Optical sensor, detection method and use

Abstract

The application discloses an optical sensor, which comprises a light source unit, a sensing unit, a reference unit and a detection unit. One detection light beam emitted by the light source unit is transmitted to the sensing unit and received by the detection unit after interacting with a target sample in the sensing unit. One reference light beam emitted by the light source unit is transmitted to the reference unit and received by the detection unit through the reference unit. The detection unit recombines the detection light beam and the reference light beam, and obtains the characteristics of the target sample by performing spectrum analysis on the recombined light beam. The application realizes high-sensitivity and wide-dynamic detection range of the sample characteristics in the modes of transmission, scattering, reflection and surface plasmon resonance by regulating the optical path difference of the double light paths and combining the phase modulation method.

Description

Technical Field

[0001] This invention belongs to the field of optical sensing technology, and specifically relates to an optical sensor, detection method, and application. Background Technology

[0002] Medical biosensing and biomarker detection currently play a crucial role in the healthcare field, aiding in early disease diagnosis, personalized medicine, treatment, and health monitoring. The rapid and highly sensitive identification and detection of biomarkers using biosensing technology can provide vital bioanalytical information for disease diagnosis and treatment, potentially driving rapid advancements in the field of medical diagnostics.

[0003] Sensitivity, response speed, and detection cost are key factors influencing the medical and biological applications of biosensors. Among them, optical biosensors, which utilize photons and light signals to analyze specific biological or chemical substances, have received widespread attention in various fields such as medicine and drug development due to their high sensitivity and real-time detection capabilities. Achieving high sensitivity in optical sensors typically requires precise control and analysis of the light signals. For example, by modulating the optical phase, the achievable sensitivity can be increased by two orders of magnitude compared to light intensity modulation methods. Summary of the Invention

[0004] One embodiment of this disclosure is a phase-modulated broadband interferometric and multi-sensing-site optical sensor for sensing and detecting the characteristics of a target sample. The optical sensor includes a light source unit, a sensing unit, a reference unit, and a detection unit. Here, "sample" and "sample object" have the same meaning.

[0005] A probe light signal emitted by the light source unit is transmitted to the sensing unit, and then received by the detection unit. After the probe light signal interacts with the target sample in the sensing unit, it is received by the detection unit.

[0006] Another reference light signal emitted by the light source unit is transmitted to the reference unit and then received by the detection unit.

[0007] The light source unit includes a light source, a first optical waveguide, a first collimating lens group, a beam splitter and a reflector arranged sequentially along the optical path.

[0008] The detection unit includes a second collimating lens group and a second optical waveguide, a third collimating lens group and a third optical waveguide arranged according to the receiving optical path, and a spectral analysis unit connected to the second and third optical waveguides respectively. The detection unit recombines and superimposes the probe beam and the reference beam, and then performs spectral analysis on the recombined beam to obtain the characteristics of the target sample.

[0009] The sensing unit includes a first front linear polarizer, a first birefringent crystal, a sample sensing unit, and a first rear linear polarizer arranged sequentially along the optical path.

[0010] The reference unit includes a second front linear polarizer, a second birefringent crystal, and a second rear linear polarizer arranged sequentially along the optical path.

[0011] The optical path difference of the first birefringent crystal is L1, and the optical path difference of the second birefringent crystal is L2, where L2 ≠ L1, and the difference ΔL = |L1 - L2|.

[0012] One or more sensing and detection sites of the optical sensor are constructed by modulating ΔL.

[0013] This disclosure provides an optical sensor based on optical interferometry and biosensing technology, which provides a dual-path optical path difference-controlled spectral interferometer. Based on the wide-spectral multi-site interference of dual-path coupling, by precisely controlling the optical path difference in the two spectral interference optical paths and combining it with the phase modulation method, it is possible to achieve autonomous design and control of the phase sensing band and wavelength position. Furthermore, it utilizes multiple phase sensing sites to perform real-time sensing of light-matter interactions based on modes such as transmission, scattering, reflection, and surface plasmon resonance, with high sensitivity and a wide dynamic range. Attached Figure Description

[0014] The above and other objects, features, and advantages of exemplary embodiments of the present invention will become readily apparent from the following detailed description taken in conjunction with the accompanying drawings. Several embodiments of the invention are illustrated in the drawings by way of example and not limitation, wherein:

[0015] Figure 1 A schematic diagram of an optical sensor configuration according to one embodiment of the present disclosure.

[0016] Figure 2 A schematic diagram of the composition of a light source and a beam splitting unit according to one embodiment of the present disclosure.

[0017] Figure 3 A schematic diagram of the composition of an optical interference sensing unit according to one embodiment of the present disclosure.

[0018] Figure 4 A schematic diagram of the composition of an optical interference reference unit according to one embodiment of the present disclosure.

[0019] Figure 5 A schematic diagram of the composition of an optical detection system unit according to one embodiment of the present disclosure.

[0020] Figure 6 A schematic diagram of a bio-optical sensing detection method according to one embodiment of the present disclosure.

[0021] Figure 7 A schematic diagram of a bio-optical sensing detection method according to one embodiment of the present disclosure.

[0022] Figure 8 A schematic diagram of a bio-optical sensing detection method according to one embodiment of the present disclosure.

[0023] Figure 9 An example diagram of bio-optical sensing detection according to one embodiment of this disclosure.

[0024] Figure 10 An example diagram of bio-optical sensing detection according to one embodiment of this disclosure.

[0025] Figure 11 An example diagram of bio-optical sensing detection according to one embodiment of this disclosure.

[0026] Figure 12 A schematic diagram of an optical sensor configuration according to one embodiment of the present disclosure.

[0027] in,

[0028] 100—Light source and beam splitting unit,

[0029] 101—Broadband light source, 102—First optical fiber, 103—First collimating lens group, 104—Beam splitter assembly, 105—Reflector.

[0030] 200—Optical Interference Sensing Unit

[0031] 201 – First pre-polarizing linear polarizer; 202 – First birefringent crystal; 203 – Replaceable sensing unit.

[0032] 203a – Reflective sensing unit, 203b – Transmissive sensing unit, 203c – Transmissive scanning sensing unit.

[0033] 204—First post-polarizing filter,

[0034] 300—Optical Interference Reference Unit

[0035] 301 – Second front linear polarizer, 302 – Second birefringent crystal, 303 – Second rear linear polarizer.

[0036] 400—Optical Inspection System Unit

[0037] 401—Second collimating lens group, 402—Second optical fiber, 403—Third collimating lens group, 404—Third optical fiber, 405—Spectral analysis unit. Detailed Implementation

[0038] Phase-modulated optical sensing systems possess numerous advantages, including high sensitivity and strong anti-interference capabilities, and are widely used in fields such as biomedical detection. It is known that optical interference between spatial light and the spectrum can be achieved through methods such as Fabryer's interferometry and common-path spectral interferometry. Among these,

[0039] Fabry-Perot interferometry boasts outstanding capabilities in high sensitivity, label-free sensing, and real-time monitoring. However, this method is highly sensitive to changes in environmental conditions such as temperature, humidity, and mechanical vibration, which generate noise during the sensing process, affecting the accuracy and reliability of sensor measurements. Furthermore, Fabry-Perot interferometry requires precise alignment of optical elements; alignment issues can impact sensor performance, leading to reduced sensitivity or unreliable measurement results.

[0040] The common-path spectral interferometry technique mainly relies on the optical path difference modulation of optical crystals and the phase abrupt change of plasmonic materials to achieve highly sensitive phase sensing. Although it has significant improvements in terms of sensitivity to environmental factors and the complexity of optical systems, the common-path spectral interferometry technique requires the phase odd change generated by surface plasmon resonance materials at specific wavelengths and polarization states to achieve biosensing. This places high demands on the selection of optical sensing materials and the repeatability of their processing and preparation.

