KR101188368B1 - Nanowires neural probe electrodes and the manufacturing method of the same - Google Patents

Abstract

The present invention relates to a nanowire nerve probe electrode and a method for manufacturing the same, and more particularly, the present invention comprises the steps of forming a nanowire on a substrate; Reinforcing the mechanical properties of the nanowires by further forming a metal layer or a polymer layer on the surface of the nanowires; And if a polymer layer is further formed on the surface of the nanowire, exposing a portion of the nanowire; a method of manufacturing a nanowire nerve probe electrode, and a nanowire nerve probe manufactured by the method Provide an electrode.
According to the present invention, by providing a nanowire probe electrode having an electrical, mechanical, biocompatible characteristics suitable for detecting a nerve signal based on nanowires, the nerve cell signal is safely detected inside or outside the living nerve cell, or It can be expected that the effect of stimulating the or to deliver the material more efficiently.

Description

Nanowire neural probe electrodes and the manufacturing method of the same

The present invention relates to a nanowire nerve probe electrode and a method for manufacturing the same, and more particularly, the present invention comprises the steps of forming a nanowire on a substrate; Reinforcing the mechanical properties of the nanowires by further forming a metal layer or a polymer layer on the surface of the nanowires; And if a polymer layer is further formed on the surface of the nanowire, exposing a portion of the nanowire; a method of manufacturing a nanowire nerve probe electrode, and a nanowire nerve probe manufactured by the method Provide an electrode.

According to the present invention, by providing a nanowire probe electrode having an electrical, mechanical, biocompatible characteristics suitable for detecting a nerve signal based on nanowires, the signal of the nerve cells can be safely sensed inside or outside the living nerve cells, or The effect can be expected to stimulate cells or deliver substances more efficiently.

In an aging society in recent years, the widespread spread of various neurological diseases, such as Alzheimer's and Huntington's chorea, is more of a concern than ever before, and finding a cure is a socially important task.

As one of the methods for effectively treating such neurological diseases, a method of using a nerve device is attracting attention, and such a treatment method is being actively adopted medically.

The treatment method using the above-described nerve device generally refers to inserting a probe electrode where a nerve cell is located to sense and stimulate its signal.

On the other hand, various electrodes have already been developed for this purpose, a typical example is a silicon probe electrode made by etching the silicon. However, electrodes developed so far have a size of several tens of micrometers to millimeters, so when inserted into the nerve cells have a problem that the nerve cells are damaged and die. In addition, it is difficult to detect the minute signal of the nerve cells, and since the spatial resolution is low, there is a disadvantage that can not properly perform the signal transmission and stimulation of the actual nerve cells.

Therefore, a method of sensing or stimulating a minute signal originating from the nerve cell with excellent spatial resolution in the living state of the nerve cell should be developed.

Nanowires, one-dimensional nanostructures, are hair-shaped nanomaterials with a diameter of 20 to 100 nm, but a few μm in length, and have a high long ratio. In general, nanowires are widely recognized as the most promising building blocks for the implementation of bottom-up semiconductor nanomaterial devices because they exhibit new physical, chemical, and excellent electrical, optical, and magnetic properties based on quantum effects. have. In addition, nanowires are the most ideal material system for understanding the source properties of materials due to their easy-to-free device characteristics that are not affected by flawless monocrystalline substrates. In particular, since nanowires have a probe structure with a large diameter of several tens of nanometers in length and a long diameter ratio of several μm, the nanowires have disadvantages of conventional micron or mm sized neural electrodes when used as nerve cell electrodes. It can be overcome.

On the other hand, when using a nanowire as a neural electrode, the mechanical strength is weak due to its small size, thin thickness, etc., it is easy to be damaged when applied to the human body, and according to the nanowire material may have unsuitable electrical characteristics to use as a neural electrode. There is a limitation in the selection of the material, and also there is a problem that the long-term human friendliness may be lacking depending on the nanowire material, there is a difficulty in using the nanowire directly as a neural electrode, mechanical, The situation should be reinforced in terms of electrical and bio-friendly.

The present invention has been made to solve the problems of the conventional neural electrode technology as described above, an object of the present invention is to nano-sensing or stimulating signals from the inside and outside of the nerve cells in a state that does not damage the nerve cells The present invention provides a wire electrode, but provides a nanowire probe electrode and a method of manufacturing the same that can be put to practical use by reinforcing weak mechanical strength.

