KR20190084420A - Bio molecular detector and method of using the same - Google Patents

Abstract

The present invention relates to a portable biomolecular detection device capable of improving the detection speed of biomolecules using a micro voltage, and a method thereof. The biomolecular detection device comprises: a power supply unit for supplying voltage and current; a micro voltage generator for receiving the voltage and current supplied from the power supply unit and generating and outputting a micro voltage; a biomolecular detector for detecting biomolecules depending on a current that changes in a state in which a target molecule is fixed on a probe molecule by applying the micro voltage generated by the micro voltage generator; a current detector for detecting the current output from the biomolecular detector; an amplifier for receiving, amplifying, and outputting the current detected by the current detector; an A/D converter for converting the current amplified by the amplifier into a digital signal and outputting the digital signal; and an MCU for receiving the digital signal converted through the A/D converter and determining whether the biomolecule is reacted.

Description

TECHNICAL FIELD The present invention relates to a biomolecule detection apparatus and method,

The present invention relates to a biomolecule detecting apparatus and a method thereof, and more particularly, to a biomolecule detecting apparatus and method which can easily detect biomolecules through a minute current and are convenient to carry.

There is a transistor-based biosensor having a structure including a transistor among biosensors that detect biomolecules by an electrical signal. This is fabricated using a semiconductor process, and it is advantageous in that an electrical signal can be converted quickly, and a lot of research has been conducted in the meantime.

Particularly, a biomolecule detection device (or a biosensor) using a field effect transistor (FET) is low in cost and time, and is easy to be combined with an IC / MEMS process.

A biosensor using an FET has a function of forming a channel of a FET by connecting a probe molecule (or a receptor molecule, an acceptor) and a target molecule (an analyte molecule, analytes) The amount of current flowing in the channel region is changed by the change of the surface charge transferred to the region, and the target molecule can be detected by using this.

In such an FET, the Debye length of the surface charge changes depending on the ionic strength of the solution, that is, the ion concentration, and the intensity of the current flowing in the channel region may be changed. Therefore, the target molecule can be detected using the FET under the condition that the ionic strength of the electrolyte solution containing the target molecule is smaller than the charge intensity of the target molecule.

However, body fluids containing biomolecules, such as blood, urine, and saliva, generally have different ion concentrations for different people and have relatively high ionic strength. Therefore, it is difficult to detect biomolecules directly by providing the biomolecules to the channel region of the FET, and reliability and reproducibility of biomolecules are deteriorated even when biomolecules are detected by measuring the current intensity of the channel region.

1 is a cross-sectional view schematically showing the structure of a conventional FET.

1, a source 22a and a drain 22b doped with an opposite polarity to the substrate 21 are formed on both sides of a substrate 21 doped with n-type or p-type, A gate 23 is formed on the substrate 21 to contact the source 22a and the drain 22b.

Generally, the gate 23 is composed of an oxide layer, a polysilicon layer and a gate electrode layer, and probe molecules are attached to the gate 23 facing the reference electrode 24. [ A probe molecule is bound to a predetermined target molecule by hydrogen bonding or the like, and the degree of binding between the probe molecule and the target molecule is measured by an electrical method.

Therefore, the current intensity flowing through the channel is different depending on whether or not the probe molecules are fixed on the surface of the gate 23 and whether the target molecules are bonded to the fixed probe molecules. Accordingly, have.

However, in order to detect target molecules, blood or secretions are collected in the field and the biomolecules are detected in a state where they are transferred to a specific place. Therefore, it takes a long time to detect biomolecules, And there is a problem that the movement of equipment for detecting biomolecules is inconvenient.

Disclosure of Invention Technical Problem [8] Accordingly, the present invention has been made keeping in mind the above problems occurring in the prior art, and it is an object of the present invention to provide a biomolecule detection apparatus and method which can improve the detection speed of biomolecules using microcurrents.

According to an aspect of the present invention, there is provided a biomolecule detection apparatus including a power supply unit for supplying a voltage and a current, a minute voltage generating unit for generating and outputting a minute voltage by receiving a voltage and a current supplied from the power supply unit, A biomolecule detecting unit for detecting a biomolecule according to a current that changes while the target molecule is fixed on the probe molecule by applying the microvoltage generated by the microvoltage generator; An A / D conversion unit for converting the current amplified by the amplifying unit into a digital signal and outputting the digital signal; and a control unit for controlling the A / D conversion unit And an MCU for receiving the digital signal converted through the unit and determining whether the biomolecule is reacted.

