Semiconductor oxide film ellipse amplitude sensor device and measurement method
By achieving p- and s-type reflection conditions on the semiconductor oxide film, combining microflower structure and polarization detection technology, the problem of insufficient sensitivity in traditional technology when measuring small molecule biological materials is solved, and high sensitivity elliptical measurement is achieved, which improves the accuracy and reliability of the measurement.
Patent Information
- Application Number
- JP2024555008
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2023-01-05
- Filing Date
- 2023-09-20
- Publication Date
- 2025-04-16
- Estimated Expiration
- Not applicable · inactive patent
AI Technical Summary
The prior art has insufficient measurement sensitivity when measuring small-molecular biological materials, resulting in unreliable results. In addition, traditional SPR sensors have errors and stability problems when measuring low-molecular weight substances.
Using semiconductor oxide film elliptical amplitude sensor equipment and measurement methods, the p- and s-type reflection conditions are realized on the semiconductor oxide film, and the interaction between biological materials and substrate is measured using microflower structure and polarization detection technology to obtain a highly sensitive elliptical measurement signal.
It is realized that high sensitivity elliptical measurement signals are obtained without the use of rotary analyzers or polarization modulators, avoiding the use of complex driving equipment, and improving the accuracy and reliability of measurements.
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Figure 2025511540000001_ABST
Abstract
Description
[Technical field]
[0001] The present invention relates to a semiconductor oxide film ellipse amplitude sensor device and a measurement method, and more particularly to a semiconductor oxide film that satisfies p-wave and s-wave non-reflection conditions, and a semiconductor oxide film ellipse amplitude sensor device and measurement method for simply obtaining a highly sensitive ellipse measurement signal by measuring only the p-wave and s-wave reflectance without using a rotating analyzer or a polarization modulation device that requires a complex driving device. [Background technology]
[0002] Reflectometry and ellipsometry are optical analysis techniques that measure the change in reflectance or polarization state of light reflected from a sample surface and analyze the measured values to determine the thickness and optical properties of a sample.
[0003] Measurement equipment that utilizes this technology includes reflectometers and ellipsometers. These are used to evaluate various nano-level thin film thicknesses and physical properties in the nano-thin film manufacturing process in the semiconductor industry. In addition, efforts are ongoing to expand the scope of use to the bioindustry and apply them to interface analysis of biological materials such as proteins, DNA, viruses, and new drug substances.
[0004] Conventional reflectometers are sufficient for evaluating the thickness and physical properties of nano-thin films with sizes of several nanometers (nm) or more, but when analyzing low molecular weight biomaterials that require sensitivity in the range of about 1 to 0.001 nanometers, there is a problem that reliability decreases due to low measurement sensitivity. Compared to reflectometers, ellipsometers have a measurement sensitivity of 0.01 nm or less, and are particularly sensitive under conditions of high refractive index contrast, such as measuring the thickness of an oxide film that has a relatively low refractive index compared to a semiconductor on a semiconductor substrate with a high refractive index.
[0005] However, in the case of the elliptical measuring device, a measurement method with improved sensitivity is required to analyze even low molecular weight biomaterials.
[0006] When analyzing biological materials, a conventional technique for improving measurement sensitivity is a surface plasmon resonance sensor (hereinafter referred to as an "SPR sensor") that combines reflectometry and surface plasmon resonance (SPR) techniques.
[0007] Surface plasmon resonance (SPR) is a phenomenon in which electrons on a metal surface are excited by light waves, causing collective vibration in the normal direction of the surface, and light energy is absorbed. SPR sensors are known to be able to measure the thickness and refractive index changes of nano-thin films in contact with metal surfaces using surface plasmon resonance, which is sensitive to the polarization characteristics of light, as well as to measure changes in the adsorption concentration of biomaterials in real time using a non-labeling method that does not use fluorescent substances.
[0008] The SPR sensor is structured by applying a thin metal film of several tens of nanometers to a material such as glass, creating a sensor on which biological materials can be bonded, and utilizing the principle that the resonance angle changes when a sample dissolved in a buffer solution is bonded to the sensor, and the resonance angle is measured by measuring reflectance. When light is incident on the SPR sensor, the glass material becomes the incident medium, passes through the thin film layer to which the biological material is bonded, and finally the buffer solution corresponds to the substrate.
[0009] In this structure, the refractive index of the buffer solution, which corresponds to the substrate material, as well as the change in the biological thin film layer due to the binding of the sample to be measured, directly affects the shift in the resonance angle. Therefore, in order to measure only the pure binding dynamics, the refractive index of the buffer solution must be measured and corrected independently.
[0010] In order to correct the change in the refractive index of the buffer solution and prevent errors due to diffusion between the sample and the buffer solution, a precise valve device, an air injection device, and a method of using two or more channels with one channel as a reference channel for correction are used. However, it is difficult to distinguish between the SPR angle change due to the refractive index change of the buffer solution and the SPR angle change due to pure adsorption and dissociation characteristics, which can always act as a cause of measurement errors. Ultimately, due to the limitations of the measurement method described above, conventional SPR sensors have fundamental difficulties in measuring the adsorption and dissociation characteristics of substances with small molecular weights such as small molecules.
[0011] In addition, conventional SPR sensors use thin films of precious metals such as gold (Au) and silver (Ag) for surface plasmon resonance, which requires high manufacturing costs. Furthermore, thin metal films have uneven surface illuminance depending on the manufacturing process, significant deviation in refractive index, and unstable optical characteristics make quantitative measurement of biomaterials difficult, and there are problems including errors due to different sensitivity characteristics at different positions when compared relative to a reference channel.
[0012] To overcome the shortcomings of SPR sensors, a biomaterial-bonded sensor layer is created on a substrate material such as silicon, and the light passes through a buffer solution in a microchannel immersion environment. The amplitude and phase of the light reflected by the substrate material are measured by the ellipsometric method under p-polarized light non-reflecting conditions. The measured amplitude is not sensitive to the change in the refractive index of the buffer solution, but is sensitive to the dynamic bonding characteristics of the biomaterial. When measuring the bonding characteristics of a biomaterial adsorbed to a substrate material in a microchannel immersion environment, the buffer solution becomes the incident medium, as opposed to SPR measurement, and the light that passes through the biomaterial adsorption layer is reflected by the substrate material.
[0013] Under these measurement conditions, the ellipse measurement angle Ψ, which indicates the measured amplitude, is not sensitive to changes in the refractive index of the incident medium, which is the buffer solution, but is sensitive only to changes in the biological thin film and the substrate material. In the case of a substrate with a stable refractive index, such as silicon, the measured ellipse measurement angle Ψ gives a signal that is sensitive only to changes in the biological thin film.
[0014] When using a prism incidence structure as shown in Figure 1, the ellipse measurement angle Δ showing the image shows a signal sensitive only to the refractive index of the buffer solution, and the thickness of the biological thin film and the refractive index of the buffer solution can be measured simultaneously.
[0015] FIG. 1 is a cross-sectional view showing a sensor for measuring the bonding characteristics of biological materials according to a prior patent (hereinafter referred to as the "measurement sensor of the prior patent") (the measurement sensor of the prior patent is a device based on the technology disclosed in Patent Document 2, which is an invention applied for and registered by the applicant of the present invention).
[0016] As shown in Fig. 1, the prior patent's biomaterial bonding property sensor is roughly composed of a prism 10, a micro-channel structure 20, a polarized light generating unit 30, and a polarized light detecting unit 40. In this case, the micro-channel structure 20 of the prior patent's biomaterial bonding property sensor has an adsorption layer 53 placed on a substrate 51 or a dielectric thin film 52 to form an immersion micro-channel 21 environment. When a buffer solution 60 in which a biomaterial sample 1 is dissolved is injected into the micro-channel 210, the biomaterial is adsorbed by the ligand 2 material formed on the surface of the dielectric thin film 52 to form an adsorption layer 53 of a predetermined thickness.
[0017] The polarized incident light generated by the polarized light generating unit 30 is incident on the boundary surface between the buffer solution 60 and the substrate 51 through the incident surface 11 of the prism at an angle that generates a p-polarized light non-reflection condition. At this time, the reflected light reflected by the substrate 51 contains optical data related to the adsorption layer of the sample 1 and the refractive index of the buffer solution. That is, in the process in which the sample 1 is adsorbed and dissociated by the ligand 2, the binding and dissociation kinetics such as the adsorption concentration, the thickness or refractive index of the adsorption layer, and the refractive index of the buffer solution change, and the measured ellipse measurement angle changes accordingly. The reflected light containing the optical data is detected by the polarization detecting unit 40. At this time, the polarization detecting unit 40 can grasp the molecular adsorption and dissociation kinetics of the sample 1 and the refractive index of the buffer solution by measuring the change due to the polarization component of the reflected light, that is, the ellipse measurement angle.
