TWI402504B - Biosensor, probe, sensing apparatus, and method for fabricatiing biosensor - Google Patents

Description

Biosensor, probe, sensing device, and biosensor manufacturing method

The present invention relates to a biosensor and a sensing device for sensing the concentration of dopamine in the brain. The present invention relates to a biosensor and a sensing device constructed using a nanowire field effect transistor.

The human brain has up to 1 trillion nerve cells, which are interconnected by a complex neural network, and each nerve cell uses a chemical molecule as a medium for communication. Among them, dopamine is an important neurotransmitter that controls brain functions such as movement, emotions and higher cognitive abilities.

According to the research, the lack of dopamine concentration in the brain can make people lose the ability to control muscles, and severe cases may lead to Parkinson's disease. Conversely, if the dopamine concentration is too high, it may cause hallucinations, delusions, irritability, and even obsessive-compulsive disorder. Therefore, the concentration of dopamine in the brain needs to be maintained within the normal range, otherwise the above conditions may occur.

Therefore, the measurement of dopamine concentration in the brain is an integral part of disease prevention and brain research. In the prior art, a dopamine sensor using 3-aminopropyltrimethoxymethane and an ion-sensitive field effect transistor has been disclosed. However, ion-selective field-effect transistors are not very sensitive (measurement range is about 1 μM), and ion-selective field-effect transistors do not respond accurately due to the low concentration of dopamine in the brain. Changes in dopamine concentration in the brain.

Therefore, it is necessary to design a dopamine concentration biosensor with higher sensitivity.

One aspect of the present invention is to provide a biosensor to accurately sense dopamine concentration to solve the above problems.

According to a specific embodiment, the biosensor of the present invention comprises a nanowire field effect transistor, a linking functional group, and a test group. Wherein, the nanowire field effect transistor has a nanowire, the functional group is connected to the nanowire, and the test group is attached to the linking functional group. The test base can be used to connect dopamine, and the nanowire field effect transistor can generate a sensing signal depending on the amount of dopamine attached to the test substrate.

Another aspect of the present invention is to provide a probe that accurately detects the concentration of dopamine in the brain to solve the problems of the prior art.

According to a specific embodiment, the probe of the present invention comprises a probe body and a biodetector, wherein the biodetector is disposed on the tip of the probe body and electrically connected to the probe body through the tip. The biosensor can comprise a nano field effect transistor, a linking functional group, and a test group, wherein the linking functional group is attached to the nanowire of the nanowire field effect transistor, and the test substrate is attached to the linking functional group.

In this embodiment, the test substrate can be used to connect dopamine, and the nanowire field effect transistor can generate a sensing signal according to the amount of dopamine attached to the test substrate. In practice, the sensing signal generated by the nanowire field effect transistor can be transmitted to the external electronic device through the tip and the probe body for sensing. Thus, the probe of this embodiment can be used to sense dopamine concentrations in the brain.

Another aspect of the present invention is to provide a sensing device that accurately detects the concentration of dopamine in the brain to solve the problems of the prior art.

According to a specific embodiment, the sensing device of the present invention comprises a probe, a biosensor, and a data processing device. The biosensor is placed on the tip of the probe and the probe is attached to the data processing device.

In this embodiment, the biodetector comprises a nanowire field effect transistor, a linking functional group, and a test group, wherein the linking functional group is attached to the nanowire on the nanowire field effect transistor, and the test substrate is connected to Attached to a functional group. Test sites can be used to link dopamine in the brain. When the test base is connected with dopamine, the nanowire field effect transistor can generate a sensing signal according to the amount of dopamine connected to the test base, and transmit the sensor signal to the data processing device through the probe, and then the data processing device can be based on the sensing signal Determine the concentration of dopamine in the brain.

Another aspect of the present invention is to provide a method of fabricating a biosensor. The biosensor fabricated by this method can accurately sense the concentration of dopamine in the brain, thereby solving the problems of the prior art.

According to a specific embodiment, the biosensor manufacturing method of the present invention comprises the steps of: first, attaching a linking functional group to a surface of a nanowire of a nanowire field effect transistor; and then, connecting the dopamine The test substrate is attached to a linking functional group to form a biosensor.

