Biomolecule detection chip and dual-polarization differential biomolecule detection method

Abstract

The invention discloses a biomolecule detection chip and a dual-polarization differential biomolecule detection method.The detection chip comprises a gold nano triangular plate (1) and a micro-annular resonant cavity (2) based on a ridge-type optical waveguide, the width of the gold nano triangular plate (1) is 20 times larger than the thickness, and the gold nano triangular plate (1) is arranged on the upper surface of the micro-annular optical waveguide (4) in a tiled mode; the micro-annular resonant cavity (2) is composed of a linear optical waveguide (3) and a micro-annular optical waveguide (4) coupled with the linear optical waveguide (3), and the linear optical waveguide (3) and the micro-annular optical waveguide (4) are both of a ridge-shaped optical waveguide structure. Based on the detection method, high-sensitivity and high-reliability single-molecule biomolecule detection is realized in a wide spectrum range from visible light to near-infrared light.

Description

Technical Field

[0001] The present invention relates to the fields of integrated photonic chips, optical sensing technology, nanotechnology and biological detection technology, and in particular to a biomolecule detection chip design and a biomolecule detection method thereof. Background Art

[0002] Biomolecule detection is an interdisciplinary field that combines knowledge from biology, chemistry, physics, engineering, and information technology. Its main purpose is to identify, quantify, or characterize various molecules in organisms, such as DNA, RNA, proteins, metabolites, etc., in order to understand the operating mechanism of biological systems, or to be used in disease diagnosis, drug development, environmental monitoring, and other aspects. Among them, biomolecule detection chips based on integrated optical sensing technology have unique advantages such as high sensitivity and rapid response. Optical sensing technology uses a variety of optical devices to convert interactions between biomolecules into quantifiable optical signals, and is widely used in environmental monitoring, biomedical testing, and other fields. A typical example is that label-free optical sensors based on optical waveguide structures (such as optical interferometers, optical microcavities, and metasurface structures) have been manufactured and applied in cutting-edge biochemical fields. These sensors use the basic principle of guiding light propagation to form a complex mechanism to achieve highly sensitive and specific environmental monitoring. Among them, the coupling system based on optical microcavity-surface plasmon can realize highly sensitive biosensors. This system couples whispering gallery mode (WGM) microresonators with localized plasmons (LSPs) on the surface of metal nanoparticles, which can not only reduce the linewidth of the LSP absorption peak, but also improve the optical response of the coupled system to subtle changes in the local dielectric environment through plasmon-induced near-field enhancement. When the WGM eigenmode excites the LSP-WGM coupling system, the LSP resonance excited by the near-field coupling will in turn modulate the WGM spectrum, thereby increasing the sensitivity of the WGM to subtle changes in the local dielectric environment, such as nanoparticles and biochemical molecules falling on the surface of the microcavity. At present, the sensitivity of this LSP-WGM system can reach the single-molecule level, indicating that it has important application value in biomedical sensors.

[0003] Gold nanotriangles (AuNTs), when illuminated by excitation light, the free electrons on the surface undergo collective resonance to form surface plasmons (LSPs), thereby greatly enhancing the local electric field and strengthening the interaction between light and matter to achieve the purpose of highly sensitive detection. Excitation light with a polarization direction parallel to the gold nanotriangles can achieve LSP resonance enhancement, but excitation light with a polarization direction perpendicular to the gold nanotriangles hardly produces LSP resonance enhancement. Therefore, AuNTs can achieve polarization-sensitive excitation LSP resonance in a wide spectral range, and AuNTs also have physical and chemical stability.

[0004] Lithium niobate (LN), as an excellent optical material, has stable physical and chemical properties, good electro-optic and acousto-optic characteristics, a high second-order nonlinear coefficient, and is transparent in the visible to mid-infrared wavelength range, thus being called "optical silicon". With the successful fabrication of lithium niobate single-crystal thin-film heterostructures, the optical waveguide structure on lithium niobate thin films (TFLN) has become a research hotspot in the field of integrated optics, and various integrated optical devices based on the lithium niobate optical waveguide structure have emerged one after another, including filters, electro-optic modulators, optical frequency combs, on-chip integrated lasers, and so on. The WGM resonator fabricated on the lithium niobate single-crystal thin-film heterostructure can have an extremely high quality factor, enabling the LSP-WGM coupling system to exhibit more excellent detection performance to meet the requirements of next-generation biophotonics applications. In this invention patent, we couple AuNTs with a resonance absorption spectrum covering a wide wavelength range from visible light to near-infrared with a high-Q thin-film lithium niobate microring resonator (TFLN-MRR) to form an ultra-high-sensitivity AuNTs-MRR detection system, achieving high-resolution and high-integration single-molecule-level biological detection in the visible to near-infrared wavelength window. Utilizing the strong polarization sensitivity of AuNTs and TFLN-MRR, a differential detection method based on the AuNTs-MRR system is developed to achieve highly reliable biological detection. By comparing the resonance peak wavelength shifts of the TE and TM polarization modes in the transmission spectrum of the AuNTs-MRR system, the analyte signal can be distinguished from the environmental change signal, thereby realizing reliable biomolecule detection. Summary of the Invention