[0018] 2 to 7 are graphs showing the change in ellipse measurement angles Ψ and △ due to the change in the film thickness under non-reflecting conditions for p-wave and s-wave in an environment where the medium is water and air. Here, the graphs in Fig. 2 to 7 are graphs obtained (measured or analyzed) using the measurement sensor of the prior patent.
[0019] In Fig. 2, the left vertical axis represents the ellipse measurement angle (Ψ in degrees) versus amplitude, the right vertical axis represents the ellipse measurement angle (△ in degrees) versus phase, and the horizontal axis represents the angle of incidence. In Fig. 3, the left vertical axis represents the amount of change in the ellipse measurement angle (Ψ) versus amplitude, the right vertical axis represents the amount of change in the ellipse measurement angle (△) versus phase, and the horizontal axis represents the angle of incidence.
[0020] In Fig. 4, the left vertical axis represents the ellipse measurement angle (Ψ in degrees) versus amplitude, the right vertical axis represents the ellipse measurement angle (△ in degrees) versus phase, and the horizontal axis represents the angle of incidence. In Fig. 5, the left vertical axis represents the amount of change in the ellipse measurement angle (Ψ) versus amplitude, the right vertical axis represents the amount of change in the ellipse measurement angle (△) versus phase, and the horizontal axis represents the angle of incidence.
[0021] In Fig. 6, the left vertical axis represents the ellipse measurement angle (Ψ in degrees) versus amplitude, the right vertical axis represents the ellipse measurement angle (△ in degrees) versus phase, and the horizontal axis represents the angle of incidence. In Fig. 7, the left vertical axis represents the amount of change in the ellipse measurement angle (Ψ) versus amplitude, the right vertical axis represents the amount of change in the ellipse measurement angle (△) versus phase, and the horizontal axis represents the angle of incidence.
[0022] Figures 2 and 3 show the change in ellipse measurement angle due to the change in thin film thickness under p-wave non-reflection conditions measured using the measurement sensor of the prior patent. Specifically, Figure 2 shows the change in Ψ and △ when the SiO2 thin film thickness changes from 3 to 6 nm on a silicon substrate under p-wave non-reflection conditions where the medium is water, and Figure 3 shows the change in Ψ and △ relative to a 3-6 nm thin film based on a 3 nm thick substrate.
[0023] In Figure 3, the change in the ellipse measurement amplitude angle Ψ is greatest at the p-wave non-reflection angle, and increases at a nearly constant rate with each 1 nm increase in thickness, while the change in the ellipse measurement phase angle △ is minimal at the p-wave non-reflection angle. In other words, at the p-wave non-reflection angle, the signal change due to the thin film thickness is concentrated at the ellipse measurement amplitude angle Ψ measured by the ellipse measurement device, and almost no change is shown in the ellipse measurement phase angle △.
[0024] FIG. 4 shows the change in Ψ and △ when the thickness of the SiO2 thin film on a silicon substrate is changed from 3 to 6 nm under p-wave non-reflection conditions with the medium being air, and FIG. 5 shows the relative change in Ψ and △ for a thin film of 3 to 6 nm with a substrate of 3 nm thickness as the reference.
[0025] In Figure 5, the change in the ellipse measurement amplitude angle Ψ is the largest at the angle of non-reflection of the p-wave, and it increases at a nearly constant rate with each 1 nm increase in thickness, and the change in the ellipse measurement phase angle △ is the smallest at the angle of non-reflection of the p-wave. As in Figures 2 and 3 where the medium is water, at the angle of non-reflection of the p-wave, the signal change due to the thin film thickness is concentrated at the ellipse measurement amplitude angle Ψ measured by the ellipse measurement device, and almost no change in the ellipse measurement phase angle △ is shown.
[0026] FIG. 6 shows the change in Ψ and △ when the thickness of the SiO2 thin film on a silicon substrate is changed from 98 to 95 nm under s-wave non-reflection conditions with the medium being air, and FIG. 7 shows the change in Ψ and △ relative to a thin film of 98 to 95 nm with a substrate of 98 nm thickness as the reference.
[0027] In Fig. 7, the change in the ellipse measurement amplitude angle Ψ is the largest at the angle of non-reflection of the s-wave, and it can be seen that it increases at a nearly constant magnitude with each 1 nm change in thickness, and the change in the ellipse measurement phase angle △ is the smallest at the angle of non-reflection of the s-wave. As in the cases of Figs. 2 to 5 where the medium is water, at the angle of non-reflection of the s-wave, the signal change due to the thin film thickness is concentrated at the ellipse measurement amplitude angle Ψ measured by the ellipse measurement device, and it can be seen that the change in the ellipse measurement phase angle △ is almost not shown.
[0028] The characteristics and limitations of the measurement sensor of the prior art will now be described with reference to Figures 8 to 11. In order to measure the ellipsometric angle, an ellipsometer must be used.
[0029] 8 and 9 are schematic diagrams and graphs relating to the measurement principle of a conventional rotational ellipsometer.
[0030] Specifically, FIG. 8 is a schematic diagram showing the measurement principle of a rotational ellipsometer equipped with a rotational polarizer 71 or analyzer 72 for reflected light, which is the most commonly used.
[0031] FIG. 9(a) is a graph relating to the case where the difference in light intensity between the p-wave and s-wave components of the light reflected by the sample becomes large, and FIG. 9(b) is a graph relating to the signal when the light intensity of the p-wave and s-wave components of the light reflected by the sample is close to the same circular polarization.
[0032] As can be seen from Figures 8 and 9, the linearity of optical signal measurement is very important to the measurement inaccuracy. When the light intensity of the p-wave and s-wave components of the light reflected by the sample is almost the same, close to circular polarization, the most ideal signal is obtained, and the greater the difference in light intensity between the p-wave and s-wave components, the greater the measurement inaccuracy. This is because when the difference between the minimum and maximum signals is large, it is difficult for all photodetectors to maintain linearity in the signal band of the photodetector being measured.
[0033] Theoretically, measurement conditions where the light intensity of p-wave and s-wave components is almost the same can be obtained when the ellipse measurement amplitude angle (Ψ) and the polarizer angle are the same, and this problem is solved by adjusting the polarizer angle. In the case of a semiconductor thin film, when measuring a thin film with a thickness of 10 nm to several hundred nm at an angle that is not p-wave non-reflecting, the amplitude angle (Ψ) value is large enough, so a sufficiently large polarizer angle of around 30 degrees is used. In the case of p-wave non-reflecting conditions, the larger the angle, the smaller the error in reflected light due to changes in the polarizer angle, and when the polarizer angle is 10 degrees or more, it shows an almost constant value, minimizing the error in measuring the reflectance of p-wave and s-wave.
[0034] FIG. 10 is a graph showing the results of measurement of a sample under p-wave non-reflection conditions using the measurement sensor of the prior patent, and FIG. 11 is a graph showing the results of measurement of a sample under s-wave non-reflection conditions using the measurement sensor of the prior patent.
[0035] 10 and 11, the left vertical axis indicates the p-wave reflectance, the right vertical axis indicates the s-wave reflectance, and the horizontal axis indicates the angle of incidence.
[0036] As can be seen from Figure 10, the measurement sensor of the prior patent allows high-sensitivity measurement under p-wave non-reflecting conditions, but the amplitude angle (Ψ) value is very small at about 1 to 5 degrees, and the reflectance of the p-wave is very low. However, the reflectance of the s-wave is very high at about 80%, so there is a possibility that the measurement error due to the difference in reflectance between the p-wave and s-wave may become large.
[0037] As can be seen from Figure 11, under s-wave non-reflection conditions, the reflectance of the s-wave is very low and the reflectance of the p-wave is very high at about 60%, so there is a possibility that the measurement error due to the difference in reflectance between the p-wave and s-wave may become large.
[0038] To overcome this, the polarizer angle is adjusted to a small angle that is almost p-polarization under p-polarization non-reflection conditions, and to an angle close to 90 degrees that is almost s-polarization under s-polarization non-reflection conditions. This can result in problems such as large measurement errors due to the polarizer angle even in response to minute changes such as vibration or optical axis alignment.
