet chemical reduction. To prepare a theta-type dual-channel metal-carbon composite probe, a carbon conductive core is generated in situ in the hollow cavity of one channel of the nano-tip hollow tube by high-temperature gas-phase pyrolysis. A metal conductive core is then generated in situ in the hollow cavity of the other channel of the nano-tip hollow tube by wet chemical reduction or in-situ electrodeposition using a metal salt solution and a reducing solution.

[0010] Furthermore, the hollow capillary has an outer diameter of 0.3-2.0 mm and an inner diameter of 0.1-0.8 mm; The inner diameter of the hollow tip of the nano-tipped hollow tube in step 2) is 5-5000 nm, and the cone angle is 0.5-10°.

[0011] Preferably, the hollow capillary has a length of 7-10 cm and the hollow tip has a length of 0.5-2 mm.

[0012] Furthermore, the wet chemical reduction in step 3) includes the following steps: ① The hollow nano-tip tube is vertically immersed in ethylene glycol with the hollow tip facing down, and the hollow tip is partially or completely immersed in ethylene glycol, so that at least the lumen of the hollow tip is filled with ethylene glycol. ②Then, the metal salt solution is injected into the cavity of the nano-tip hollow tube from the end away from the hollow tip. Then, the nano-tip hollow tube is vertically inserted into the reducing solution with the hollow tip facing down, and the hollow tip is partially or completely immersed in the reducing solution. ③ After heating the nano-tipped hollow tube from step ② along with the reducing solution at 90-150℃ for at least 8 hours, let it cool naturally to room temperature, and then clean it.

[0013] Furthermore, the in-situ electrodeposition method in step 3) includes the following steps: a. The hollow nano-tip tube is vertically immersed in ethylene glycol with the hollow tip facing down, and the hollow tip is partially or completely immersed in ethylene glycol, so that at least the lumen of the hollow tip is filled with ethylene glycol. b. Then, the metal salt solution is injected into the cavity of the nano-tip hollow tube from the end away from the hollow tip. Then, the nano-tip hollow tube is vertically inserted into the reduction solution with the hollow tip facing down, and the hollow tip is partially or completely immersed in the reduction solution. c. Insert a lead wire into the end of the nano-tipped hollow tube away from the hollow tip and make physical contact with the conductive material; apply a cyclic voltage through the lead wire, with a voltage of −20 V to +5 V and a scan rate of 0.01–100 V / s; Conductive cores with different configurations were prepared based on the number of cycles. When the number of cycles was 10-50, the prepared conductive core had a porous / open structure that allowed liquid to pass through; when the number of cycles was 100-500, the prepared conductive core had a dense / sealed structure. Furthermore, the conductive metallic material in step 3) is one of Pt, Au, Ag, Pd, or Cu.

[0014] Furthermore, the high-temperature gas-phase pyrolysis method in step 3) includes the following steps: i) Place the nano-tipped hollow tube into the reaction tube with the hollow tip facing the gas inlet. Under the protection of inert gas, raise the temperature of the reaction tube to 500-1200°C at a rate of 5-10°C / min. ii) Introduce carbon source gas, maintain the temperature at 500–1200°C for a period of time, and then allow it to cool naturally.

[0015] Furthermore, in step ii), different holding times are selected based on the configuration of the conductive core of the nanoelectrode probe to be prepared: If the conductive core of the nanoelectrode probe to be prepared is solid, the heat preservation deposition time is 0.5-1h; If the conductive core of the nanoelectrode probe to be prepared is hollow, the heat preservation deposition time is 1-4 hours.

[0016] Furthermore, the carbon source gas is selected from at least one of methane, ethane, propane, ethylene, acetylene, benzene, toluene, and ethanol, and the carrier gas of the carbon source gas is selected from at least one of argon, nitrogen, hydrogen, and helium.

[0017] Based on the same inventive concept, this invention also provides a nanoelectrode probe, which is prepared by the method of in-situ growth of conductive material nanoelectrode probe based on pre-stretched hollow capillary tube.

[0018] Based on the same inventive concept, the present invention also provides applications of nanoelectrode probes, which are used in electrochemical sensing, single-cell analysis or scanning probe microscopy detection.

[0019] The beneficial effects achieved by this invention are as follows: This invention first constructs a nano-tipped hollow tube with a conical hollow tip, and then grows a conductive core in situ inside the tube using different methods depending on the type of nano-electrode probe to be prepared. This not only avoids the problems of interface adhesion and leakage in the preparation of metal nano-electrode probes, but also has universal preparation parameters for different metals, and can also prepare nanoscale carbon electrode probes and their hollow conductive probe bodies as needed.

[0020] The conductive core of the metal nanoelectrode probe is generated in situ on the inner wall of the tube using metal salt solution and reducing solution via wet chemical reduction or in-situ electrodeposition. The conductive material adheres tightly to the glass substrate, resulting in a tight interface that significantly reduces the risk of interface gaps, leakage, background current, and signal drift, thereby improving detection stability and accuracy. Furthermore, the preparation parameters do not require complex exploration for different metals, making the process highly versatile. The size of the carbon conductive core of the metal nanoelectrode probe is determined by the inner diameter of the nanotube cavity and is not limited by the diameter of the carbon fiber, which can stably meet the requirements for the nano-scale fabrication of carbon electrodes.

