A drug chiral detection device based on a metal resonance optical fluid chip

Abstract

A kind of drug chiral detection device based on metal resonance optical fluid chip, including light source module, polarization control module, beam splitter, polarization conversion module, resonance optical fluid chip, polarization control module includes the quarter-wave plate and linear polaroid that are sequentially arranged along the direction of light path, one side of beam splitter is provided with first photoelectric detector, polarization conversion module includes two quarter-wave plates, resonance optical fluid chip includes the upper silver film layer and lower silver film layer that are arranged in parallel and the cavity layer formed between upper silver film layer and lower silver film layer, one side of resonance optical fluid chip is provided with second photoelectric detector.The metal resonance optical fluid chip of the present application combines polarization light modulation structure, realizes the high-precision detection of chiral drug, by optimizing the interaction of optical field and chiral medium, significantly improve the detection sensitivity, reduce sample demand, and realize high-throughput, integrated detection process.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of biomedicine, in particular to a chiral detection technology, and particularly to a drug chiral detection device based on a metal resonance optical fluid chip. BACKGROUND

[0002] Chirality is a basic property in modern science, which widely exists in the structures of biological macromolecules such as DNA, polysaccharide and amino acid. The definition of chirality can be described as: just like the left and right hands of a person, the mirror image of an object and itself cannot be superimposed by translation, rotation and other changes, and such a property is called chirality. For biological macromolecules, they are often connected by carbon chains, and oxygen, hydrogen, nitrogen, phosphorus atoms or groups composed of these elements are connected on the carbon chains. When atoms or groups are connected to the carbon chain, the corresponding covalent bond positions are different, the atoms and groups connected by the carbon element are the same, only the corresponding covalent bond positions are different, so that they cannot be superimposed with the mirror image, and thus have chirality. Objects like this that are mirror images of each other are called enantiomers. In the field of life science and human medicine, chirality plays an extremely important role. Enantiomers of chiral drugs show completely different biological activities and effects. In most cases, the pharmacological activity of one enantiomer of a pair of chiral drugs is significantly higher than that of the other, and in some cases, some enantiomers of chiral drugs can produce opposite effects and have serious side effects such as poisoning, teratogenicity, etc. Therefore, in the field of pharmacokinetics and pharmacodynamics, the ability to identify chirality with high sensitivity and high speed is very necessary.

[0003] The existing drug chirality detection technology mainly includes the following means: optical rotation detection is based on the deflection angle of the polarization direction of linearly polarized light after passing through a chiral medium (specific rotation). Its principle is simple, but the sensitivity is low. The traditional method needs a long light path (several meters) and a large sample amount. In order to overcome the shortcomings of the traditional optical rotation method, the improved method based on hollow optical fiber reduces the sample consumption to 38.9 μL through miniaturized light path design (such as hollow optical fiber), but the light path is still 2.2 m; circular dichroism (CD) detection analyzes the characteristics of elliptically polarized light caused by the difference in absorption coefficient of left / right circularly polarized light by chiral medium. The sensitivity is high, but the signal is weak and depends on complex instruments (such as polarization modulators); in addition, the "twisted" optical metamaterial enhanced CD detection uses plasmonic metamaterial to amplify the interaction between chiral molecules and light field, which enhances the CD signal by about 100 times, but the preparation process is complex and depends on high-cost metamaterial preparation technology, which is high in cost and difficult to integrate; the cascade prism method separates the propagation directions of left / right circularly polarized light through multiple prisms, which directly shows the chirality difference, but the sensitivity is insufficient, the device is complex and needs to be precisely calibrated; the method based on diffraction angle uses the diffraction angle change caused by the refractive index difference for detection, which requires high light path calibration and stable environment, and has high requirements for the stability of experimental environment, and is only suitable for specific wavelength and medium conditions. In general, the traditional methods (such as optical rotation method and CD method) are mature but limited by sensitivity, the structure optimization technology (hollow optical fiber and metamaterial) improves the performance through miniaturization or signal amplification, the optical path design method (cascade prism and diffraction angle) depends on complex devices, and the frontier direction (spin-orbit coupling) needs further technical breakthrough to realize application.

[0004] The existing drug chirality detection technology generally has low sensitivity, large sample requirement, complex operation and other problems, which is difficult to meet the rapid detection requirements of trace chiral drugs in biological samples (such as blood and cell culture medium). SUMMARY

[0005] The purpose of the present application is to provide a drug chirality detection device based on a metal resonant optical fluid chip, which solves the technical problems of low sensitivity, large sample requirement and complex operation in the prior art.