[0039] In order to obtain all of the ellipse measurement amplitude angle Ψ and phase angle △ under non-reflection conditions for the p-wave and s-wave, it is unavoidable to deal with the problem that measurement errors due to the polarizer angle become large even with minute changes such as vibration and optical axis alignment, as explained above.
[0040] However, as can be seen from Figs. 2 to 7, under the p-wave or s-wave non-reflection conditions, the signal change due to the thin film thickness is concentrated in the ellipse measurement amplitude angle Ψ, and the change in the ellipse measurement phase angle △ is hardly shown, so it is understood that only the amplitude value Ψ is required.
[0041] Under the non-reflecting condition of p-wave and s-wave, the information on the change of the film thickness can be effectively obtained only by the ellipsoid measurement amplitude angle (Ψ), which can be easily obtained from the p-wave and s-wave reflectance values proposed in this invention without any complicated driving device.
[0042] The ellipse measurement amplitude angle (Ψ) and phase angle (△) can be calculated from the ratio of the reflection coefficients rp and rs of the p-wave and s-wave as shown in the following formula. An ellipse measurement device must be used that can simultaneously measure the amplitude of the reflection coefficient and the phase changes δp and δs of the p-wave and s-wave after reflection.
[0043]
number
[0044] In order to measure the ellipsometric phase angle (△) in addition to the ellipsometric amplitude angle (Ψ), a complex driving device such as rotating a polarizer, analyzer, compensator, etc. or polarization modulation using a piezoelectric birefringence element must be used, which may make it difficult to use as a simple on-site inspection device.
[0045] However, if only the ellipse measurement amplitude angle (Ψ) is measured, it can be easily calculated from the ratio of the p-wave and s-wave reflectances Rp and Rs without using a complicated ellipse measurement device.
[0046]
number
[0047] [Patent Document 1] Republic of Korea Patent Publication No. 10-1105328 [Patent Document 2] Republic of Korea Patent Registration No. 10-1383652 Summary of the Invention [Problem to be solved by the invention]
[0048] In order to solve the above problems, the object of the present invention is to provide a semiconductor oxide film that satisfies the p-wave and s-wave non-reflection conditions, and a semiconductor oxide film ellipse amplitude sensor device and measurement method that can easily obtain a highly sensitive ellipse measurement signal by measuring only the p-wave and s-wave reflectance without using a rotating analyzer or a polarization modulator that requires a complicated driving device.
[0049] The technical problems that the present invention aims to achieve are not limited to those mentioned above, and other technical problems not mentioned will be clearly understood by those having ordinary skill in the art to which the present invention pertains from the following description. [Means for solving the problem]
[0050] In order to achieve the above-mentioned object, the present invention is configured to provide a microchannel structure including a support base, a dielectric thin film formed on a substrate formed on the support base, a lid having an entrance window and a reflection window on one side and the other side, respectively, provided on the support base, and a microchannel which is a channel formed by combining the lid and the support base; a sample injection unit which injects a buffer solution containing a biological material sample into the microchannel to form an adsorption layer of the sample on the dielectric thin film; a polarization generation unit which irradiates the adsorption layer with polarized incident light through the entrance window at an incident angle (θ) that satisfies a p-wave or s-wave non-reflection condition; and a polarization detection unit which separates and measures the reflected light reflected by the adsorption layer and passed through the reflection window in terms of p-wave and s-wave reflectances, and detects an ellipse measurement amplitude angle, the polarization detection unit comprising a polarization splitting unit which splits the reflected light into two polarized lights, and a light detection unit which detects each of the two lights to obtain predetermined optical data.
[0051] In an embodiment of the present invention, the polarization detection unit may further include a processor electrically connected to the optical detection unit for deriving a measurement value based on the optical data, and a detection compensator for delaying the phase of the polarization component of the reflected light.
[0052] In an embodiment of the present invention, the processor may measure only the reflectance ratio of the two beams, p-beam and s-beam, obtained by separating the reflected beam, to obtain an amplitude ellipsometric constant (Ψ) of ellipsometric measurement, thereby deriving the measurement values including the adsorption concentration, and adsorption and dissociation constants of the sample.
[0053] In an embodiment of the present invention, the light detection unit may include a p-wave detector for detecting a p-wave of the two light beams, and an s-wave detector for detecting an s-wave of the two light beams.
[0054] In an embodiment of the present invention, the polarization splitting unit may include a light splitter that splits the reflected light into two lights, and a coating layer that is formed by coating on a surface of the light splitter and polarizes the reflected light.
[0055] In an embodiment of the present invention, the polarization splitting unit may further include a cube formed by recessing the combination of the coating layer and the light splitter therein.
[0056] In an embodiment of the present invention, the polarization splitting unit may include a light splitter that splits the reflected light into two lights, a first split polarizer that is a polarizer that polarizes one of the two lights, and a second split polarizer that is a polarizer that polarizes the other of the two lights.
[0057] In an embodiment of the present invention, the polarized light generating unit may include a light source that irradiates a predetermined light, an incident polarizer that is a polarizer for generating polarized light, and an incident compensator that phase-delays the polarized component of the incident light.
[0058] In an embodiment of the present invention, the polarization generating unit may further include a collimating lens that provides parallel light to the incident polarizer, and a focusing lens that converges the parallel light that has passed through the polarizer to increase the amount of light of the incident light.
[0059] In an embodiment of the present invention, the incident light generated by the polarized light generating unit may be a linearly polarized light, a circularly polarized light, an elliptically polarized light, or a non-polarized light source.
[0060] In an embodiment of the present invention, the cover may include a plurality of partitions separating the internal space, thereby forming a plurality of microchannels.
[0061] In an embodiment of the present invention, the microchannel structure may include a plurality of dielectric thin films, and a plurality of different samples may be adsorbed on each of the plurality of dielectric thin films.
[0062] The present invention to achieve the above object includes a first step in which the sample injection unit injects a buffer solution containing the sample into the microchannel of the microchannel structure; a second step in which the sample flows into the microchannel and is adsorbed to the dielectric thin film to form the adsorption layer; a third step in which the polarized light generation unit polarizes a predetermined light and makes the light incident on the adsorption layer through the entrance window of the microchannel structure at an incident angle that satisfies a non-reflection condition for p-wave or s-wave; a fourth step in which the reflected light reflected by the adsorption layer passes through the reflection window and is incident on the polarization detection unit; and a fifth step in which the polarization detection unit measures only the reflectance ratio between the p-wave and the s-wave of the reflected light and calculates an amplitude ellipsometric constant (Ψ) of ellipsometry using the reflectance ratio between the p-wave and the s-wave.
[0063] In order to achieve the above object, the present invention provides a microchannel structure including a support base, a dielectric thin film formed on a substrate formed on the support base, a lid portion provided on the support base, and a microchannel that is a channel formed by combining the lid portion and the support base, a sample injection portion for injecting a buffer solution containing a biological material sample into the microchannel to form an adsorption layer of the sample on the dielectric thin film, a polarization generating portion for irradiating the adsorption layer with polarized incident light through the incident window at an incident angle (θ) that satisfies a p-wave or s-wave non-reflection condition, and a polarization detecting portion for separately measuring the reflected light reflected by the adsorption layer and passing through the reflection window in terms of p-wave and s-wave reflectances and detecting an ellipse measurement amplitude angle, wherein a plurality of adsorption layers are formed within one microchannel, the polarization generating portion irradiates each of the plurality of incident light beams onto each of the plurality of adsorption layers, and the polarization detecting portion detects each of the plurality of reflected light beams due to the plurality of incident light beams to obtain predetermined optical data.
[0064] In order to achieve the above object, the present invention provides a microchannel structure including a support base, a dielectric thin film formed on a substrate formed on the support base, a lid provided on the support base with an entrance window and a reflection window on one side and the other side, and a microchannel formed by combining the lid and the support base; a sample injection unit for injecting a buffer solution containing a biological material sample into the microchannel to form an adsorption layer of the sample on the dielectric thin film; a polarization generation unit for irradiating the adsorption layer with polarized incident light through the entrance window at an incident angle (θ) that satisfies a p-wave or s-wave non-reflection condition; and a polarization detection unit for separating and measuring the reflected light reflected by the adsorption layer and passing through the reflection window in terms of p-wave and s-wave reflectances, and detecting an ellipse measurement amplitude angle, the polarization detection unit including a polarization splitting unit for separating the reflected light into two polarized lights, and a light detection unit for detecting each of the two lights to obtain predetermined optical data, and the polarization generation unit including a light expander for expanding the irradiation area of the incident light. Effect of the Invention
[0065] The effect of the present invention having the above-mentioned configuration is that by applying the semiconductor oxide film ellipse amplitude sensor, it is possible to simply measure the ellipse amplitude with high sensitivity by measuring only the p-wave and s-wave reflectance of a semiconductor oxide film that satisfies the p-wave and s-wave non-reflection conditions and without using a rotating analyzer or a polarization modulation device that requires a complex driving device.