[0021] Furthermore, during the preparation of carbon electrodes, the carbon probe with a solid conductive electrode or a hollow carbon probe with conductive tube walls and a through-hole can be prepared by adjusting the heat preservation deposition time, with flexible and adjustable configuration.

[0022] Multiple probes can be prepared simultaneously, resulting in good batch consistency and high efficiency. Attached Figure Description

[0023] Appendix Figure 1 This is an optical microscope image of the drawn nano-tipped hollow tube according to an embodiment of the present invention.

[0024] Appendix Figure 2 An optical microscope image of the Pt probe prepared in an embodiment of the present invention.

[0025] Appendix Figure 3 High-resolution transmission electron microscope (TEM) image of the Pt probe prepared for an embodiment of the present invention.

[0026] Appendix Figure 4 Cyclic voltammetry (CV) curves of the Pt probe prepared in this embodiment of the invention.

[0027] Appendix Figure 5 This is a carbon probe TEM image of the solid electrode prepared in an embodiment of the present invention.

[0028] Appendix Figure 6 This is a high-resolution scanning electrochemical imaging image of a carbon probe of a solid electrode prepared in an embodiment of the present invention.

[0029] Appendix Figure 7 TEM image of the hollow carbon probe of the hollow electrode prepared in the embodiment of the present invention. Detailed Implementation

[0030] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0031] Unless otherwise specified, the experimental methods used in the following embodiments are conventional methods; the experiments used in the following embodiments... Unless otherwise specified, all materials were purchased from commercial channels.

[0032] Unless otherwise specified, a hollow capillary is a single-tube capillary.

[0033] This invention provides a method for preparing an electrode probe with an in-situ grown conductive core based on a pre-stretched hollow capillary, comprising the following steps: 1) Select hollow capillaries of different glass materials according to the type of nanoelectrode probe to be prepared; the outer diameter of the hollow capillaries is 1.0 mm, the inner diameter is 0.5-0.8 mm, and the length is 7-10 cm.

[0034] If the nanoelectrode probe to be prepared is a metal nanoelectrode probe, borosilicate glass should be selected. If the nanoelectrode probe to be prepared is a carbon nanoelectrode probe, quartz glass should be selected; Specifically, θ-type dual-channel (with a partition dividing the tube into two halves) or multi-channel hollow capillaries can also be selected to prepare composite electrodes, such as metal-carbon composite electrode probes.

[0035] If the nanoelectrode probe to be prepared is a single-channel metal-carbon composite probe, quartz glass should be selected; If the nanoelectrode probe to be prepared is a theta-type dual-channel probe, where both channels of the theta-type dual-channel probe are metal nanoelectrodes, borosilicate glass or quartz glass shall be selected; if at least one channel of the theta-type dual-channel probe is a carbon nanoelectrode, quartz glass shall be selected. In this step, hollow capillaries of different materials are selected according to the subsequent processes for preparing different types of nanoelectrode probes. For example, if the subsequent process for preparing metal nanoelectrode probes involves a lower heating temperature, such as about 90-150°C, then low-cost borosilicate glass can be used. However, the subsequent process for carbon nanoelectrode probes involves a higher heating temperature, specifically above 900°C. If borosilicate glass is used, it will soften and deform at 900°C.

[0036] 2) The capillary is drawn into two nano-tipped hollow tubes with a conical hollow tip at one end; the length of the nano-tipped hollow tube is 3.5-5cm, and the length of the conical hollow tip is 0.5-2mm; during normal operation, the hollow capillary is drawn into two nano-tipped hollow tubes with similar specifications. Preferably, after drawing, the nano-tipped hollow tubes that meet the above dimensions are inspected and screened using an optical microscope.

[0037] Specifically, this step includes the following steps: I) Install the capillary tube into the clamp of a laser drawing instrument (such as the Sutter P-2000). The two ends of the tube are fixed by clamps, and the middle part is suspended in the heating area.

[0038] II) Set parameters such as heating power (Heat, °C), pulling force (Pull, N), speed (Velocity, cm / s), and delay (Delay, s) on the drawing apparatus. The combination of parameters determines the size of the tip and the cone angle. The parameter combinations set according to the material of the hollow capillary are shown below: Hollow capillary tubes made of borosilicate glass: Heat 350-450, Pull 80-150, Vel 30-80, Del 120-200; Hollow capillary tube of quartz glass: Heat 600-800, Pull 100-200, Vel 20-60, Del 120-200.

[0039] The ultimate goal of setting the above parameters is to make the tip of the drawn nano-tipped hollow tube have an inner diameter of 5-5000 nm (preferably 20-1000 nm) and a cone angle of 0.5-10°.

[0040] III) The pulling device is activated, and the middle part of the capillary tube body is heated by a laser (P-2000 uses a CO2 laser for heating, and the temperature is controlled by the Heat parameter) to soften the glass, while the clamps at both ends pull it outward. The tube body is broken in the middle, forming two nano-tipped hollow tubes with conical hollow tips.