The advantages and spirit of the present invention can be as detailed by the following invention and The drawings are further understood.

Referring to FIG. 1, FIG. 1 is a schematic diagram of a biosensor 1 according to an embodiment of the present invention. As shown in FIG. 1, the biosensor 1 comprises a nanowire field effect transistor 10, a linking functional group 12, and a test base 14, wherein the nanowire field effect transistor 10 is provided with a nanowire 100, and a functional group is attached. 12 is attached to the surface of the nanowire 100. In addition, test substrate 14 is attached to a linking functional group 12. Please note that for the sake of simplicity of the drawing, only the one side of the nanowire 100 is connected to the test substrate 14 and the functional group 12 is connected. However, in practice, the other side of the nanowire 100 can also be connected for testing. The group 14 and the linking functional group 12.

In practice, two electrodes can be connected at both ends of the nanowire 100 as the drain and source of the nanowire field effect transistor 10. When the nature of the nanowire 100 changes, the nanowire field effect transistor 10 changes its electrical characteristics to produce a signal change. For example, when the surface of the nanowire is connected with different substances, the conductivity of the nanowire may change according to the amount of the connecting substance, so that the nanowire field effect transistor is in different operating states.

In this embodiment, the nanowire 100 can be a nanowire, the linking functional group 12 can be 3-aminopropyltriethoxymethane, and the test group 14 can be 4-hydroxybenzeneboronic acid. The invention is not limited thereto. The thiol group in the linking functional group 12 (3-aminopropyltriethoxymethane) can be bonded to the oxy group on the surface of the nanowire 100, and in addition, the amino group in the linking functional group 12 can be bonded to the test group 14 ( Carboxyl linkage of 4-hydroxybenzeneboronic acid). Test group 14 can be attached to dopamine and when test group 14 is linked to dopamine At this time, the conductivity of the nanowire 100 changes to cause the nanowire field effect transistor 10 to generate a signal. Please note that the number of the linking functional groups 12 and the test groups 14 connected to the nanowire 100 can be determined according to the needs of the user or the designer in practice, and is not limited to the specific embodiment. The more the test group 14 is attached to the dopamine, the more pronounced the characteristics of the nanowire 100 change, as well as the signal generated by the nanowire field effect transistor 10.

Referring to FIG. 1 again, the nano field effect transistor 10 further includes a substrate 102, a dielectric layer 104, and a support structure 106, wherein the dielectric layer 104 covers the substrate 102, and the support structure 106 is disposed on Above the dielectric layer 104. The nanowires 100 are disposed on both sides of the support structure 106 and supported by the support structure 106. In practice, the formation of the nanowires may first deposit the material of the nanowires around the support structure and its surroundings. For example, if the desired nanowire material is tantalum, a layer of tantalum material is deposited on and around the support structure. Next, the support structure and the material layer around it are etched, wherein the material layer located near the bottom of the support structure remains different after the etching according to the etching method and its parameters. Since the support structure is elongated in this embodiment, the material extending along the bottom of the support structure and remaining may form elongated strips of nanowires. Please note that in practice, the above-described nanowire field effect transistors may have different structures and are not limited to the specific embodiments of the present invention. What's more, the nanowire field effect transistor can also be replaced by a carbon nanotube field effect transistor, depending on the needs of the user or the designer.

In the above specific embodiment, the nanowire field effect transistor 10 of the biosensor 1 can change the signal generated according to the number of dopamine connected to the test substrate 14. Therefore, it can be used to sense the concentration of dopamine in the brain.

Referring to FIG. 2, FIG. 2 is a schematic diagram of a probe 2 according to another embodiment of the present invention. Probe 2 can be used as a brain probe to detect dopamine concentrations in the brain. As shown in FIG. 2, the probe 2 includes a probe body 20 and a biosensor 22, wherein the biosensor 22 is disposed on the tip of the probe body 20.