[0005] Aiming at the technical problems existing in the above-mentioned prior art, the present invention aims to propose a biomolecule detection chip and a biomolecule detection method with dual-polarization difference. A biological detection chip is formed by coupling gold nanotriangles and a microring resonator based on a ridge optical waveguide structure. By comparing the resonance peak wavelength shifts of the TE polarization mode and the TM polarization mode in the transmission spectrum, the biological signal and the environmental change signal are analyzed to achieve highly sensitive and high-precision detection of biomolecules.

[0006] The present invention is realized by the following technical solutions:

[0007] In a first aspect, a biomolecule detection chip proposed by the present invention, the detection chip includes gold nanotriangles 1 and a microring resonator 2 based on a ridge optical waveguide. Among them, the width of the gold nanotriangles 1 is 20 times larger than the thickness, and they are arranged on the upper surface of the microring optical waveguide 4 in a tiled manner. The microring resonator 2 is composed of a straight optical waveguide 3 and a coupled microring optical waveguide 4, and both the straight optical waveguide 3 and the microring optical waveguide 4 are of ridge optical waveguide structure.

[0008] In some embodiments, light with different polarization states excites the gold nanorods 1, generating different plasma resonance electric field enhancement effects. When the polarization direction of the light is parallel to the gold nanorods 1, the free electrons on the surface of the gold nanorods oscillate collectively, forming local surface plasmons, so as to obtain enhanced resonance local electric fields and corresponding enhanced optical field energies.

[0009] In some embodiments, visible light to near-infrared light covering the wavelength band of 650nm to 1700nm excites the gold nanorods 1 to generate plasma resonance enhancement.

[0010] In some embodiments, the coupling distance and coupling length between the linear optical waveguide 3 and the micro-ring optical waveguide 4 simultaneously satisfy the coupling resonance of the TE polarization mode and the TM polarization mode. The polarization direction of the TE polarized light is parallel to the upper surface of the micro-ring optical waveguide 4, and the polarization direction of the TM polarized light is perpendicular to the upper surface of the micro-ring optical waveguide 4. The two polarization modes achieve coupling resonance in the micro-ring resonator 2 based on the ridge optical waveguide.

[0011] In some embodiments, the evanescent field generated by the TE polarization mode on the upper surface of the micro-ring optical waveguide 4 is strong, and the evanescent field generated by the component of the TM polarization mode whose polarization direction is parallel to the upper surface of the micro-ring optical waveguide 4, i.e., the TM-z polarization mode, on the upper surface of the micro-ring optical waveguide 4 is weak.

[0012] In some embodiments, the TE polarization mode light and the TM polarization mode light in the micro-ring resonator 2 based on the ridge optical waveguide have different free spectral ranges.

[0013] In some embodiments, the resonance of the gold nanorods is proportional to the absorption loss of light. The stronger the resonance of the gold nanorods, the greater the optical transmission loss of the micro-ring resonator 2.

[0014] In some embodiments, the TE mode of the biomolecule detection chip excites strong plasmon resonance of the gold nanorods and a large local electric field. Biomolecules can cause a significant shift in the wavelength of the TE mode in the transmission spectrum of the biomolecule detection chip; the TM mode of the biomolecule detection chip excites weak plasmon resonance of the gold nanorods and a small local electric field, and biomolecules cannot cause a significant shift in the wavelength of the TM mode in the transmission spectrum of the biomolecule detection chip.

[0015] In some embodiments, the wavelength shift of the TE mode in the transmission spectrum of the biomolecule detection chip is affected by both biomolecules and environmental noise. The wavelength shift of the TM mode in the transmission spectrum of the biomolecule detection chip is only affected by environmental noise. Subtracting the wavelength shift of the TM mode from the wavelength shift of the TE mode in the transmission spectrum of the biomolecule detection chip can eliminate the influence of environmental noise.

[0016] In a second aspect, the present invention proposes a biomolecule detection method based on dual polarization difference of a biomolecule detection chip, including:

[0017] Utilize the light with the polarization direction of the TE mode transmitted in the micro-ring resonator 2 based on the ridge optical waveguide being parallel to the triangular gold sheet to excite the enhancement of the plasmon resonance electric field of the triangular gold nanoparticle sheet 1, resulting in the broadening of the TE resonance peak linewidth following the absorption loss of the triangular gold nanoparticle sheet 1, while the linewidth of the TM resonance peak with the polarization direction perpendicular to the triangular gold sheet remains unchanged;

[0018] With the enhancement of the plasmon resonance electric field caused by the TE polarized light, the wavelength shift of the resonance peak of the TE polarization mode is caused by biomolecules, while the resonance peak of the TM polarization mode does not shift;

[0019] Compare the wavelength shifts of the resonance peaks of the TE polarization mode and the TM polarization mode in the transmission spectrum, and analyze the biological signal and the environmental change signal to achieve biomolecule detection;

[0020] This detection method realizes single-molecule highly sensitive and highly reliable biomolecule detection in the wide spectral range from visible light to near-infrared light.