[0041] Furthermore, optical interference sensing technologies, including Fabry-Perot interferometry and common-path spectral interferometry, have limited multiplexing capabilities. That is, they have a low ability to perform multi-channel multiplexing detection of optical signals using a single biosensor, and cannot effectively extract multiple optical information or perform multiple analyte sensing.

[0042] The limitations of the aforementioned technologies restrict the widespread application of interferometric sensing technology in fields such as biomedical detection. Therefore, the purpose of this disclosure is to provide an optical phase sensing detection method and sensor with high sensitivity, strong anti-interference capability, and optical multiplexing detection capability. This overcomes the shortcomings of existing optical phase modulation biosensing methods, which are complex and have high requirements for optical sensing media. It enables multimodal, multi-mode, high-sensitivity phase optical sensing for general biosensing processes, thereby enhancing the application of optical sensing in biomedicine and other fields.

[0043] According to one or more embodiments, such as Figure 12 As shown. A spectral interferometer sensor based on dual-path optical path difference modulation includes:

[0044] The light source and beam splitting unit are configured to provide a broadband optical signal with a certain width as a carrier signal in the sensing and detection process;

[0045] The optical sensing unit is configured to sense changes in refractive index, absorbance, and biomolecule binding, and detects the target sample through a broadband beam.

[0046] An optical reference unit is configured to provide beam signals with different spectral interference frequencies in the optical path of the optical sensing unit;

[0047] The optical detection system unit is configured to provide spectral signal acquisition, superposition, and optical phase analysis calculation for two different beam signals from the optical sensing and optical reference units.

[0048] The light source and beam-splitting unit include:

[0049] Configured to produce a multicolor light source with a wide spectrum of light beams;

[0050] A first optical fiber waveguide element configured to transmit optical signals;

[0051] The first collimating lens group is configured to control the collimated output of the optical signal;

[0052] A beam splitter or beam splitter configured to generate two beams of optical signals in the same wavelength band;

[0053] Configured as a reflector assembly for concentrating one optical signal.

[0054] Here, the light source, the first optical fiber, the first collimating lens group, the beam splitter, and the reflector assembly are arranged along the optical signal path. Here, the first optical fiber, or the first optical waveguide, is not strictly necessary; the optical signal can also be transmitted via spatial light.

[0055] The optical sensing unit includes:

[0056] A first pre-polarizer that modulates a broadband beam to produce a linear polarization state.

[0057] A first birefringent crystal lens that adds an optical path difference to the optical components of linearly polarized light along the o-axis and e-axis;

[0058] A sensing and detection unit configured to realize the interaction between light and the substance to be detected;

[0059] The first post-polarizer is configured to sort output optical signals with different polarization states.

[0060] Here, the first front linear polarizer, the first birefringent crystal, the sensing and detection unit, and the first rear linear polarizer are arranged sequentially along the optical signal path and direction. The sensing and detection unit can be replaced with different forms, such as a reflective sensing unit, a transmissive sensing unit, or a transmissive scanning sensing unit.

[0061] The optical reference unit includes:

[0062] A second pre-polarizer that modulates a broadband beam to produce a linearly polarized state;

[0063] A second birefringent crystal lens is used to add optical path difference to the optical components of linearly polarized light along the o-axis and e-axis;

[0064] A second post-polarizer is configured to sort output optical signals with different polarization states.

[0065] Here, the second pre-polarizer, the second birefringent crystal, and the second post-polarizer are arranged sequentially along the optical path and direction.

[0066] The optical inspection system unit includes:

[0067] The second and third collimating lens groups collect two beams of sensor light signals propagating in free space;

[0068] The optical waveguide elements, such as the second and third optical fibers, are configured to transmit the collected optical signals.

[0069] A spectral analysis unit configured to receive and integrate optical signals collected by two optical fiber waveguide elements.

[0070] Here, the second collimating lens group and the second optical fiber are connected to the spectral analysis unit along the optical path, and the third collimating lens group and the third optical fiber are connected to the spectral analysis unit along the optical path.

[0071] Preferably, in the optical sensing unit, the sensing and detection unit can be a combination of any one or more of the following units:

[0072] Parallel light transmission sensing unit based on collimated beam parallel incident on the sample to be detected;

[0073] The focused light scanning transmission sensing unit uses a lens to adjust the collimated beam to focus onto the sample to be tested.

[0074] A total internal reflection sensing unit that uses a prism to couple an incident radiation beam to a dielectric sensing interface at an angle of incidence.

[0075] A prism is configured to couple the incident radiation beam to the surface plasmon resonance sensing unit at a tilted incident angle to the surface plasmon resonance material thin film sensing interface.

[0076] An incident radiation beam is coupled to a localized surface plasmon resonance sensing unit containing a localized surface plasmon resonance nanoparticle sensing medium.

[0077] The parallel light transmission sensing unit further includes transparent cavity containers such as cuvettes and PDMS microfluidics.

[0078] The focused light scanning transmission sensing unit further includes a focusing lens, a PDMS microfluidic sample chamber, and a collimating receiving lens group. Surface plasmon resonance sensing units and localized surface plasmon resonance sensing units are two different forms of plasmon resonance sensing units. The different types of sensing units mentioned above can be combined as needed, such as a combination of "reflective + plasmon sensing" or "transmission + plasmon sensing," to address the characteristics of different sample media and improve detection accuracy.

[0079] The total reflection sensing unit further includes:

[0080] A prism is used to couple a light beam to a sensing interface at an angle of incidence.

[0081] A non-metallic dielectric sensing layer on a transparent substrate is used to interact with obliquely incident light waves and sense changes in the physical, chemical, and biological states of the interface through the incident photoelectric magnetic field.

[0082] The non-metallic dielectric sensing layer further includes thin film materials or micro / nano metamaterial structures that can generate optical near fields such as evanescent waves and artificial surface polaritons.

[0083] Microfluidics, or fluid cavities, are used to introduce liquid or gas samples to be detected into the dielectric sensing layer for interaction.

[0084] In a total internal reflection (TIR) ​​sensing unit, incident light, due to the angle between the incident light and the interface, is deflected towards the upper plane of the prism during refraction. When the incident angle exceeds the critical angle for TIR, light propagating from a denser medium (high refractive index medium) to a less dense medium (low refractive index medium) undergoes TIR. In this case, the light energy propagates as an electromagnetic wave along the non-metallic dielectric sensing layer of the transparent substrate, generating an evanescent wave at the interface. By utilizing the interaction between the evanescent wave generated by TIR and the target molecule in the sample, chemical, biological, or physical processes occurring in the sample can be detected and analyzed. For example, in biosensors, biomolecules with specific functions are immobilized on the surface of the dielectric sensing layer, and the target molecule is detected by detecting the resonance phenomenon caused by the binding of the evanescent wave with the target molecule in the sample. The TIR light wave carries phase information in the form of a carrier wave and exits from the other refractive surface of the prism, ultimately being received by the detection unit for quantitative or qualitative analysis. The specific functional biomolecules mentioned here refer to biomolecules that can interact with the biomolecules to be detected in the sample. For example, these could be protein antibodies, detecting antigens in the sample based on the specific interaction between protein antigens and antibodies; single-stranded DNA sequences, detecting nucleic acid sequences in the sample based on DNA or RNA double-strand hybridization; or specific functional proteases, which achieve detection by reacting with reactants in the sample through biocatalysis. Since the detection process involves the direct observation of the interaction between the "specific functional biomolecule" and the "biomolecules in the sample," it is necessary to immobilize the "specific functional biomolecule" on the sensor surface to achieve highly sensitive detection of biomolecules in the sample.

[0085] The surface plasmon resonance sensing unit further includes:

[0086] A prism is used to couple a light beam to a sensing interface at an angle of incidence.

[0087] A surface plasmon resonance metal thin film sensing layer located on a transparent substrate is used to interact with obliquely incident light waves and sense changes in the physical, chemical, and biological states of the interface through the electromagnetic field of surface plasmon resonance.

[0088] The surface plasmon resonance metal thin film sensing layer may further include a multilayer sensing layer consisting of one or more thin film materials such as noble metals, transition metal nitrides, and metal oxides.