In the present embodiment, biosensor 22 further includes a nanowire field effect transistor 220, a linking functional group 222, and a test substrate 224. The linking functional group 222 is attached to the nanowire 2200 of the nanowire field effect transistor 220, the test substrate 224 is attached to the linking functional group 222, and the other end of the test substrate 224 is linked to dopamine. The nanowire field effect transistor 220 can be electrically connected to the probe body 20 through the tip of the needle. Please note that the biosensor 22 of the present embodiment is substantially the same as the biosensor 1 of the previous embodiment, and details are not described herein again. Therefore, when the test base 224 of the biosensor 22 is connected to the dopamine, the sensing signal generated by the nanowire field effect transistor 220 can be transmitted to the probe body 20.

The probe 2 of the above specific embodiment can be further connected to a sensing device to process the sensing signal generated by the biosensor to determine the dopamine concentration. Referring to FIG. 3, FIG. 3 is a schematic diagram of a sensing device 3 according to another embodiment of the present invention. As shown in FIG. 3, the sensing device 3 includes a probe 30, a biosensor 32, and a data processing device 34.

In the present embodiment, the biosensor 32 is disposed on the tip of the probe 30 body, and the biosensor 32 includes a nano field effect transistor 320, a connection functional group 322, and a test base 324. Similarly, the linking functional group 322 is attached to the nanowire 3200 of the nanowire field effect transistor 320. The test group 324 is attached to the linking functional group 322, and the other end of the test group 324 is linked to dopamine. Since the biosensor 32 of the present embodiment is substantially the same as the biosensors 1 and 22 of the above specific embodiment, it will not be described herein. The nano field effect transistor 320 is electrically coupled to the data processing device 34 through the tip of the probe 30 and the body.

In the present embodiment, when the test substrate 324 is connected to the dopamine, the nano field effect transistor 320 can generate a sensing signal according to the amount of dopamine to which the test substrate 324 is connected, and the sensing signal can be transmitted to the probe 30 to the probe 30. Data processing device 34. The data processing device 34 can determine the dopamine concentration based on the received sensing signal. In practice, the sensing device of the present invention can sense a dopamine concentration ranging from 1 fM to 1 pM (ie, 10 ^-15 M to 10 ^-12 M), thereby accurately sensing dopamine concentration and is suitable for use in Dopamine concentration sensing in the brain.

In addition, please refer to Figure 4A. Figure 4A is a schematic illustration of a sensing device 4 in accordance with another embodiment of the present invention. As shown in FIG. 4A, the specific embodiment differs from the above specific embodiment in that the sensing device 4 of the specific embodiment further includes an alerting device 46 connected to the data processing device 44. When the determined dopamine concentration is higher than the first predetermined value, the data processing device 44 may send the first control signal to control the alert device 46 to send the first alert signal. On the other hand, if the determined dopamine concentration is lower than the second predetermined value, the data processing device 44 can transmit the second control signal to control the alert device 46 to send the second alert signal. In practice, the first preset value and the second preset value may be set according to the normal dopamine concentration range in the brain. Therefore, when the data processing device determines that the dopamine concentration in the brain is abnormal, the warning device notification can be controlled. Medical care or other phase Close personnel. Please note that other units of the sensing device 4 of the present embodiment (the probe 40, the biosensor 42 and the data processing device 44, etc.) are substantially the same as the corresponding units of the above specific embodiments, so Let me repeat.

Please refer to FIG. 4B. FIG. 4B is a schematic diagram of the sensing device 5 according to another embodiment of the present invention. As shown in FIG. 5, the specific embodiment is different from the above specific embodiment in that the sensing device 5 of the specific embodiment further includes a feedback device 58 connected to the data processing device 54. The data processing device 54 can send a third control signal based on the determined dopamine concentration to cause the feedback device 58 to feedback control the dopamine concentration. For example, when the data processing device 54 determines that the dopamine concentration in the brain is too high, the feedback device 58 can reduce the dopamine concentration in the brain, and on the other hand, when the data processing device 54 determines that the dopamine concentration in the brain is too low, feedback Device 58 can increase the concentration of dopamine in the brain. The above-mentioned feedback control can be judged and controlled by the data processing device 54 in practice, or can be combined with the warning device 46 of the previous embodiment to notify the medical staff and manually controlled by the medical staff. Similarly, other units of the sensing device 5 of the present embodiment (probe 50, biosensor 52, data processing device 54, etc.) are substantially the same as the corresponding units of the above specific embodiments, so Let me repeat.