[0006] The application provides a drug chirality detection device based on a metal resonant optical fluid chip, which comprises, in sequence along an optical path direction, a light source module, a polarization control module, a beam splitter, a polarization conversion module and a resonant optical fluid chip.

[0007] Further, the thickness of the upper silver film layer is 30-50 nm, the thickness of the lower silver film layer is 300 nm, and the height of the cavity layer is 200-500 nm.

[0008] Further, the parallelism tolerance of the upper surface and the lower surface of the cavity layer is less than 4 angular seconds on any 1 cm measurement length.

[0009] Further, the light source module comprises a 532 nm single longitudinal mode laser, and the exit end of the 532 nm single longitudinal mode laser is connected with a pinhole collimator.

[0010] Further, an angle adjusting module is further included, the angle adjusting module comprises a turntable and a driving device for driving the rotation of the turntable, and the resonant optical fluid chip is fixedly arranged on the turntable, and the angle resolution of the turntable is 0.01°.

[0011] Further, the response time of the second photodetector is ≤1 ms, and the dynamic range covers 0.1-100 μW.

[0012] Compared with the prior art, the effect of the application is positive and obvious. The metal resonant optical fluid chip of the application combines a polarization light modulation structure, realizes high-precision detection of chiral drugs, significantly improves the detection sensitivity by optimizing the interaction of the optical field and the chiral medium, is simple to operate, reduces the sample demand, and realizes a high-throughput and integrated detection process. BRIEF DESCRIPTION OF DRAWINGS

[0013] Figure 1 It is a schematic view of a drug chirality detection device based on a metal resonant optical fluid chip.

[0014] Figure 2 A front view of the use state of the resonant optical fluid chip in the drug chiral detection device based on the resonant optical fluid chip.

[0015] Figure 3 A perspective view of the use state of the resonant optical fluid chip in the drug chiral detection device based on the resonant optical fluid chip.

[0016] Figure 4 A left-handed circularly polarized light reflection schematic diagram of the use state of the resonant optical fluid chip in the drug chiral detection device based on the resonant optical fluid chip.

[0017] Figure 5 A right-handed circularly polarized light reflection schematic diagram of the use state of the resonant optical fluid chip in the drug chiral detection device based on the resonant optical fluid chip.

[0018] Figure 6 A linear relationship between the reflectivity difference D and the drug concentration (methotrexate MTX) is shown in the schematic diagram.

[0019] Figure 7 A linear relationship between the reflectivity difference D and the drug concentration (amlodipine ADP) is shown in the schematic diagram.

[0020] Figure 8 A schematic diagram of the dynamic change monitoring result of the chiral drug concentration in the culture medium in the in-vitro experiment.

[0021] Figure 9 A schematic diagram of the dynamic change of the chiral drug concentration in the animal blood sample in the in-vivo experiment. DETAILED DESCRIPTION

[0022] The present application is further described below in conjunction with the embodiments, but the present application is not limited to the embodiments, and any similar changes using the present application should be included in the protection scope of the present application. The use of up, down, front, back, left, right, middle, inner, outer and other directions in the present application is only for the convenience of clear description, and is not a limitation on the technical solutions of the present application.

[0023] As Figures 1-5As shown, the present application provides a kind of drug chiral detection device based on metal resonant optical fluid chip, including light source module 1, polarization control module, beam splitter 2, polarization conversion module, resonant optical fluid chip 3 in turn along optical path direction, polarization control module includes half-wave plate 4 and linear polarizer 5 in turn along optical path direction, one side of the beam splitter 2 is provided with first photoelectric detector 6, the first photoelectric detector 6 is correspondingly arranged with the first beam splitting port of beam splitter 2, the polarization conversion module is correspondingly arranged with the second beam splitting port of beam splitter 2, the polarization conversion module includes two quarter-wave plates 7 in turn along optical path direction, two quarter-wave plates 7 are used to convert linearly polarized light into left-handed circularly polarized light and right-handed circularly polarized light respectively, resonant optical fluid chip 3 includes upper silver film layer 8 and lower silver film layer 9 arranged in parallel and cavity layer 10 formed between upper silver film layer 8 and lower silver film layer 9, cavity layer 10 is connected with microinjector 11 by conduit, one side of resonant optical fluid chip 3 is provided with second photoelectric detector 12, and second photoelectric detector 12 is used to detect the reflected light intensity of resonant optical fluid chip 3, and the signal output ends of first photoelectric detector 6 and second photoelectric detector 12 are electrically connected with a data processing unit.