[0089] Microfluidics, or fluid cavities, are used to introduce liquid or gas samples to be tested into a metal thin film layer for interaction.

[0090] In a surface plasmon resonance (SPR) sensing unit, incident light is deflected towards the upper plane of a prism due to the angle between the incident light and the interface. When the incident angle exceeds the critical angle for total internal reflection, total internal reflection occurs, causing the light to travel from a denser medium (high refractive index medium) to a less dense medium (low refractive index medium). A sensing layer containing a SPR metal thin film is placed at the total internal reflection interface. In this case, the incident light energy is reflected as electromagnetic waves, generating SPR in the metal thin film sensing layer and propagating along it, producing an evanescent wave at the interface based on enhanced SPR. By utilizing the interaction between the SPR generated by total internal reflection and the target molecule in the sample, chemical, biological, or physical processes occurring in the sample can be detected and analyzed. For example, in biosensors, biomolecules with specific functions are immobilized on the surface of a metal sensing layer, and the target molecule is detected by detecting the resonance phenomenon caused by the binding of the SPR with the target molecule in the sample. The light wave, which is reflected by total internal reflection, carries phase information in the form of a carrier wave and exits from the other refractive surface of the prism. It is then received by the detection unit for quantitative or qualitative analysis.

[0091] The localized surface plasmon resonance sensing unit further includes:

[0092] A prism is used to couple a light beam to a sensing interface at an angle of incidence.

[0093] The metal nanoparticle layer located on a transparent substrate can achieve sensing and detection based on the principle of localized surface plasmon resonance.

[0094] Microfluidics, or fluid cavities, are used to introduce liquid or gas samples to be tested into a layer of metal nanoparticles for interaction.

[0095] In a localized surface plasmon resonance (LSPR) sensing unit, incident light is deflected towards the upper plane of a prism due to the angle between the incident light and the interface. When the incident angle exceeds the critical angle for total internal reflection, total internal reflection occurs, causing light to travel from an optically denser medium (high refractive index medium) to an optically less dense medium (low refractive index medium). By placing a metal nanoparticle sensing layer incorporating LPR at the total internal reflection interface, the incident light energy is converted into electromagnetic waves, generating LPR in the metal nanoparticle sensing layer. The confinement of the photoelectromagnetic field by the nanostructure amplifies the electromagnetic field around the metal nanoparticles, thus creating an enhanced optical near-field at the interface based on LPR. By utilizing the interaction between the LPR generated by total internal reflection and the target material in the sample, chemical, biological, or physical processes occurring in the sample can be detected and analyzed. For example, in biosensors, biomolecules with specific functions are immobilized on the surface of metal nanoparticles, and the detection of target molecules is achieved through the phase response caused by the interaction of light and matter. The totally internally reflected light wave carries phase information in the form of a carrier wave, exits from another refractive surface of the prism, and is finally received by the detection unit for quantitative or qualitative analysis.

[0096] In this embodiment of the present disclosure, preferably, the birefringent optical crystal is a transparent optical medium that allows for the addition of different optical paths depending on its orientation. Furthermore, the optical path difference added by the two optical crystals, one in the sensing detection optical path and the other in the sensing reference optical path, has a non-zero difference. That is, the optical path difference of the first birefringent crystal is L1, the optical path difference of the second birefringent crystal is L2, and L2 ≠ L1, with the difference ΔL = |L1 - L2|, where ΔL is not equal to 0. This allows the optical signals in the dual optical paths to be modulated by the birefringent optical crystal and received and superimposed by the optical detection system, generating one or more phase sensing points based on the superposition of anti-phase waves for sensing and detection.

[0097] In this embodiment, within a limited wavelength range, one or more anti-phase sensing sites are constructed by modulating the optical path difference between two beams using a birefringent crystal in one of the two beams. A method to improve sensing sensitivity is achieved by superimposing optical phase response values ​​using optical sensors at multiple phase sensing sites; a method to broaden the dynamic detection range of sensing is also achieved by superimposing optical phase response values ​​using optical sensors at multiple phase sensing sites.

[0098] The principle of this disclosure is to utilize birefringent crystals with different optical path differences to construct spectral interference signals with different periods and frequencies in two optical paths. During the superposition of the two optical paths, multiple anti-phase phase sensing sites can be constructed through the optical vernier effect. During the sensing process, changes in light intensity and phase in the detection optical path can cause phase transitions at phase singularities in the spectrum, thereby achieving a highly sensitive sensing function.

[0099] According to the multi-site phase sensing method of this disclosure, multiple phase sensing sites with sensitive responses can be constructed within a specific spectral range. During phase data processing, a Fourier transform is performed on the sine wave near each sensing site to extract the periodic phase corresponding to the wavelength, and the real-time phase response value is calculated. The detection system of this disclosure has a simple composition, and the refractive index detection resolution can reach up to 6.344 × 10⁻⁶. -8 RIU, and by coordinating multiple resonant sensing points, broadens the dynamic detection range of the sensing system, thereby achieving more accurate quantitative biosensing functions.

[0100] The dual-path optical path difference modulated spectral interferometer sensor and method of this disclosure are used for detecting, quantifying and / or characterizing target samples.

[0101] According to one or more embodiments, this disclosure provides a dual-path optical path difference controlled spectral interferometry method, including:

[0102] A broadband light source is connected to the front end of the optical system to provide a signal source and carrier signal for spectral interference;

[0103] Two independent optical modulation optical paths are designed in the optical system, namely the sensing optical path and the reference optical path;

[0104] The sensing optical path includes a light source collimation unit, a linear polarizer, a birefringent crystal, a sensing and detection unit, a linear polarizer, and a light signal collecting lens group;

[0105] The optical path difference of the birefringent crystal C1 in the sensing optical path is L1, which is used to generate the interference spectrum in the sensing optical path.

[0106] The sensing and detection unit is a replaceable module that can be used for functions such as parallel light transmission sensing, focused light scanning transmission sensing, total internal reflection sensing, surface plasmon resonance sensing, and local surface plasmon resonance sensing.

[0107] The reference optical path includes a light source collimating unit, a linear polarizer, a birefringent crystal, a linear polarizer, and a light signal collecting lens group;

[0108] The optical path difference of the birefringent crystal C2 in the reference optical path is L2, which is used to generate the reference interference spectrum. L2 ≠ L1, and ΔL = |L1 - L2| is used to design and adjust the number of sensing sites in the superimposed interference spectrum.

[0109] By adjusting the thickness of the two birefringent crystals, the optical path difference ΔL can be accurately controlled. The higher the optical path difference, the more phase sensing sites are generated within a specific spectral range.

[0110] A spectral analysis system is connected to the back end of the optical system to receive and analyze spectral interference signals and phase response values.

[0111] In the spectral analysis process, the number of phase sensing sites and their corresponding wavelength positions within a specific spectral range are first determined. Then, a phase analysis window of a certain width (e.g., 50 nm) is selected based on the wavelength position. Within each analysis window, the corresponding phase sensing site is calculated to obtain the relative response value corresponding to the wavelength. The phase response value of each sensing site can be used to analyze different detectable substances individually, or it can be summed to calculate the highly sensitive sensing response of the same object.

[0112] According to one or more embodiments, this disclosure provides a method for realizing transmission optical sensing in a dual-path optical path difference controlled spectral interferometry system, including:

[0113] In the sensing optical path of the optical system, a sensing and detection unit based on collimated light parallel transmission can be set up to realize the direct interaction between the sample to be detected and the incident light in the optical path;

[0114] The interaction between the sample to be tested and the incident light in the optical path includes, but is not limited to, light absorption, light scattering, stimulated emission, and optical phase change, thereby enabling the detection and sensing of the sample to be tested.

[0115] The sensing and detection method based on collimated parallel light transmission includes the following steps:

[0116] A reaction chamber such as a cuvette is set in the sensing optical path, and the sample is aligned with the optical path so that the optical path can effectively pass through the sample and fully interact with the sample.