[0021] Compared with the prior art, the advantages and achieved positive technical effects of the present invention are as follows:

[0022] 1) A biomolecule detection chip composed of a coupling structure of the triangular gold nanoparticle sheet 1 (AuNTs) and the micro-ring resonator 2 (TFLN-MRR) based on the ridge optical waveguide is designed, which can generate the plasmon resonance enhancement effect under the excitation of visible light to near-infrared light covering the wavelength band from 650 nm to 1700 nm, and also has the advantages of simple structure, low processing cost and low energy consumption;

[0023] 2) The triangular gold nanoparticle sheet is excited by light with different polarization states to generate different plasmon resonance electric field enhancement effects, including the excitation light with the polarization direction of the light field energy parallel to the plane of the triangular gold nanoparticle sheet generating the plasmon resonance field strength, and the excitation light with the polarization direction of the light field energy perpendicular to the plane of the triangular gold nanoparticle sheet not generating the plasmon resonance enhancement; the excitation light band of the plasmon resonance enhancement generated by the triangular gold nanoparticle sheet covers the visible light to near-infrared light range from 650 nm to 1700 nm, realizing label-free, highly reliable and highly sensitive biomolecule detection working in the near-infrared band. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 It is a schematic structural diagram of a biomolecule detection chip of the present invention;

[0025] Figure 2It is a simulation diagram of the optical field distribution of TE and TM polarized light in a lithium niobate ridge optical waveguide structure. (2a) is a simulation diagram of the optical field distribution of TE polarized light in a lithium niobate ridge optical waveguide, and (2b) is a simulation diagram of the optical field distribution of TM-z polarized light in a lithium niobate ridge optical waveguide;

[0026] Figure 3 It is a simulation diagram of the optical field distribution for optically exciting the local surface plasmon resonance of gold nanorods (AuNTs). (3a) is a simulation diagram of the enhanced local optical field of AuNTs caused by the excitation light with the polarization direction parallel to the plane of the nanorods (AuNTs), and (3b) is a simulation diagram of the optical field distribution of AuNTs caused by the excitation light with the polarization direction perpendicular to the plane of the nanorods (AuNTs);

[0027] Figure 4 It is the resonance absorption spectrum diagram and morphological characterization diagram of gold nanorods (AuNTs). (4a) is the resonance absorption spectrum diagram of AuNTs from the visible light to the near-infrared wavelength range and the schematic diagram of the side length of the gold nanorods (AuNTs), and (4b) is the schematic diagram of the thickness of the gold nanorods (AuNTs);

[0028] Figure 5 It is the microscopic characterization diagram and transmission spectrum comparison diagram of the biomolecule detection chip according to the embodiment of the present invention. (5a) to (5c) are the microscopic characterization diagrams of the biomolecule detection chip, (5d) is the comparison diagram of the transmission spectral lines of the TE mode when the MRR bare cavity and an excessive amount of AuNTs are placed on the MRR, (5e) is the comparison diagram of the transmission spectral lines of the TM mode when the MRR bare cavity and an excessive amount of AuNTs are placed on the MRR, and (5f) is the comparison diagram of the transmission spectral lines of the hybrid mode (both TE mode and TM mode exist simultaneously in the spectrum) when the MRR bare cavity and an excessive amount of AuNTs are placed on the MRR;

[0029] Figure 6 It is the transmission spectrum diagram of the biomolecule detection chip; (6a) is the transmission spectrum diagram of the biomolecule detection chip, (6b) to (6d) show that as the number of biomolecules increases and interference factors are inserted, the resonant peak wavelength of the TE mode will be affected by both factors, while the TM mode will only be affected by the interference factors, and (6e) shows that subtracting the resonant peak wavelength shift of the TM polarization mode from the resonant peak wavelength shift of the TE polarization mode can remove the influence of environmental noise;

[0030] Reference numerals: 1. Gold nanorods (AuNTs), 2. Micro-ring resonator based on ridge optical waveguide (LNTF-MRR), 3. Straight optical waveguide, 4. Micro-ring optical waveguide, 10. Receive optical signal, 20. Resonant optical signal. Detailed implementation manners

[0031] Next, the technical solutions will be clearly described in conjunction with the drawings and embodiments.

