KR20150106541A - Appratus for detecting drug and detecting method of drug using the apparatus - Google Patents

Appratus for detecting drug and detecting method of drug using the apparatus Download PDF

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Publication number
KR20150106541A
KR20150106541A KR1020140028730A KR20140028730A KR20150106541A KR 20150106541 A KR20150106541 A KR 20150106541A KR 1020140028730 A KR1020140028730 A KR 1020140028730A KR 20140028730 A KR20140028730 A KR 20140028730A KR 20150106541 A KR20150106541 A KR 20150106541A
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South Korea
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drug
white light
sensing chip
tio
storage space
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KR1020140028730A
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Korean (ko)
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최원열
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강릉원주대학교산학협력단
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Priority to KR1020140028730A priority Critical patent/KR20150106541A/en
Priority to PCT/KR2014/003186 priority patent/WO2015137555A1/en
Publication of KR20150106541A publication Critical patent/KR20150106541A/en

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
    • G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
    • G01N21/78—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator producing a change of colour

Abstract

A focusing lens for focusing the white light emitted from the white light source and collecting reflected light emitted from the sensor unit; and a light source for measuring a spectrum wavelength of the reflected light transmitted from the focusing lens, And a sensor unit provided below the focusing lens to emit the focused white light emitted from the focusing lens and emit the reflected light to the white light, wherein the sensor unit comprises a titanium substrate, A porous sensing chip provided on a part of the substrate and facing the storage space and having TiO 2 nanotubes formed thereon; a sidewall for forming a storage space for temporarily storing the liquid mixed with the drug, And a sensing chip And a discharge pipe for discharging the drug mixture liquid contained in the storage space. The drug detection device according to claim 1, And a drug detection method using the same. According to the present invention, the drug can be detected by an in-vitro experiment through optical interference biosensing.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a drug detection apparatus and a drug detection method using the drug detection apparatus.

The present invention relates to a drug detection apparatus and a drug detection method, and more particularly, to a drug detection apparatus capable of detecting a drug through an in-vitro experiment through optical interference biosensing and a drug detection method using the same will be.

Traditional drug delivery has been through oral or intravenous injections and has repeated the toxic level or less than the lowest effective dose because the drug concentration has risen beyond necessity. Repeated administration of these drugs presents the risk of causing adverse effects due to the toxicity of the drug to the patient.

The drug delivery system that incorporates nanotechnology is a method in which the drug attached to the surface of the nanoparticles reaches the target site in the form of nanoparticles and the drug is delivered to the target site. Thus, the drug positioned on the surface of the nanoparticles may be temporarily overdosed have. In addition, there is a problem in that a technique for controlling the amount of elution in nanoparticles is not secured, and a long-term stable drug administration can not be achieved.

Therefore, in consideration of the case of being injected into the body of an animal or human body through the drug delivery system, a drug detection apparatus and a drug detection apparatus capable of detecting the amount of drug elution in the body of an animal or human body as an in- A method is required.

Korean Patent Publication No. 10-2013-0043101

The present invention provides a drug detection apparatus and a drug detection method capable of detecting a drug through in-vitro experiments through optical interference biosensing.

A focusing lens for focusing the white light emitted from the white light source and collecting reflected light emitted from the sensor unit; and a light source for measuring a spectrum wavelength of the reflected light transmitted from the focusing lens, And a sensor unit provided below the focusing lens to emit the focused white light emitted from the focusing lens and emit the reflected light to the white light, wherein the sensor unit comprises a titanium substrate, A porous sensing chip provided on a part of the substrate and facing the storage space and having TiO 2 nanotubes formed thereon; a sidewall for forming a storage space for temporarily storing the liquid mixed with the drug, And a sensing chip And a discharge pipe for discharging the drug mixture liquid contained in the storage space. The drug detection device according to claim 1, wherein the drug detection device further comprises: to provide.

The drug may be selected from the group consisting of contrast agents including fluorescent particles or magnetic particles, chlorhexidine, tetracycline, minocycline (minocycline), doxorubicin, paclitaxel, camptothecin, cholorimus, rapamycin, thioctic acid, Lt; / RTI >

The light-transmitting substrate may be a glass or acrylic transparent substrate, and the spectrometer may be a CCD (charged coupled device) spectrometer.