[0024] Further, the thickness of the upper silver film layer 8 is 30-50 nm, the thickness of the lower silver film layer 9 is 300 nm, and the height of the cavity layer is 200-500 nm.

[0025] Further, the parallelism tolerance of the upper surface and the lower surface of the cavity layer 10 is less than 4 angular seconds on any 100 mm measurement length.

[0026] Further, the light source module 1 includes a 532 nm single longitudinal mode laser, and the exit end of the 532 nm single longitudinal mode laser is connected with a pinhole collimator.

[0027] Further, an angle adjusting module is further included, the angle adjusting module includes a turntable 13 and a driving device for driving the rotation of the turntable 13, the resonant optical fluid chip 3 is fixedly arranged on the turntable 13, and the angle resolution of the turntable 13 is 0.01°.

[0028] Further, the response time of the second photoelectric detector 12 is ≤1 ms, and the dynamic range covers 0.1-100 μW.

[0029] Specifically, the specific structure and principle of the light source module 1, the beam splitter 2, the half-wave plate 4, the linear polarizer 5, the photoelectric detector, the microinjector 11, the data processing unit, the 532 nm single longitudinal mode laser, the pinhole collimator and the driving device in the present application and other not fully described places all adopt the known scheme in the prior art, and those skilled in the art are all aware of it, which will not be repeated here.

[0030] Working principle of the present application:

[0031] Light source module 1: 532 nm single longitudinal mode laser is used as the probe light source, the outgoing linearly polarized laser enters the polarization control module, and the beam direction is adjusted by the pinhole collimator.

[0032] Polarization control module: composed of half-wave plate 4 and linear polarizer 5, used to adjust the power and polarization state of the incident laser. The half-wave plate 4 can be rotated to control the output power (0-100%), and the linear polarizer 5 is fixed to maintain the linear polarization direction.

[0033] Beam splitter 2: the outgoing laser of the polarization control module enters the beam splitter 2, which divides the incident light into two beams, one of which is used as reference light to monitor the power fluctuation of the light source in real time by the first photodetector 6, and the other is used as probe light to enter the polarization conversion module.

[0034] Polarization conversion module: contains two switchable quarter-wave plates 7, which convert linearly polarized light into left circularly polarized light (LCP) and right circularly polarized light (RCP) respectively. Switching scheme of the two quarter-wave plates 7: the two quarter-wave plates 7 are fixed on the two sliders of the translation slide rail, and the two sliders are driven to move along the translation slide rail by the motor and transmission mechanism; when left circularly polarized light (LCP) is needed to be generated, the quarter-wave plate 7 (LCP) is driven to translate to the center of the light path, while the other quarter-wave plate 7 (RCP) is moved out of the light path; when right circularly polarized light (RCP) is needed to be generated, the quarter-wave plate 7 (RCP) is driven to translate to the center of the light path, while the other quarter-wave plate 7 (LCP) is moved out of the light path.

[0035] As shown in Figures 2-5 Resonant optical fluid chip 3 (MROC): is the core detection component, composed of upper silver film layer 8, lower silver film layer 9 and cavity layer 10. The cavity layer 10 is used to fill the chiral medium sample to be measured, and the microinjector 11 is connected to realize sample injection and cleaning. On any 100 mm measurement length, the parallelism error of the upper and lower surfaces of the cavity layer 10 is less than 4 angular seconds, which ensures the high efficiency of the resonant optical waveguide mode.

[0036] Left circularly polarized light or right circularly polarized light reaches the metal resonant optical fluid chip 3. When the propagation constant of the incident light satisfies the wave vector matching condition, the light will be coupled into the MRW (MRW includes the upper silver film layer 8, the lower silver film layer 9 and the guided wave layer, the guided wave layer includes the cavity layer 10 and the chiral medium), and the ultra-high order guided mode (UOM) of the MRW is excited, forming a standing wave field in the guided wave layer.