[0041] IV) Examine the hollow tips of the nano-tipped hollow tubes using an optical microscope to screen out those with no broken or bent hollow tips.

[0042] 3) Depending on the type of nanoelectrode probe to be prepared, a conductive core is generated in situ within the hollow cavity of the nano-tip hollow tube. If nanometal nanoelectrode probes are to be prepared, a metal conductive core can be generated in situ within the hollow cavity of a nano-tip hollow tube by means of wet chemical reduction or in-situ electrodeposition using metal salt solution and reducing solution. If carbon nanotube electrode probes are to be prepared, carbon conductive cores can be generated in situ within the hollow cavity of a nanotube using a carbon source through high-temperature gas-phase pyrolysis. To prepare a single-channel metal-carbon composite probe, a carbon conductive material layer is first generated in situ within the hollow cavity of a nano-tip hollow tube using high-temperature gas-phase pyrolysis. Then, a metal conductive material layer is deposited on the carbon conductive material layer using wet chemical reduction.

[0043] Specifically, if the nanoelectrode probe to be prepared is a metal nanoelectrode probe, a metal conductive core is generated in situ within the hollow cavity of a nano-tipped hollow tube using a metal salt solution and a reducing solution via wet chemical reduction. The principle is that inside the nano-tipped hollow tube, metal grows from the tip of the tube's cavity through wet chemical reduction, gradually forming a continuous metal core, ultimately resulting in a nano-metal electrode with a glass shell encasing the metal core. Specifically, a polyol (such as ethylene glycol) is used as a solvent and a soft reducing agent. The metal salt solution is filled into the cavity, and then the nano-tipped hollow tube is immersed in a reducing solution containing a strong reducing agent. The entire tube is then placed in a muffle furnace for heating. During heating, ethylene glycol generates reducing aldehyde species at high temperatures, continuously reducing metal ions to metal atoms, which nucleate and grow from the hollow tip, eventually forming a continuous metal core. Its key feature is non-self-limiting growth. Even if the opening of the hollow tip is blocked by metal, the metal can continue to grow inside the tube in the direction away from the hollow tip, forming a continuous metal column several hundred micrometers long (100-500 μm, preferably 200-400 μm), which is a solid metal core conductive electrode.

[0044] The in-situ generation of a metallic conductive material layer via wet chemical reduction includes the following steps: ① The hollow nano-tip tube is vertically immersed in ethylene glycol (EG) with the hollow tip facing down to a depth of 1-5 mm. The hollow tip is partially or completely immersed in ethylene glycol and automatically filled by capillary force, so that at least the cavity of the hollow tip is filled with ethylene glycol. A low metal salt concentration zone is formed near the hollow tip (i.e., 0.5-2 mm from the tip), which prevents the high concentration of metal salts in the subsequent backfill from directly contacting the opening of the hollow tip, thereby reducing or avoiding disordered nucleation on the outer surface of the hollow tip.

[0045] ② Inject the metal salt solution into the cavity of the nano-tipped hollow tube using a syringe from the end furthest from the hollow tip (the injection volume is 80-90% of the volume of the nano-tipped hollow tube). Then, vertically insert the nano-tipped hollow tube with the hollow tip facing down into a glass vial containing the reducing solution (immersion depth 2-10 mm). The solution fills the cavity of the nano-tipped hollow tube from the end furthest from the hollow tip, forming a concentration gradient with the EG already present at the hollow tip.

[0046] In this step, different metal salts are selected according to the conductive metal of the metal nanoelectrode probe to be prepared, and different metal salt solutions are prepared by dissolving them in ethanol. For example, H2PtCl6 is selected for Pt metal, HAuCl4 is selected for Au metal, AgNO3 is selected for Ag metal, K2PdCl4 is selected for Pd metal, and CuSO4 is selected for Cu metal.

[0047] The concentration of the metal salt in the metal salt solution is 0.01-1 M, preferably 0.05-0.3 M.

[0048] In practical applications, if the concentration of the metal salt is too low (below 0.01M), the growth rate will be extremely slow, and the metal core will appear discontinuous. If the concentration of the metal salt is too high (above 1M), a large number of disordered nuclei will form on the outer surface of the hollow tip, affecting the probe's insulation.

[0049] The reducing solution is prepared using NaBH4 as a reducing agent and ethylene glycol as a solvent. The concentration of NaBH4 in the reducing solution is 50-400 mM, preferably 100-200 mM.

[0050] ③ After heating the nano-tipped hollow tube from step ② along with the reducing solution at 90-150°C (preferably 100-130°C) for at least 8 hours (specifically, 8-48 hours, preferably 12-24 hours), and then allowing it to cool naturally to room temperature, the tube is repeatedly washed inside and out with ultrapure water and ethanol to remove residual metal salt solution and byproducts. During the heating process, ethylene glycol generates aldehyde species at high temperatures, continuously reducing metal ions to metal atoms; simultaneously, NaBH4 provides strong reducing power, accelerating nucleation and growth in the hollow tip region. The metal begins to nucleate from the hollow tip and then continues to grow inward along the lumen, eventually forming a continuous metal core.