The TiO 2 nanotubes may have a length in a direction parallel to the direction in which the focused white light is incident on the sensing chip, and the inner diameter of the TiO 2 nanotubes may have a size of 1 to 300 nm.

According to another aspect of the present invention, there is provided an optical pickup device comprising: a white light source for emitting white light; a focusing lens for focusing white light emitted from the white light source and collecting reflected light emitted from the sensor; A porous sensing chip provided on a part of the titanium substrate and facing the storage space, the porous sensing chip having TiO 2 nanotubes formed thereon; A light-transmitting substrate which is spaced apart from the sensing chip and which is provided in close contact with the upper portion of the side wall, and a liquid- An inlet pipe, and a discharge port for discharging the drug mixture liquid contained in the storage space The method comprising the steps of: preparing a sensor section including a discharge tube; introducing a drug-mixed liquid into the storage space through the inlet tube; emitting white light from the white light source; Focusing on the sensing chip through the focusing lens; collecting the reflected light, which is interfered after the white light is incident, by using the spectrometer; and fast Fourier transforming the collected reflected light, And detecting the drug by measuring the optical thickness exhibited by the drug.

The drug may be selected from the group consisting of contrast agents including fluorescent particles or magnetic particles, chlorhexidine, tetracycline, minocycline (minocycline), doxorubicin, paclitaxel, camptothecin, cholorimus, rapamycin, thioctic acid, Lt; / RTI >

The light-transmitting substrate may be a glass or acrylic transparent substrate, and the spectrometer may be a CCD (charged coupled device) spectrometer.

The TiO 2 nanotubes may have a length in a direction parallel to the direction in which the focused white light is incident on the sensing chip, and the inner diameter of the TiO 2 nanotubes may have a size of 1 to 300 nm.

According to the drug detection apparatus and the drug detection method of the present invention, the drug can be detected as an in-vitro experiment through optical interference biosensing.

1 is a schematic view of a drug detection device according to a preferred embodiment of the present invention.
FIGS. 2 and 3 are diagrams for explaining a method of forming a sensing chip on a titanium substrate.
4 is a schematic configuration diagram of an apparatus for performing an anodic oxidation method.
5 is a view showing a state in which deionized water (DI Water) is flowed into the storage space 130 through the inflow pipe 160 for one day and then mixed with bone morphogenetic protein-2 (BMP-2) And the effective optical thickness (EOT) over time while flowing the liquid.

Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the accompanying drawings. However, it should be understood that the following embodiments are provided so that those skilled in the art will be able to fully understand the present invention, and that various modifications may be made without departing from the scope of the present invention. It is not. Wherein like reference numerals refer to like elements throughout.

A drug detection apparatus according to a preferred embodiment of the present invention includes: a white light source for emitting white light; a focusing lens for focusing white light emitted from the white light source and collecting reflected light emitted from the sensor unit; And a sensor unit provided below the focusing lens and adapted to emit the focused white light emitted from the focusing lens and emit the reflected light to the white light, wherein the spectral sensor measures the intensity of the reflected light, The sensor unit includes a titanium substrate, a porous sensing chip provided in a partial region of the titanium substrate and facing the storage space, the TiO 2 nanotube being formed on the titanium substrate, A side wall for forming a storage space And a discharge tube for discharging the drug mixture liquid contained in the storage space, the discharge tube for discharging the drug mixture liquid contained in the storage space, the discharge tube for discharging the drug mixture liquid contained in the storage space, .

The drug may be selected from the group consisting of contrast agents including fluorescent particles or magnetic particles, chlorhexidine, tetracycline, minocycline (minocycline), doxorubicin, paclitaxel, camptothecin, cholorimus, rapamycin, thioctic acid, Lt; / RTI >

The light-transmitting substrate may be a glass or acrylic transparent substrate, and the spectrometer may be a CCD (charged coupled device) spectrometer.

The TiO 2 nanotubes may have a length in a direction parallel to the direction in which the focused white light is incident on the sensing chip, and the inner diameter of the TiO 2 nanotubes may have a size of 1 to 300 nm.

