KR101198259B1 - Optical biosensor and method for detecting biological material using holey fiber - Google Patents

Abstract

An optical biosensor using a porous fiber includes a core region including germanium; A long period grating formed in said core region; And a cladding region arranged around the core region and including one or more holes configured to inject a biomaterial. In this case, the long period grating may be configured to convert a core mode optical signal having a resonance wavelength into a cladding mode optical signal. The optical biosensor using the porous optical fiber can be manufactured in a large amount because the manufacturing cost is low and the long period grating for the detection of the biomaterial is simple, and the diameter of the hole located in the cladding region can be increased to increase sensitivity.

Description

Optical biosensor and biomaterial detection method using porous optical fiber {OPTICAL BIOSENSOR AND METHOD FOR DETECTING BIOLOGICAL MATERIAL USING HOLEY FIBER}

Embodiments relate to an optical biosensor and a biomaterial detection method using a porous fiber.

A biosensor is a device that can selectively detect a substance to be analyzed by combining a biological receptor having a recognition function with a specific material with an electrical or optical transducer and converting a biological interaction and a recognition response into an electrical or optical signal. It is called. Since the biosensor can detect the presence or absence of a biomaterial and a change in concentration, the biosensor is applied to various fields such as medical care, environment, and food. Substances that can be detected by the biosensors include proteins such as DNA, antigens, antibodies, blood sugar, and chemicals.

Recently, a label-free method can be used to detect biomaterials simply and quickly without using fluorescent materials, rather than labeling biomaterials by measuring fluorescence after binding fluorescent materials to proteins. Research on free type of biosensor is being conducted. Among the label-free biosensors, research has been conducted to optically detect biomaterials such as biosensors in which long-period gratings are formed on side-polished fibers and biosensors in which long-period gratings are formed on photonic crystal fibers. It is becoming.

1 is a photograph showing a cross section of a conventional biosensor in which a long period grating is formed on a photonic crystal optical fiber.

Referring to FIG. 1, a biosensor having a long period grating formed on a photonic crystal fiber detects biomaterials using a plurality of air holes arranged in an array in a cladding region of the optical fiber and having a diameter of micrometers. . However, due to the nature of the photonic crystal optical fiber, the long-period grating cannot be easily and consistently produced by the ultraviolet (UV) irradiation method. In addition, although the number of air holes located in the cladding region is large, the size of the air holes is remarkably small, which may limit the sensitivity.

2 is a schematic view showing a conventional biosensor in which a long period grating is formed on a side polished optical fiber.

Referring to FIG. 2, a biosensor in which a long period grating is formed on a side polished optical fiber, removes a coating from a part of the optical fiber 21 and places the removed part in a groove formed in the quartz block 22. After polishing the surface of the block 22 is formed by depositing a photoresist (23) in a lattice shape of a predetermined period (Λ) on the polished surface. However, this requires a difficult process of side polishing the optical fiber 21 close to the core portion, which is time-consuming and expensive due to the process of fabricating a lattice similar to the semiconductor process. In addition, since the curvature exists in the optical fiber 21 during the side polishing process of the optical fiber 21, the sensing unit that can actually detect the biomaterial in the biosensor is only about 1 cm in length, the sensitivity is limited. have.

According to an aspect of the present invention, it is possible to manufacture a long period grating by a simple process, the production cost is reduced, mass production is possible, optical biosensor and biomaterial detection method using a porous fiber with improved sensitivity Can be provided.

According to an embodiment, an optical biosensor includes: a core region including germanium; A long period grating formed in said core region; And a cladding region arranged around the core region and including one or more holes configured to inject a biomaterial. In this case, the long period grating may be configured to convert a core mode optical signal having a resonance wavelength into a cladding mode optical signal.

According to one or more exemplary embodiments, a biomaterial detection method includes: injecting a biomaterial into at least one hole located in a cladding region of an optical fiber; Injecting an optical signal into a core region of the optical fiber including germanium and having a long period lattice formed thereon; Converting a core mode optical signal having a resonance wavelength into a cladding mode optical signal using the long period grating; And measuring an optical signal passing through the core region.

An optical biosensor using a porous fiber according to an aspect of the present invention is less expensive to manufacture than a biosensor using a conventional photonic crystal optical fiber or a side polished single mode optical fiber, and has a long period for detecting biomaterials. The production of the grating is simple, there is an advantage that can be manufactured in large quantities. In addition, since the diameter of the hole located in the cladding region of the porous optical fiber is large, there is an advantage of increasing the sensitivity of the optical biosensor.