[0051] 4) Insert a lead wire into the end of the nano-tipped hollow tube furthest from the hollow tip to make physical contact with the conductive material. This is done by using conductive silver paste or a bonding method to connect a tungsten microwire (or copper wire) to the conductive material inside the tube, ensuring a smooth electrical path. Then, seal the end of the capillary tube facing away from the hollow tip with epoxy resin.

[0052] Metal nanoelectrodes can be fabricated in situ by generating a conductive metal layer through wet chemical reduction, enabling mass production. For example, multiple hollow nanotubes can be simultaneously inserted into the same glass bottle containing a reducing solution and heated together in a muffle furnace. Up to dozens of probes can be grown at once, significantly improving production efficiency.

[0053] The preparation of metal nanoelectrode probes by in-situ electrodeposition includes the following steps: a. Immerse the hollow nano-tip tube vertically into ethylene glycol (EG) with the hollow tip facing down to a depth of 1-5 mm. Part or all of the hollow tip is immersed in ethylene glycol and automatically filled by capillary force, so that at least the cavity of the hollow tip is filled with ethylene glycol. b. Inject the metal salt solution into the cavity of the nano-tipped hollow tube using a syringe from the end furthest from the hollow tip (the injection volume is 80-90% of the volume of the nano-tipped hollow tube). Then, vertically insert the nano-tipped hollow tube with the hollow tip facing down into a glass vial containing the reducing solution (immersion depth 2-10 mm).

[0054] The specific operations of steps a and b are the same as steps ① and ② of the wet chemical reduction method above, and will not be repeated here.

[0055] c. Insert a lead wire into the end of the hollow nanotube furthest from the hollow tip to make physical contact with a conductive material; apply a cyclic voltage through the lead wire, ranging from −20 V to +5 V, with a scan rate of 0.01–100 V / s, to electrochemically drive the reducing agent into the tube cavity, where it reacts with the metal salt solution to form deposited metal (the tube contains a metal precursor solution, and the outside contains a solution containing the reducing agent. When a negative voltage is applied, metal ions are reduced and deposited near the tip; simultaneously, external NaBH4 diffuses into the tube cavity through the tip opening under the drive of the electric field, providing additional reducing force).

[0056] Furthermore, this step allows for precise control of the deposition amount to prepare metal conductive cores with different configurations by controlling the number of voltage cycles. When the number of cycles is 10-50, the prepared metal conductive core has a porous / open structure that allows liquid to pass through, i.e., a porous metal deposition layer; when the number of cycles is 100-500, the prepared metal conductive core has a dense / sealed structure (the metal deposition layer is dense enough to completely seal the tip), i.e., a dense metal deposition layer.

[0057] In other words, with fewer electrodeposition cycles, a discontinuous, porous, sponge-like metal deposition layer (conductive core) is obtained. This porous structure allows analyte solutions to pass through, making it particularly suitable for scenarios where solutions need to pass through, such as bipolar electrochemiluminescence (ECL) detection, where channels need to be preserved. With more cycles, the deposition layer becomes increasingly dense, eventually completely sealing the tip.

[0058] Specifically, the nanoelectrode probe to be prepared is a carbon nanoelectrode probe. It utilizes a carbon source to generate carbon conductive material in situ within the hollow cavity of a nano-tipped hollow tube via high-temperature vapor-phase pyrolysis. That is, carbon is deposited on the inner wall of the tube cavity through high-temperature vapor-phase pyrolysis (CVD). Depending on the deposition time, two configurations of carbon conductive cores can be obtained: Solid carbon conductive core: The deposition time is long (about 3 hours), and the carbon layer completely fills the cavity to form a solid carbon rod.

[0059] Hollow carbon conductive core: Short deposition time (30 minutes to 1 hour), carbon only forms a thin layer on the tube wall (thickness of about 2nm to 1 μm), and a hollow channel is retained in the middle, that is, the hollow tip has a hollow opening with a carbon coating.

[0060] The preparation of nano-carbon electrode probes via high-temperature gas-phase pyrolysis includes the following steps: i) Place the nano-tipped hollow tube into the quartz reaction tube with the hollow tip facing the gas inlet, purge with argon (Ar) gas, and then raise the temperature of the reaction tube to 500-1200°C (preferably 800-1000°C) at 5-10°C / min under argon protection. ii) Introduce carbon source gas, maintain the temperature at 500-1200°C for a period of time, then turn off the carbon source, retain argon gas, and slowly cool down to room temperature.

[0061] The carbon source gas is selected from at least one of methane, ethane, propane, ethylene, acetylene, benzene, toluene, and ethanol, and the carrier gas of the carbon source gas is selected from at least one of argon, nitrogen, hydrogen, and helium.

[0062] The flow rate of the carbon source gas is 10-5000 sccm; the flow rate of the carrier gas is 10-10000 sccm.

[0063] Furthermore, nitrogen- or boron-containing gases can be added to the carbon source to dope the carbon conductive material with N or B.

[0064] Besides shortening the time, the carbon layer thickness can also be controlled by lowering the temperature or reducing the methane flow rate. Ion flow testing confirms that the tip is passable (allows ion flow to pass through).