A drug detection method according to a preferred embodiment of the present invention includes: a white light source for emitting white light; a focusing lens for focusing white light emitted from the white light source and collecting reflected light emitted from the sensor unit; Preparing a spectrometer for measuring a change in intensity of a transmitted spectrum of the reflected light by measuring a spectral wavelength of the transmitted light, a porous sensing chip provided in a partial region of the titanium substrate and facing the storage space and formed of TiO 2 nanotubes, A sidewall for forming a storage space for temporarily storing the liquid mixed with the drug, provided on the titanium substrate, a transparent substrate spaced apart from the sensing chip and closely contacting the upper surface of the sidewall, An inlet pipe for introducing the drug-mixing liquid, The method comprising the steps of: preparing a sensor portion including a discharge tube for discharging a drug-mixing liquid contained in the drug solution; introducing a drug-mixed liquid into the storage space through the inlet tube; emitting white light from the white light source; Focusing the white light emitted from the white light source on the sensing chip through the focusing lens; collecting the reflected light interfered with after the white light is incident using the spectrometer; And detecting the drug by measuring the optical thickness represented by the drug in the sensing chip.

The drug may be selected from the group consisting of contrast agents including fluorescent particles or magnetic particles, chlorhexidine, tetracycline, minocycline (minocycline), doxorubicin, paclitaxel, camptothecin, cholorimus, rapamycin, thioctic acid, Lt; / RTI >

The light-transmitting substrate may be a glass or acrylic transparent substrate, and the spectrometer may be a CCD (charged coupled device) spectrometer.

The TiO 2 nanotubes may have a length in a direction parallel to the direction in which the focused white light is incident on the sensing chip, and the inner diameter of the TiO 2 nanotubes may have a size of 1 to 300 nm.

Hereinafter, a drug detection apparatus and a drug detection method using the same according to a preferred embodiment of the present invention will be described.

First, the drug detection device will be described in more detail. 1 is a schematic view of a drug detection device according to a preferred embodiment of the present invention.

Referring to FIG. 1, a drug detection apparatus according to a preferred embodiment of the present invention includes a white light source 10 for emitting white light, a white light source 10 for focusing the white light emitted from the white light source 10, A focusing lens 20 for collecting reflected light, a spectrometer 30 for measuring a change in intensity by measuring a spectral wavelength of the reflected light transmitted from the focusing lens 20, And a sensor unit 100 provided in the focusing lens 20 to receive the focused white light 60 and emit reflected light to the white light.

The sensor unit 100 includes a titanium substrate 110 and a porous sensing chip 120 provided on a portion of the titanium substrate 110 and facing the storage space 130 to form a TiO 2 nanotube. A side wall 140 formed on the titanium substrate 110 to form a storage space 130 for temporarily storing a liquid (drug-mixing liquid) mixed with the drug, and a side wall 140 spaced apart from the sensing chip 120 A light transmitting substrate 150 provided in close contact with an upper portion of the side wall 140, an inlet 160 for introducing a drug mixing liquid into the storage space 130, And an outlet 170 for discharging the water. The sensor unit 100 may further include a pedestal 180 for supporting the pedestal 180 and the titanium substrate 110 may be positioned on the pedestal 180.

The white light source 10 is a lamp that emits white light, and a tungsten lamp that emits white light.

The focusing lens 20 focuses the white light emitted from the white light source 10 and collects the reflected light 70 emitted from the sensor unit 100. The white light source 10 and the focusing lens 20 may be connected through a first cable 40 such as an optical fiber.

The spectrometer 30 measures the spectral wavelength of the reflected light transmitted from the focusing lens 20 and measures the change in intensity. The spectrometer 30 may be an example of a CCD (charged coupled device) spectrometer. The spectrometer 30 and the focusing lens 20 may be connected through a second cable 50 such as an optical fiber.

The sensing chip 120 is provided in a partial region of the titanium substrate 110 and has TiO 2 nanotubes formed therein to exhibit porosity. The sensing chip 120 is adjacent to the storage space 130 and the liquid flowing into the storage space 130 flows into the TiO 2 nanotube formed in the sensing chip 120. The sensing chip 120 is provided to face the light transmitting substrate 150 as a final point at which the focused white light emitted from the focusing lens 20 reaches. The TiO 2 nanotubes may have a length in a direction parallel to the direction in which the focused white light is incident on the sensing chip 120, and the inner diameter of the TiO 2 nanotubes is preferably 1 to 300 nm . A method of forming the sensing chip 120 will be described later.