[0117] The sample contains light-absorbing and scattering components such as dyes and colloidal gold. By adding analytes such as ions and biomolecules under continuous light irradiation, the light absorption, scattering, light radiation, and phase state of the sample are changed.

[0118] After being superimposed with the reference optical path, it is received by the spectrometer at the end of the optical system, thus obtaining the spectral interference signal under the action of the optical vernier effect;

[0119] The change in sensing quantity in the experimental optical path is obtained by performing phase calculation and signal analysis on the phase sensing sites within the interference spectrum signal.

[0120] Preferably, the standard reagent sample of this disclosure is a colloidal gold solution with surface modification, and the optical path length of the sample interaction with light is 10 mm.

[0121] Preferably, the analyte in the parallel transmission sensing detection mode of this disclosure is a NaCl ion solution, and the concentration in the reaction system can be 4 ng / mL, 8 ng / mL, 12 ng / mL, or 16 ng / mL, respectively.

[0122] A sensing unit based on focused light transmission scanning can be set in the sensing optical path of an optical system to realize continuous scanning of different sites on the sample to be tested by focused incident light or continuous monitoring and sensing of a small area at the same site. The sensing and detection method based on focused light transmission scanning includes the following steps:

[0123] A focusing lens group, a sensing reaction cavity, a sensing reaction cavity displacement system, and a collimating receiving lens group are set in the sensing optical path to align the focused light with the sample to be tested, so that the optical path can effectively pass through a specific position of the sample and fully interact with the sample.

[0124] The sample contains light-absorbing and scattering components such as dyes, gold nanoparticles, and dielectric metasurfaces. By changing the ion concentration, refractive index, and biomolecule concentration under continuous light irradiation, the light absorption, scattering, light radiation, and phase state of the sample are altered.

[0125] The displacement system can move the sensing reaction cavity, thereby changing the detection and scanning area;

[0126] After the signals from the detection optical path and the reference optical path are superimposed, they are received by the spectrometer at the end of the optical system, thus obtaining the spectral interference signal under the action of the optical vernier effect;

[0127] The change in sensing quantity in the experimental optical path is obtained by performing phase calculation and signal analysis on the phase sensing sites within the interference spectrum signal.

[0128] Preferably, the standard chip sample used in the collimated transmission scanning sensing mode of this invention is a matrix sample of gold nanoislands (40 nm) densely distributed on a 2 mm thick glass substrate, with an interaction area between the sample and light of 0.1 x 0.1 mm. 2 ;

[0129] Preferably, in this disclosure, the gold nanoisland chip sample is bonded to a PDMS microfluidic (2mm wide channel) system, and the biological sample to be detected flows into the microfluidic system for sensing.

[0130] According to one or more embodiments, a method for realizing reflective optical sensing in a dual-path optical path difference controlled spectral interferometry system includes:

[0131] In the sensing optical path of the optical system, a sensing and detection unit based on total internal reflection can be set up to realize the interaction between the sample to be detected and the total internal reflection light in the optical path through evanescent waves or surface plasmon resonance.

[0132] The interaction between the sample to be tested and the incident light in the optical path includes, but is not limited to, light absorption, light scattering, stimulated emission, and optical phase changes caused by evanescent waves or surface plasmon resonance, thereby achieving real-time detection and sensing of the sample to be tested. The sensing and detection method based on total internal reflection includes the following steps:

[0133] In the sensing optical path, total internal reflection optical devices such as prisms and a sensing reaction cavity are set up, and the sample is aligned with the total internal reflection optical path so that the total internal reflection light and the sample in the reaction cavity can fully interact at the sensing interface.

[0134] The sensing interface can be a glass interface based on evanescent waves, a metal thin film interface based on surface plasmon resonance, or a gold nanoparticle matrix interface based on local surface plasmon resonance.

[0135] The sensing interface can be modified with antibodies, single-stranded nucleic acid molecules, and two-dimensional materials as receptors for specific detection. The sample to be tested on the surface of the interface can be a liquid or a gas, and the sample contains components such as dyes and biomolecules. It can also interact with the sensing interface to change physical quantities such as the interface refractive index, mass, light absorption and scattering, thereby changing the intensity and phase state of the total internal reflection light.

[0136] After being superimposed with the reference optical path, the signal is received by the spectrometer at the end of the optical system. This yields the spectral interference signal under the influence of the optical vernier effect.

[0137] The change in sensing quantity in the experimental optical path is obtained by performing phase calculation and signal analysis on the phase sensing sites within the interference spectrum signal.

[0138] In one embodiment, preferably, the standard chip sample in the total internal reflection sensing mode of this disclosure is a gold nano-island (40 nm) matrix sample densely distributed on a 2 mm thick glass substrate, or a gold film sample with a thickness of 46-50 nm on a 2 mm thick glass substrate, or a gold-silver alloy nano-island (40 nm) matrix sample densely distributed on a 2 mm thick glass substrate.

[0139] Preferably, in this disclosure, the optical chip is bonded to the PDMS microfluidic (2mm wide channel) system, the total internal reflection spot covers the microfluidic reaction cavity, and the biological sample to be detected flows into the microfluidic reaction cavity for total internal reflection mode sensing;

[0140] Preferably, in the total internal reflection sensing mode, the standard test sample for refractive index detection in this disclosure is an aqueous solution of sodium chloride (NaCl) with a mass percentage of 2%, 4%, 6%, 8%, 10%, 12%, 14%, 16%, 18%, and 20%.

[0141] Preferably, in the total reflection sensing mode, the standard test sample for biomolecular sensing in this disclosure uses interleukin-6 (IL-6) protein molecules with concentrations of 1 pg / mL, 1 ng / mL, and 1 ug / mL, and the surface of the sensing chip is modified with IL-6 antibody to achieve specific detection of IL-6.

[0142] According to one or more embodiments, a multi-site phase sensing method and a spectral interferometric sensing signal analysis method based on birefringent crystal design include:

[0143] In optical systems, by adjusting the optical path difference between optical crystals in two beams, it is possible to construct a single or multiple phase sensing sites.

[0144] Preferably, during the optical sensing process, the phase of the interference spectrum is processed and extracted using methods such as fast Fourier transform, windowed Fourier transform, or wavelet transform to obtain the phase response value of each spectral sensing point, which is used for quantitative or qualitative analysis of the sensing.

[0145] Preferably, in the optical system, multiple phase sensing sites are constructed by adjusting the optical path difference between the optical crystals in the two light paths, enabling sensing of the same biological sample or target sample. By summing the optical responses of multiple sensing sites, the sensing sensitivity is improved and the detection limit is optimized.

[0146] Preferably, in the optical system, multiple phase sensing sites are constructed by adjusting the optical path difference between the optical crystals in the two beams, and the multiple phase sensing sites have different dynamic response ranges.

[0147] During the detection process, the dynamic detection range is broadened by summing the optical response values ​​of multiple sensing sites.

[0148] According to one or more embodiments, such as Figure 12 As shown, a spectral interferometric sensor based on dual-path optical path difference control includes a light source and beam splitting unit 100, an optical interferometric sensing unit 200, an optical interferometric reference unit 300, and an optical detection system unit 400.

[0149] like Figure 2The diagram shows the core components of the light source and beam splitting unit in the optical spectral interferometric sensing signal analysis unit. The light source and beam splitting unit 100 includes a broadband light source, optical fiber, collimating lens group, beam splitting optical components, and a reflector. The broadband light source 101 can be an LED light source in the visible and near-infrared bands, used to transmit optical signals; optical waveguide elements 102, such as optical fibers, can transmit the optical signals; the collimating lens group 103 can adjust the light emitted from the optical fiber to output collimated light; the beam splitting component 104 is a beam splitting prism or beam splitter, used to split the optical signal into two paths; and the reflector assembly 105 is used to adjust the propagation direction of the split optical path. The light source and beam splitting unit 100 provides broadband light source and optical signal output for two parallel working optical paths.