[0065] Specifically, a methane / argon system is used as the carbon source. The high-temperature pyrolysis parameters are: 900°C, CH4 400 sccm + Ar 600 sccm. A solid conductive core is prepared after 3 hours of deposition, and a hollow conductive core is obtained after 45 minutes. The deposition rate can be slowed down by lowering the temperature to 800°C or reducing the CH4 flow rate to 200 sccm. The hollow carbon probe prepared above can achieve two functions with a single probe. For example, it can be used for electrochemical detection using the conductive carbon layer on the tube wall, and also utilizes the hollow channels of the conductive material to allow liquids or particles to pass through for single-cell puncture, intracellular drug delivery, and electrochemical impedance pulsation (ERP) detection and measurement of single liposomes / exosomes.

[0066] When the nanoelectrode probe to be prepared is a single-channel metal-carbon composite probe, a carbon conductive material layer is first generated in situ within the hollow cavity of the nano-tip hollow tube using high-temperature vapor phase pyrolysis. Then, a metal conductive material layer is deposited on the carbon conductive material layer using wet chemical reduction. The high-temperature vapor phase pyrolysis method is the same as the wet chemical reduction method described above.

[0067] When the nanoelectrode probe to be prepared is a dual-channel metal-carbon composite probe, after sharpening (the de-sharpening operation is the same as for the single-channel capillary, with quartz glass as the capillary material), a metal conductive material is generated in situ in one channel using wet chemical reduction, and then a carbon conductive material is generated in situ in the other channel using high-temperature gas-phase pyrolysis. That is, there are two independent working electrodes on one probe.

[0068] Furthermore, the preparation method also includes step 6), which can be performed before step 5), meaning that the order of steps 5 and 6 does not affect the preparation of the final product.

[0069] 6) It can also appropriately trim the tip of the electrode according to whether precise control of the tip electrode surface is required, for example, by cutting the tip with a focused ion beam (FIB) to obtain a flat, disc-shaped electrode surface. Mechanical polishing or wet etching can also be used.

[0070] Specifically, wet etching involves immersing the tip in hydrofluoric acid (HF, concentration 0.1%–49%). HF dissolves glass / quartz but not metal or carbon, thus exposing the conductive core.

[0071] Focused ion beam (FIB) cutting uses an ion beam to flatten the tip at the nanoscale, resulting in a flat, disk-shaped electrode surface. Mechanical polishing involves grinding the tip flat on a precision polishing disc; Electrochemical activation involves cyclic voltammetry scans in the electrolyte to clean and activate the electrode surface.

[0072] The following are specific application examples.

[0073] The specific operation of drawing the single-channel hollow nanotip used to prepare the metal nanoelectrode probe in the following embodiment is as follows: Borosilicate glass capillaries (approximately 1.0 mm outer diameter, 0.5 mm inner diameter, and 10 cm length) are drawn. The specific drawing operation is as follows: I) The capillary is mounted onto the chuck of a laser drawing instrument (Sutter P-2000). The two ends of the tube are fixed by clamps, and the middle part is suspended in the heating area.

[0074] II) Set parameters such as heating power (Heat), pulling force (Pull), speed (Velocity), and delay (Delay) on the drawing instrument.

[0075] Heat 350, Pull 80, Vel 30, Del 120; III) The drawing apparatus is activated. Laser heating softens the glass in the middle section of the capillary tube while the clamps at both ends pull it outwards. The tube breaks in the middle, forming two nano-tipped hollow tubes with conical hollow tips. The inner diameter of the tip of the drawn nano-tipped hollow tube is 200 nm, and the cone angle is 5°. The length of the nano-tipped hollow tube is 5.2 cm, and the length of the hollow tip is 2 mm.

[0076] IV) Examine the hollow tips of the nano-tipped hollow tubes using an optical microscope to screen out those with no broken or bent hollow tips.

[0077] The specific operation of drawing the single-channel hollow nanotip used to prepare the carbon nanotube electrode probe in the following example is as follows: The drawing process involves using a quartz capillary tube (approximately 1.0 mm outer diameter, 0.7 mm inner diameter, and 10 cm length). The specific steps of the drawing process are as follows: I) Install the capillary tube into the clamp of the laser drawing instrument (Sutter P-2000). The two ends of the tube are fixed by clamps, and the middle part is suspended in the heating area.

[0078] II) Set parameters such as heating power (Heat), pulling force (Pull), speed (Velocity), and delay (Delay) on the drawing instrument. Heat 800, Pull 200, Vel 60, Del 120.

[0079] III) The drawing apparatus is activated, and the middle section of the capillary tube body (P-2000 uses a CO2 laser for heating, with a heating power of 800) is heated by a laser to soften the glass, while the clamps at both ends pull it outwards. The tube body is broken in the middle, forming two nano-tipped hollow tubes with conical hollow tips. The inner diameter of the tip of the drawn nano-tipped hollow tube is 200 nm, and the cone angle is 5°. The length of the nano-tipped hollow tube is 5.2 cm, and the length of the hollow tip is 2 mm.

[0080] IV) Examine the hollow tips of the nano-tipped hollow tubes using an optical microscope to screen out those with no broken or bent hollow tips.