[0032] Example 1

[0033] As Figure 1 shown, a biomolecule detection chip of the present invention is formed by coupling gold nanorods 1 (AuNTs) and a micro-ring resonator 2 (TFLN-MRR) based on a ridge optical waveguide. Among them, the micro-ring resonator 2 is based on a ridge optical waveguide structure, the gold nanorods 1 are arranged on the upper surface of the micro-ring optical waveguide part 4 in a tiled manner, and the width of the gold nanorods 1 is 20 times larger than the thickness. Anisotropy causes the extension of the electron oscillation path in the longitudinal mode (the longitudinal mode is the polarization mode with the polarization direction parallel to the gold triangle), the restoring force of the electrons oscillating along the long axis is weakened, resulting in a reduction of the resonance energy, the corresponding frequency of the required photons is reduced, and the wavelength of the resonance mode is longer (redshift). The micro-ring resonator 2 is composed of a straight optical waveguide 3 and a coupled micro-ring optical waveguide 4, and both the straight optical waveguide 3 and the micro-ring optical waveguide 4 are of ridge optical waveguide structure.

[0034] The optical signal is introduced into the detection chip from the straight optical waveguide 3, and the received optical signal is obtained. After the received optical signal is coupled into the micro-ring waveguide 4, a resonant optical signal is obtained, and the resonant optical signal is then exported from the straight optical waveguide 3. The resonant light transmitted in the micro-ring waveguide excites the gold nanorods 1 (AuNTs) on the surface, realizing local light field enhancement to utilize the locally enhanced light field for biomolecule detection. The TE mode excitation light with the polarization direction parallel to the gold nanorods 1 (AuNTs) can realize light field enhancement, but the TM mode excitation light with the polarization direction perpendicular to the gold nanorods 1 (AuNTs) hardly enhances the light field. The gold nanorods 1 (AuNTs) achieve polarization-sensitive light excitation. As Figure 2 shown, the light field intensity of (2a) is nearly 5000 times larger than that of (2b). The gold nanorods 1 (AuNTs) achieve differential excitation of the TE and TM polarization modes.

[0035] As Figure 3 shown, the prepared gold nanorods 1 (AuNTs) have strong absorption resonance for light in the wavelength range of 650 nm to 1700 nm. The gold nanorods 1 (AuNTs) can be used to achieve light field enhancement in the wavelength range of 650 nm to 1700 nm. At the same time, the thickness of the gold nanorods 1 (AuNTs) is less than 10 nm, the side length is greater than 200 nm, and the anisotropy ratio is greater than 20.

[0036] In an integrated waveguide, the TM mode also has a polarization component parallel to the gold nanotriangle 1 (AuNTs) on the upper surface of the microring waveguide, that is, the TM-z polarization mode, which can also excite the local electric field resonance enhancement of the gold nanotriangle 1 (AuNTs) on the upper surface of the microring waveguide. Therefore, a ridge optical waveguide structure needs to be designed to eliminate the influence of the TM-z polarization mode. In addition, in order to ensure that the free spectral ranges of the TE polarization mode and the TM polarization mode in the microring resonator 2 (MRR) are different to distinguish the resonance peak information of the two polarization modes in the transmission spectrum of the AuNTs-MRR system, the effective refractive indices of the TE polarization mode and the TM polarization mode in the waveguide are made different by designing a ridge optical waveguide structure. The specific implementation scheme: Under the condition of a lithium niobate thin film with a thickness of 600 nm, the ridge width W of the lithium niobate ridge optical waveguide is set to 1800 nm, and the outer ridge height h is greater than or equal to 300 nm, ensuring that the effective refractive indices of the TE polarization mode and the TM polarization mode in the waveguide are different, and the optical field energies of the TE polarization mode and the TM-z polarization mode on the upper surface of the waveguide are different. At this structural size, as Figure 4 shown, on the upper surface of the waveguide, the energy of the TE polarization mode is 10 times greater than that of the TM-z polarization mode.

[0037] Specifically, light with different polarization states excites the gold nanotriangle 1 to produce different plasma resonance electric field enhancement effects, including the excitation light with a polarization direction parallel to the plane of the gold nanotriangle 1 generating an enhanced plasma resonance field strength, and the excitation light with a polarization direction perpendicular to the plane of the gold nanotriangle 1 not generating plasma resonance enhancement.

[0038] Specifically, the excitation light band for the plasma resonance enhancement realized by the gold nanotriangle 1 covers the visible light to near-infrared light range from 650 nm to 1700 nm.

[0039] Specifically, the coupling spacing gap and the coupling length length between the linear optical waveguide 3 and the microring optical waveguide 4 can simultaneously satisfy the coupling resonance of the TE polarization mode and the TM polarization mode; the polarization direction of the TE mode light is parallel to the upper surface of the waveguide, and the polarization direction of the TM mode light is perpendicular to the upper surface of the waveguide, and both polarization modes can couple and resonate in the MRR.

[0040] Specifically, the microring resonator (MRR) based on the ridge optical waveguide structure includes two polarization modes: the TE polarization mode has a stronger evanescent field strength on the upper surface of the waveguide, and the TM-z polarization mode (the component of the TM mode with a polarization direction parallel to the upper surface of the waveguide) has a weaker evanescent field strength on the upper surface of the waveguide.