[0150] like Figure 3 The diagram shows the core components of the optical interference sensing unit in the optical spectral interferometric sensing signal analysis unit. The optical interference sensing unit 200 includes a front linear polarizer, a birefringent crystal L1, a replaceable sensing detection unit, and a rear linear polarizer. The front linear polarizer 201 modulates broadband light to generate linearly polarized light; the birefringent crystal 202, made of birefringent crystal materials such as YVO4, adds an optical path difference to the o-axis and e-axis components of the linearly polarized light; the replaceable sensing detection unit 203 is used for sensing, utilizing the interaction between light and matter to achieve various modes such as a total internal reflection sensing unit 203a (reflection type), a parallel light sensing unit 203b (transmission type), and a transmission scanning sensing unit 203c; the rear linear polarizer 204 sorts the output light signals of the sensing units under different polarization states.

[0151] like Figure 4 The diagram shows a schematic of the core components of the optical interference reference unit in the optical spectral interferometric sensing signal analysis unit. The optical interference reference unit 300 includes a front linear polarizer, a birefringent crystal L2, and a rear linear polarizer. The front linear polarizer 301 is used to modulate broadband light to generate linearly polarized light; the birefringent crystal 302 is made of birefringent crystal materials such as YVO4 and has an optical path difference L2 different from the optical crystal in the optical interference sensing unit; the rear linear polarizer 303 is used to sort the output light signals of the optical interference reference unit under different polarization states.

[0152] like Figure 5The diagram shows a schematic of the core components of the optical detection system unit within the optical spectral interferometric sensing signal analysis unit. The optical detection system unit 400 includes a collimating lens group 401 that receives the optical path of the optical interferometric sensing unit, collecting the sensed light in free space and effectively coupling the optical signal to an optical waveguide element 402 (such as an optical fiber) for signal transmission; the optical detection system unit 400 also includes a collimating lens group 403 that receives the optical path of the optical interferometric reference unit and couples the optical signal to an optical waveguide element 404 (such as an optical fiber); the spectral analysis unit 405 includes components that can receive and integrate the optical signals collected by both optical waveguide elements 402 and 404, and derive the interference spectrum in a specific wavelength band. In this embodiment, a spectrometer with a visible light band of 500-740 nm and a Y-shaped optical fiber are used to collect the two optical signals.

[0153] According to one or more embodiments, an optical sensor. For example... Figure 6 (a) is a schematic diagram of the optical path design and sensing principle of dual-path optical path difference-controlled spectral interference. Figure 6 (b) is an experimental result showing the optical vernier effect generated by the superposition of the interference spectra of the optical interference sensing optical path and the optical interference reference optical path in the embodiments of this disclosure. Figure 6 (c) represents multiple phase sensing sites generated under different optical path differences and combinations of optical crystals.

[0154] In this embodiment, two types of YVO4 birefringent crystals, 202 and 302, with different thicknesses are used. At the same wavelength frequency, the birefringent crystals add different optical path differences to the optical components of different polarization states in the optical path, such as p-polarized light and s-polarized light. Therefore, two different specific interference spectral signals with frequencies f1 and f2 can be generated in the interference spectra of the sensing unit and the reference unit, respectively. Figure 6 As shown in (b), by superimposing two beams of light in the spectral signal collected by the spectrometer, multiple highly sensitive phase sensing sites based on the vernier effect, i.e., anti-phase points, can be generated.

[0155] By changing the optical path difference between crystal 202 and crystal 302, different numbers of phase sensing sites can be designed and constructed within a specific spectral range. For example... Figure 6As shown in (c), crystal combination-1 is a phase sensing spectrum generated by YVO4 birefringent crystals with thicknesses of 400 μm and 430 μm, which can generate 5 reliable phase sensing sites in the wavelength range of 400 nm to 1000 nm; crystal combination-2 is a phase sensing spectrum generated by YVO4 birefringent crystals with thicknesses of 400 μm and 450 μm, which can generate 8 reliable phase sensing sites in the wavelength range of 400 nm to 1000 nm; crystal combination-3 is a phase sensing spectrum generated by YVO4 birefringent crystals with thicknesses of 400 μm and 500 μm, which can generate 17 phase sensing sites in the wavelength range of 400 nm to 1000 nm.

[0156] The experimental results shown in the embodiments of this disclosure demonstrate that increasing the optical path difference can effectively increase the number of phase sensing sites in the spectrum.

[0157] According to one or more embodiments, an optical sensor. For example... Figure 7 (a) Schematic diagram of collimated light transmission phase sensing of optical interference sensing unit. Figure 7 (b) is a schematic diagram of the focused light scanning transmission phase sensing of the optical interference sensing unit in an embodiment of this disclosure. Figure 7 (c) is a schematic diagram of a transmission phase-sensing colloidal gold sample in a discrete state in solution, as described in an embodiment of this disclosure. The colloidal gold sample can be surface-modified or altered to achieve the recognition and colorimetric reaction of ions and biomolecules. Figure 7 (d) is a schematic diagram showing the sample state of the transmission phase sensing colloidal gold sample after participating in the colorimetric reaction and the aggregation state of colloidal gold in the solution in the embodiments of this disclosure. Figure 7 (e) In this embodiment of the disclosure, the transmission phase sensing technology is used to analyze the interference changes of colloidal gold samples in the spectral range of 586nm to 590nm under the action of ion samples of different concentrations. Figure 7 (f) In this embodiment of the disclosure, the transmission phase sensing technology is used to analyze the changes in optical phase response of colloidal gold samples in the spectral range of 586nm to 590nm under the action of ion samples of different concentrations. Figure 7 (g) is a quantitative standard curve established by analyzing the phase response using transmission phase sensing technology in this embodiment of the present disclosure.

[0158] In this embodiment of the disclosure, two optical sensing modes, parallel light transmission and focused light transmission scanning, are first verified. Figure 7 (a) and Figure 7(b) Replaceable experimental units for parallel light transmission phase sensing and focused light transmission scanning phase sensing are shown respectively. A 0.013 mM colloidal gold solution was used to characterize the sensing performance. The surface of the gold nanoparticles in the colloidal gold solution was modified with a sodium citrate surface stabilizer. Before sensing, the surface stabilizer ensured high dispersion of the colloidal gold nanoparticles due to the stable surface charge density and ionic strength of the dispersion medium, resulting in high absorbance of 530 nm visible light and a wine-red overall solution color. In the sensing experiments, 20 μL of 2%, 4%, 6%, and 8% sodium chloride solutions were added to 1 mL of colloidal gold solution, respectively. According to the Derjaguin–Landau–Verwey–Overbeek (DLVO) theory, the addition of sodium chloride ion solution affects the electronic double layer on the colloidal gold surface, reducing the electrorepulsive force between colloidal gold particles. As the distance between colloidal gold nanoparticles decreases, the selective absorption spectrum of light changes, leading to a colorimetric reaction. Figure 7 (d) is shown.

[0159] Throughout the reaction, the optical signal from the experimental optical path is used to monitor the dynamic reaction process of the colloidal gold in real time and is superimposed on the optical signal from the reference optical path in the spectrometer. At a spectral position of 590 nm, signals such as... can be designed to be generated. Figure 7 The interference spectrum shown in (e) clearly shows a phase change at the phase sensing site. The reference spectrum is the interference spectrum in deionized water (DI), and samples -1, -2, -3, and -4 are samples after adding 20 μL of 2%, 4%, 6%, and 8% sodium chloride solution, respectively. After phase signal processing and analysis, the following can be calculated: Figure 7 (f) shows the phase response radian value at a wavelength of 590 nm. The phase response values ​​of different salt particle concentrations under the single-wavelength sensing condition at 590 nm can be used to calculate the standard sensing quantitative fitting curve in parallel light transmission mode, i.e., y = 0.1582 × x + 0.02947, and based on this, the detection limit (LOD) of the sensing system for NaCl ions is evaluated to be 98 μg / mL.