[0066] In addition, the present invention has an advantage that, in the conventional measurement method, under the p-wave non-reflection condition, the reflectance of the p-wave is very low and the reflectance of the s-wave is very high, and therefore, due to the principle of ellipse measurement in which the polarizer is rotated and the measurement is performed by the same photodetector, it is difficult for the photodetector to maintain linearity from a very low signal band to a very high signal band, and thus the measurement error may be large. However, the present invention can measure the p-wave and s-wave signals with high sensitivity in a certain signal band of each detector by each photodetector.
[0067] In particular, with the existing measurement method, a polarizer angle of 5 degrees or less was used, and there was a possibility that a measurement error due to the polarizer angle would occur even with a small polarizer angle due to minute changes such as vibration or optical axis alignment. However, by applying the semiconductor oxide film elliptical amplitude sensor, the reflectance of the p-wave and s-wave is measured with separate photodetectors, and stable measurement can be performed at a sufficiently large polarizer angle without errors due to changes in the polarizer angle.
[0068] In addition, the ellipse amplitude sensor device of the present invention is a small and simple sensor device for use in on-site diagnosis. In the existing measurement method, in order to measure the ellipse measurement angles Ψ and △, a complex driving device such as rotating a polarizer, analyzer, compensator, etc., or polarization modulation using a piezoelectric birefringence element must be used, which limits its use as a simple on-site diagnosis device. However, when the ellipse amplitude sensor device of the present invention is applied, there is no driving device for polarizer rotation or polarization modulation, and it can be used as a highly sensitive on-site diagnosis sensor device by only measuring the reflectance.
[0069] Furthermore, when using the elliptical amplitude sensor device of the present invention, highly sensitive measurement of biological binding substances is possible in a non-labeled manner in a liquid-immersed microchannel environment, and the device may be widely used in various industries such as the bio, medical, food, and environmental industries.
[0070] It is understood that the effects of the present invention are not limited to the effects described above, but include all effects that can be inferred from the configuration of the invention described in the detailed description of the present invention or the claims. [Brief description of the drawings]
[0071] [Figure 1] 1 is a cross-sectional view showing a sensor for measuring the bonding characteristics of biological materials according to a prior patent. [Diagram 2] 1 is a graph showing the change in the measured ellipse measurement angles Ψ and △ due to the change in the thin film thickness under non-reflecting conditions of p-wave and s-wave in an environment where the medium is water and air, using the measurement sensor of the prior patent. [Diagram 3] 1 is a graph showing the change in the measured ellipse measurement angles Ψ and △ due to the change in the thin film thickness under non-reflecting conditions of p-wave and s-wave in an environment in which the medium is water and air, using the measurement sensor of the prior patent. [Figure 4] 1 is a graph showing the change in the measured ellipse measurement angles Ψ and △ due to the change in the thin film thickness under non-reflecting conditions of p-wave and s-wave in an environment in which the medium is water and air, using the measurement sensor of the prior patent. [Diagram 5] 1 is a graph showing the change in the measured ellipse measurement angles Ψ and △ due to the change in the thin film thickness under non-reflecting conditions of p-wave and s-wave in an environment in which the medium is water and air, using the measurement sensor of the prior patent. [Figure 6] 1 is a graph showing the change in the measured ellipse measurement angles Ψ and △ due to the change in the thin film thickness under non-reflecting conditions of p-wave and s-wave in an environment in which the medium is water and air, using the measurement sensor of the prior patent. [Figure 7] 1 is a graph showing the change in the measured ellipse measurement angles Ψ and △ due to the change in the thin film thickness under non-reflecting conditions of p-wave and s-wave in an environment in which the medium is water and air, using the measurement sensor of the prior patent. [Figure 8] 1 is a schematic diagram showing the measurement principle of a conventional rotational ellipsometer and a graph related thereto; [Figure 9] 1 is a schematic diagram showing the measurement principle of a conventional rotational ellipsometer and a graph related thereto; [Figure 10] 1 is a graph showing a case where a measurement was performed on a sample under p-wave non-reflection conditions using the measurement sensor of the prior art. [Figure 11] 1 is a graph showing a case where a measurement was performed on a sample under s-wave non-reflection conditions using the measurement sensor of the prior patent. [Figure 12] 1 is a schematic diagram showing a configuration of an ellipse amplitude sensor device according to an embodiment of the present invention; [Figure 13] 1 is a perspective view of a microchannel structure and a cover according to an embodiment of the present invention; [Figure 14] 1 is a perspective view showing separation of a microchannel structure and a cover according to an embodiment of the present invention; [Figure 15]FIG. 1 is a schematic diagram showing a configuration of an elliptical amplitude sensor device according to an embodiment of the present invention. [Figure 16] 1 is a schematic diagram showing a configuration of an elliptical amplitude sensor device according to a first embodiment of the present invention. [Figure 17] FIG. 11 is a schematic diagram showing the configuration of an elliptical amplitude sensor device according to a second embodiment of the present invention. [Figure 18] FIG. 11 is a schematic diagram showing the configuration of an elliptical amplitude sensor device according to a third embodiment of the present invention. [Figure 19] FIG. 11 is a schematic diagram showing the configuration of an elliptical amplitude sensor device according to a fourth embodiment of the present invention. [Figure 20] FIG. 13 is a schematic diagram showing the configuration of an elliptical amplitude sensor device according to a fifth embodiment of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0072] A most preferred embodiment of the present invention
[0073] The present invention will be described below with reference to the accompanying drawings. However, the present invention may be implemented in various different forms and is not limited to the embodiments described below. In order to clearly describe the present invention in the drawings, parts that are not related to the description are omitted, and similar parts are designated by similar reference numerals throughout the specification.
[0074] Throughout the specification, when a part is said to be "connected (connected, in contact, bonded)" to another part, this includes not only the case where the part is "directly connected" to another part, but also the case where the part is "indirectly connected" to another part through another member in between. In addition, when a part is said to "include" a certain component, this does not mean that the other component is excluded, but that the part may further include the other component, unless otherwise specified.
[0075] The terms used in this specification are merely used to describe specific embodiments and are not intended to limit the present invention. A singular expression includes a plural expression unless otherwise clearly intended in the context. In this specification, the terms "include" or "have" are intended to specify the presence of a feature, number, step, operation, component, part, or combination thereof described in the specification, and do not preclude the presence or additional possibility of one or more other features, numbers, steps, operations, components, parts, or combinations thereof.
[0076] The present invention will now be described in detail with reference to the accompanying drawings.
[0077] FIG. 13 is an oblique view of the micro flow channel structure 100 and the lid portion 150 according to the first embodiment of the present invention, FIG. 14 is an oblique view showing the separation of the micro flow channel structure 100 and the lid portion 150 according to the first embodiment of the present invention, and FIG. 15 is a schematic diagram showing the configuration of the elliptical amplitude sensor device according to the first embodiment of the present invention.
[0078] As shown in Figs. 13 to 15, the ellipse amplitude sensor device of the present invention includes a support 110, a dielectric thin film 130 formed on a substrate 120 formed on the support 110, a cover 150 provided on the support 110 with an entrance window 151 and a reflection window 152 on one side and the other side, and a microchannel 160 formed by combining the cover 150 and the support 110, a sample injection unit 200 for injecting a buffer solution containing a biomaterial sample into the microchannel 160 to form an adsorption layer 140 of the sample on the dielectric thin film 130, a polarized light generating unit 300 for irradiating the polarized incident light through the entrance window 151 to the adsorption layer 140 at an incident angle (θ) that satisfies the p-wave or s-wave non-reflection condition, and a polarization detecting unit 400 for detecting an ellipse measurement amplitude angle by separating and measuring the reflected light reflected by the adsorption layer 140 and passing through the reflection window 152 in terms of p-wave and s-wave reflectance.
[0079] The present invention is for measuring the adsorption and dissociation kinetics of biological materials including small molecules using ellipsometry and reflectometry, and may have a structure in which a buffer solution containing a biological material sample (not shown) is injected into the microchannel structure 100 in the sample injection section 200.
[0080] The support 110 may have a rectangular plate shape and may have a groove 112 in which the substrate 120 and the dielectric thin film 130 are formed. The support 110 may have a plurality of inlet channels 161 on one side of the support 110 and a plurality of outlet channels 162 on the other side of the support 110.