[0041] Specifically, the free spectral ranges (FSR) of the TE polarization mode light and the TM polarization mode light in the microring resonator (MRR) based on the ridge optical waveguide are different.

[0042] Specifically, the TE-polarized light transmitted in the micro-ring resonator (MRR) based on a ridge optical waveguide can excite the enhanced local surface plasmon (LSP) resonance electric field of the gold nanorods (AuNTs), resulting in an increase in the linewidth of the TE resonance peak due to the absorption loss of the gold nanorods (AuNTs). However, the TM-polarized light transmitted cannot excite the enhanced local surface plasmon (LSP) resonance electric field of the gold nanorods (AuNTs). Therefore, the linewidth of the TM resonance peak remains unchanged.

[0043] Specifically, due to the enhanced local surface plasmon (LSP) resonance electric field effect generated by the TE-polarized light, biomolecules will cause a wavelength shift of the resonance peak of the TE mode, while the resonance peak of the TM mode will not be affected by biomolecules and will not shift.

[0044] Specifically, external interference factors such as laser frequency fluctuations, thermal noise, detector noise, crosstalk between device components, and environmental changes can cause the same wavelength shift of the resonance peaks of the TE and TM polarization modes.

[0045] Specifically, the wavelength shift of the resonance peak of the TE polarization mode will be affected by both environmental interference factors and biomolecules, while the wavelength shift of the resonance peak of the TM polarization mode is mainly affected by environmental interference factors. By comparing the wavelength shifts of the resonance peaks of the TE and TM polarization modes in the transmission spectrum of the AuNTs-MRR system, the analyte signal and the environmental change signal can be distinguished, thereby achieving accurate biomolecule detection.

[0046] Specifically, single-molecule highly sensitive and highly reliable biomolecule detection is achieved in the wide spectral range from visible light to near-infrared.

[0047] Specifically, compared with short wavelengths, near-infrared light has a deeper penetration depth in biological tissues, which is more conducive to in-vivo biological detection applications.

[0048] Embodiment 2

[0049] The biomolecule detection method based on dual-polarization differential of a biomolecule detection chip according to the present invention includes the following steps:

[0050] The TE-polarized light transmitted in the micro-ring resonator 2 based on a ridge optical waveguide excites the enhanced plasmon resonance electric field of the gold nanorods 1, resulting in an increase in the linewidth of the TE resonance peak following the absorption loss of the gold nanorods 1, while the linewidth of the TM resonance peak remains unchanged;

[0051] Due to the enhanced plasmon resonance electric field effect generated by the TE-polarized light, biomolecules can cause a wavelength shift of the resonance peak of the TE polarization mode, while the resonance peak of the TM polarization mode does not shift;

[0052] Compare the resonant peak wavelength shifts of the TE polarization mode and the TM polarization mode in the transmission spectrum, and analyze the biological signals and environmental change signals to achieve the precise detection of biomolecules.

[0053] The specific description of realizing biomolecule detection by combining the resonant peak wavelength shift and analyzing the biological signals and environmental change signals is as follows:

[0054] For the triangular gold flakes, the oscillation modes of its free electrons in different directions will separate to form multiple resonance peaks; it exhibits two local surface plasmon resonance (LSP) modes: longitudinal and transverse. The transverse mode is the mode where the resonance direction is perpendicular to the triangular gold flakes, with a shorter oscillation path and corresponding to higher energy (blue light or visible light region); the longitudinal mode is the mode where the resonance direction is parallel to the triangular gold flakes, with a longer oscillation path and corresponding to lower energy (red light or near-infrared region). Therefore, when using 1550 near-infrared light, only when the light polarization direction is parallel to the triangular gold flakes, the surface free electrons of the triangular gold flakes will oscillate collectively to form local surface plasmons, enhancing the local electric field of resonance by hundreds of times and the corresponding light field energy by tens of thousands of times, thereby greatly enhancing the interaction between light and matter;

[0055] The resonance of the triangular gold flakes is proportional to the optical absorption loss. The stronger the resonance of the triangular gold flakes, the greater the transmission loss of the microring resonator 2;

[0056] According to the transmission characteristics of the microring resonator, the transmission loss of the microring resonator is positively correlated with its resonance linewidth;

[0057] Utilize the fact that the polarization direction of the TE mode light transmitted in the microring resonator 2 based on the ridge waveguide is parallel to the triangular gold flakes, to excite the enhancement of the plasma resonance electric field of the gold nanoscale triangular flakes 1, resulting in the broadening of the TE resonance peak linewidth following the absorption loss of the gold nanoscale triangular flakes 1, and the polarization direction of the TM mode is perpendicular to the triangular gold flakes, so the TM resonance peak linewidth remains unchanged;