It should be noted that the signal transmission between the above specific embodiments can be performed by wired or wireless transmission, and the present invention does not limit this.

Please refer to FIG. 1 and FIG. 5 together. FIG. 5 is a diagram showing the invention according to the present invention. A flow chart of the steps of a biosensor manufacturing method of a specific embodiment, which can be used to fabricate the biosensor 1 as shown in FIG. The flow steps of the method of the specific embodiment are illustrated by the biosensor 1 of FIG.

As shown in Figure 5, the method of this embodiment includes the steps as described below. In step S60, the surface of the nanowire 100 of the nanowire field effect transistor 10 is treated with an alcohol solution containing 3-aminopropyltriethoxymethane (APTES), and then the APTES is connected to the nanowire 100. surface. Among them, the APTES attached to the nanowire 100 is the linking functional group 12 shown in FIG. In practice, the surface of the nanowire 100 can be reacted for 30 minutes using an aqueous alcohol solution having a 2% APTES concentration, although the invention is not limited thereto.

In step S62, 4-hydroxybenzeneboronic acid (CPBA) is attached to the amino group of APTES by the aid of a crosslinking agent to form biosensor 1. The CPBA connected to the APTES is the test base 14 shown in FIG.

In step S64, the nanowire field effect transistor is placed on the tip of the probe. Step S64 can integrate the biosensor 1 on the brain probe and can be directly used to perform dopamine concentration sensing in the brain. Please note that the present invention does not limit the sequence of step S64. For example, the nanowire field effect transistor can be first placed on the probe and then connected to the test substrate and the functional group on the nanowire, or the test base can be connected first. And the surface of the nanowire-based device is connected to the probe and the nanowire field effect transistor is placed on the probe.

Referring to FIG. 6 , FIG. 6 is a partial schematic diagram showing the connection of the dopamine molecule 8 by the biosensor 7 produced by the method of FIG. 5 . As shown in Figure 6, One end of the linking functional group 72 (APTES) is attached to the polycrystalline silicon nanowire 70 of the sensor 7, and the other end of the linking functional group 72 is coupled to a test substrate 74 (CPBA). The test base 74 can be attached to the dopamine molecule 8, and when the test group 74 is attached to the dopamine molecule 8, the nanowire field effect transistor (for the sake of simplicity of the drawing, FIG. 6 does not depict the nano field effect transistor) The number of connected dopamine molecules 8 produces a sensing signal.

Compared with the prior art, a biosensor made of a nanowire field effect transistor can sensitively sense dopamine, and thus can be used in an instrument such as a brain probe that requires accurate measurement. In addition, the sensing device combined with the biosensor, probe and data processing device can instantly monitor the dopamine concentration in the brain of the patient. Moreover, the sensing device can also be used to adjust the concentration of dopamine in the brain to prevent dopamine. A disease caused by a concentration imbalance.

The features and spirit of the present invention will be more apparent from the detailed description of the preferred embodiments. On the contrary, the intention is to cover various modifications and equivalents within the scope of the invention as claimed. Therefore, the scope of the patented scope of the invention should be construed as broadly construed in the

1, 22, 32, 42, 52, 7‧‧‧ biosensors

10, 220, 320, 420, 520‧‧‧ nanometer field effect transistor

12, 222, 322, 422, 522, 72‧‧‧ linkage functional groups

14, 224, 324, 424, 524, 74‧‧‧ test base

100, 2200, 3200, 4200, 5200, 70‧‧‧ nanowires

102‧‧‧Substrate

104‧‧‧ dielectric layer

106‧‧‧Support structure

2, 30, 40, 50‧ ‧ probe

20‧‧‧ probe body

3, 4, 5‧‧‧ sensing equipment

34, 44, 54‧‧‧ data processing equipment

46‧‧‧Warning device

58‧‧‧Return device

S60~S64‧‧‧ Process steps

8‧‧‧Dopamine molecule

1 is a schematic diagram of a biosensor according to an embodiment of the present invention.

Figure 2 is a schematic illustration of a probe in accordance with another embodiment of the present invention.

3 is a schematic diagram of a sensing device in accordance with another embodiment of the present invention.