According to another aspect of the present invention, there is provided a biomolecule detection method comprising: preparing a FET for detecting biomolecules; fixing a probe molecule in a channel region of the FET; Applying a microvoltage to the FET; Fixing the target molecule on the probe molecule; Measuring a current flowing to a channel region where the probe terminal is fixed; Amplifying the measured current to a desired magnitude and outputting the magnitude; Converting the amplified current into a digital signal; And detecting biomolecules through the set program after receiving the converted digital signal.

The biomolecule detection apparatus and method according to the embodiments of the present invention have the following effects.

In other words, it is possible to detect the biomolecule directly on the site because it is portable, and the detection speed of the biomolecule can be improved by using the microcurrent.

1 is a cross-sectional view schematically showing the structure of a conventional FET
2 is a schematic view showing a biomolecule detection apparatus according to the present invention
3 is a block diagram showing the micro-voltage generator of FIG. 2 in more detail;
FIG. 4 is a view showing more specifically the biomolecule detecting unit of FIG. 2
5 is a flowchart showing a biomolecule detection method according to the present invention

BRIEF DESCRIPTION OF THE DRAWINGS The advantages and features of the present invention, and how to accomplish them, will become apparent by reference to the embodiments described in detail below with reference to the accompanying drawings. The present invention may, however, be embodied in many different forms and should not be construed as being limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the concept of the invention to those skilled in the art. Is provided to fully convey the scope of the invention to those skilled in the art, and the invention is only defined by the scope of the claims. Like reference numerals refer to like elements throughout the specification.

The terminology used herein is for the purpose of illustrating embodiments and is not intended to be limiting of the present invention. In the present specification, the singular form includes plural forms unless otherwise specified in the specification. As used herein, the terms 'comprises' and / or 'comprising' mean that the stated element, step, operation and / or element does not imply the presence of one or more other elements, steps, operations and / Or additions. Also, in this specification, when it is mentioned that a film is on another film or substrate, it means that it may be formed directly on another film or substrate, or a third film may be interposed therebetween.

FIG. 2 is a schematic view of a biomolecule detection apparatus according to the present invention, and FIG. 3 is a configuration diagram showing the microvoltage generator of FIG. 2 in more detail.

As shown in FIG. 2, the biomolecule detecting apparatus 100 according to the present invention includes a power supply unit 110 for supplying necessary voltages and currents, a power supply unit 110 for receiving voltage and current from the power supply unit 110, A microvoltage generation unit 120 for generating and outputting a voltage; and a microvoltage generation unit 120 for applying a microvoltage to detect a biomolecule according to a current that changes in a state where target molecules are fixed on the probe molecule A current detection unit 140 for detecting a current output from the biomolecule detection unit 130 and an amplification unit 130 for receiving and amplifying the current detected by the current detection unit 140 An A / D converter 160 for converting the current amplified by the amplifier 150 into a digital signal and outputting the converted digital signal; M for determining the presence or absence of the biomolecule And a display unit 180 for displaying the presence or absence of a reaction or the current value with respect to the presence or absence of the reaction of the biomolecules in the MCU 170.

Here, the power supply unit 110 may use a rechargeable battery of 7.4 V, but the capacity of the rechargeable battery does not need to be limited to 7.4 V and is for explaining the embodiment of the present invention. Therefore, Can be used.

As shown in FIG. 3, the micro-voltage generating unit 120 includes a filter unit 121 receiving noise from a power source supplied from the power supply unit 110, A noise removing unit 123 for removing a noise included in a voltage dropped from the lower portion 122 of the first voltage river 122, A voltage controller 125 for receiving a voltage from which the noise is removed from the voltage regulator 123 and controlling the voltage, a second voltage lower portion 124 for receiving the voltage of the first voltage lower portion 122, ).