[0037] The detection principle of the resonant optical fluid chip 3 is as follows: when the incident light acts on the upper silver film layer 8 of the MRW, the evanescent field excited and the intrinsic mode in the waveguide layer resonate, so as to be coupled into the waveguide layer of the MRW. The intrinsic mode of the MRW is closely related to the thickness and dielectric coefficient of the waveguide layer. Therefore, changing the dielectric coefficient of the waveguide layer can cause the resonance condition of the intrinsic mode of the MRW and the incident light to deviate, the total light reflection spectrum to deviate, the intensity and phase of the reflected light to change, and the reflectivity difference D of the left / right circularly polarized light to linearly change with the concentration and enantiomer type of the chiral drug. At the same time, since the dielectric coefficients of the chiral medium for the left / right circularly polarized light are different (the difference in refractive index corresponds to the difference in real part, and the difference in absorption coefficient corresponds to the difference in imaginary part), the reflectivity of the MRW with the chiral medium as the waveguide layer for the left / right circularly polarized light is different, and the reflectivity difference is proportional to the concentration of the chiral medium, and the positive / negative sign corresponds to the left / right chirality of the chiral medium.

[0038] The angle adjusting module: the optical fluid chip is fixed on the turntable 13, and the driving device drives the turntable 13 and the resonant optical fluid chip 3 to rotate, so as to adjust the incident angle, make the reflectivity of the transverse electric mode (TE) and the transverse magnetic mode (TM) polarization mode consistent, and ensure the stable coupling efficiency when the left circularly polarized light and the right circularly polarized light are incident. The turntable 13 is kept fixed during the detection process.

[0039] The signal detection module: the second photodetector 12 is used to measure the intensity of the reflected light passing through the resonant optical fluid chip 3.

[0040] The data processing unit: the detection values of the first photodetector 6 and the second photodetector 12 are combined to calculate the reflectivity difference D of the left circularly polarized light and the right circularly polarized light, and then the concentration and chirality of the chiral drug are output in real time in combination with the calibration curve (the linear relationship between the reflectivity difference D and the concentration of the chiral drug).

[0041] Figure 6 、 Figure 7 The linear relationship between the reflectivity difference D and the concentration of the chiral drug is obtained through the calibration experiment. Before the cell experiment and the animal experiment, the calibration experiment is performed, and the standard solution of the chiral drug is measured in the laboratory. The measured experimental data are used as a scale in the subsequent experiments. First, 10% (volume percentage) DMSO standard solutions of R / S-MTX and R / S-ADP with concentrations of 0.1 mg / mL, 0.2 mg / mL, 0.3 mg / mL, 0.5 mg / mL, 0.8 mg / mL, 1.0 mg / mL, 1.5 mg / mL, and 2 mg / mL are configured, and then the four kinds of solutions are measured respectively. After each measurement is completed, the cavity layer 10 is cleaned with a 10% DMSO blank solution to remove the residual sample. Figure 6Fig. 7 shows the reflectivity difference D of 10% DMSO standard solution of MTX and ADP, respectively. The results show that for the same drug, the R-enantiomer has a positive reflectivity difference D which increases linearly with the concentration of the chiral drug. The S-enantiomer has a negative reflectivity difference D which decreases linearly with the concentration of the chiral drug. The absolute value of the reflectivity difference D of R-MTX and S-MTX has a proportional coefficient of 0.0030±0.0001, -0.0032±0.0001 mL / mg, respectively. The proportional coefficient of R-ADP and S-ADP is 0.0044±0.0002, -0.0046±0.0003 mL / mg, respectively. The results of the two satisfy the expected relationship that the proportional coefficient of the same drug has opposite signs and equal size. At the same time, ADP has a larger proportional coefficient because the difference of the dielectric coefficient of ADP to the circularly polarized light of different directions is larger than that of MTX. For the same chiral drug, the absolute value of the difference D increases with the concentration of the sample, and they are in a positive proportional relationship. For the two enantiomers of a chiral drug, the absolute value of the difference D is equal at the same concentration, but the signs are opposite. In addition, different chiral drugs have different optical rotation and circular dichroism because of the difference of the dielectric coefficient of left / right circularly polarized light. In other words, the slope of the difference D is different. Therefore, in theory, if the slope of the reflectivity difference D of the chiral drug is known, by measuring the reflectivity difference D of the unknown sample concentration of the chiral drug, the corresponding concentration and which enantiomer can be obtained. At the same time, by measuring the reflectivity difference D of different kinds of chiral drugs with known concentration, the type of chiral drug can be distinguished.