1 is a photograph showing a cross section of a conventional biosensor in which a long period grating is formed on a photonic crystal optical fiber.
2 is a schematic view showing a conventional biosensor in which a long period grating is formed on a side polished optical fiber.
3 is a perspective view of an optical biosensor according to an embodiment.
4 is a cross-sectional view of an optical biosensor according to an embodiment.
5 is a schematic diagram illustrating a process of injecting a substance into an optical biosensor according to one embodiment.
6A and 6B are photographs illustrating a cross section of an optical biosensor according to embodiments.
7A is a graph illustrating a change in transmission spectrum according to a material stacked in a hole of an optical biosensor according to an embodiment.
7B is a graph illustrating a change in peak wavelength according to a material stacked in a hole of an optical biosensor according to an embodiment.
8A is a graph illustrating a change in a transmission spectrum according to a change in refractive index of a hole in an optical biosensor according to an embodiment.
8B is a graph illustrating a change in peak wavelength according to a change in refractive index of a hole in an optical biosensor according to an embodiment.

Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings.

3 is a perspective view of an optical biosensor according to an embodiment.

Referring to FIG. 3, the optical biosensor 100 includes a core region 1, a long period grating 8 formed in the core region 1, and a cladding region 2 surrounding the core region 1. ) May be included. The core region 1 may include germanium (Ge). For example, the core region 1 may be a region in which germanium is added to glass or silica, which is a base material constituting the core region 1 and the cladding region 2. The cladding region 2 may comprise one or more holes 3 arranged around the core region 1. Each hole 3 may be formed through the cladding region 2 in the longitudinal direction. The core region 1 and the cladding region 2 configured as described above constitute a porous fiber.

The long period grating 8 may be formed in the core region 1. The long period grating 8 refers to a portion configured such that the refractive index of the material constituting the core region 1 changes at a constant period Λ. For example, the refractive index of the long period grating 8 may be in the form of repeating increase and decrease with the period Λ. In one embodiment, the long-period grating 8 periodically irradiates ultraviolet rays UV to the core region 1 including germanium, thereby increasing the refractive index in the irradiated portion of the core region 1. It can be formed using a phenomenon. When the long period grating 8 is formed by the ultraviolet irradiation method, the long period grating 8 can be formed by a relatively simple process, so that the manufacturing process and the cost can be reduced. The long period grating 8 may be formed to have a predetermined length L along the longitudinal direction of the core region 1.

The long period grating 8 may convert at least a portion of the core mode optical signal traveling in the core region 1 in the porous optical fiber to the cladding mode. In general, the optical signal propagating in the porous optical fiber is configured to propagate only in the core region 1 by total reflection, but when the long period grating 8 is formed in the core region 1, the period of the long period grating 8 The specific wavelength component of the optical signal determined according to Λ) is converted into the cladding mode optical signal. Specifically, the optical signal proceeds to the cladding region 2 without total reflection at the wavelength at which the optical signal satisfies the resonance condition determined by Equation 1 below. In this specification, the wavelength satisfying Equation 1 is referred to as the resonance wavelength. Refer.

In Equation 1, λ represents a resonant wavelength, and Λ represents a period of the long period grating 8. In addition, n _core represents the effective refractive index of the core region 1, n _clad represents the effective refractive index of the cladding region (2).

Therefore, when measuring the intensity of the optical signal transmitted through the core region (1) at the output terminal of the optical signal, the optical signal is not reflected at the resonant wavelength converted into the cladding mode by the long period grating 8, the transmittance is reduced, This appears as a loss in the transmission spectrum.

The resonant wavelength at which the optical signal is converted into the cladding mode in the long period grating 8 is determined based on the refractive index of the core region 1 and the refractive index of the cladding region 2 as well as the period Λ of the long period grating 8. . Inserting a particular biomaterial (not shown) into the hole 3 of the cladding region 2 allows the cladding region 2 to be compared with the case where the inside of the hole 3 is empty or filled with a predetermined buffer material. The effective refractive index of is changed. As a result, the resonant wavelength caused by the long period grating 8 is shifted due to the biomaterial. Accordingly, the presence, type, and / or amount of the biomaterial can be detected by measuring the change in the peak wavelength of the optical signal passing through the core region 1 in the cladding mode and showing a low transmittance.

4 is a cross-sectional view of an optical biosensor according to an embodiment.