[0081] Specifically, an inlet and an outlet channel 162 of the microchannel 160 are formed on one side and the other side of the groove portion 112, and each of the groove portion 112, the inlet channel 161, and the outlet channel 162 may be formed by a semiconductor etching process or an exposure process.
[0082] The substrate 120 may be formed in the groove 112 of the support 110 in the form of a rectangular plate, and may be made of at least one material selected from silicon, a dielectric material, and a semiconductor material. When the substrate 120 is made of silicon, silicon has the advantage of being inexpensive and providing constant and stable physical properties.
[0083] In addition, when a semiconductor or dielectric is used as the substrate 120, the semiconductor or dielectric has a large refractive index difference with the biomaterial, so that the measurement sensitivity can be relatively increased compared to silicon under p-wave or s-wave non-reflecting conditions. In addition, the substrate 120 may have a complex refractive index of about 3.8391+i0.018186 at 655 nm.
[0084] The dielectric thin film 130 formed on the substrate 120 may be composed of any one of a transparent semiconductor oxide film and a glass film. The dielectric thin film 520 may have a thickness of more than 0 to 10 mm. Here, the dielectric thin film 130 may be formed of a semiconductor oxide film or a glass film having a thickness that satisfies the p-wave or s-wave non-reflection condition, and may be formed to be transparent.
[0085] An example of the most easily obtainable dielectric thin film 130 is a silicon oxide film (SiO2) formed by naturally oxidizing silicon and growing it to a thickness of several nanometers. The refractive index of the silicon oxide film is approximately 1.456 at 655 nm, which is significantly different from the refractive index of the substrate 120 made of silicon, and can contribute to improving the measurement sensitivity of the present invention.
[0086] A glass film made of optical glass may be used as the dielectric thin film 130. The dielectric thin film 130 made of silicon, silicon oxide film or glass film can be manufactured to have a constant refractive index compared to a metal thin film such as gold or silver, and therefore has the advantage of being able to provide stable optical characteristics and reduce manufacturing costs.
[0087] The cover 150 is mounted on the support 110 and may have an incident window 151 and a reflective window 152 on one side and the other side, respectively. Each of the incident window 151 and the reflective window 152 may have a curved shape having a predetermined curvature or a flat shape.
[0088] Specifically, the incident window 151 and the reflective window 152 may be formed in the form of a curved plate having a certain curvature so that the incident light and the reflected light can be perpendicularly incident. The cover 150 may have a plurality of partitions 153 that separate the internal space, thereby forming a plurality of micro channels 160.
[0089] 14, a plurality of partition walls 153 may be provided to form a micro-scale fine channel 160. Although only the entrance window 151 and the reflection window 152 of the cover 150 may be made of a transparent material such as glass or a transparent synthetic resin material, for ease of manufacture, the entire cover 150 including the entrance window 151, the reflection window 152 and the partition walls 153 may be integrally formed using a molding method or the like.
[0090] On the other hand, examples of synthetic resin materials that may be used include acrylic resins such as PMMA (polymethyl methacrylate), and silicon-based materials such as polydimethylsiloxane (PDMS).
[0091] The microchannel 160 is a passage through which a buffer solution containing a sample flows in or out, and a plurality of microchannels 160 may be formed. That is, each space between the partitions 153 of the cover 150 communicates with an inlet channel 161 and an outlet channel 162 formed in the support 110, thereby forming a plurality of microchannels 160 in the microchannel structure 100. Here, the width of the microchannel 160 may have a microscale of 1 mm or less.
[0092] 12, the sample injection unit 200 may inject a buffer solution containing a sample of a low molecular weight biomaterial (not shown) into the inlet 161 of the micro channel 160. The sample injection unit has a structure for dissolving the sample in the buffer solution to a certain concentration, and may include a valve device (not shown) capable of injecting and blocking the buffer solution into the micro channel 160.
[0093] At this time, the sample injection unit may inject buffer solutions into the microchannels 160 of each channel with different sample concentrations or with time lags. Meanwhile, when the buffer solution is injected into the microchannels 160, a part of the sample (not shown) is adsorbed onto the dielectric thin film 130 to form an adsorption layer 140 of a predetermined thickness.
[0094] Here, the adsorption layer 140 may be a multi-layer film composed of various biomaterials including self-assembled monolayers that match the binding properties of various biomaterials, immobilization materials, and small molecules that bind to the immobilization materials.
[0095] In addition to using a buffer solution as the medium discharged from the sample injection unit 200, gas may be used as the medium of the microchannel 160 to measure biomarkers contained in the gas. Here, air may be used as the gas, but the gas is not limited thereto, and other gases may be used instead of air. In this case, air containing biomarkers may be injected into the microchannel 160 from the sample injection unit 200.
[0096] 14, the micro-channel structure 100 may include a plurality of dielectric thin films 130, and a plurality of samples different from each other may be adsorbed on each of the plurality of dielectric thin films 130. As a result, a plurality of adsorption layers 140 different from each other may be formed.
[0097] Specifically, the micro flow paths 160 may be formed separately in correspondence with each of the plurality of dielectric thin films 130, and a plurality of different samples may be input into each of the plurality of inflow paths 161, and a plurality of different adsorption layers 140 may be formed as each sample passes through each of the dielectric thin films 130.
[0098] In such a case, by forming multiple adsorption layers 140 in one micro-channel structure 100, optical data for multiple samples can be collected using one micro-channel structure 100, thereby improving the analytical efficiency of biological materials in the samples.
[0099] The polarized light generating unit 300 may serve to irradiate the adsorption layer 140 with polarized incident light through the incident window 151 of the microchannel structure 100. The polarized light generating unit 300 may include a light source 350 that irradiates a predetermined light, an incident polarizer 330 that is a polarizer for generating polarized light, and an incident compensator 320 that delays the phase of the polarized component of the incident light.
[0100] The polarized light generating unit 300 may further include a collimating lens 340 that provides parallel light to the incident polarizer 330, and a focusing lens 310 that converges the parallel light that has passed through the polarizer to increase the amount of incident light.
[0101] Here, a focusing lens 310 may be formed at a position closest to the micro-channel structure 100, and an incident compensator 320, an incident polarizer 330, a collimating lens 340 and a light source 350 may be arranged in sequence next to the focusing lens 310 in a direction away from the micro-channel structure 100.
[0102] The polarized incident light has p-polarized and s-polarized components, and in order to increase the signal-to-noise ratio, light close to p-polarized light may be incident. In this case, in the present invention, the incident light may be irradiated at an incident angle (θ) that satisfies the p-polarized non-reflection condition.
[0103] In the ellipsometric equation, the complex reflection coefficient ratio (ρ) is the reflection coefficient for s-polarized light (r s ) versus the reflection coefficient of p-polarized light (r p ), i.e., ρ=r p / r s The non-reflection condition for p-polarized light can be expressed as the reflection coefficient of p-polarized light (r p ) is close to 0, and the s-polarized light non-reflection condition is when the reflection coefficient (r s ) has a value close to 0. The p-polarized light non-reflection condition is similar to the surface plasmon resonance condition of a conventional SPR sensor, and is the condition under which the measurement sensitivity of the present invention is maximized.
[0104] The incident light generated by the polarized light generating unit 300 may be linearly polarized, circularly polarized, elliptically polarized, or unpolarized light source 350. The light source 350 may be any light source with good focusing efficiency, such as various lamps emitting monochromatic light or white light in the infrared, visible, or ultraviolet wavelength bands, light-emitting diodes (LEDs), semiconductor laser diodes (LDs) including solid-state, liquid-, and gas lasers, and laser diodes, and tungsten filament lamps. The light source 350 may also have a structure capable of varying the wavelength depending on the structure of the optical system.
[0105] On the other hand, near the above-mentioned non-reflecting condition of p-polarized light, the magnitude of the optical signal of the reflected light may be relatively small. In this case, by irradiating the sample with a high amount of light using a laser with coherence, the signal-to-noise ratio can be increased, enabling highly sensitive measurements.
[0106] The polarizer is provided with a polarizing plate and polarizes the light emitted from the light source 350. At this time, the polarized light components include a p-wave parallel to the incident plane and an s-wave perpendicular to the incident plane.
[0107] The collimating lens 340 may receive light from the light source 350 and provide parallel light to the input polarizer 330. The focusing lens 310 may converge the parallel light that has passed through the input polarizer 330 to increase the amount of incident light. The input compensator 320 may also serve to phase-retard the polarization components of the input light.