[0042] The specific operation process is as follows: first, turn on the 532 nm laser, adjust the half-wave plate 4 and the linear polarizer 5 to stabilize the probe light power; drive the turntable 13 to rotate by the driving device, adjust the incident angle of the resonant optical fluid chip 3 to make the reflectivity of TE and TM polarization modes consistent. Use the microinjector 11 to inject the blank solution (such as 10% DMSO) into the cavity layer 10, clean the residual sample to ensure the baseline stability; inject the chiral drug solution to be tested (such as DMSO solution of S / R-MTX or S / R-ADP) into the cavity layer 10 through the microinjector 11 and the catheter. Switch the quarter-wave plate 7 to generate left circularly polarized light and right circularly polarized light in turn, which are incident to the resonant optical fluid chip 3 and reflected to the second photodetector 12 on the upper silver film layer 8 of the resonant optical fluid chip 3. The second photodetector 12 records the reflected light intensity I L / R 反射, the first photodetector 6 synchronously records the light source power I 光源 . The data processing unit calculates the reflectivity R of left / right circularly polarized light L / R : R L / R = I L / R 反射 / I 光源 , and further calculates the reflectivity difference D: D = R L - R R . The positive and negative signs of the reflectivity difference D correspond to the chiral direction (positive for R type, negative for S type), and the absolute value is proportional to the drug concentration. The reflectivity difference D is compared with the pre-stored calibration curve (such as the slope of MTX 0.0030 mL / mg, the slope of ADP 0.0044 mL / mg), and the chiral drug concentration and chiral type are output.

[0043] The core innovation of the present application is that the resonant optical fluid chip 3 (MROC) structure design: the resonance effect of the upper silver film layer 8, the lower silver film layer 9 and the cavity layer 10 significantly amplifies the dielectric response of the chiral medium, and improves the detection sensitivity; Dynamic light path adjustment: the turntable 13 real-time calibrates the incident angle, ensures the balance of TE / TM polarization mode reflectivity, and eliminates environmental interference; Microfluid integration: the microinjector 11 system realizes efficient injection and cleaning of trace samples (such as cell culture medium, blood), and supports continuous detection.

[0044] The key parameters and optimization of the present application are that the resonant optical fluid chip 3 design: the thickness of the upper silver film layer 8 is 30-50 nm, the thickness of the lower silver film layer 9 is 300 nm, and the cavity height is 200-500 nm, which matches the characteristics of the chiral medium; Incident angle adjustment accuracy: the angle resolution of the turntable 13 reaches 0.01°, which ensures that the TE / TM mode reflectivity calibration error is less than 1%; Signal detection sensitivity: the response time of the second photodetector 12 is ≤1 ms, and the dynamic range covers 0.1-100 μW; Calibration method: a linear regression model is established by using known concentration S / R enantiomer standard solution (0.1-2 mg / mL), which ensures that the detection error is ≤5%.

[0045] Example 1: Figure 8The result of monitoring the dynamic change of the drug concentration in the cell experiment is shown in the figure, which shows the change of the chiral drug concentration in the culture medium after the melanoma B16 cells are cultured for different time under the action of 100 μmol / L S- / R-MTX. It can be seen that the concentration of the MTX drug in the culture medium gradually decreases over time, indicating that the MTX drug gradually enters the B16 cells and plays a role at this time, and the speed of the change of the MTX drug concentration gradually slows down. The change trend of the MTX drug concentration is the steepest just after being added, indicating that the absorption speed of the B16 cells to the MTX is fast at this time. With the passage of time, the B16 cells are gradually saturated with the MTX, and part of the B16 cells are inactivated under the action of the MTX, so that the absorption speed of the B16 cells to the MTX decreases. And after a long time of co-culture, the drug concentration change curve in the culture medium gradually approaches the horizontal, which means that the absorption of the B16 cells to the MTX in the culture medium gradually stops, indicating that a large number of B16 cells are inactivated. At the same time, by comparing the change of the drug concentration of the two enantiomers of the MTX over time, it can be found that the drug concentration curve of S-MTX decreases faster, which can enter the B16 cells at a faster speed. In the period from 3 h to 6 h, the drug concentration difference between the two is the largest. And after a long time of culture, the difference between the drug concentrations of the two gradually becomes smaller. It shows that the present application can measure the change of the chiral drug concentration in the cell experiment.