The side wall 140 is provided on the titanium substrate 110 and forms a storage space 130 for temporarily storing the drug-mixing liquid. The side wall 140 serves to seal the liquid contained in the storage space 130 so as not to leak to the outside and may be made of a material such as silicone or rubber and may be made of a material that does not chemically react with a drug contained in the liquid There is no limitation in material.

The light-transmitting substrate 150 is spaced apart from the sensing chip 120 and is provided in close contact with the top of the side wall 140. The light-transmitting substrate 150 is made of a transparent material that can transmit white light, and may be made of glass, acrylic, or the like. The light-transmitting substrate 150 is provided to face the sensing chip 120 and is positioned below the focusing lens 20. [

The liquid may be a liquid containing a drug to be detected, for example, a drug may be mixed with deionized water, or a drug may be mixed with blood. Drug means a contrast agent including fluorescent particles or magnetic particles, chlorhexidine, tetracycline, minocycline (minocycline), doxorubicin, paclitaxel, camptothecin, sirolimus, rapamycin, thioctic acid, Forming agents, functional agents, functional ingredients, and the like. Examples of the bone growth factor include bone morphogenetic protein-2 (BMP-2). Examples of the functional ingredient include components constituting the body of a human or animal such as calcium (Ca), phosphorus (P), and magnesium (Mg). The detection device according to the preferred embodiment of the present invention may detect biomaterials such as bacteria and specific proteins in addition to the above-mentioned drugs. Examples of such biomaterials include E. coli, food poisoning bacteria such as O157: H7, and the like.

The inlet pipe 160 is a conduit or pipe for introducing liquid into the storage space 130. The drug-mixing liquid is introduced into the storage space 130 through the inlet pipe 160.

The discharge pipe 170 is a conduit or pipe for discharging the drug-mixing liquid contained in the storage space 130 to the outside. The liquid contained in the storage space 130 flows and is discharged to the outside through the discharge pipe 170.

Hereinafter, the drug detection method will be described in more detail.

A flow cell method is used to send the drug to the sensing chip 120 and a liquid such as distilled water or deionized water is used for a flow cell. The flow moves the drug toward the sensing chip 120 that is performing the actual optical interference biosensing. The drug-mixing liquid is prepared to flow through the storage space to detect the drug. Distilled water, blood, and the like into the storage space through the inflow pipe 160. The distilled water may be first flowed through the inlet pipe before introducing the drug-mixing liquid to flow out the impurities in the storage space to the outside. The drug mixed liquid flowing into the storage space 130 is partially introduced into the TiO 2 nanotubes formed in the sensing chip 120.

When the drug mixture liquid is contained in the storage space, the white light source 10 emits white light. The white light emitted from the white light source 10 is focused on the sensing chip 120 through the first cable 40 and the focusing lens 20. More specifically, the white light emitted from the white light source 10 flows into the focusing lens 20 through the first cable 40, and the focusing lens 20 focuses the white light emitted from the white light source 10 And the white light emitted from the focusing lens 20 is transmitted through the light transmitting substrate 150 and focused on the sensing chip 120. Part of the white light thus focused is transmitted through the surface of the sensing chip 120 and enters the sensing chip 120, and a part of the white light is reflected from the surface of the sensing chip 120. The drug mixture liquid is also present in the TiO 2 nanotubes of the sensing chip 120. In the white light, the reflected light reflected from the surface of the drug and the white light reflected from the bottom surface of the drug cause an interference phenomenon. The degree of interference is determined by the size and refractive index of the drug.

The reflected light coming out from the interference is collected using the spectrometer 30. The reflected light coming from the interference is transmitted to the spectrometer 30 through the focusing lens 20 and the second cable 50. The collected reflected light is subjected to fast Fourier transform to measure the optical thickness indicating the remaining amount of the drug. From this, it is possible to detect the drug.

And collects reflected light coming from the sensing chip 120 using the spectrometer 30. The collected reflected light is subjected to fast Fourier transform to measure the optical thickness exhibited by the drug in the sensing chip 120. The drug changes the optical thickness, from which it is possible to detect the drug.