For example, when a power of 7.4V is supplied from the power supply unit 110, the voltage is lowered to 5V from the first voltage lower portion 122 and to 3.3V from the second voltage lower portion 124, And a microvoltage lowered to 0.5 V is generated in the second transistor 125. At this time, it is also possible to provide a number of voltage drop portions greater than the first and second voltage drop portions 122 and 124. That is, it is possible to generate a desired microvoltage through repetition of a plurality of voltage drop and rectification operations to obtain a lower fine voltage.

Here, a voltage of 3.3 V lowered through the second voltage lower portion 124 is used as a power source for driving the display portion 180.

The voltage control unit 125 controls the biomolecule detection unit 130 (not shown) according to the operation of a control switch unit (not shown) that turns on / off the biomolecule detection apparatus 100 according to an embodiment of the present invention. As shown in Fig.

The noise eliminator 123 is used to supply a higher quality power to the analog circuit in a circuit that handles analog and digital signals together. In particular, the noise eliminator 123 outputs the output voltage of the first voltage lower portion 122 through a low- So that a good quality power can be supplied to the analog circuit.

The biomolecule detector 130 includes FETs including source and drain electrodes, a channel region between the source and drain electrodes, and probe molecules fixed to the channel region.

The microvoltage generated by the microvoltage generator 120 is supplied to the biomolecule detector 130 through a protection circuit (not shown) formed of a buffer. Further, a protection circuit unit (not shown) made of a diode may be additionally provided between the microvoltage generator 120 and the biomolecule detector 130 to protect the power supply unit 110 from static electricity or external noise have.

The biomolecule detector 130 is a biosensor capable of detecting biomolecules according to a change in current flowing in a channel region. The biomolecule detector 130 has a probe molecule fixed to a channel region of the FET, and a target molecule That is, biomolecules or analytes), the current value changes due to the microvoltage applied in the channel region. At this time, body fluid or secretion of the biomolecule to be detected is dropped to the target molecule, and presence or absence of the biomolecule is detected according to the reaction with the target molecule.

In addition, the Debye length of the surface charge changes depending on the ionic strength of the solution provided in the channel region, that is, the concentration of the ions, so that the intensity of the current flowing in the channel region may vary.

When a biomolecule target molecule having the same DNA as the biomolecule to be detected is placed on the probe molecule of the biomolecule detection unit 130 and a microvoltage is applied and the biomolecule is dropped, the biomolecule detection unit 130 When reacting with DNA, microcurrent flows through the FET.

 On the other hand, a stabilization buffer solution for stabilizing the charges around the probe molecules can be supplied.

The biomolecule detection unit 130 can measure a current according to a current that changes depending on the biomolecule supplied to the channel region of the FET, and detects biomolecules by analyzing the measured current value.

The current detector 140 is disposed at the output terminal of the biomolecule detector 130. When the microvoltage generated by the microvoltage generator 120 is applied to the biomolecule detector 130, The current flows, and the current at this time is detected. In the meantime, although the current detection is described in the embodiment of the present invention, the voltage is detected and the detected voltage is used to calculate a current value by an operation programmed in the MCU 170 and display the current value through the display unit 180 It is possible.

The amplification unit 150 is composed of an operational amplifier. The current detected by the current detection unit 140 is small and is configured to amplify the current. However, the present invention is not limited to this configuration. For example, two amplifiers may be connected in series or three OP amplifiers may be serially configured to amplify the amplified signals to a desired size. It is possible.

The MCU 170 analyzes the digital signal corresponding to the current value of the current detector 140 inputted through the amplifier 150 to diagnose whether or not the biomolecule detected by the biomolecule detector 130 is reacted To the display unit (180).

Meanwhile, the MCU 170 automatically analyzes the current value of the current detector 140 inputted as a digital signal through a preset program.

The display unit 180 may be controlled by the MCU 170 and may be displayed by any one of numerals, graphs, and OX, so that the operator can visually identify whether biomolecules are detected more quickly. At this time, the display unit 180 may display red or blue according to presence or absence of biomolecule detection through one LED.

The biomolecule detecting apparatus 100 according to the present invention applies a minute voltage to the biomolecule detecting unit 130 to measure and amplify the current flowing through the target molecule on the probe terminal in response to the biomolecule, .