[0058] According to the mode perturbation theory, for a specific mode, the ratio of the spatial energy where the biomolecule is located to the total energy of the microring resonator is equal to the ratio of the resonance wavelength shift of the resonator caused by the biomolecule to the working wavelength. Since the TE mode is excited by the triangular gold flakes to form an extremely strong local electric field, when the biomolecule falls here, the spatial energy where the biomolecule is located is enhanced by tens of thousands of times, so the wavelength shift of the TE mode also increases by tens of thousands of times. At this time, the TM mode has no resonance enhancement, and the wavelength shift of the TM mode is extremely small. Therefore, the wavelength shift of the TM mode hardly changes compared to the wavelength shift of the TE mode. In other words, with the enhancement effect of the plasma resonance electric field generated by the TE polarized light, the biomolecule causes the wavelength shift of the TE polarization mode resonance peak, while the TM polarization mode resonance peak does not shift;

[0059] Compare the resonant peak wavelength shifts of the TE polarization mode and the TM polarization mode in the transmission spectrum, and analyze the biological signals and environmental change signals to achieve precise detection of biomolecules.

[0060] Specifically, this detection method realizes single-molecule highly sensitive and highly reliable biomolecule detection in the wide spectral range from visible light to near-infrared.

[0061] As Figure 5 shown, (5a)-(5c) show the scanning electron microscope images of the gold nanorod triangle (AuNTs)-micro-ring resonator (MRR) coupling structure. The specific preparation process is to dilute the AuNTs solution with a concentration of 12.5 pM by 106 times with pure water, remove the protein in the solution by centrifugation, and then drop it on the TFLN-MRR. Appropriate concentration of AuNTs can achieve highly sensitive biomolecule detection. Dry the AuNTs-MRR coupling system in a hair dryer at 60 °C for 30 minutes to cure it, and rinse it with pure water for 1 minute to remove the unstable AuNTs that may interfere with biomolecule detection. To measure the polarization sensitivity of the AuNTs-MRR coupling system, a tunable laser (Santec TSL-570, tuning wavelength range: 1480-1640 nm) and a three-paddle fiber polarization controller are used to generate TE and TM polarized light, and a lens fiber is used to couple it to the TFLN-MRR with the help of an alignment coupling platform. The transmission spectrum power is measured by an optical power meter. Figure 5 d shows that after depositing AuNTs on the TFLN-MRR, the linewidth of the TE mode resonant peak in the transmission spectrum broadens and the Q value decreases. This energy loss in the MRR can be attributed to the local surface plasmon (LSP) resonance excited by the TE mode and the energy absorption of AuNTs. In contrast, Figure 5 e shows that there is no energy loss in the resonant peak of the TM mode, indicating that the TM mode in the MRR cannot excite LSP resonance and can therefore be used to exclude interference signals. Figure 5 f shows that the free spectral range of the TM mode is 0.16 nm, and the free spectral range of the TE mode is 0.15 nm. The free spectral ranges of the TM mode and the TE mode are different. Therefore, the TM mode and the TE mode can be distinguished in the transmission spectrum of the biomolecule detection chip.

[0062] As Figure 6 shown, Figure 6 a shows that in the test spectrum of biomolecules, the TE mode resonant peak and the TM mode resonant peak can be accurately distinguished. Assemble a microfluidic controller to deposit the same concentration of BSA (bovine serum albumin) solution per drop with high precision at a specific position in the AuNTs-MRR system. Figure 6Figures 6b - 6d show that the deposition of BSA on the AuNTs - MRR system only causes a red - shift of the resonance peak of the TE mode, while the resonance peak of the TM mode remains unaffected. After the first drop of the solution (each drop contains 5 - 6 BSA molecules), the interaction between the localized surface plasmon (LSP) resonance of AuNTs and the TE mode in the MRR is affected, resulting in a red - shift of approximately 2 pm in the resonance peak of the TE mode. Figure 6 Figure 6d shows that continuous addition of BSA causes a continuous red - shift of almost the same magnitude (less than 4 pm) in the resonance peak of the TE mode. In contrast, the almost unaffected TM resonance peak indicates that the TM mode propagating in the MRR cannot excite the interaction between the LSP of AuNTs and BSA. If the light source fluctuates, for example, its wavelength suddenly increases by 50 pm, the resonance peaks of both the TE and TM modes will drift by almost the same range Δλ ∼ 50 pm, as Figure 6 shown in Figures 6c and 6d. This confirms that the influence of external interference on the transmission of TE and TM modes in the MRR is similar. This also indicates that the resonance peak shift of the TM mode can be used as a reference to remove interference signals. Therefore, the wavelength shift Δλ of the TE mode TE subtracted by the wavelength shift Δλ of the TM mode TM is the signal from BSA molecules. Figure 6 Figure 6e shows that as BSA molecules are continuously deposited, the difference between Δλ TE - Δλ TM increases linearly, so that the number of BSA molecules can be estimated by dividing the total wavelength red - shift range of the resonance peak by the red - shift range caused by a single BSA molecule. In fact, information about a single molecule can even be inferred from the transmission spectrum. It can be seen that the differential measurement here is crucial for the accuracy of the AuNTs - MRR sensing system.