[0081] Example 1: Preparation of platinum nanoelectrode probes This embodiment uses wet chemical reduction or in-situ electrodeposition to prepare platinum nanoelectrode probes using metal salt solutions and reducing solutions, including the following steps: ① The hollow nano-tip tube is vertically immersed in ethylene glycol with the hollow tip facing down to a depth of 5 mm. The hollow tip is partially or completely immersed in ethylene glycol, so that at least the cavity of the hollow tip is filled with ethylene glycol. A low metal salt concentration zone is formed in the region of the hollow tip to prevent the high concentration of metal salts that are subsequently backfilled from directly contacting the opening of the hollow tip, thereby reducing or avoiding disordered nucleation on the outer surface of the hollow tip.

[0082] ② A Pt metal salt solution (prepared by dissolving H2PtCl6 in ethylene glycol, with a concentration of 0.1M) is injected into the cavity of the nano-tipped hollow tube using a syringe (the injection volume is 80%-90% of the cavity volume of the nano-tipped hollow tube). Then, the nano-tipped hollow tube is vertically inserted into a glass vial containing a reducing solution (the concentration of NaBH4 in the reducing solution is 200mM (dissolved in ethanol)) with the hollow tip facing down, with the immersion depth being 5mm. The solution fills the cavity of the nano-tipped hollow tube from the end away from the hollow tip, forming a concentration gradient with the pure EG already present at the hollow tip.

[0083] ③ After heating the nano-tipped hollow tube from step ② together with the reducing solution at 120°C for 16 hours, and then naturally cooling it to room temperature, the inside and outside of the tube were repeatedly washed with ultrapure water and ethanol to remove residual metal salt solution and byproducts.

[0084] ④ Insert a lead wire into the end of the nano-tipped hollow tube furthest from the hollow tip to make physical contact with the conductive material. That is, use conductive silver paste to make physical contact with the conductive material inside the tube to ensure a smooth electrical path. Then seal the end of the capillary tube facing away from the hollow tip with epoxy resin.

[0085] ⑤ The tip of the probe is ground smooth using a polishing pad.

[0086] Optical microscope images of the nano-tipped hollow tube used to prepare the platinum nanoelectrode probe in this embodiment are shown below. Figure 1 Optical microscope images and transmission electron microscope images of the platinum nanoelectrode probe prepared in this embodiment are shown in [the images]. Figure 2 and Figure 3 .

[0087] Depend on Figure 1 As can be seen, the hollow tip of the nano-tipped hollow tube is generally a slender cone shape, gradually tapering from the left side of the tube to the right, eventually contracting into a thin tip with a hollow internal structure, serving as the cavity for subsequent growth of conductive materials. Figure 2 As can be seen, the probe is a slender cone shape, gradually tapering from the left side of the tube to the right, eventually narrowing into a fine tip. The outer glass wall of the tip is transparent, revealing a continuous platinum core inside, indicating that platinum has been successfully and continuously grown inside the tube. Furthermore, the platinum core at the probe tip is over 100 micrometers long, and the glass wall is thin and smooth. Figure 3 As can be seen, platinum has a large atomic number, which creates a significant contrast difference with the surrounding glass in the TEM image, making it easy to distinguish. The glass is mainly composed of silicon and oxygen, with a small atomic number, and there is a clear interface between it and the platinum core. The outermost layer is the background area (vacuum). Without sample obstruction, it is clearly visible that the platinum metal core is continuously distributed inside the cavity, extending all the way to the vicinity of the probe tip. The outer wall of the glass wraps around the platinum core, forming a complete insulating layer. The interface between the platinum core and the glass wall is clear and tightly bonded. No obvious interface gaps or voids were observed under TEM resolution. This confirms that the platinum nanoelectrode probe prepared in Example 1 was grown in situ on the inner wall of the glass, with a tight bond. The interface between the platinum and the glass wall is tightly bonded, and no obvious gaps or voids were observed.

[0088] The cyclic voltammetry (CV) results of the platinum nanoelectrode probe from Example 1 in a standard redox probe solution (1 mM ferrocene methanol FcMeOH + 0.1 M KCl) are presented. CV is the most commonly used characterization method in electrochemistry to verify whether the electrode is functioning correctly. The results are shown in [Figure 1]. Figure 4 , Figure 4 The horizontal axis represents voltage (V), and the vertical axis represents current (pA, i.e., picoampere, 10). - 12 A) The curve exhibits a standard sigmoid steady-state voltammogram: the current is close to zero at low voltage, and rises rapidly to a plateau (approximately 13 pA) as the voltage increases; this is the "diffusion-limited current," a typical characteristic of nanoelectrodes. The curve is very clean, with no obvious hysteresis, and the forward and reverse scans almost completely overlap, indicating good electrode sealing and the absence of parasitic ion currents (i.e., no leakage). Figure 4 The results show that the platinum nanoelectrode probe prepared in Example 1 has good electrochemical activity and sealing properties, with no leakage and stable performance. The S-shaped steady-state CV curve is the "gold standard" for verifying high-quality nanoelectrodes.