The change in refractive index caused by the drug present in the sensing chip 120 is used to sense the drug. Fabry-parot interference reflections are used to measure refractive index changes.

It is preferable to focus the surface of the sensing chip 120 on which the focused white light is incident so as to be included in a circle having a diameter of 0.1 to 1 mm. At this time, the reflected light coming from the interference from the sensing chip 120 can be collected using a spectrometer (e.g., Ocean optics S-2000) 30.

Hereinafter, a method of measuring interference reflected light on the sensing chip 120 will be described. It is possible to measure the intensity variation according to the wavelength of the reflected light spectrum by using the spectrometer 30 in a state where the drug mixing liquid is not dispensed to the sensing chip 120, It is possible to measure the change of the intensity according to the wavelength of the reflected light spectrum.

First, the interference phenomenon with the Fabry-Perot will be explained. When a mirror with a high reflectance is placed parallel to each other and light is incident on the mirror, the light transmitted through the mirror transmits some light on the surface of the parallel mirror, but most of the light repeats transmission and reflection. On the opposite side of the incidence direction, the number of reflections between the two mirrors is transmitted through the lower mirror, where each light exhibits interference as much as the path difference.

When the focused white light is incident on the sensing chip 120, an interference pattern related to the optical thickness appears due to the optical path difference between the upper end portion and the lower end portion.

The optical thickness refers to the distance between the upper end portion and the opposite lower end portion, that is, the length of the space in which the drug-mixing liquid is loaded in the sensing chip 120, as described above. At this time, if a drug is contained between the upper and lower ends, the thickness of the drug becomes the optical thickness.

Equation (1) shows the relationship between the refractive index (n) and the optical thickness (L).

[Equation 1]

m? = 2nL

Where m is the interference order,? Is the maximum interference wavelength obtained in the m-order, n is the index of refraction according to the sensing chip 120 and the drug, and L is the optical thickness of the drug.

The optical thickness L can be changed. The longer the optical thickness, the greater the number of fringes and changes the characteristics of the interference wavelength.

When the white light is irradiated onto the sensing chip 120, a reflection waveform in the form of a Fabry-Perot fringe appears due to the optical path difference between the upper end portion and the lower end portion of the sensing chip 120.

As the drug mixture liquid is administered, the reflected waveform of the Fabry-Perof fringe shape can confirm the intensity change of the white light and the shift of the reflection wavelength.

We attempt fast Fourier transformation (FFT) on the spectrum for the reflected wavelength in the form of a Fabry-Perof fringe for white light. Fast Fourier transform is an algorithm designed to reduce the number of operations when computing a discrete fourier transform based on Fourier transform. Fast Fourier transform is a function calculation method that converts the temporal flow sound information into frequency flow.

When a reflected light spectrum is subjected to a fast Fourier transform (FFT), a peak having a specific optical thickness can be obtained, and this optical thickness is referred to as an effective optical thickness. This effective optical thickness is shifted according to the change of the spectrum depending on the size and the refractive index of the drug contained in the sensing chip 120.

Hereinafter, a method of forming the sensing chip 120 on the titanium substrate 110 will be described.

2 and 3, a sensing chip 120 including TiO 2 nanotubes is formed on the titanium substrate 110 by anodic oxidation. When the anodic oxidation method described below is applied to the titanium substrate 110, TiO 2 nanotubes are formed, and the sensing chip 120 refers to a region where the TiO 2 nanotubes are formed.

A plurality of TiO 2 nanotubes longitudinally extending inward from the first surface 112 of the titanium substrate 110 are formed when the TiO 2 nanotubes are formed by the anodic oxidation method. TiO 2 nanotubes TiO 2 nano-forming the length of the inner direction there is to be formed yirumyeonseo a longitudinal direction perpendicular to the inner direction, perpendicular to the first surface 112 of the titanium substrate 110 against the exposed surface 112 A plurality of tubes are formed.

Hereinafter, a method of forming TiO 2 nanotubes by anodic oxidation will be described in more detail.

The titanium substrate 110 is immersed in a cleaning solution and is cleaned using an ultrasonic cleaning machine.