4A is a schematic diagram of a sensing device in accordance with another embodiment of the present invention.

Figure 4B is a schematic diagram of a sensing device in accordance with another embodiment of the present invention.

FIG. 5 is a flow chart showing the steps of a method for fabricating a biosensor according to an embodiment of the present invention.

Figure 6 is a partial schematic view showing the biosensor connected to the dopamine molecule produced by the method of Figure 5.

1‧‧‧Biosensor

10‧‧‧Nano line field effect transistor

12‧‧‧Connecting functional groups

14‧‧‧Test base

100‧‧‧Nami Line

102‧‧‧Substrate

104‧‧‧ dielectric layer

106‧‧‧Support structure

Claims (14)

A probe for detecting a concentration of dopamine in the brain, the probe comprising: a probe body including a tip; and a biosensor disposed on the tip, the biosensor comprising: a rice-line field effect transistor electrically connected to the probe body through the tip of the probe, the nanowire field effect transistor having a nanowire; a connecting functional group connecting the nanowire; and a test base connected to The linking functional group is used to connect at least one dopamine; wherein, when the test group is linked to the at least one dopamine, the nanowire field effect transistor generates a sensing signal according to the amount of the at least one dopamine. The probe of claim 1, wherein the linking functional group is 3-aminopropyltriethoxymethane. The probe of claim 1, wherein the test is 4-hydroxybenzeneboronic acid. The probe of claim 1, wherein the nanowire field effect transistor further comprises: a substrate; a dielectric layer covering the substrate; and a support structure disposed on the dielectric layer The nanowire is disposed on a side of the support structure and above the dielectric layer. A sensing device for sensing a concentration of dopamine in the brain, the sensing device comprising: a probe comprising a probe body having a tip; a biosensor disposed on the tip, the biosensor comprising: a nanowire field effect transistor through which the tip The probe body is electrically connected, the nanowire field effect transistor has a nanowire; a connecting functional group is connected to the nanowire; and a test base is connected to the connecting functional group, and the test base is used for connecting At least one dopamine in the brain; and a data processing device coupled to the probe; wherein the nanowire field effect transistor generates a sensing based on the amount of the at least one dopamine when the test group is attached to the at least one dopamine And transmitting, by the probe, the sensing signal to the data processing device, the data processing device determining the dopamine concentration according to the sensing signal. The sensing device of claim 5, wherein the linking functional group is 3-aminopropyltriethoxymethane. The sensing device of claim 5, wherein the test is 4-hydroxybenzeneboronic acid. The sensing device of claim 5, wherein the nanowire field effect transistor further comprises: a substrate; a dielectric layer covering the substrate; and a support structure disposed on the dielectric layer The nanowire is disposed on a side of the support structure and above the dielectric layer. The sensing device of claim 5, further comprising a warning device connected to the data processing device, when the data processing device determines The first control signal is sent when the dopamine concentration is higher than a first preset value, and the warning device sends a first warning signal according to the first control signal. The sensing device of claim 5, further comprising a warning device connected to the data processing device, and transmitting a second control signal when the data processing device determines that the dopamine concentration is lower than a second preset value, And the alerting device sends a second alert signal according to the second control signal. The sensing device of claim 5, further comprising a feedback device connected to the data processing device, the data processing device transmitting a third control signal according to the determined dopamine concentration, and the feedback device is The third control signal feedback controls the dopamine concentration. A probe making method for making a probe for sensing a concentration of dopamine in the brain, the method comprising the steps of: attaching a 3-aminopropyltriethoxymethane to one a surface of a nanowire of a nanowire field effect transistor; a 4-hydroxyphenylboronic acid attached to one of the terminal amino groups of the 3-aminopropyltriethoxymethane to form the biosensor; The nanowire field effect transistor is placed on one of the probe tips. The method of claim 12, further comprising the step of treating the surface of the nanowire with an alcohol solution containing one of the 3-aminopropyltriethoxymethane, and then the 3-aminopropane A triethoxymethoxymethane is attached to the surface of the nanowire. The method of claim 12, further comprising the step of assisting attachment of the 4-hydroxybenzeneboronic acid to the terminal amine group of the 3-aminopropyltriethoxymethane by a crosslinking agent.