[0160] According to one or more embodiments, an optical sensor. For example... Figure 8 (a) is a schematic diagram of total reflection phase sensing based on the optical sensing principles of evanescent wave, surface plasmon resonance, and local surface plasmon resonance in the dual-path optical path difference modulated spectral interferometry technique. Figure 8 (b) is a plasmonic material (chip) that can be used for total reflection phase sensing in the embodiments of this disclosure, including a biochip based on a gold film, a gold nanoisland particle matrix, or a gold-silver alloy nanoisland particle matrix. Figure 8(c) is an atomic force microscopy scan of the gold nanoisland particle matrix. Figure 8 (d) is a dual-resonance phase sensing spectrum constructed in the wavelength range of 530nm to 620nm based on dual-path optical path difference modulated spectral interferometry and gold nano island particle matrix biochip. Figure 8 (e) shows the dual-wavelength sensing results of the multi-constructed dual-resonance phase sensing spectrum for 0.5% NaCl sample-1, which can be used to analyze the refractive index resolution (RIR) of the system.

[0161] In this case study, three optical phase sensing modes are validated: total reflection-based evanescent wave sensing mode, surface plasmon resonance sensing mode, and local surface plasmon resonance sensing mode. Figure 8 (a) An optical interferometry system based on total internal reflection is demonstrated in evanescent wave sensing modes with surface plasmon resonance (SPR) and localized surface plasmon resonance (LSPR). In the optical path of this embodiment, an evanescent wave is generated at the total internal reflection interface of a prism using the total internal reflection mode. Evanescent waves can be applied to interface sensing, such as changes in refractive index at the interface, and the binding of biomolecules. Simultaneously, through methods such as... Figure 8 The gold film shown in (b) can generate evanescent wave electric field enhancement based on the surface plasmon resonance (SPR) principle, thereby improving the sensitivity of phase sensing.

[0162] Meanwhile, nanoparticle optical chips composed of structures such as gold nanoislands (AuNI) or gold-silver alloy nanoislands can be further utilized to excite an electromagnetic field based on LSPR local surface plasmon resonance at the interface, thereby constructing an electromagnetic field with higher intensity and higher spatial resolution and realizing highly sensitive plasmonic biosensing.

[0163] In this embodiment, the sensitivity and refractive index detection resolution of the dual-path optical path difference-controlled spectral interferometry sensing method based on total internal reflection mode are further verified using the AuNIs nanochip as an example. Figure 8 (c) First, atomic force microscopy images of AuNI gold nanoparticles are shown. In the AuNI chip, self-assembled gold particles with an average diameter of 40 nm are densely distributed on a transparent glass substrate. The chip is assembled with a microfluidic or flow cell and placed on the upper surface of a prism that produces total internal reflection, so that the collimated beam in the optical interference sensing path is totally internally reflected at the sensing site and finally received.

[0164] By adjusting the thickness of the birefringent crystal and the optical path difference between the experimental and reference optical paths, a structure such as... can be formed. Figure 8 (d) shows the multi-sensor site interference spectrum, where the optical interference spectrum produces two sites at 553 nm and 588 nm that can be used for high-sensitivity phase sensing.

[0165] In the experiment, a reference interference spectrum was first constructed using deionized water (DI water), as shown by the blue dashed line in Figure 8d. Subsequently, a 0.5% sodium chloride solution was injected into the sensing cavity using a syringe pump or peristaltic pump, increasing the refractive index from 1.3330 to 1.33387. This change in refractive index alters the LSPR evanescent wave generated at the chip sensing interface and the electromagnetic field vibration state, affecting the phase of the emitted light. (As shown...) Figure 8 As shown in (d), at the two sensitive wavelength positions, in addition to the change in light intensity, the phase of the interference spectrum also undergoes a significant transition. The phase transition at the two wavelengths can be extracted using the windowed Fourier transform (WFT) method.

[0166] like Figure 8 As shown in (e), a refractive index change of 0.00087 refractive index units (RIU) results in a phase change of approximately 0.48 radians at 553 nm and a higher phase response change exceeding 2.4 radians at 588 nm in the dual-path optical path difference modulated spectral interferometer sensor. Refractive index resolution (RIR) refers to the smallest refractive index change that a sensing technique or instrument can detect or resolve. The sensitivity of this sensing method to refractive index changes can be measured by calculating the RIR. The refractive index resolution (RIR) is defined as:

[0167]

[0168] Where δn bulk The value of the refractive index change in the sensing system. Let be the phase response value of the LSPR sensing system, assuming the standard deviation of the phase fluctuation. 1.75×10 -4 Using the formula above, the volume refractive index resolution (RIR) of the LSPR-based dual-path optical path difference modulated spectral interferometer at 553 nm wavelength can be calculated to be 3.172 × 10⁻⁶ radians. -7 The volume refractive index resolution (RIR) at 588 nm is 6.344 × 10⁻⁶. -8 RIU.

[0169] Figure 9 (a) is a spectrum of four phase sensing sites constructed in the wavelength range of 520 nm to 630 nm using dual-path optical path difference modulated spectral interferometry and gold nano island particle matrix biochip. Figure 9 (b) shows the multi-wavelength phase sensing results of 0.5% NaCl and 2% NaCl salt solutions based on the multi-phase sensing spectral interferometry technique with dual optical path difference control. By superimposing the phase responses at multiple sites, the refractive index resolution and sensitivity of the sensor can be improved.

[0170] In this embodiment, based on the multi-site phase sensing spectral interferometry technique with dual optical paths and dual optical path control, multiple phase sensing sites can be constructed within a limited spectral range. For example... Figure 9 As shown in (a), phase sensing points at four wavelengths of 535 nm, 558 nm, 583 nm and 615 nm can be constructed in the spectral range of 520 to 640 nm.

[0171] In further verification experiments, a structure was first constructed using deionized water, as shown below. Figure 9 (a) shows the reference interference spectrum for "State-1". Subsequently, 0.5% and 2% sodium chloride solutions were injected into the sensing fluid cavity, respectively. Real-time sensing experiments were conducted to further verify the response characteristics of multiple sensing sites when sensing the same refractive index change. After Fourier transform data processing, the following results can be obtained: Figure 9 (b) shows the phase response values ​​at four different wavelengths. The 535nm phase sensing site exhibits the most sensitive optical sensing performance, while the 615nm phase sensing site shows weaker optical sensing sensitivity. Because the initial phase and interference state differ at each wavelength during the sensing process of the same refractive index change or biomolecule binding, the sensitivities at multiple sensing sites are not the same, resulting in slightly different phase responses. In data processing, the phase sensing response values ​​from multiple sites can be superimposed to obtain a highly sensitive quantitative standard curve.

[0172] Figure 10 This is a real-time phase response result of the refractive index gradient change of a 0-20% NaCl solution detected by dual-path optical path difference-controlled spectral interferometry. Based on this phase summation and sensing principle, multi-site phase sensing spectral interferometry is used to continuously monitor and sense multiple standard samples with different refractive indices in real time. During the experiment, eleven standard samples were prepared, including 1 mL of deionized water and sodium chloride solutions with mass percentages of 2%, 4%, 6%, 8%, 10%, 12%, 14%, 16%, 18%, and 20%, and were sequentially injected into the biosensor detection cavity of the AuNIs sensor chip. Due to the continuous increase in refractive index, a continuously rising phase response value can be obtained. By superimposing the phase response values ​​of four sensing sites, a result can be obtained as shown below. Figure 10 The phase response change curve is shown.

[0173] Figure 11 (a) is a graph showing the normalized phase response range of the dual-path optical path difference modulated spectral interferometry technique during the sensing process at four resonant sites. Figure 11 (b) is a result of the wide dynamic range obtained by superimposing the phase response of multiple resonant sites in the dual-path optical path difference controlled spectral interferometry technique, which is used for high-sensitivity phase sensing during large refractive index changes.