[0108] The polarization detector 400 receives the light reflected by the adsorption layer 140 through the reflection window 152, and the polarization detector 400 may detect a change in the polarization state of the reflected light.
[0109] The polarization detection section 400 may include a polarizing beamsplitter 420 that splits the reflected light into two polarized lights, and a light detection unit 430 that detects each of the two lights and obtains predetermined optical data.
[0110] The polarization detection section 400 may further include an arithmetic processor 440 electrically connected to the optical detection unit 430 for deriving a measurement value based on the optical data, and a detection compensator 410 for phase-delaying the polarization component of the reflected light.
[0111] Here, a detection compensator 410 may be formed at a position closest to the micro-channel structure 100, and a polarization splitting unit 420, an optical detection unit 430 and an arithmetic processor 440 may be arranged in sequence next to the detection compensator 410 in a direction away from the micro-channel structure 100.
[0112] The polarization splitting unit 420 may split the reflected light into two lights, each of which may be polarized at the same time. The structure of such a polarization splitting unit will be described in detail below.
[0113] As described above, two polarized lights are generated by the polarization splitting unit, and the light detection unit 430 may include a p-wave detector 431 that detects the p-wave of the two lights, and an s-wave detector 432 that detects the s-wave of the two lights.
[0114] Here, the p-wave detector 431 may include any one of a CCD type solid-state imaging element, a photomultiplier tube, and a silicon photodiode, and the s-wave detector 432 may include any one of a CCD type solid-state imaging element, a photomultiplier tube, and a silicon photodiode.
[0115] Each of the P-wave detector 431 and the S-wave detector 432 may detect the incident light, obtain optical data, and convert the data into an electrical signal. In this case, the optical data from each detector contains information about the change in the polarization state of each of the two lights.
[0116] The calculation processor 440 measures only the reflectance ratio of the p-wavelength light and the s-wavelength light, which are the two lights obtained by separating the reflected light, and calculates the amplitude ellipsometric constant (Ψ) of the ellipsometric method, thereby deriving measurement values including the adsorption concentration of the sample and the adsorption and dissociation constants.
[0117] Specifically, the arithmetic processor 440 can obtain electrical signals from the optical detection unit 430 and derive measurement values. The arithmetic processor 440 is equipped with a predetermined analysis program using reflectometry and ellipsometry, and extracts and analyzes the optical data converted into electrical signals to derive measurement values such as the adsorption concentration of the sample, the thickness of the adsorption layer 140, the adsorption constant, the dissociation constant, and the refractive index.
[0118] At this time, it is preferable that the calculation processor 440 obtains an amplitude ellipsometric constant (Ψ) for the amplitude of the ellipsometric method to improve the measurement sensitivity, and derives the measurement value. Here, the amplitude ellipsometric constant (Ψ) can be derived by the following mathematical formula.
[0119]
number
[0120] Here, Ψ is the amplitude ellipse constant, Rp is the reflectance of the p-wavelength light detected by the p-wavelength detector 431 among the two beams obtained by the separation of the reflected beam, and Rs is the reflectance of the s-wavelength light detected by the s-wavelength detector 432 among the two beams obtained by the separation of the reflected beam.
[0121] FIG. 16 is a schematic diagram of the configuration of an elliptical amplitude sensor device according to a first embodiment of the present invention, FIG. 17 is a schematic diagram of the configuration of an elliptical amplitude sensor device according to a second embodiment of the present invention, and FIG. 18 is a schematic diagram of the configuration of an elliptical amplitude sensor device according to a third embodiment of the present invention.
[0122] 16 to 18 show schematic details relating to each configuration, and an embodiment in which the lid portion 150 is removed from each of the embodiments associated with FIGS. 16 to 18 may also be implemented.
[0123] In particular, in FIGS. 16 to 18, the structure related to the polarization splitting unit 420 is disclosed, and other configurations of the polarization splitting section are excluded for the purpose of concretely describing the polarization splitting unit 420. FIG.
[0124] 16, the polarization splitting unit 420 may be formed of a polarizing plate beam splitter. Specifically, the polarization splitting unit 420 may include a beam splitter 421 that splits the reflected light into two beams, and a coating layer 422 that is formed by coating the surface of the beam splitter 421 and polarizes the reflected light.
[0125] Here, the input polarizer 330 and the input compensator 320 may rotate at a specific angle to form linearly polarized light, circularly polarized light, or elliptically polarized light, or may form unpolarized input light. The polarized light generator may form an input angle that satisfies the p-wave and s-wave non-reflection conditions due to the thickness of the silicon oxide film.
[0126] 17, the polarization splitting unit 420 may be formed of a cube-shaped polarization splitter (Polarizing Beamsplitter Cube). Specifically, the polarization splitting unit 420 may include a beam splitter 421 that splits the reflected light into two beams, a coating layer 422 that is formed by coating the surface of the beam splitter 421 and polarizes the reflected light, and a cube 423 that is formed by drawing a combination of the coating layer 422 and the beam splitter 421 into the inside.
[0127] FIG. 15 also relates to an elliptical amplitude sensor device according to a second embodiment, and as can be seen from FIG. 15, the cube 423 is formed in a box shape, and the cube 423 may include an incident hole 423a through which the reflected light is incident, an s-wave hole 423c through which the s-wave light, which is one of the two lights polarized and separated by the light splitter 421 and the coating layer 422, passes, and a p-wave hole 423b through which the other light, the p-wave light, passes.
[0128] Here, the input polarizer 330 can be rotated at a particular angle, and the input compensator 320 can also be rotated at a particular angle.
[0129] In the cases of Figures 16 and 17, the reflected light is polarized while passing through coating layer 422, and this polarized reflected light is split into two lights while passing through light splitter 421, and one light may be transmitted to s-wave detector 432 and the other light may be transmitted to p-wave detector 431.
[0130] As can be seen from FIG. 18, the polarization splitting unit 420 may include a beam splitter 421 that splits the reflected light into two lights, a first split polarizer 424a that is a polarizer that polarizes one of the two lights, and a second split polarizer 424b that is a polarizer that polarizes the other light of the two lights.
[0131] Specifically, the reflected light is split into two beams as it passes through the beam splitter 421, and one of the two beams may be polarized as it passes through the first split polarizer 424a, and the p-wave beam may be transmitted to the p-wave detector 431, and the other of the two beams may be polarized as it passes through the second split polarizer 424b, and the s-wave beam may be transmitted to the s-wave detector 432.
[0132] With the above-mentioned structure, the reflected light is separated into p-wave and s-wave by the polarization detector 400, and is detected by the p-wave detector 431 and the s-wave detector 432, respectively. As a result, the reflectance of the p-wave and the reflectance of the s-wave can be immediately derived, and the amplitude ellipse constant (Ψ) can be derived from the ratio of the reflectance of the p-wave and the reflectance of the s-wave according to the above [mathematical formula].
[0133] This allows for simple and highly sensitive measurement of the ellipticity amplitude by measuring only the p-wave and s-wave reflectance without using a rotating analyzer or a polarization modulator that requires a complex drive. Also, the p-wave and s-wave signals can be measured with high sensitivity in a fixed signal band of each detector by using the respective photodetectors.
[0134] Furthermore, when using the elliptical amplitude sensor device of the present invention, rotation of the polarizer of the polarization splitting unit 420 or the polarization detection unit 400 as described above is not required, so there is no need for a driving device for polarizer rotation or polarization modulation, and the device may be used as a highly sensitive on-site diagnostic sensor device that only measures reflectance.
[0135] Hereinafter, a measurement method for an ellipse amplitude sensor performed using the ellipse amplitude sensor device of the present invention will be described.
[0136] First, in a first step, the sample injection unit 200 may inject a buffer solution containing a sample into the microchannels 160 of the microchannel structure 100. In this first step, a plurality of buffer solutions containing samples of different concentrations may be injected into each of the plurality of microchannels 160.
[0137] Here, the sample injection unit 200 can inject buffer solutions containing samples of different concentrations into each of the micro channels 160 of the multiple channels. Also, the buffer solution can be injected at different times into each of the micro channels 160. Also, the buffer solution can be injected into only some of the micro channels 160, and the remaining micro channels 160 can be left unused.
[0138] Then, in a second step, a sample may be flowed into the microchannel 160, and the sample may be adsorbed onto the dielectric thin film 130 to form the adsorption layer 140. In this second step, a plurality of different sample substances may be adsorbed onto each of the plurality of dielectric thin films 130 located inside each of the plurality of microchannels 160.