In addition, another object of the present invention is to provide a nanowire probe electrode and a method of manufacturing the same to improve the efficiency of the application of nanowires as a neural probe electrode by making it more complete in consideration of the electrical and bio-friendly characteristics of the nanowires. It is.

The present invention to achieve the above object, forming a nanowire on a substrate; Reinforcing the mechanical properties of the nanowires by further forming a metal layer or a polymer layer on the surface of the nanowires; And if a polymer layer is further formed on the surface of the nanowires, exposing a portion of the nanowires.

Reinforcing conductivity on the nanowires so that the nanowires have a desired electrical conductivity; it is preferable to further include.

Reinforcing the conductivity; is preferably by the method of applying a p-type or n-type dopant in the nanowire matrix, or a method of coating a conductive material on the surface of the nanowire.

Adding a biocompatible material to the metal layer or the polymer layer formed on the surface of the nanowire or the nanowire;

Adding the biocompatible material; is preferably coated with multiple para-xylene (poly para-xylene, poly p-xylylene).

It is preferable to further include; electrically insulating the substrate or a portion of the substrate and the nanowires.

Forming nanowires on the substrate; is preferably a method of directly growing a nanowire on the substrate or a method of etching a portion of the substrate.

The length of the nanowire is in the range of 0.1 ~ 50㎛, the thickness is preferably in the range of 5 ~ 500nm.

In addition, the present invention is prepared by the above method, in order to achieve the above object, is integrated with the substrate is easy to handle, can prevent the damage of nerve cells, the nanowire nerve probe electrode is secured mechanical strength to provide.

In addition, the present invention, in order to achieve the above object, in the nanowire nerve probe electrode manufactured by the method, the substrate portion is located outside the neurons, the nanowire portion is located inside the nerve cells It provides a method of using a nanowire nerve probe electrode.

According to the present invention as described above, while providing a nanowire probe electrode structure that can detect or stimulate the nerve signals in and out of the nerve cells without damaging the nerve cells, the durability is further improved as a result of reinforcing mechanical strength The effect that nanowire probe electrode can be put to practical use is expected.

In addition, by enhancing the electrical properties of the nanowire probe to a practical level, it is expected to have an effect of broadening the selection of nanowire materials and at the same time clearly detecting and correctly analyzing a signal transmitted from a human neuron.

In addition, when the nanowire is applied to the human body by reinforcing the bio-friendly features of the nanowire probe to the practical level, it is expected that the effect of preventing various side effects in advance and having a practical meaning.

1 is a schematic diagram showing the structure of a nanowire probe electrode according to an embodiment of the present invention.
Figure 2 is a schematic diagram showing the structure of the nanowire probe electrode according to another embodiment of the present invention.
3 is a microstructure photograph of a nanowire formed on a substrate according to an embodiment of the present invention.
Figure 4 is a graph showing the measurement of the electrical properties of the nanowires according to an embodiment of the present invention.
FIG. 5 is a microstructure photograph of nanowires coated with Au by a method of providing low electrical resistance to nanowires according to an embodiment of the present invention.
6 is a graph showing the electrical resistance value of the Au-coated nanowires according to an embodiment of the present invention.
FIG. 7 is a microstructure photograph of nanowires after coating with multiple para-xylene polymers to maintain adhesion to a substrate and nanowires according to an embodiment of the present invention.
8 is a microstructure photograph of a silica film coated to electrically insulate a substrate and nanowires according to an embodiment of the present invention.
9 is a microstructure photograph of the exposed state of the nanowire end according to an embodiment of the present invention.
10 is a microstructure photograph of culturing nerve cells on a nanowire probe electrode according to an embodiment of the present invention.
11 is a graph of a signal of a nerve cell measured by the nanowire probe electrode according to an embodiment of the present invention.

The present invention will be described in more detail with reference to the accompanying drawings as follows.