For example, in order to detect avian influenza, blood or feces collected in the field has conventionally been carried in a research room equipped with a separate analyzing device, which makes it impossible to perform a rapid inspection, thereby increasing the damage thereof , The present invention can directly detect the presence or absence of a biomolecule on the spot by dropping blood or excrement collected on the spot on a target molecule and detecting a current by applying microvoltage to the probe terminal.

In other words, since the present invention can detect avian influenza directly on the spot, it can prevent the second bird from being damaged by proceeding to block or prevent the attack of chicken, duck and wild bird contaminated with avian influenza virus infection more rapidly Can be prevented.

For this purpose, the present invention can prepare the target molecules provided on the probe terminals in advance and appropriately replace them if necessary, so that the biomolecules can be detected more quickly, and more convenient to carry.

FIG. 4 is a view showing the biomolecule detection unit of FIG. 2 in more detail.

As shown in FIG. 4, the biomolecule detection unit 130 includes FETs and probe molecules 132.

The FET includes an n-type or a p-type FET and includes a substrate 133, source and drain electrodes 135 and 136, and a channel region 137.

A bulk semiconductor substrate may be used as the substrate 133 on which the FET is formed, and an SOI (Silicon-On-Insulator) substrate may be used to reduce the leakage current of the FET and increase the driving current . As the substrate 133, an arbitrary substrate formed of an insulating material such as silicon oxide, titanium oxide, acrylic resin, epoxy resin, or polyimide may be used.

The source and drain electrodes 135 and 136 are spaced apart from each other at a predetermined interval on the substrate 133. A gate 134 is formed between the source and drain electrodes 135 and 136, A voltage may be applied to the drain electrode 136 and a channel region 137 may be formed between the source and drain electrodes 135 and 136.

The channel region 137 may be a doped layer doped with an impurity, or may include a semiconductor layer.

The doping layer may be a diffusion layer formed through impurity diffusion in a semiconductor substrate, an ion implantation layer formed through impurity ion implantation, or an epitaxial layer formed through epitaxial growth. The doping layer may have a conductive type complementary to the substrate 133. For example, when the conductivity type of the substrate 133 is n-type, the conductivity type is p-type.

The surface of the channel region 137 including the doping layer between the source and drain electrodes 135 and 136 may be surface-treated so that the probe molecules 132 may be fixed. That is, for example, a carboxyl group (-COOH), a thiol group (-SH), a hydroxyl group (-OH), a silane group, an amine group or an epoxy group may be induced on the surface of the surface-treated doping layer.

The channel region 137 between the source and drain electrodes 135 and 136 is formed of a doping layer and a gate electrode is formed on the semiconductor substrate 134 between the source and drain electrodes 135 and 136 It is possible. The source and drain electrodes 135 and 136 may be a doped region doped with an impurity in the semiconductor substrate 134.

On the channel region 137, probe molecules 132 for detecting biomolecules (i.e., target molecules) are fixed. The probe molecules 132 can be immobilized on the channel region 137 surface of the FET using the organic molecules either directly in the channel region 137 or as intermediate carrier molecules. The probe molecules 132 may be proteins, cells, viruses, or nucleic acids depending on the biomolecules to be detected.

In the channel region 137 of the FET in which the probe molecules 132 are fixed, target molecules for reaction with body fluids or secretions collected for the detection of biomolecules are fixedly installed. The biomolecule may be a nucleic acid or a protein.

The nucleic acid refers to various nucleic acids, a pseudonucleic acid, or a hybrid thereof, and may be selected from the group consisting of DNA, RNA, PNA (peptide nucleic acid), LNA (Locked Nucleic Acid), and hybrids thereof. In addition, the nucleic acid may be an oligonucleotide or a PCR product, but is preferably a PCR product or a purified product thereof.

The protein may be selected from the group consisting of, for example, an enzyme, a substrate, an antigen, an antibody, a ligand, an aptamer, and a receptor.

The Debye length of the surface charge changes depending on the reaction between the target molecule and the biomolecules loaded on the probe molecule 132, and the intensity of the current flowing in the channel region may be changed.

5 is a flowchart showing a biomolecule detection method according to the present invention.