[0063] Experimental test results: Therefore, a biomolecule detection chip based on the AuNTs - MRR system of the present invention can achieve highly reliable and highly sensitive detection of biomolecules in a wide wavelength range from visible light to near - infrared.

[0064] Example 2:

[0065] The synthesis procedure of AuNTs (gold nanorods) with an anisotropy ratio greater than 20 (thickness 10 nm, side length 200 nm) of the present invention includes continuous controlled growth of AuNTs after preparing gold seeds. First, a gold seed solution is prepared by adding HAuCl4 (0.01 M, 1 mL) to 36 mL of water and adding trisodium citrate (1 mL, 10 mM). After stirring for 20 minutes, NaBH4 (1 mL, 100 mM) is quickly added, and the seed solution is aged at 25 °C for 2 hours.

[0066] Next, three growth solutions (GS1, GS2, and GS3) were prepared separately as follows: In GS1, 10 mL of CTAB (0.05 M), 0.25 mL of HAuCl4 (10 mM), 0.05 mL of NaOH (0.1 M), 50 μL of KI (10 mM), and 0.04 mL of ascorbic acid (0.1 M) were mixed. In GS2, 10 mL of CTAB (0.05 M), 0.25 mL of HAuCl4 (10 mM), 0.05 mL of NaOH (0.1 M), 50 μL of KI (10 mM), and 0.08 mL of ascorbic acid (0.1 M) were combined. In GS3, 100 mL of CTAB (0.05 M), 3 mL of HAuCl4 (10 mM), 0.5 mL of NaOH (0.1 M), 0.5 mL of KI (10 mM), and 0.4 mL of ascorbic acid (0.1 M) were mixed.

[0067] The growth process involved sequentially adding 1 mL of the gold seed solution to GS1, briefly mixing for 1 second, and then transferring 1 mL of the mixed GS1 to GS2 and gently shaking for 5 seconds. Subsequently, 1 mL of the mixed GS2 was added to GS3. After gentle manual stirring for 10 seconds, the solution was left to stand for 24 hours to promote the growth of AuNTs. After the growth period ended, the bottom precipitate was collected and centrifuged at 8500 revolutions per minute for 10 minutes, and this step was repeated twice. The final obtained AuNTs were dispersed in 2 mL of CTAB (5 mM) solution for further characterization and application.

[0068] Example 3:

[0069] The micro-ring resonator (MRR) of the present invention was fabricated on a 0.6-μm-thick thin-film lithium niobate (TFLN);

[0070] Step 1, Chromium metal layer deposition:

[0071] First, a 170-nm-thick chromium (Cr) metal layer was deposited on a 600-nm-thick lithium niobate (LiNbO3) thin-film wafer using electron beam evaporation (EBE). This chromium layer will serve as a mask material in subsequent lithography and etching steps.

[0072] Step 2, Photoresist coating and patterning:

[0073] Next, a 2-μm-thick photoresist was spin-coated on the chromium layer. Then, using a stepper, the designed waveguide structure and marker pattern were transferred from the photomask to the photoresist layer through ultraviolet lithography. This step was achieved by ultraviolet irradiation, which selectively changed the chemical properties of the photoresist for subsequent pattern transfer.

[0074] Step 3, dry etching of the chromium layer:

[0075] Use an inductively coupled plasma (ICP) etching device to dry etch the chromium layer to form a chromium mask according to the pattern defined in the photoresist. To ensure that all unwanted chromium is completely removed, slight over-etching can be performed during the etching process. After the etching is completed, immerse the chip in a photoresist stripper at 80 °C for 30 minutes and rinse with a solvent to thoroughly remove the photoresist, exposing the underlying lithium niobate surface.

[0076] Step 4, dry etching of lithium niobate:

[0077] Use the ICP etching device again, this time to dry etch the lithium niobate thin film to fabricate a waveguide structure and a marking pattern according to the previously formed chromium mask. The etching depth is 300 nanometers, and this step is crucial for preparing the final lithium niobate optical waveguide structure.

[0078] Step 5, removal of the chromium mask:

[0079] Finally, immerse the etched wafer in a chromium etchant at 40 °C for 3 minutes to completely remove all the chromium masks, exposing a pure lithium niobate surface. In this way, the preliminary processing of the lithium niobate chip is completed, and it is ready for the next step of processing or can be directly used in applications.

[0080] According to the above preparation method, a biomolecule detection chip based on the AuNTs-MRR system of the present invention can be obtained.

[0081] Based on the embodiments of the present invention, all other embodiments and technical substitutions and deformations of the embodiments obtained by those of ordinary skill in the art without departing from the spirit of the present invention and without making creative efforts shall fall within the protection scope of the present invention.