In the present invention, in implementing a nanowire for a probe used in nerve cells, by coating a metal or a polymer, the nanowire is flexible and retains durability against external impact, thus providing a nanowire having excellent mechanical properties. In addition, the present invention has a first feature, and the present invention also provides a method for reinforcing the electrical conductivity to the commercialization level when the nanowire uses a material having a commercialization level of electrical conductivity, or when such a material is not used. In order to enhance the electrical properties in order to broaden the range of material selection for nanowires has a second feature, and the present invention also has side effects such as rejection reaction when the nanowires are used in a living body Should not be produced, depending on the choice of materials. When preparing the nanowire probe by using the material which could lead to possible for there to be accepted given the bio-compatible by a biocompatible process here made available without difficulty in nerve cells, characterized in the third.

In particular, according to an embodiment of the present invention as described below, by applying a multi-para-xylene which is a biocompatible material to the nanowires of the present invention, to enhance the bio-compatibility, while nano by multi-para-xylene The mechanical strength reinforcement effect of the wire can also be achieved simultaneously. That is, according to the present invention, by using multiple para-xylene, mechanical strength and biocompatibility can be simultaneously realized.

The present invention has a comprehensive feature in that the electrical properties, mechanical properties, and bio-friendly properties are organically harmonized and implemented in the nanowires, and it should be noted that the nanowires having excellent quality can be manufactured by such organic harmonization. .

1 is a schematic diagram showing the structure of a nanowire probe electrode according to an embodiment of the present invention.

As shown, the nanowire according to an embodiment of the present invention,

(1) growing nanowires on a substrate,

(2) forming, for example, a metallic conductive layer on the nanowire so that the nanowire sufficiently secures electrical conductivity as a probe for nerve cells;

(3) reinforcing the mechanical strength of the nanowires or realizing biocompatibility by introducing a polymer layer, for example, on the nanowires on which the electrically conductive layers are formed;

(4) further introducing an insulating layer on the polymer layer in order to have conductivity up to the substrate to prevent disturbance of signals propagated from nerve cells;

(5) Finally, the nanowire probe electrode for nerve cells was prepared by removing the polymer layer and the insulating layer from the attachment of the nanowires so that the attachment of the nanowires in direct contact with the nerve cells receives a signal from the nerve cells. can do.

On the other hand, Figure 2 is a schematic diagram showing the structure of the nanowire probe electrode according to another embodiment of the present invention. As shown, for example, a metal coating layer is not formed in the nanowire probe electrode, in which case the nanowire is not coated with, for example, a metal layer by removing the polymer layer and the insulating layer from the attachment of the nanowire. May allow direct contact with nerve cells.

The embodiment shown in FIG. 2 excludes, for example, a metal layer that is applied from the embodiment shown in FIG. 1 to improve electrical conductivity to a practical level. That is, FIG. 2 illustrates a case in which the nanowire itself uses a material that sufficiently secures electrical conductivity as a probe electrode, or a material doped with an n-type or p-type conductive material directly to the material, instead of applying a metal coating layer.

3 is a microstructure photograph of a nanowire formed on a substrate according to an embodiment of the present invention. As shown, it can be seen that the nanowires generally have a thickness in the range of 5 to 500 nm and have a length in the range of 0.1 to 50 μm.

Figure 4 is a graph showing the measurement of the electrical properties of the nanowires according to an embodiment of the present invention. In the graph shown as shown, the electrical resistance value of the nanowire, which can be estimated from the current-to-voltage ratio of the nanowire, is about 150 k? Cm. That is, depending on the material, it means that the desired electrical resistance value could not be obtained with the measured nanowire material.

In order for the nanowires to be commercially available as probes for nerve cells, it is preferable that the nanowires generally have an electrical resistance value of 1 to 500 Ω.cm. However, depending on the type of nanowire material adopted, it may not hold the electrical resistance value in the above range. At this time, the nanowires can be treated in various ways to obtain a suitable electrical resistance value.

First, when fabricating the probe electrode by directly growing the nanowire, a method of lowering the electrical resistance value of the nanowire using a specific dopant. For example, in the case of silicon nanowires, boron (B) or phosphorus (P) may be supplied to the silicon nanowire growth process to obtain desired electrical resistance values.