[0139] Next, in the third step, the polarized light generating unit 300 can polarize a predetermined light and make it incident on the adsorption layer 140 through the entrance window 151 of the micro-channel structure 100 at an incident angle that satisfies the p-wave or s-wave non-reflection condition. Here, the polarized incident light has p-wave and s-wave polarization components. On the other hand, the incident light may have an incident angle (θ) that satisfies the p-wave non-reflection condition.
[0140] Then, in a fourth step, the light reflected by the adsorption layer 140 may pass through the reflection window 152 and enter the polarization detection unit 400. After that, in a fifth step, the polarization detection unit 400 may measure only the reflectance ratio between the p-wave and the s-wave of the reflected light, and calculate the amplitude ellipsometric constant (Ψ) of the ellipsometric method using the reflectance ratio between the p-wave and the s-wave.
[0141] Here, the fifth step may include a fifth step (5-1) of polarizing the reflected light into p-wave and s-wave by the polarization splitting unit 420, a fifth step (5-2) of detecting the polarized reflected light by the light detection unit 430 to obtain predetermined optical data, and a fifth step (5-3) of using the calculation processor 440 to calculate the ellipsometric constant (Ψ) for the ellipsometric amplitude using the reflectance ratio between the p-wave and the s-wave, thereby deriving measured values including the adsorption concentration, adsorption and dissociation constants of the sample.
[0142] The remaining details regarding the measurement method of the ellipse amplitude sensor of the present invention are the same as those described above for the measurement device of the ellipse amplitude sensor of the present invention.
[0143] Fig. 19 is a schematic diagram showing the configuration of an elliptical amplitude sensor device according to a fourth embodiment of the present invention, in which the cover 150 is omitted for ease of understanding.
[0144] As can be seen from FIG. 19, the ellipse amplitude sensor device of the present invention includes a support 110, a dielectric thin film 130 formed on a substrate 120 formed on the support 110, a cover 150 provided on the support 110, and a microchannel 160, which is a channel formed by combining the cover 150 and the support 110, a sample injection unit 200 for injecting a buffer solution containing a biomaterial sample into the microchannel 160 to form an adsorption layer 140 of the sample on the dielectric thin film 130, a polarized light generating unit 300 for irradiating the polarized incident light through the incident window 151 onto the adsorption layer 140 at an incident angle (θ) that satisfies the p-wave or s-wave non-reflection condition, and a polarization detecting unit 400 for detecting an ellipse measurement amplitude angle by separating and measuring the reflected light reflected by the adsorption layer 140 and passing through the reflection window 152 in terms of p-wave and s-wave reflectance.
[0145] Also, a plurality of adsorption layers 140 may be formed in one microchannel 160, and the polarized light generating unit 300 may irradiate a plurality of incident lights onto each of the plurality of adsorption layers 140. Specifically, a plurality of dielectric thin films 130 may be formed in one microchannel 160, and may be arranged along the flow direction of the sample.
[0146] In the elliptical amplitude sensor device according to the fourth embodiment of the present invention, the polarization generating unit 300 may include a light source 350 that irradiates a predetermined light, an incident polarizer 330 which is a polarizer for generating polarized light, a collimating lens 340 that provides parallel light to the incident polarizer 330, a diffractive optical element (Beam splitter DOE) 511 that splits the light passing through the incident polarizer 330 into multiple incident lights, and a focusing lens 512 that disperses the multiple incident lights to each of the multiple adsorption layers 140.
[0147] Here, a focusing lens 512 may be formed at a position closest to the micro-channel structure 100, and a diffractive optical element 511, an incident polarizer 330, a collimating lens 340 and a light source 350 may be arranged in sequence next to the focusing lens 512 in a direction away from the micro-channel structure 100.
[0148] The polarization detection unit 400 may include a light detection unit 430 that detects each of a plurality of reflected lights caused by a plurality of incident lights and obtains predetermined optical data. The polarization detection unit 400 may also include a parallel control lens 513 that is a lens that passes the plurality of reflected lights so that the plurality of reflected lights travel in parallel to each other, and a calculation processor 440 that is electrically connected to the light detection unit 430 and derives a measurement value based on the optical data.
[0149] Here, the parallel control lens 513 may be formed of a concave lens, and the light detection unit 430 may include a p-wave detector 431 that detects the p-wave light of the two light beams, and an s-wave detector 432 that detects the s-wave light of the two light beams.
[0150] As described above, since a plurality of reflected beams are formed, a plurality of p-beams due to the plurality of reflected beams may be transmitted to the p-beam detector 431 and detected, and a plurality of s-beams due to the plurality of reflected beams may be transmitted to the s-beam detector 432 and detected.
[0151] Therefore, the p-wave detector 431 may be formed with a plurality of p-wave detectors for detecting a plurality of p-wave light beams, and one of the plurality of p-wave detectors may be irradiated onto one of the plurality of p-wave detectors.
[0152] The s-wave detector 432 may be formed with a plurality of s-wave detectors for detecting a plurality of s-wave light beams, and one of the plurality of s-wave light beams may be irradiated onto one of the plurality of s-wave detectors.
[0153] Here, the p-wave detector may include any one of a CCD type solid-state imaging element, a photomultiplier tube, and a silicon photodiode, and the s-wave detector may include any one of a CCD type solid-state imaging element, a photomultiplier tube, and a silicon photodiode.
[0154] The processor 440 obtains data on a plurality of p-wave light reflectances using the optical data obtained by each of the plurality of p-wave detectors, calculates an average of the plurality of p-wave light reflectances, and derives a p-wave light reflectance value for calculating the amplitude ellipsometric constant (Ψ) of the ellipsometric method.
[0155] Similarly, the processor 440 can obtain data on multiple s-wave light reflectances using the optical data obtained by each of the multiple s-wave detectors, calculate an average of the multiple s-wave light reflectances, and derive an s-wave light reflectance value for calculating the amplitude ellipsometric constant (Ψ) of the ellipsometric method.
[0156] As described above, the arithmetic processor 440 calculates the amplitude ellipse constant (Ψ) using the average value of a plurality of p-wave reflectances and the average value of a plurality of s-wave reflectances. Therefore, the errors of the p-wave reflectances and the s-wave reflectances are reduced. As a result, the error of the amplitude ellipse constant (Ψ) is reduced, and the accuracy of the analysis of the sample is improved.
[0157] Among the components included in the elliptical amplitude sensor device according to the fourth embodiment of the present invention, such as the above-mentioned multiple dielectric thin films 130 and the optical detection unit 430, details of the remaining components, except for those components that differ from the elliptical amplitude sensor device according to the first embodiment of the present invention, are the same as those described for the elliptical amplitude sensor device according to the first embodiment of the present invention.
[0158] Fig. 20 is a schematic diagram showing the configuration of an elliptical amplitude sensor device according to a fifth embodiment of the present invention, in which the cover 150 is omitted for ease of understanding.
[0159] As shown in FIG. 20, the ellipse amplitude sensor device of the present invention includes a support 110, a dielectric thin film 130 formed on a substrate 120 formed on the support 110, a cover 150 provided on the support 110 with an entrance window 151 and a reflection window 152 on one side and the other side, and a microchannel 160 which is a channel formed by combining the cover 150 and the support 110, a sample injection unit 200 for injecting a buffer solution containing a sample of a biomaterial into the microchannel 160 to form an adsorption layer 140 of the sample on the dielectric thin film 130, a polarized light generation unit 300 for irradiating the polarized incident light through the entrance window 151 to the adsorption layer 140 at an incident angle (θ) that satisfies the p-wave or s-wave non-reflection condition, and a polarization detection unit 400 for detecting an ellipse measurement amplitude angle by separating and measuring the reflected light reflected by the adsorption layer 140 and passing through the reflection window 152 in terms of p-wave and s-wave reflectance.
[0160] Here, the polarized light generating unit 300 may include a light expander 521 that expands the irradiation area of the incident light. The polarized light generating unit 300 may include a light source 350 that irradiates a predetermined light, a collimating lens 340 that provides parallel light to the incident polarizer 330, and the incident polarizer 330 that is a polarizer for generating polarized light.
[0161] As can be seen from FIG. 20, the area of the incident light may be increased by the optical expander 521 so that the incident light is incident on the dielectric thin film 130, and the light with the increased area may be reflected and transmitted to the polarization detection unit 400.