Referring to FIG. 4, the cross-sectional diameter d ₁ of the core region 1 in the optical biosensor 100 may be about 8.7 μm. In addition, the cross-sectional diameter d ₂ of the one or more holes 3 formed in the cladding region 2 may be about 20 μm or more. The larger the cross-sectional diameter d ₂ of the hole 3 is, the better the sensitivity of the optical biosensor 100 is. In addition, the spacing d ₃ between the core region 1 and the one or more holes 3 may be about 15 μm or less. The smaller the distance d ₃ between the core region 1 and the hole 3, the better the sensitivity of the optical biosensor 100 is. Compared with the conventional biosensor using a photonic crystal optical fiber, the sensitivity of the optical biosensor 100 is large because the size of the hole 3 into which the biomaterial is injected is large and the hole 3 is located adjacent to the core region 1. Is improved.

However, the above-described numerical range is merely exemplary, and the size of the core region 1 and one or more holes 3, the distance between the core region 1 and the hole 3, and the like may be used to facilitate the injection and detection of the biomaterial. It can be appropriately changed by those skilled in the art, and is not limited to a specific configuration.

In one embodiment, the optical biosensor 100 may further include a Poly-L-Lysine (PLL) 4 located in one or more holes 3. When the cladding region 2 is made of a silica material, since the silica has a negative charge, the biomaterial to be detected may also not be easily injected into the hole 3 when the terminal has a negative charge. In this case, it is possible to increase the bond between the biomaterial and the inner surface of the hole 3 made of silica by inserting the PLL (4) having a positive charge at both ends.

Further, in one embodiment, the optical biosensor 100 may further comprise a probe material 5 located in one or more holes 3. The probe material 5 may be a material that specifically binds to the biomaterial to be detected. For example, when the biomaterial to be detected is a predetermined target DNA, the probe material 5 may be a probe DNA that complementarily binds to the target DNA. After the probe material 5 is injected, the biomaterial (eg, target DNA) 6 to be detected may be injected into one or more holes 3.

FIG. 5 is a schematic diagram illustrating a process for injecting the materials described above with reference to FIG. 4 into a hole of an optical biosensor.

Referring to FIG. 5, an optical biosensor 100 is inserted into a tube 11 of a syringe 9, and pressure is applied to the syringe 9 to inject the injection material 10 into one or more holes of the optical biosensor 100. (3) can be injected into. For example, the injection material 10 may be a buffer, a PLL, a probe material, and / or a target biomaterial. In this case, in order to allow the injection material 10 to sufficiently enter the hole 3, the end portion of the tube 11 into which the optical biosensor 100 is inserted may be sealed. For example, an end portion of the optical biosensor 100 and the tube 11 may be sealed using a material such as epoxy 12.

The process of manufacturing the structure as shown in FIG. 4 using the syringe 9 is as follows. First, pressure is applied to the syringe 9 to inject the PLL 4 into the hole 3 of the optical biosensor 100, and then a predetermined time until the PLL 4 adheres to the surface inside the hole 3. Can be preserved at room temperature for a while. Next, after the probe material 5 is injected into the hole 3 in the same manner, the probe material 5 can be stored at room temperature until the probe material 5 is bonded to the PLL 4. Finally, the target biomaterial 6 can be injected into the hole 3. In the above process, the PLL 4, the probe material 5, and the bio material 6 may all be stacked in a single layer.

In the above, the process of injecting the substance into the hole of the optical biosensor has been described with reference to the syringe. For example, a vacuum pump may be used to inject PLL, probe material, and / or target biomaterial, and the like into the hole.

6A and 6B are photographs illustrating a cross section of an optical biosensor according to embodiments. 6A and 6B, in the optical biosensor, the number of one or more holes 3 formed in the cladding region 2, the shape and size of each hole 3, the core region 1 and the hole 3 The spacing between) may vary depending on the embodiment. Therefore, it can be appropriately changed by those skilled in the art to facilitate the injection and detection of the biomaterial, and is not limited to the specific configuration.

7A is a schematic graph illustrating a change in transmission spectrum as a material is stacked in a hole in an optical biosensor according to an exemplary embodiment. In the present specification, the transmission spectrum refers to a result obtained by measuring the optical signal passing through the core region of the optical biosensor for each wavelength.