Second, when the nanowire is manufactured by chemical etching, when the substrate to be etched is selected to have a sufficiently low electrical resistance value, the nanowire can obtain a sufficiently low electrical resistance value. In this case, the chemical etching method is a general method of obtaining nanowires by placing a mask corresponding to the diameter of the nanowires on the substrate and preventing the etching, and etching the other portions using an etchant. . This can be said to be the case that the nanowire itself is adopted as a material having a sufficiently low electrical resistance value.

Third, the nanowires, which have a relatively high electric resistance value and do not have a commercially available electric resistance value, are grown once, and as a subsequent process, a coating layer having electric conductivity on the surface can be formed so that the nanowires have a desired electric resistance value. have. For example, when the metal is coated on the surface of the nanowire, an electric resistance value low enough to be applied as a neural electrode can be obtained. As described later, when the substrate itself has a sufficiently low electrical resistance value or is processed to lower the electrical resistance value, since the signal transmitted from the neuron can be sensed and transmitted from both the substrate and the nanowire, the signal is disturbed. Alternatively, the substrate portion will need to be insulated separately, as this may lead to inaccuracies in the analysis of the sensed signal.

5 illustrates nanowires coated with gold (Au) as an example of providing electrical conductivity to nanowires. As shown, the interface between the coating layer and the nanowire matrix is well observed.

Since gold has excellent electrical conductivity, irrespective of the nanowire material, the electrical resistance value of the nerve probe electrode made of nanowire can be lowered to a desired value, and thus, the nanowire material can be selected widely. However, when adopting a nanowire material, the bond with gold should be considered.

Figure 6 is a graph showing the measurement of the electrical properties of the nanowires coated with gold (Au) according to an embodiment of the present invention. As shown, it can be seen that gold coated nanowires exhibit electrical resistance values low enough to carry signals generated from nerves. That is, the electric resistance value of the gold-coated nanowires from the current-voltage ratio of FIG. 6 shows that an appropriate electric resistance value within a range that can be used as a neural electrode is about 250 Ωcm.

7 is a multi-para-xylene polymer (parylene, parylene, poly para-Xylene, poly) to maintain adhesion to the substrate and the nanowires and prevent the nanowires from being damaged by an embodiment of the present invention. p-Xylene) was used to coat the nanowires and then take a microstructure picture.

Parylene here is a trade name of chemically deposited multi para-xylene, or multi p-xylene. Multiple para-xylene is an isomer of xylene, a fragrant carbohydrate, based on a benzene ring substituted with two methyl groups. Here, para- or p- means that the methyl groups are at symmetrical positions of the benzene rings.

Multipara-xylene is commonly used as an anti-humidant or insulator, and has excellent biocompatibility and biosafety, a very low degree of surface fibrosis, non-toxicity, and blood compatibility.

Therefore, coating such multiple para-xylene on the nanowires complements the weak mechanical properties of the nanowires, such as enhancing the adhesion of the nanowires to the substrate and preventing damage to the nanowires, and at the same time, the nanowires are used for nerve cells. It can have two effects simultaneously, such as giving biocompatibility for use as a probe electrode.

It can be seen that such multiple para-xylene layers are coated with a thickness equivalent to twice the thickness of the nanowires, as shown. In addition, the multiple para-xylene is coated so as to contact the substrate, thus not only damage the nanowires themselves, but also has the effect of enhancing the contact strength to the contact surface with the substrate. Since the multiple para-xylene is coated on the nanowire or the nanowire and the substrate, there is an effect of greatly improving the weak mechanical properties such as damage of the nanowire.

Thereafter, an insulating layer is coated on the surfaces of the substrate and the nanowire to remove the electrical conductivity of the substrate. In this regard, a photograph of an insulating layer coated on the surface of the substrate and the nanowire is shown in FIG. 8. The nanowires grown on the substrate are responsible for the detection and stimulation of neuronal signals, so it is necessary to functionally separate the substrate from the nanowires. Therefore, it can be achieved by coating a material having an electrically insulating property on the surface of the substrate. That is, by coating the insulating layer, it is possible to prevent the signal transmitted from the neuron from being disturbed due to the conductivity of the substrate. That is, by coating an insulating layer, a signal generated at the contact surface between the cell and the nanowire electrode may be measured, and when there is no insulation layer, a signal is generated at the contact surface between the cell and the substrate, thereby disturbing the signal measured at the nanowire.