[0162] In this case, the area of the dielectric thin film 130 may be increased in response to the area of the incident light, and the internal volume of the microchannel 160 may also be increased accordingly, so that a large amount of buffer solution may be passed through the microchannel 160, or a buffer solution of a sample containing biological materials with relatively large particles may be passed through the microchannel 160 to perform analysis on the sample.
[0163] Among the components included in the elliptical amplitude sensor device according to the fifth embodiment of the present invention, such as the dielectric thin film 130 with the increased area and the polarization generating unit 300, details of the remaining components, except for those components that differ from the elliptical amplitude sensor device according to the first embodiment of the present invention, are the same as those described for the elliptical amplitude sensor device according to the first embodiment of the present invention.
[0164] The above description of the present invention is for illustrative purposes only, and those skilled in the art will understand that the present invention can be easily modified in other specific forms without changing the technical idea or essential features of the present invention. Therefore, it should be understood that the above-described embodiments are illustrative in all respects and are not limiting. For example, each component described as a single type may be implemented in a distributed form, and similarly, each component described as a distributed type may be implemented in a combined form.
[0165] The scope of the present invention is defined by the claims set forth below, and all modifications and variations that fall within the meaning and scope of the claims and their equivalent concepts are included within the scope of the present invention. [Explanation of symbols]
[0166] 100 Microchannel structure 110 Support stand 112 Groove 120 Substrate 130 Dielectric Thin Film 140 Adsorption layer 150 Lid 151 Entrance window 152 Reflective Window 153 Bulkhead 160 Microchannel 161 Inflow channel 162 Exhaust channel 200 Sample injection section 300 Polarized light generating unit 310 Focusing Lens 320 Incidence Compensator 330 Input polarizer 340 Collimating Lens 350 light source 400 Polarization detector 410 Detection compensator 420 Polarization splitting unit 421 Light splitter 422 Coating layer 423 Cube 423a Entrance hole 423b P-hall 423c S-hall 424a First split polarizer 424b Second split polarizer 430 Light detection unit 431 P-detector 432 s-wave detector 440 Processing Unit 511 Diffractive Optical Elements 512 Focusing Lens 513 Parallel Control Lens 521 Light Magnifier
Claims
1. a support base; a dielectric thin film formed on a substrate formed on the support base; an incident window and a reflection window on one side and the other side, respectively; a cover part provided on the support base; and a micro-channel which is a channel formed by combining the cover part and the support base; a sample injection unit for injecting a buffer solution containing a sample of a biological material into the microchannel to form an adsorption layer of the sample on the dielectric thin film; a polarized light generating unit that irradiates the polarized incident light through the entrance window onto the adsorption layer at an incident angle (θ) that satisfies the p-wave or s-wave non-reflection condition; a polarization detector for measuring the reflected light reflected by the adsorption layer and passing through the reflection window by separating the p-wave and s-wave reflectances and detecting an ellipse measurement amplitude angle; The polarization detection unit includes a polarization splitting unit that splits the reflected light into two polarized lights, and a light detection unit that detects each of the two lights and obtains predetermined optical data. A semiconductor oxide film elliptical amplitude sensor device.
2. The polarization detection unit a processor electrically coupled to the optical detection unit for deriving a measurement based on the optical data; A detection compensator that delays the phase of the polarization component of the reflected light.
2. The semiconductor oxide elliptical amplitude sensor device of claim 1.
3. The calculation processor measures only the reflectance ratio of the two lights, p-wave and s-wave, resulting from the separation of the reflected light, and calculates the amplitude ellipsometric constant (Ψ) of the ellipsometric method, thereby deriving the measured values including the adsorption concentration, adsorption and dissociation constants of the sample.
3. The semiconductor oxide elliptical amplitude sensor device of claim 2.
4. The optical detection unit comprises: a p-phase detector for detecting a p-phase light of the two light beams; and an s-wave detector for detecting the s-wave light of the two light beams.
2. The semiconductor oxide elliptical amplitude sensor device of claim 1.
5. The polarization splitting unit is a light splitter for splitting the reflected light into two lights; a coating layer formed on the surface of the light splitter and polarizing the reflected light; 2. The semiconductor oxide elliptical amplitude sensor device of claim 1.
6. The polarization splitting unit further comprises a cube formed by drawing the combination of the coating layer and the light splitter into the cube.
6. The semiconductor oxide elliptical amplitude sensor device of claim 5.
7. The polarization splitting unit is a light splitter for splitting the reflected light into two lights; a first split polarizer that polarizes one of the two beams of light; a second split polarizer that polarizes the other of the two light beams; 2. The semiconductor oxide elliptical amplitude sensor device of claim 1.
8. The polarized light generating unit is A light source that irradiates a predetermined light; An input polarizer for generating polarized light; an incident compensator that delays the phase of the polarization component of the incident light; 2. The semiconductor oxide elliptical amplitude sensor device of claim 1.
9. The polarized light generating unit is a collimating lens for providing parallel light to the input polarizer; a focusing lens that converges the parallel light that has passed through the polarizer and increases the amount of the incident light.
9. The semiconductor oxide elliptical amplitude sensor device of claim 8.
10. The incident light generated by the polarized light generating unit is a linearly polarized light, a circularly polarized light, an elliptically polarized light, or a non-polarized light source.
2. The semiconductor oxide elliptical amplitude sensor device of claim 1.
11. The cover has a plurality of partitions that separate the internal space, thereby forming a plurality of microchannels.
2. The semiconductor oxide elliptical amplitude sensor device of claim 1.
12. The microchannel structure includes a plurality of dielectric thin films, and a plurality of different samples are adsorbed on each of the plurality of dielectric thin films.
12. The semiconductor oxide elliptical amplitude sensor device of claim 11.
13. A method for measuring a semiconductor oxide film elliptical amplitude using the semiconductor oxide film elliptical amplitude sensor device according to claim 1, a first step in which the sample injection unit injects a buffer solution containing the sample into the microchannel of the microchannel structure; a second step in which the sample is introduced into the microchannel and the sample is adsorbed onto the dielectric thin film to form the adsorption layer; a third step in which the polarized light generating unit polarizes a predetermined light, and causes the polarized light to enter the adsorption layer through the entrance window of the microchannel structure at an incident angle that satisfies a p-wave or s-wave non-reflection condition; a fourth step in which the light reflected by the adsorption layer passes through the reflection window and is incident on the polarization detection unit; and a fifth step of measuring only the reflectance ratio between the p-wave and the s-wave of the reflected light by the polarization detection unit, and calculating an amplitude ellipse measurement constant (Ψ) of the ellipse measurement method using the reflectance ratio between the p-wave and the s-wave.
14. a support base; a dielectric thin film formed on a substrate formed on the support base; an incident window and a reflection window on one side and the other side, respectively, and a cover part provided on the support base; and a microchannel which is a channel formed by combining the cover part and the support base; a sample injection unit for injecting a buffer solution containing a sample of a biological material into the microchannel to form an adsorption layer of the sample on the dielectric thin film; a polarized light generating unit that irradiates the polarized incident light through the entrance window onto the adsorption layer at an incident angle (θ) that satisfies the p-wave or s-wave non-reflection condition; a polarization detector for measuring the reflected light reflected by the adsorption layer and passing through the reflection window by separating the p-wave and s-wave reflectances and detecting an ellipse measurement amplitude angle; Multiple adsorption layers are formed within one microchannel, the polarized light generating unit irradiates each of the plurality of adsorption layers with a plurality of incident lights, The polarization detection unit includes a light detection unit that detects each of a plurality of reflected lights due to the plurality of incident lights and obtains predetermined optical data. A semiconductor oxide film elliptical amplitude sensor device.
15. a support base; a dielectric thin film formed on a substrate formed on the support base; an incident window and a reflection window on one side and the other side, respectively; a cover part provided on the support base; and a micro-channel which is a channel formed by combining the cover part and the support base; a sample injection unit for injecting a buffer solution containing a sample of a biological material into the microchannel to form an adsorption layer of the sample on the dielectric thin film; a polarized light generating unit that irradiates the polarized incident light through the entrance window onto the adsorption layer at an incident angle (θ) that satisfies the p-wave or s-wave non-reflection condition; a polarization detector that separates and measures the reflected light reflected by the adsorption layer and passing through the reflection window in terms of p-wave and s-wave reflectance, and detects an ellipse measurement amplitude angle; the polarization detection unit includes a polarization splitting unit that splits the reflected light into two polarized lights, and a light detection unit that detects each of the two lights and obtains predetermined optical data; The polarized light generating unit includes a light expander that expands the irradiation area of the incident light. A semiconductor oxide film elliptical amplitude sensor device.
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