In the biomolecule detection method according to the present invention, as shown in FIG. 5, a FET for detecting biomolecules is prepared, and a probe molecule is fixed to a channel region of the FET (S110). That is, the probe molecules can be fixed on the surface of the doping layer of the FET.

Here, the probe molecule immobilized in the channel region of the FET may be, for example, a protein, a nucleic acid, an organic molecule, or an inorganic molecule. In the case of a protein molecule, it may be an antigen, an antibody, a substrate protein, an enzyme, a coenzyme, or the like. And in the case of nucleic acids, DNA, RNA, PNA, LNA or their hybrid.

Subsequently, a microvoltage is applied to the FET (S120), and target molecules are fixed on the probe molecules (S130).

Here, a biomolecule to be detected, that is, a target molecule (or analytes) is included. The target molecule is a substance such as blood (serum or plasma), urine or saliva obtained from a living body.

Next, a current flowing to the channel region where the probe terminal is fixed is measured (S140), and the measured current is amplified to a desired size (S150).

Subsequently, the amplified current is converted into a digital signal (S160), and the biomolecule is detected through the set program by receiving the converted digital signal (S170).

 Therefore, the present invention can detect the biomolecules more quickly by measuring and amplifying the current flowing between the probe molecules in the channel region of the FET and the target molecule by applying a minute voltage.

While the present invention has been described in connection with what is presently considered to be practical exemplary embodiments, it is to be understood that the invention is not limited to the disclosed embodiments, but, on the contrary, It will be understood. It is therefore to be understood that the above-described embodiments are illustrative and not restrictive in every respect.

110: power supply unit 120:
130: biomolecule detector 140: current detector
150: amplification unit 160: A / D conversion unit
170: MCU 180:

Claims (10)

A power supply unit for supplying voltage and current,
A microvoltage generator for generating and outputting a microvoltage by receiving the voltage and current supplied from the power supply,
A biomolecule detecting unit for detecting a biomolecule according to an electric current that changes while the target molecule is fixed on the probe molecule by applying the microvoltage generated by the microvoltage generator,
A current detector for detecting a current output from the biomolecule detector,
An amplifier for receiving the current detected by the current detector, amplifying the current, and outputting the amplified current;
An A / D converter for converting the current amplified by the amplifier into a digital signal and outputting the digital signal;
And an MCU for receiving the digital signal converted by the A / D converter and determining whether the biomolecule is reacted. The biomolecule detection apparatus according to claim 1, further comprising a display unit for displaying a result transmitted through the MCU. The biomolecule detecting apparatus according to claim 1, wherein the biomolecule detecting unit comprises FET and probe molecules. The biomolecule detecting apparatus according to claim 3, wherein the channel region of the FET comprises any one of a doping layer doped with an impurity, a semiconductor layer, an oxide layer, a compound layer, a carbon nanotube (CNT), or a semiconductor nanowire. The biomolecule detection apparatus according to claim 1, wherein the amplification unit comprises at least one or more OP amplifiers. [2] The apparatus of claim 1, wherein the microvoltage generator comprises: a filter unit that receives power supplied from the power supply unit and suppresses noise; A noise suppression unit for removing noise included in a voltage lowered from the first voltage gradient, a voltage control unit for receiving a noise-removed voltage from the noise suppression unit and controlling the voltage, And a second voltage drop unit that receives the negative voltage and drops the voltage again. 7. The biomolecule detection apparatus of claim 6, wherein the noise removing unit removes noise from a circuit that handles the analog signal and the digital signal together to supply a good power source to the analog circuit. The biomolecule detection apparatus according to claim 1, wherein the probe molecule is composed of DNA, RNA, protein, cell, or chemical substance. Preparing a FET for detecting a biomolecule, and fixing the probe molecule in a channel region of the FET;
Applying a microvoltage to the FET;
Fixing the target molecule on the probe molecule;
Measuring a current flowing to a channel region where the probe terminal is fixed;
Amplifying the measured current to a desired magnitude and outputting the magnitude;
Converting the amplified current into a digital signal;
Detecting a biomolecule through a set program that receives the converted digital signal. 10. The biomolecule detection method according to claim 9, wherein the probe molecule is selected from the group consisting of DNA, RNA, protein, cell, and chemical substance.

Images