TiO 2 having a nanotube structure is formed on the cleaned titanium substrate 110. The nanotube structure of TiO 2 (TiO 2 nanotubes) can be formed by anodic oxidation. As the electrolytic solution used in the anodic oxidation method, an electrolyte solution in which fluorine (F) is added to sulfuric acid, orthophosphoric acid, oxalic acid, sodium sulfate, citric acid aqueous solution or a mixture thereof can be used. An organic electrolytic solution in which fluorine (F) is added to glycerol, ethylene glycol or a mixture thereof may also be used. The anodic oxidation method is carried out under the conditions of an applied voltage of 10 to 120 V and a temperature of 0 to 50 캜 in the electrolytic solution as described above. The diameter and length of the nanotubes can be controlled according to the electrolyte.

4 is a schematic configuration diagram of an apparatus for performing an anodic oxidation method.

Referring to FIG. 4, electrolyte, applied voltage, anodic oxidation time, temperature, and the like are important factors for anodization. The anodizing apparatus includes an electrochemical bath 210, an electrolyte 220, an anode 230, a cathode 240, a power supply 250, a magnetic stirrer 280 A magnet bar 290 for stirring, a chiller 285, a thermometer 295, and the like.

TiO 2 has an energy gap of 3.2 eV, is chemically and biologically stable and does not corrode well. TiO 2 exists in three forms: anatase phase, rutile phase and brookite phase, and TiO 2 on anatase phase is converted to rutile phase when treated at a high temperature of 1100 ° C. or higher. TiO 2 may be prepared to have an anatase phase in nanotube form using anodization according to a preferred embodiment of the present invention.

The anodic oxidation equipment includes an electrochemical bath 210, an anode 230 to which a positive voltage is applied and TiO 2 of a nanotube structure is formed, and an anode 230 to which electrons are supplied to the titanium (Ti) An electrolytic solution 220 contained in the electrolytic bath 210 and a power supply means 250 for supplying a voltage to the anode 230 and the cathode 240. The anode 230 and the cathode 240 are spaced apart from each other by a predetermined distance. The anode 230 uses a titanium substrate 110.

A titanium substrate 110 is prepared to form a nanotube structure of TiO 2, and the titanium substrate 110 is mounted on the anode 230. As the cathode 240, an acid-resistant metal such as platinum (Pt), tantalum (Ta), silver (Ag), or gold (Au) is used. The anode 230 is spaced apart from the cathode 240 so that it can be locked in the electrolyte 220. The anode 230 and the cathode 240 are connected to a power supply 250 for applying a voltage or a current. The voltage applied to the anode 230 is about 0V to 300V, and the voltage applied to the cathode 240 is about 0V to -300V. The voltage difference between the anode 230 and the cathode 240 is appropriately adjusted in consideration of the diameter of the formed nanotube, the length of the nanotube, and the like.

The electrolyzer 210 is provided with a chiller 285 for preventing an abrupt temperature rise due to an exothermic reaction during an anodizing process and for increasing the uniformity of electrolysis or chemical reaction on the entire metal film, A magnetic stirrer 280 and a stirrer magnetic bar 290 are provided to facilitate the anodizing process with stirring. In addition, although not shown, a temperature regulating device such as a hot plate for maintaining the temperature in the electrolytic bath at a constant level may be provided.

Electrolyte 220 facilitates the transfer of charged electrons and ions to form TiO 2 on the surface of titanium (Ti) metal. The titanium metal ion (Ti 4 + ) is dissolved in the electrolyte solution 220 at the interface between the electrolyte solution 220 and the TiO 2 , and the electrolyte solution 220 is dissolved in the O 2 solution to form TiO 2 at the interface between the TiO 2 and the titanium substrate 110. - , and OH - ions.

In the anodic oxidation process, water molecules (H 2 O) in the electrolyte (220) are electrolytically decomposed into hydrogen ions (H + ) and hydroxyl group ions (OH - ) as shown in the following reaction formula (1).

[Reaction Scheme 1]

H 2 O → H + + OH -

The hydrogen ion H + moves toward the cathode 240 and is coupled with electrons between the surface of the electrolyte 220 and the surface of the cathode 240 to be released as hydrogen gas H 2 .