[0082] Based on the embodiments of the present invention, all other embodiments and technical substitutions and deformations of the embodiments obtained by those of ordinary skill in the art without departing from the spirit of the present invention and without making creative efforts shall fall within the protection scope of the present application of the present invention.

Claims

1. A biomolecule detection chip, characterized in that, The detection chip includes gold nanorods (1) and a micro-ring resonator (2) based on a ridge optical waveguide. Among them, the width of the gold nanorods (1) is 20 times larger than the thickness, and it is arranged on the upper surface of the micro-ring optical waveguide (4) in a tiled manner. The micro-ring resonator (2) is composed of a straight optical waveguide (3) and a coupled micro-ring optical waveguide (4), and both the straight optical waveguide (3) and the micro-ring optical waveguide (4) are ridge optical waveguide structures.

2. The biomolecule detection chip according to claim 1, wherein Light with different polarization states excites the gold nanorods (1), generating different plasma resonance electric field enhancement effects, including that the polarization direction of the light is parallel to the gold nanorods (1), causing the collective oscillation of the surface free electrons of the gold nanorods to form localized surface plasmons, so as to obtain an enhanced resonant local electric field and corresponding enhanced optical field energy.

3. The biomolecule detection chip according to claim 1, characterized in that, Visible light to near-infrared light covering the wavelength range of 650nm to 1700nm excites the gold nanorods (1) to generate plasma resonance enhancement.

4. The biomolecule detection chip according to claim 1, wherein The coupling distance and coupling length between the straight optical waveguide (3) and the micro-ring optical waveguide (4) simultaneously satisfy the coupling resonance of the TE polarization mode and the TM polarization mode. The polarization direction of the TE polarized light is parallel to the upper surface of the micro-ring optical waveguide (4), and the polarization direction of the TM polarized light is perpendicular to the upper surface of the micro-ring optical waveguide (4). The two polarization modes achieve coupling resonance in the micro-ring resonator (2) based on the ridge optical waveguide.

5. A biomolecule detection chip according to claim 1, characterized in that, The evanescent field intensity generated by the TE polarization mode on the upper surface of the micro-ring optical waveguide (4) is strong, and the evanescent field intensity generated by the component of the TM polarization mode whose polarization direction is parallel to the upper surface of the micro-ring optical waveguide (4), that is, the TM-z polarization mode, on the upper surface of the micro-ring optical waveguide (4) is weak.

6. A biomolecule detection chip according to claim 1, characterized in that, The TE polarization mode light and the TM polarization mode light in the micro-ring resonator (2) based on the ridge optical waveguide have different free spectral ranges.

7. A biomolecule detection chip according to claim 1, characterized in that, The resonance of the gold nanorods is proportional to the optical absorption loss. The stronger the resonance of the gold nanorods, the greater the optical transmission loss of the micro-ring resonator (2).

8. A biomolecule detection chip according to claim 1, characterized in that, For the biomolecule detection chip, the TE mode excites strong plasmon resonance of the gold nanorods and a large local electric field. Biomolecules can cause a significant shift in the wavelength of the TE mode in the transmission spectrum of the biomolecule detection chip; the TM mode of the biomolecule detection chip excites weak plasmon resonance of the gold nanorods and a small local electric field, and biomolecules cannot cause a significant shift in the wavelength of the TM mode in the transmission spectrum of the biomolecule detection chip.

9. A biomolecule detection chip according to claim 1, characterized in that, The wavelength shift of the TE mode in the transmission spectrum of the biomolecule detection chip is affected by both biomolecules and environmental noise. The wavelength shift of the TM mode in the transmission spectrum of the biomolecule detection chip is only affected by environmental noise. Subtracting the wavelength shift of the TM mode from the wavelength shift of the TE mode in the transmission spectrum of the biomolecule detection chip can remove the influence of environmental noise.

10. A biomolecule detection method with dual polarization difference is implemented based on a biomolecule detection chip according to any one of claims 1 to 9, characterized in that, Including: By using the light with the polarization direction of the TE mode transmitted in the micro-ring resonator (2) based on the ridge optical waveguide being parallel to the triangular gold sheet, the plasma resonance electric field of the triangular gold sheet (1) is excited to be enhanced, resulting in the broadening of the TE resonance peak linewidth following the absorption loss of the triangular gold sheet (1), and the linewidth of the TM resonance peak with the polarization direction of the TM mode perpendicular to the triangular gold sheet remaining unchanged; With the enhancement effect of the plasma resonance electric field generated by the TE polarized light, the wavelength of the resonance peak of the TE polarization mode is shifted by biomolecules, while the resonance peak of the TM polarization mode does not shift; By analyzing the wavelength shift of the resonance peaks of the TE polarization mode and the TM polarization mode in the differential transmission spectrum, biological signals and environmental change signals are analyzed to achieve highly reliable detection of biomolecules; This detection method realizes the detection of single-molecule biomolecules in a wide spectrum range from visible light to near-infrared light.

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