In FIG. 7A, a graph 710 shows a transmission spectrum when only a buffer material is injected into a hole of an optical biosensor, and a graph 720 shows a transmission spectrum when a PLL is injected into a hole. In addition, the graph 730 shows the transmission spectrum when the probe DNA is injected in addition to the PLL, and the graph 740 shows the transmission spectrum when the target DNA is injected in addition to the PLL and the probe DNA. Since PLL, probe DNA, and target DNA have inherent refractive indices, the refractive index of the hole increases as each material is stacked, and as a result, the wavelength of the optical signal converted into the cladding mode is shifted by the long period lattice. This corresponds to the peak wavelength having the smallest magnitude of transmittance in the transmission spectrum of FIG. 7A.

FIG. 7B is a schematic graph showing the shift of the peak wavelength according to each stacked material in the transmission spectrum shown in FIG. 7A. In FIG. 7B, the four wavelengths 715, 725, 735, and 745 correspond to peak wavelengths due to the long period grating in the transmission spectra 710, 720, 730, and 740 shown in FIG. 7A, respectively. As shown, the peak wavelength due to the long period grating shifts as the material is deposited in the holes of the optical biosensor. Thus, by measuring the peak wavelength in reverse, it is possible to detect the biomaterial injected into the hole.

8A is a graph illustrating a change in a transmission spectrum according to a change in refractive index of a hole in an optical biosensor according to an embodiment. In FIG. 8A, the four graphs 810, 820, 830, and 840 each show transmission normalized for each wavelength when the refractive index of the hole of the optical biosensor is about 1, about 1.33, about 1.36, and about 1.39. Spectral graph. At this time, a long period grating having a period (Λ) of about 344 μm and a total length (L) of about 3.5 cm was used as the long period grating formed in the core region. As shown, it can be seen that the peak wavelength of the transmission spectrum decreases as the refractive index of the hole increases.

FIG. 8B is a graph showing the shift of the peak wavelength according to the refractive index of the hole in the transmission spectrum shown in FIG. 8A. In FIG. 8B, the four wavelengths 815, 825, 835, and 845 correspond to peak wavelengths due to the long period grating in the transmission spectra 810, 820, 830, and 840 shown in FIG. 8A, respectively. As shown, it can be seen that as the refractive index of the hole increases, the peak wavelength due to the long period lattice decreases. Therefore, the refractive index of the hole can be measured from the change of the peak wavelength, and the biomaterial injected into the hole can be detected.

Although the present invention described above has been described with reference to the embodiments illustrated in the drawings, this is merely exemplary, and it will be understood by those skilled in the art that various modifications and variations may be made therefrom. However, such modifications should be considered to be within the technical protection scope of the present invention. Therefore, the true technical protection scope of the present invention will be defined by the technical spirit of the appended claims.

Claims (11)

A core region comprising germanium;
A long period grating formed in said core region;
A cladding region arranged around the core region and including one or more holes configured to inject biomaterial; And
Including poly-L-lysine located within the hole,
The long period grating is an optical biosensor using a porous optical fiber, characterized in that configured to convert a core mode optical signal of a resonant wavelength into a cladding mode optical signal.
The method of claim 1,
And the resonant wavelength is determined based on an effective refractive index of the one or more holes.
delete The method of claim 1,
Optical biosensor using a porous optical fiber, characterized in that it further comprises a probe material which is located in the hole and can be combined with a bio material.
The method of claim 1,
Optical biosensor using a porous optical fiber, characterized in that the cross-sectional diameter of the at least one hole is 20 ㎛ or more.
The method of claim 1,
An optical biosensor using a porous optical fiber, wherein an interval between the core region and the one or more holes is 15 μm or less.
Injecting the biomaterial into at least one hole located in the cladding region of the optical fiber;
Injecting an optical signal into a core region of the optical fiber including germanium and having a long period lattice formed thereon;
Converting a core mode optical signal having a resonance wavelength into a cladding mode optical signal using the long period grating; And
And measuring the optical signal passing through the core region.
8. The method of claim 7,
And the resonance wavelength is determined based on an effective refractive index of the one or more holes.
8. The method of claim 7,
And forming the long period grating by irradiating the core region with ultraviolet rays.
8. The method of claim 7,
Injecting the biomaterial into the one or more holes,
Injecting poly-L-lysine into the one or more holes;
Injecting probe material into the one or more holes; And
And injecting a biomaterial coupled to the probe material into the one or more holes.
8. The method of claim 7,
Injecting the biomaterial into the one or more holes is a biomaterial detection method using a porous optical fiber, characterized in that performed using a syringe or a vacuum pump.

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