[0089] Example 2: Preparation of carbon nanoelectrode probes In this embodiment, a carbon conductive material is generated in situ within the hollow cavity of a nano-tipped hollow tube using a high-temperature gas-phase pyrolysis method. The conductive material (i.e., the conductive core) prepared in this embodiment is a solid carbon electrode probe.

[0090] Specifically, the steps include the following: i) Place the nano-tipped hollow tube into the quartz reaction tube with the hollow tip facing the gas inlet, purge with argon (Ar) gas, and then raise the temperature of the reaction tube to 900°C under argon protection. ii) Introduce carbon source gas: methane (CH4) 400 sccm and argon (Ar) 600 sccm; after deposition at 900℃ for 3 hours (methane continuously decomposes on the inner wall of the quartz tube, the carbon layer continues to thicken, and eventually completely fills the tube lumen in the tip area), turn off the methane, retain the argon, and slowly cool down to room temperature.

[0091] iii) Insert a lead wire into the end of the nano-tipped hollow tube furthest from the hollow tip to make physical contact with the conductive material. That is, use conductive silver paste to make physical contact with the conductive material inside the tube to ensure a smooth electrical path. Then seal the port of the capillary tube facing away from the hollow tip with epoxy resin.

[0092] iv) The tip of the probe is ground smooth with a polishing pad.

[0093] The TEM and high-resolution scanning electrochemical imaging images of the carbon nanoelectrode probes prepared in this embodiment are shown below. Figure 5 and Figure 6 ,Depend on Figure 5 As can be seen, the interior region of the carbon nanotube electrode probe is filled with carbon. Carbon is continuously deposited within the tube to form a solid fill, and at the very tip, the tube is completely filled with carbon, forming a solid carbon rod. A quartz outer wall surrounds the carbon core, providing insulation and mechanical support. With a scale bar of 200 nm, it can be seen that the probe tip's outer diameter is on the order of hundreds of nanometers. Therefore, this embodiment successfully fills the interior of a quartz nanotube completely with carbon, forming a solid carbon probe. Figure 6 This image shows a high-resolution scanning electrochemical image of a gold triangle nanosheet on a silica insulating substrate using a carbon nanoparticle electrode probe in this embodiment. The solution was 1 mM ferrocene methanol (FcMeOH) + 0.1 M KCl. A voltage of 0.4 V was applied to the probe, while no voltage was applied to the substrate. The image of the gold triangle nanosheet is clearly visible (the metal has strong conductivity, providing positive feedback to the probe, resulting in a larger current; the substrate is insulating, providing negative feedback, resulting in a smaller current). This indicates that the probe is very sensitive to current changes, and the image resolution can reach the nanometer level.

[0094] Example 3: Preparation of carbon nanotube electrode probes In this embodiment, a carbon conductive material is generated in situ within the hollow cavity of a nano-tipped hollow tube using a high-temperature gas-phase pyrolysis method. The conductive material (i.e., the conductive core) prepared in this embodiment is a carbon electrode probe with a hollow channel.

[0095] Compared to Example 2, in this embodiment, the deposition at 900℃ for 45 minutes (CH4 400sccm + Ar 600sccm) is the same as in Example 2, except that in step ii).

[0096] TEM images of the carbon nanoelectrode probe prepared in this embodiment are shown below. Figure 7 ,Depend on Figure 7 As can be seen, the probe tip exhibits a three-layer structure (outer wall - carbon layer - hollow). The outermost quartz outer wall provides insulation and mechanical support; the middle carbon core is a carbon coating on the inner wall of the quartz capillary lumen, which is conductive and forms the electrode portion of the probe; and the innermost layer is the hollow channel within the carbon core, representing the unfilled portion of the lumen, allowing liquids and particles to pass through. Therefore, this invention, by controlling the CVD deposition time, can prepare both solid and hollow carbon probes on the same equipment. The hollow configuration retains interconnected nanochannels while maintaining a conductive carbon layer on the tube wall.

[0097] The present invention and its embodiments have been described above. This description is not restrictive, and the embodiments shown are only one of the embodiments of the present invention. The actual structure is not limited to this. In conclusion, if those skilled in the art are inspired by this description and design similar structures and embodiments without departing from the spirit of the present invention, they should all fall within the protection scope of the present invention.

Claims

1. A method for preparing a nanoelectrode probe with an in-situ grown conductive core based on a pre-stretched hollow capillary, characterized in that, Includes the following steps: 1) The hollow glass capillary tube is drawn into two nano-point hollow tubes with a conical hollow tip at one end; 2) Depending on the type of nanoelectrode probe to be prepared, a conductive core is generated in situ within the hollow cavity of the nano-tip hollow tube; If metal nanoelectrode probes are to be prepared, a metal conductive core can be generated in situ within the hollow cavity of a nano-tip hollow tube by means of wet chemical reduction or in-situ electrodeposition using metal salt solution and reducing solution. If carbon nanotube electrode probes are to be prepared, carbon conductive cores can be generated in situ within the hollow cavity of a nanotube using a carbon source through high-temperature gas-phase pyrolysis. To prepare a single-channel metal-carbon composite probe, a carbon conductive material layer is first generated in situ in the hollow cavity of a nano-tip hollow tube by high-temperature gas phase pyrolysis, and then a metal conductive material layer is deposited on the carbon conductive material layer by wet chemical reduction. If a theta-type dual-channel metal-carbon composite probe is to be prepared, a carbon conductive core can be generated in situ within the hollow cavity of a nano-tipped hollow tube by high-temperature gas-phase pyrolysis. A metal conductive core can then be generated in situ within the hollow cavity of the nano-tipped hollow tube by wet chemical reduction or in-situ electrodeposition using a metal salt solution and a reducing solution.