The hydroxyl group ion (OH - ) migrates toward the anode 230 and is separated into oxygen ions (O 2 - ) and hydrogen ions (H + ) in the natural oxide film formed on the surface of the anode 230 (titanium substrate). At this time, the separated oxygen ion (O 2 - ) penetrates the natural oxide film and reacts with the titanium ion (Ti 4 + ) between the natural oxide film and the titanium to form TiO 2 as shown in the following reaction formula 2.

[Reaction Scheme 2]

Ti 4 + + 2O 2 - > TiO 2

Also, the hydrogen ion (H + ) reacts with TiO 2 to partially break the bond between titanium (Ti) and oxygen to form a hydroxide, which is dissolved in the electrolyte solution 220. That is, oxide etching occurs on the surface between the TiO 2 and the electrolyte solution 220. TiO 2 is formed at the interface between the natural oxide film and the titanium (Ti) film, and TiO 2 is etched at the interface between the TiO 2 and the electrolyte 220 to form a nanotube-type TiO 2 on the anatase. Although there is no accurate theory for the nanotube formation process, local overcurrent occurs in TiO 2. Oxide etching by the electrolyte is locally accelerated by the exothermic reaction caused by the overcurrent, and nanotubes are formed .

If this is expressed as a reaction formula, the following reaction formula 3 is obtained.

[Reaction Scheme 3]

Ti + 2H 2 O → TiO 2 + 4H + + 4e -

The water molecules in the electrolyte solution meet with the Ti metal at the anode and TiO 2 is formed as shown in Equation 3.

The TiO 2 thus formed is dissociated as shown in Scheme 4 by a small amount of fluorine ion (F - ) contained in the electrolyte solution.

[Reaction Scheme 4]

TiO 2 + 6F - + 4H + - [TiF 6 ] 2 - + 2H 2 O

This dissociation occurs across the entire TiO 2 and forms nano-sized nanotubes. Also, as the anodic oxidation time is increased, the oxidation reaction of Reaction Formula 3 and the dissociation reaction of Reaction Formula 4 occur at the same time, from which TiO 2 having nanotubes can be obtained. The inside diameter of the nanotube is 1 to 300 nm in diameter.

The thickness of the TiO 2 (corresponding to the length of the nanotube) is determined according to the following equation (1) by the voltage U a supplied from the power supply 250 and the electric field intensity E a of the oxide film : do.

[Equation 1]

d ox = U a / E a = K a · U a

Here, K a is an anodic oxidation constant.

In the case of forming the nanotube structure of TiO 2 , the diameter of the nanotube, the length of the nanotube can be controlled by suitably controlling the concentration of the electrolyte, the intensity of the applied voltage, the processing time, and the temperature of the electrolytic bath.

When using an anode oxidation to form a TiO 2 nano-tube structure, it is possible to heat treatment in order to crystallize the TiO 2 of the nanotube structure. Specifically, the nanotube-structured TiO 2 is heated at a rate of 2 to 5 ° C per minute in an air atmosphere, heat-treated at 350 to 550 ° C for 10 minutes to 6 hours, and then naturally cooled.

As described above, there is an advantage that the specific surface area of the sensing chip 120 can be maximized by forming the nanotube by the anodic oxidation process on the flat titanium substrate 110.

5 is a view showing a state in which deionized water (DI Water) is flowed into the storage space 130 through the inflow pipe 160 for one day and then mixed with bone morphogenetic protein-2 (BMP-2) And the effective optical thickness (EOT) over time while flowing the liquid.

5, white light is emitted from a white light source 10, white light emitted from a white light source 10 is focused on a sensing chip 120 through a focusing lens 20, And the optical thickness of the BMP-2 in the sensing chip 120 is measured by fast Fourier transforming the collected reflected light. The optical thickness difference? OT was about 120 nm.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed exemplary embodiments, This is possible.