[0174] By superimposing the phase values ​​of multiple sensing sites, a wider dynamic detection range can be obtained, which is a prominent advantage of multi-site phase sensing spectral interferometry and sensors. In the phase detection process at a single sensing site, such as... Figure 11 As shown in (a), each detection site has a different optimal detection dynamic range. S-1, S-2, S-3, and S-4 are the dynamic detection ranges obtained after phase response normalization. In the detection of wide refractive index changes or biosensing, special cases such as insensitive detection (refractive index below the detection range) and oversaturated detection (refractive index detection exceeding the dynamic detection range) may occur, affecting continuous detection during the sensing process. By superimposing the response values ​​of the four phase points, the following can be obtained: Figure 11 (b) shows an ultra-wide dynamic range, which facilitates the detection of target molecules in different baseline states during biosensing processes. For example, it enables highly sensitive real-time sensing and detection of specific biomolecules based on different buffer solutions and refractive media.

[0175] In actual sensor sample detection, multi-channel biosensing capabilities with spectral multiplexing can be achieved by analyzing and processing multiple phase sensing sites separately. This is another prominent advantage of multi-site phase sensing spectral interferometry and sensors in the biomedical application field. By constructing multiple phase sensing sites in the spectrum, parallel detection of multiple disease biomarkers in the same sample can be carried out. For example, viral infection may cause the expression of immune antibodies in patients. By detecting IgG antibodies, IgM antibodies, IgA antibodies, and viral antigens separately at multiple phase detection sites in the spectrum, the concentration correlation of different antibodies can be used to determine the stage of infection. For example, in the early stage of infection, the concentration of IgM antibodies is high and the concentration of IgG antibodies is low; while in the later stage of infection or recovery, the concentration of IgG antibodies increases significantly, while the concentration of IgM antibodies decreases. Another typical application scenario is the parallel sensing and rapid detection of multiple inflammatory factors in patient blood samples or tissue fluid samples. During the sensing process, multiple inflammatory factors in the same patient sample are detected in parallel at multiple phase sensing sites, such as typical interleukin-1 (IL-1), TNF-α, and interferon-γ. By detecting the levels of multiple inflammatory factors in parallel, the degree and type of the body's inflammatory response can be rapidly assessed, enabling diagnosis, treatment guidance, intervention decisions, and prognostic monitoring for inflammation-related diseases, including infections, trauma, autoimmune diseases, and tumors.

[0176] According to one or more embodiments, such as Figure 1 As shown. An optical sensor includes a light source unit, a sensing unit, a reference unit, and a detection unit.

[0177] A probe beam emitted by the light source unit is transmitted to the sensing unit, where it interacts with the target sample and is then received by the detection unit. A reference beam emitted by the light source unit is transmitted to the reference unit and received by the detection unit. The detection unit then recombines the probe and reference beams and performs spectral analysis on the recombined beam to obtain the characteristics of the target sample.

[0178] Furthermore, in the embodiments of this disclosure, the optical sensor products described above may have different definitions or forms.

[0179] For example, when designing an optical sensing component, the component includes a light source unit, a sensing unit, and a reference unit. A probe beam emitted by the light source unit is transmitted to the sensing unit, interacts with the target sample in the sensing unit, and then exits to the first optical path interface of the optical sensing component. A reference beam emitted by the light source unit is transmitted to the reference unit, passes through the reference unit, and then exits to the second optical path interface of the optical sensing component.

[0180] The first and second optical path interfaces of the optical sensing component are simultaneously connected to a detection unit. The detection unit recombines the received probe beam and reference beam, and then performs spectral analysis on the recombined beam to obtain the characteristics of the target sample. Here, the light source unit, sensing unit, and reference unit are designed within a single component, connected to the detection unit via interfaces to achieve the detection of sample characteristics. This detection unit can be a specially designed optoelectronic device or a general-purpose spectrometer.

[0181] For example, a spectral acquisition component can be designed, including a sensing unit and a reference unit. The spectral acquisition component has a third optical path interface and a fourth optical path interface, which are connected to an external light source unit. Additionally, the spectral acquisition component also has a fifth optical path interface and a sixth optical path interface.

[0182] A probe beam emitted by a light source unit is transmitted to a sensing unit through the third optical path interface of the spectral acquisition component. After interacting with the target sample in the sensing unit, it exits to the fifth optical path interface of the spectral acquisition component. A reference beam emitted by the light source unit is transmitted to a reference unit through the fourth optical path interface, and then exits to the sixth optical path interface of the spectral acquisition component.

[0183] The fifth and sixth optical paths of the spectral acquisition component are simultaneously connected to a detection unit. The detection unit recombines the received probe beam and reference beam, and then performs spectral analysis on the recombined beam to obtain the characteristics of the target sample. Here, the sensing unit and reference unit are designed on a single spectral acquisition component, connected to the light source unit via a front-end interface, and connected to the detection unit via a rear-end structure. This design allows different spectral acquisition components to achieve different sample detection purposes by combining different light source units.

[0184] In summary, the beneficial effects of this disclosure include:

[0185] 1. The present invention discloses a spectral interferometry technique based on dual optical path difference that can achieve sensitive phase sensing. The phase sensing site is constructed by superimposing the components of two interfering lights in the external optical path.

[0186] Compared to traditional light intensity signal modulation methods, phase sensing methods exhibit higher sensitivity, reducing the detection limit (LoD) of biomolecules and disease biomarkers by two orders of magnitude. Meanwhile, the phase sensing method achieved by dual-path interferometry is directly constructed by superimposing external optical path interference signals, thus having better applicability to various sensing detection modes and sensing media materials. It can serve as a universal technical means in various optical sensing fields, with broad practicality and application value.

[0187] 2. This disclosure discloses a dual-path optical path difference-controlled spectral interferometry technique that can design and realize multiple phase wavelength detection sites within the spectral range, increasing the reusability and throughput of interferometric sensing. Because of the scheme disclosed herein, multiple different phase sensing sites can be constructed by adjusting the optical path difference between the optical crystals in the two optical paths. Therefore, each constructed phase sensing site can serve as a detection channel for a marker, thereby greatly improving the reusability and throughput of biosensing.

[0188] In traditional phase modulation detection processes, spectroscopy can only provide qualitative or quantitative analysis results for a single detection target. However, the multi-channel detection method constructed in this disclosure can use each phase sensing site as an independent sensing unit. By marking and sensing multiple targets on the same chip, and using the detection channels of different phase sensing sites to read the concentration and quantity information of different targets, it can achieve the multiplexing capability of a single spectrum and improve the detection throughput.

[0189] 3. The present invention discloses a spectral interferometry technique based on dual optical path difference that can achieve highly sensitive detection of transmission-type colorimetric reactions. The colorimetric sensing detection results are accurate and fast, and can achieve dynamic real-time monitoring.

[0190] Transmission sensing utilizes the interaction between light and matter during propagation to analyze light absorption. While transmission sensing methods are generally simple and rapid, their sensitivity is insufficient. This disclosure significantly improves the sensitivity of transmission sensing through a phase modulation detection method, enabling the detection accuracy and sensitivity of real-time transmission sensing methods such as colorimetric reactions.

[0191] 4. The present invention discloses a spectral interferometry technique based on dual optical path difference that enables highly sensitive surface plasmon resonance sensing with total internal reflection. The sensing is not limited by the phase change of plasmons in the sensing material and is an enabling technology for the use of broad absorption spectral materials in biosensing.

[0192] Total internal reflection sensing modes can generally be divided into two main types: evanescent wave-based and surface plasmon resonance-based sensing modes.

[0193] Sensing methods based on total internal reflection evanescent waves suffer from weak signal response and low sensitivity due to their reliance on light intensity modulation, making them unsuitable for detecting interactions and binding of small molecules or low-concentration biological samples. This disclosure enables phase modulation and detection modes, thereby improving the sensitivity of the total internal reflection evanescent wave sensing mode.