Of course, the nanowires must remove the insulating layer therefrom in order to restore conductivity as described later. This is shown in Figure 8, the substrate and the nanowires were coated with a silica film.

9 is a microstructure photograph of the attachment of the nanowires according to an embodiment of the present invention. When the nanowires are doped, all of the coating layers existing on the attachment of the nanowires are removed except for the nanowires, and when the nanowires are coated with gold, for example, all of the gold coating layers and the nanowires are removed. Therefore, the nanowires inserted into the neurons alone retransmit signals transmitted from the neurons, thereby solving the problem of signal transmission disturbance by the substrate as described above.

Figure 10 shows a microstructure photograph of the culture of nerve cells on the nanowires according to an embodiment of the present invention. Nanowires can be seen penetrating the lump-like neurons in the center. The substrate is underneath the nerve cell Note that not shown. 10 As shown, since the nanowires have a fine size, the nanowire probe electrodes can be inserted into the neurons without damaging the neurons.

In FIG. 11, the nanowire probe electrode according to an embodiment of the present invention shows a graph of a result of measuring a signal transmitted from a nerve cell in a nerve cell. FIG. 11 shows the change in voltage over time, showing that the change in positive voltage results from the action of the action potential of the neuron, and thus the nanowire neural electrode can measure the electrical transmission signal of the neuron. On the other hand, the negative voltage variation in FIG. 11 is electrical noise coming out of the measuring machine.

Hereinafter, the present invention has been described in more detail with reference to Examples, but the present invention is not limited by the following Examples, and those skilled in the art to which the present invention pertains within the technical spirit of the present invention. Various modifications are possible.

≪ Example 1 >

In this embodiment, silicon was selected as a nanowire material, and more specifically, silicon nanowires were grown on a silicon substrate using silane as a raw material, and doped by an implantation method to secure desired electrical conductivity. After that, by using a chemical vapor deposition method to the nanowires or nanowires and the substrate is coated with a multi-para-xylene as a polymer to improve the mechanical properties and at the same time to give biocompatibility. Afterwards, the nanowire ends were exposed while removing the polymer using plasma.

By culturing the nerve cells on the prepared nanowire substrate, it was confirmed that the nanowires penetrate into the cells while the neurons are alive.

<Example 2>

As in Example 1, silicon nanowires were grown on a silicon substrate using silane as a raw material, but in order to give a desired electric resistance value to the nanowires, the surface was coated with a thickness of about 10 nm. The electrical conductivity of the nanowires was secured. Then, by using a chemical vapor deposition method to coat the nanowires or nanowires and the multi-para-xylene as a polymer on the substrate to improve the mechanical properties and at the same time to give biocompatibility. Afterwards, the nanowire ends were exposed while removing the polymer using plasma.

By culturing the nerve cells on the prepared nanowire substrate, it was confirmed that the nanowires penetrate into the cells while the neurons are alive.

Claims (10)

Forming nanowires on the substrate;
Reinforcing the mechanical properties of the nanowires by further forming a metal layer or a polymer layer on the surface of the nanowires;
If a polymer layer is further formed on the surface of the nanowire, exposing a portion of the nanowire; And
Electrically insulating said substrate or a portion of said substrate and said nanowire;
And,
Biostructure of nanowires from the multiple para-xylene by coating multiple para-xylene (poly (p-xylylene)) from the metal or polymer layer formed on the surface of the nanowire or the nanowire to the portion of the substrate to which the nanowire is connected Method for producing a nanowire nerve probe electrode, characterized in that to reinforce affinity and mechanical properties at the same time. The method of claim 1,
And reinforcing conductivity on the nanowires so that the nanowires have a desired electrical conductivity. The method of manufacturing a nanowire nerve probe electrode further comprising: The method of claim 2,
Reinforcing the conductivity;
And a method of adding a p-type or n-type dopant in the nanowire matrix, or coating a conductive material on the surface of the nanowire. delete delete delete The method of claim 1,
Forming a nanowire on the substrate; is a method of directly growing a nanowire on the substrate or a method of etching a portion of the substrate. The method of claim 7, wherein
The length of the nanowires is in the range of 0.1 ~ 50㎛, the thickness of the nanowire nerve probe electrode manufacturing method characterized in that the range of 5 ~ 500nm. delete delete

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