10: source of white light 20: focusing lens
30: Spectrometer 40: First cable
50: second cable 60: focused white light
70: reflected light 100: sensor part
110: titanium (Ti) substrate 120: sensing chip
130: storage space 140: side wall
150: light-transmitting substrate 160: inlet pipe
170: discharge pipe 180: pedestal
210: electrolytic cell 220: electrolytic solution
230: anode 240: cathode
250: power supply means 280: magnetic stirrer
285: Cooling unit 290: Magnet bar for stirring
295: Thermometer

Claims (8)

A white light source for emitting white light;
A focusing lens for focusing the white light emitted from the white light source and collecting reflected light emitted from the sensor part;
A spectrometer for measuring a spectral wavelength of the reflected light transmitted from the focusing lens to measure a change in intensity; And
And a sensor unit provided below the focusing lens to emit the focused white light emitted from the focusing lens and emit the reflected light to the white light,
The sensor unit includes a titanium substrate;
A porous sensing chip provided in a part of the titanium substrate and facing the storage space and formed of TiO 2 nanotubes;
A side wall provided on the titanium substrate to form a storage space for temporarily storing liquid mixed with the drug;
A light-transmitting substrate spaced apart from the sensing chip and closely contacting the upper surface of the sidewall;
An inlet pipe for introducing the drug-mixing liquid into the storage space; And
And a discharge pipe for discharging the drug-mixing liquid contained in the storage space.
The method according to claim 1, wherein the drug is selected from the group consisting of contrast agents including fluorescent particles or magnetic particles, chlorhexidine, tetracycline, minocycline (minocycline), doxorubicin, paclitaxel, camptothecin, sirolimus, rapamycin, And a periodontal ligament forming factor.
The light-emitting device according to claim 1, wherein the light-transmitting substrate is made of a glass or acrylic transparent substrate,
Wherein the spectrometer comprises a charged coupled device (CCD) spectrometer.
The method of claim 1, wherein the TiO 2 nanotubes have lengths in a direction parallel to a direction in which focused white light is incident on the sensing chip,
Wherein the inner diameters of the TiO 2 nanotubes have a size of 1 to 300 nm.
A focusing lens for focusing the white light emitted from the white light source and collecting the reflected light emitted from the sensor unit; and a condenser lens for measuring the spectral wavelength of the reflected light transmitted from the focusing lens, Preparing a spectrometer for measurement;
A porous sensing chip provided in a partial region of the titanium substrate and facing the storage space and having TiO 2 nanotubes formed thereon; and a liquid reservoir provided on the titanium substrate for forming a storage space for temporarily storing the liquid mixed with the drug A light-transmitting substrate spaced apart from the sensing chip and closely contacted with the upper portion of the side wall, an inlet pipe for introducing the drug-mixing liquid into the storage space, an outlet pipe for discharging the drug- Preparing a sensor unit including the sensor unit;
Introducing a drug-mixed liquid into the storage space through the inlet tube;
Emitting white light from the white light source and focusing the white light emitted from the white light source onto the sensing chip through the focusing lens;
Collecting reflected light that is interfered with after the white light is incident using the spectrometer; And
And detecting the drug by measuring the thickness of the optical light reflected by the drug in the sensing chip by performing a fast Fourier transform on the collected reflected light.
6. The method of claim 5, wherein the drug is selected from the group consisting of a contrast agent comprising fluorescent particles or magnetic particles, chlorhexidine, tetracycline, minocycline (minocycline), doxorubicin, paclitaxel, camptothecin, sirolimus, rapamycin, A periodontal ligament forming factor.
6. The light-emitting device according to claim 5, wherein the light-transmitting substrate is a glass or acrylic transparent substrate,
Wherein the spectrometer uses a charged coupled device (CCD) spectrometer.
The method of claim 5, wherein the TiO 2 nanotubes have lengths in a direction parallel to the direction in which the focused white light is incident on the sensing chip,
Wherein the inner diameter of the TiO 2 nanotube has a size of 1 to 300 nm.
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EP2604344A3 (en) * 2007-03-28 2014-07-16 BioNano Genomics, Inc. Methods of macromolecular analysis using nanochannel arrays
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KR101105328B1 (en) * 2009-11-23 2012-01-16 한국표준과학연구원 Apparatus and method for quantifying the binding and dissociation kinetics of molecular interactions

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WO2019198859A1 (en) * 2018-04-10 2019-10-17 강릉원주대학교산학협력단 Optical sensor enabling real-time analysis of organic solvent and method for analyzing organic solvent in real time
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