Biochemical sensor with high sensitivity, high flux and high selectivity and sensing method thereof

Abstract

The invention provides a high-sensitivity, high-flux and high-selectivity biochemical sensor and a sensing method thereof. The high-sensitivity, high-flux and high-selectivity biochemical sensor comprises a light-emitting device, a container, a dispersion device, a sensing device, an array type detection chip and a calculation unit connected with the array type detection chip, according to the sensor, a coordination polymer is used as a sensing device, an array type detection chip is used as a signal detection element, and fluorescent light which is emitted by the coordination polymer and has relatively weak light intensity is used as a perturbation signal; and sensing by solving the matrix equation for multiple times and detecting whether the peak value of the restored spectral line of the standard signal with relatively strong light intensity under the influence of the perturbation signal is changed or not. The technical problems that an existing biochemical sensor is large in size, complex in structure, high in cost, low in flux, low in sensitivity, narrow in detection wave band, single in detection object, incapable of achieving real-time detection and the like are solved.

Description

Technical Field

[0001] The invention relates to a biochemical sensor with high sensitivity, high throughput and high selectivity and a sensing method thereof, and relates to the technical field of biochemical sensing. Background Art

[0002] In the ecosystem, the abnormal content of biological molecules, biomarkers, toxin molecules, drug molecules, heavy metal ions, etc. is often closely related to the health of organisms. Therefore, real-time monitoring of the content of related molecules and ions in the environment and organisms through biochemical sensors is of great significance for environmental quality assessment, disease diagnosis and treatment. Nowadays, biochemical sensor technology has become a new economic growth point connecting biology, chemistry, and information technology, and has been widely used in various fields of the national economy, such as clinical diagnosis, industrial control, food analysis, environmental protection, drug development, and biochips. Although there are many methods for people to use biochemical sensors to sense and detect substances containing certain special biological or chemical components, these methods have their own advantages and disadvantages. For example, the electrochemical method is a qualitative or quantitative method based on the correlation between the change of electrical signals caused by the target and the concentration or other physical parameters, and has the characteristics of high sensitivity. However, most of the test results of instruments using electrochemical methods are not stable enough. Due to the many interference factors of immune response or aptamer response, the test results are difficult to repeat in many cases, so it is difficult to industrialize.

[0003] In addition to electrochemical methods, more biochemical sensing instruments use spectroscopic methods, such as ultraviolet spectroscopy, infrared spectroscopy, Raman spectroscopy, fluorescence spectroscopy, etc. Ultraviolet spectroscopy belongs to electronic spectroscopy and can only be used to analyze and determine the types of certain compounds, and cannot analyze saturated organic compounds. Infrared spectroscopy is not limited to this. It is caused by the vibrational energy level of the molecule and accompanied by the transition of the rotational energy level. It can be used to identify and determine the molecular structure of the compound, for qualitative analysis and structural research, and its characteristic is higher than that of ultraviolet spectroscopy. However, infrared spectroscopy also has disadvantages. For example, infrared spectroscopy requires sample preparation, cannot be measured in glass containers, is not suitable for aqueous solution determination, and has limited information when analyzing inorganic compounds.

[0004] To this end, some people have proposed a sensor detector based on Raman spectroscopy. Raman spectroscopy is based on the Stokes scattering generated by the interaction between light and chemical bonds in materials, and can provide detailed information on the chemical structure, phase and morphology, crystallinity, and molecular interactions of samples. Compared with infrared spectroscopy, Raman spectroscopy can measure aqueous solutions, and the measurement does not require special sample preparation. It can be measured in glass containers, and has better performance when measuring inorganic compounds. Therefore, it often complements infrared spectroscopy. However, the Raman light signal is generally very weak, and it is difficult to detect directly without an expensive Raman spectrometer. In addition, many compounds do not have Raman activity. For some compounds with Raman activity, they may emit fluorescence. Since fluorescence is much stronger than the light signal of Raman spectroscopy, it will interfere with the Raman light signal and reduce the signal-to-noise ratio of the Raman sensor.