[0046] Example 2: Figure 9 The chiral drug metabolism curve of the blood sample in the animal experiment is shown, which shows the change of the concentration of the hypertensive drug in the rat body over time after the tail vein is administered for 0.5 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 4 h, 6 h, 8 h, 10 h, and 12 h. It can be seen from the result that the concentration of ADP in the blood of the rat decreases sharply in the first three hours, and then the metabolism rate gradually decreases. At the same time, the concentration of S-ADP in the blood is higher than that of R-ADP, indicating that the metabolism speed of S-ADP is slower, which can produce a sustained effect on hypertension. Finally, with the metabolism of the rat body, the concentrations of the two drugs continue to decrease, and the difference between the concentrations of the two drugs gradually decreases. This shows that the present application can detect the change of the drug concentration in the rat body over time.

[0047] The metal resonant optical fluid chip 3 of the present application combines the polarization light modulation technology to realize high-precision detection of chiral drugs, optimizes the interaction between the light field and the chiral medium, significantly improves the detection sensitivity, reduces the sample demand, and realizes a high-throughput and integrated detection process. Specifically, the following advantages are achieved:

[0048] 1. Ultra-high sensitivity: The reflectivity difference detection sensitivity reaches 5 times that of traditional polarimetry, and can identify 10 -6 level dielectric coefficient difference.

[0049] 2. Micro-detection: Sample consumption is as low as microliter level, suitable for cell metabolism, animal blood and other micro-detection scenarios.

[0050] 3. Fast response: Single detection time is less than 5 minutes, supporting real-time dynamic monitoring.

[0051] 4. Wide applicability: It has been verified for the detection of chiral drugs such as methotrexate (MTX) and amlodipine (ADP), and can be extended to other chiral compounds.

[0052] 5. Biological compatibility: The device is verified through cell experiments (B16 melanoma cells) and animal experiments (rat hypertension model), and can be directly applied to biomedical research.

[0053] The application can be applied to laboratory detection: used for quality control in the synthesis process of chiral drugs, quickly distinguishing enantiomeric purity; biomedical research: monitoring the metabolic kinetics of chiral drugs in cell culture or animal models; clinical diagnosis: combined with microfluidic technology, realizing the instant detection (POCT) of chiral drugs in blood or body fluid.

Claims

1. A drug chiral detection device based on a metal resonant optical fluidic chip, characterized in that, The application relates to a light source module, a polarization control module, a beam splitter, a polarization conversion module and a resonant light fluid chip which are sequentially arranged along the light path direction, the polarization control module comprises a half-wave plate and a linear polarizer which are sequentially arranged along the light path direction, one side of the beam splitter is provided with a first photoelectric detector, the first photoelectric detector is arranged in correspondence with a first splitting port of the beam splitter, the polarization conversion module is arranged in correspondence with a second splitting port of the beam splitter, the polarization conversion module comprises two quarter-wave plates which are sequentially arranged along the light path direction, the two quarter-wave plates are respectively used for converting linearly polarized light into left-handed circularly polarized light and right-handed circularly polarized light, the resonant light fluid chip comprises an upper silver film layer and a lower silver film layer which are arranged in parallel and a cavity layer which is formed between the upper silver film layer and the lower silver film layer, the cavity layer is connected with a microinjector through a conduit, one side of the resonant light fluid chip is provided with a second photoelectric detector, the second photoelectric detector is used for detecting the reflected light intensity of the resonant light fluid chip, and the signal output ends of the first photoelectric detector and the second photoelectric detector are electrically connected with a data processing unit.

2. The drug chirality detection device based on the metal resonant optical fluidic chip according to claim 1, characterized in that: The thickness of the upper silver film layer is 30-50 nm, the thickness of the lower silver film layer is 300 nm, and the height of the cavity layer is 200-500 nm. 3.The drug chiral detection device based on the metal resonant optical fluidic chip according to claim 1, characterized in that: The parallelism tolerances of the upper surface and the lower surface of the cavity layer are both less than 4 angular seconds on any 1cm measuring length.

4. The drug chirality detection device based on the metal resonant optical fluidic chip according to claim 1, characterized in that: The light source module comprises a 532nm single-longitudinal-mode laser, and the exit end of the 532nm single-longitudinal-mode laser is connected with a pinhole collimator.

5. The drug chirality detection device based on the metal resonant optical fluidic chip according to claim 1, characterized in that: The angle adjusting module comprises a rotary table and a driving device used for driving the rotary table to rotate, the resonant light fluid chip is fixedly arranged on the rotary table, and the angle resolution of the rotary table is 0.01 degrees.

6. The drug chirality detection device based on the metal resonant optical fluidic chip according to claim 1, characterized in that: The response time of the second photoelectric detector is less than or equal to 1ms, and the dynamic range covers 0.1-100 muW.

Images