2. The method for preparing a nanoelectrode probe based on an in-situ grown conductive core using a pre-stretched hollow capillary, as described in claim 1, is characterized in that... The hollow capillary has an outer diameter of 0.3-2.0 mm and an inner diameter of 0.1-0.8 mm. The inner diameter of the hollow tip of the nano-tipped hollow tube in step 1) is 5-5000 nm, and the cone angle is 0.5-10°; The length of the hollow tip is 0.5-2mm.

3. The method for preparing a nanoelectrode probe based on an in-situ grown conductive core using a pre-stretched hollow capillary, as described in claim 1, is characterized in that... The wet chemical reduction method in step 2) includes the following steps: ① The hollow nano-tip tube is vertically immersed in ethylene glycol with the hollow tip facing down, and the hollow tip is partially or completely immersed in ethylene glycol, so that at least the lumen of the hollow tip is filled with ethylene glycol. ②Then, the metal salt solution is injected into the cavity of the nano-tip hollow tube from the end away from the hollow tip. Then, the nano-tip hollow tube is vertically inserted into the reducing solution with the hollow tip facing down, and the hollow tip is partially or completely immersed in the reducing solution. ③ After heating the nano-tipped hollow tube from step ② along with the reducing solution at 90-150℃ for at least 8 hours, cool it to room temperature and then clean it.

4. The method for preparing a nanoelectrode probe based on an in-situ grown conductive core using a pre-stretched hollow capillary, as described in claim 1, is characterized in that... Step 2) involves the following steps in the in-situ electrodeposition process: a. The hollow nano-tip tube is vertically immersed in ethylene glycol with the hollow tip facing down, and the hollow tip is partially or completely immersed in ethylene glycol, so that at least the lumen of the hollow tip is filled with ethylene glycol. b. Then, the metal salt solution is injected into the cavity of the nano-tip hollow tube from the end away from the hollow tip. Then, the nano-tip hollow tube is vertically inserted into the reduction solution with the hollow tip facing down, and the hollow tip is partially or completely immersed in the reduction solution. c. Insert a lead wire into the end of the nano-tipped hollow tube away from the hollow tip and make physical contact with the conductive material; apply a cyclic voltage through the lead wire, with a voltage of −20 V to +5 V and a scan rate of 0.01–100 V / s; Conductive cores with different configurations were prepared based on the number of cycles. When the number of cycles was 10-50, the prepared conductive core had a porous / open structure that allowed liquid to pass through; when the number of cycles was 100-500, the prepared conductive core had a dense / sealed structure.

5. A method for preparing a nanoelectrode probe based on an in-situ grown conductive core using a pre-stretched hollow capillary, as described in claim 3 or 4, characterized in that... The material of the metal conductive core in step 2) is one of Pt, Au, Ag, Pd, or Cu.

6. The method for preparing a nanoelectrode probe based on an in-situ grown conductive core using a pre-stretched hollow capillary, as described in claim 2, is characterized in that... Step 2) involves the following steps in high-temperature gas-phase pyrolysis: i) Place the nano-tipped hollow tube into the reaction tube with the hollow tip facing the gas inlet. Under the protection of inert gas, raise the temperature of the reaction tube to 500-1200°C at a rate of 5-10°C / min. ii) Introduce carbon source gas, maintain the temperature at 500-1200°C for a period of time, and then cool it down.

7. The method for preparing a nanoelectrode probe based on an in-situ grown conductive core using a pre-stretched hollow capillary, as described in claim 6, is characterized in that... In step ii), different holding times are selected based on the configuration of the conductive core of the nanoelectrode probe to be prepared: If the conductive core of the prepared nanoelectrode probe is solid, the heat preservation deposition time is 1-4 hours. If the conductive core of the prepared nanoelectrode probe has a hollow configuration, the heat preservation deposition time is 0.5-1h.

8. The method for preparing a nanoelectrode probe based on an in-situ grown conductive core using a pre-stretched hollow capillary, as described in claim 7, is characterized in that... The carbon source gas is selected from at least one of methane, ethane, propane, ethylene, acetylene, benzene, toluene, and ethanol, and the carrier gas of the carbon source gas is selected from at least one of argon, nitrogen, hydrogen, and helium.

9. A nanoelectrode probe, characterized in that, The nanoelectrode probe is prepared by the method of in-situ growth of conductive core based on pre-stretched hollow capillary as described in any one of claims 1 to 8.

10. The application of the nanoelectrode probe according to claim 9, characterized in that, The nanoelectrode probes are used in electrochemical sensing, single-cell analysis, or scanning probe microscopy.

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