[0194] Another beneficial sensing mode is surface plasmon resonance (SPR) based sensing methods. The traditional approach to this method primarily utilizes the phase modulation effect of SPR materials at specific wavelengths to construct phase sensing sites and implement sensing applications. However, this traditional method places high demands on the optical properties of the sensing material, requiring it to possess phase response capabilities at specific wavelengths.

[0195] This disclosure constructs an independent design of phase sensing sites through external optical path design, breaking the limitations of plasmonic phase sensing materials. It can not only apply a variety of broadband absorption optical materials with excellent biological and chemical properties to biosensing, but also expand the application scope of biosensing.

[0196] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any person skilled in the art can easily conceive of various equivalent modifications or substitutions within the technical scope disclosed in the present invention, and these modifications or substitutions should all be covered within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope of the claims.

Claims

1. An optical sensor, characterized in that, It includes a light source unit, a sensing unit, a reference unit, and a detection unit. One probe beam emitted by the light source unit is transmitted to the sensing unit, where it interacts with the target sample and is then received by the detection unit. One reference beam emitted by the light source unit is transmitted to the reference unit, and then received by the detection unit. The detection unit recombines the probe beam and the reference beam, and then performs spectral analysis on the recombined beam to obtain the characteristics of the target sample. The sensing unit includes a first birefringent crystal, and the reference unit includes a second birefringent crystal. The optical path difference of the first birefringent crystal is: The optical path difference of the second birefringent crystal is ,and Difference , The optical sensor has one or more sensing and detection sites, and ,as well as , Numerical combinations are related.

2. The optical sensor according to claim 1, characterized in that, In the sensing unit, a first front linear polarizer, a first birefringent crystal, a sensing and detection unit, and a first rear linear polarizer are arranged sequentially along the optical path.

3. The optical sensor according to claim 2, characterized in that, A first light source collimation unit is provided in front of the first front linear polarizer.

4. The optical sensor according to claim 1, characterized in that, In the reference unit, a second front linear polarizer, a second birefringent crystal, and a second rear linear polarizer are sequentially arranged along the optical path.

5. The optical sensor according to claim 4, characterized in that, A second light source collimation unit is provided in front of the second front linear polarizer.

6. The optical sensor according to claim 1, characterized in that, The light source unit includes a light source, a first collimating lens group, a beam splitter and a reflector arranged sequentially along the optical path.

7. The optical sensor according to claim 6, characterized in that, In the light source unit, the light emitted from the light source is guided into the first collimating lens group through a first light waveguide connected to the light source.

8. The optical sensor according to claim 1, characterized in that, The detection unit includes a second collimating lens group and a second optical waveguide, a third collimating lens group and a third optical waveguide arranged according to the receiving optical path, and a spectral analysis unit connected to the second optical waveguide and the third optical waveguide respectively.

9. The optical sensor according to claim 2, characterized in that, The sensing unit is any one or a combination of total reflection sensing unit, transmission sensing unit, and plasmonic sensing unit.

10. The optical sensor according to claim 9, characterized in that, The transmissive sensing unit is either a parallel light transmissive sensing unit or a focused light scanning transmissive sensing unit.

11. The optical sensor according to claim 9, characterized in that, The plasmon sensing unit is a surface plasmon resonance sensing unit or a localized surface plasmon resonance sensing unit.

12. The optical sensor according to claim 9, characterized in that, The total internal reflection sensing unit includes, Prism; A sensing layer covers the surface of the prism to serve as a sensing interface; as well as The sample fluid cavity is used to introduce the sample to be tested into the sensing interface.

13. The optical sensor according to claim 9, characterized in that, The transmissive sensing unit uses a collimated beam, parallel light, or focused light to incident on the sample to be detected.

14. The optical sensor according to claim 9, characterized in that, The plasmonic sensing unit includes, Prism; A sensing layer covers the surface of the prism to serve as a sensing interface; as well as The sample fluid cavity is used to introduce the sample to be tested into the sensing interface.

15. Use of an optical sensor as described in any one of claims 1 to 14, characterized in that, The optical sensor is used to detect the characteristics of the target sample.

16. A sample sensing and detection device, characterized in that, The device includes the optical sensor as described in any one of claims 1 to 11.

17. A biosensor detection chip, characterized in that, The chip includes the optical sensor as described in any one of claims 1 to 11.

18. A sample sensing and detection method, characterized in that, include, A probe beam is generated from the light source unit, and the probe beam is transmitted to the sensing unit. After interacting with the target sample, it is received by the detection unit. A reference beam is generated from the light source unit, the reference beam is transmitted to the reference unit, and then received by the detection unit via the reference unit; After the probe beam and the reference beam are recombined, the characteristics of the target sample are obtained by performing spectral analysis on the recombined beam. The sensing unit includes a first birefringent crystal, and the reference unit includes a second birefringent crystal. The optical path difference of the first birefringent crystal is: The optical path difference of the second birefringent crystal is ,and Difference , By setting and setting different , The sensing units are combined to design one or more sensing and detection sites.

19. The sample sensing and detection method according to claim 18, characterized in that, The sample is a colloidal gold sample, and the detection method for the colloidal gold sample includes, The sensing unit is configured as a transmissive sensing unit. Different concentrations of sodium chloride solution were added to the colloidal gold sample solution to form colloidal gold sample solutions of different concentrations. The phase change at a preset phase sensing detection wavelength site was observed by detecting colloidal gold sample solutions of different concentrations using a transmission sensing unit. The phase response values ​​of colloidal gold sample solutions of different concentrations at the preset wavelength spectral positions were calculated to obtain the standard sensing quantitative fitting curve.

20. The sample sensing and detection method according to claim 18, characterized in that, The sample is a plasmonic material, including biochips based on gold films, gold nanoisland particle matrices, and gold-silver alloy nanoisland particle matrices. The detection methods for the plasmonic material sample include... The sensing unit is configured as a total internal reflection sensing unit or a plasmonic sensing unit. Deionized water and sodium chloride solutions of different concentrations were injected into the sample fluid chamber. The phase response value of the sample is obtained by calculating the refractive index of samples with different concentrations.

21. An optical sensing component, characterized in that, It includes a light source unit, a sensing unit, and a reference unit. One probe beam emitted by the light source unit is transmitted to the sensing unit, where it interacts with the target sample and then exits to the first optical path interface of the optical sensing component. One reference beam emitted by the light source unit is transmitted to the reference unit, and then exits through the reference unit to the second optical path interface of the optical sensing component. The first and second optical paths of the optical sensing component are simultaneously connected to a detection unit. The detection unit recombines the received probe beam and reference beam, and then performs spectral analysis on the recombined beam to obtain the characteristics of the target sample. The sensing unit includes a first birefringent crystal, and the reference unit includes a second birefringent crystal. The optical path difference of the first birefringent crystal is: The optical path difference of the second birefringent crystal is ,and Difference , The optical sensing component has one or more sensing detection sites, and ,as well as , Numerical combinations are related.

22. A spectral acquisition component, characterized in that it includes a sensing unit and a reference unit. The spectral acquisition component has a third optical path interface and a fourth optical path interface, which are connected to an external light source unit. In addition, the spectral acquisition component also has a fifth optical path interface and a sixth optical path interface. One probe beam emitted by the light source unit is transmitted to the sensing unit through the third optical path interface of the spectral acquisition component. After interacting with the target sample in the sensing unit, it exits to the fifth optical path interface of the spectral acquisition component. A reference beam emitted by the light source unit is transmitted to the reference unit through the fourth optical path interface of the spectral acquisition component, and then exits to the sixth optical path interface of the spectral acquisition component via the reference unit. The fifth and sixth optical paths of the spectral acquisition component are simultaneously connected to a detection unit. The detection unit recombines the received probe beam and reference beam, and then performs spectral analysis on the recombined beam to obtain the characteristics of the target sample. The sensing unit includes a first birefringent crystal, and the reference unit includes a second birefringent crystal. The optical path difference of the first birefringent crystal is: The optical path difference of the second birefringent crystal is ,and Difference , The spectral acquisition component has one or more sensing detection sites, and ,as well as , Numerical combinations are related.

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