[0005] Compared with Raman sensors, fluorescence sensors have a higher signal-to-noise ratio. In particular, fluorescence sensors based on metal organic framework compounds (MOFs) have become an excellent representative of fluorescence sensors due to their high porosity, chemical tunability, high stability and selectivity. Resonance energy transfer, competitive absorption, chemical reactions, etc. will lead to the enhancement or quenching of the fluorescence intensity emitted by MOF materials during the detection process. However, the fluorescence intensity stimulated by MOF materials is still very weak, and traditional MOF sensors generally require special fluorescence spectrometers for sensing detection, which limits the widespread application of MOF sensors.

[0006] In addition, there are SPR sensors and LSPR sensors. SPR sensors have high sensitivity, but because phase matching conditions must be met to achieve the resonance effect, the detection band range with high sensitivity is very narrow; in addition, the Kretschmann structure commonly used in SPR sensors requires the use of prisms and precise adjustment of the incident angle, so the volume is large and the optical path is complex; in comparison, the LSPR sensor has a simple optical path, but the LSPR sensor has a wider resonance peak, and the signal-to-noise ratio and sensitivity are generally lower than those of SPR sensors.

[0007] Taking into account the shortcomings of the above-mentioned biochemical sensors, we urgently need to develop biochemical sensors with higher sensitivity and signal-to-noise ratio, better selectivity and stability, simpler optical paths, smaller size, lower cost, and the ability to sense a variety of different substances. Summary of the invention

[0008] Technical problem: The purpose of the present invention is to provide a biochemical sensor and a sensing method thereof which is highly sensitive, high-throughput, miniaturized, label-free, can detect multiple substances simultaneously, and can detect in real time. It solves the technical problems of the biochemical sensors described in the background technology, such as large size, complex production, high cost, low flux, low sensitivity, narrow detection band, relatively single detection object, and inability to detect in real time.

[0009] The invention objective of the present invention is specifically achieved by adopting the following technical solutions:

[0010] A biochemical sensor with high sensitivity, high throughput and high selectivity, which includes a light-emitting device, a container, a dispersion device, a sensor device, an array detection chip and a computing unit connected to the array detection chip; the light-emitting device includes at least one light source; the container contains at least one substance to be detected; the dispersion device can cause the incident light emitted by the light-emitting device to the surface of the dispersion device to have a dispersion effect, and the dispersion effect can cause incident light of different wavelengths and the same intensity to form different light intensity distributions on the surface of the array detection chip after passing through the same part of the dispersion device, and the light intensity distributions formed by incident light of the same wavelength and the same intensity after passing through different parts of the dispersion device are also different; the sensor device includes at least one coordination polymer, which is a compound in which metal ions and organic ligands are connected by coordination bonds and has adsorption properties or fluorescence emission properties for specific substances; the fluorescence excitation band of the coordination polymer in the sensor device is partially consistent with the spectral wavelength range of the emission light of any light source in the light-emitting device. The coordination polymer in the sensor device is placed in the container and is in full contact with the substance to be tested. When the concentration or physical property of the substance to be tested changes, the fluorescence property of the corresponding coordination polymer will also change. The different pixel elements of the array detection chip detect the light emitted from various parts of the dispersion device and irradiated at the position of each pixel element after the dispersion effect, and the fluorescence emitted from various parts of the sensor device and irradiated at the position of each pixel element. The calculation unit uses the light signal irradiated on the surface of the dispersion device as the standard signal and the fluorescence signal emitted by the coordination polymer as the perturbation signal, and restores the spectral line of the standard signal with stronger light intensity under the influence of the perturbation signal, and obtains the spectral restoration lines corresponding to the substance to be tested at different times according to the results detected by the array detection chip at different times, detects whether the spectral restoration lines corresponding to the substance to be tested at different times change, and judges the concentration change or physical property change of the substance to be tested according to the detection results.

[0011] Preferably, the light emitting device of the biochemical sensor comprises a first light source and a second light source; the light emitted by the first light source can irradiate the pixel elements at different positions of the array detection device after passing through the dispersion device but does not directly irradiate the sensor device; the light emitted by the second light source irradiates the sensor device but does not directly irradiate the array detection device, but the fluorescence excited by the light emitted by the second light source on the sensor device irradiates the pixel elements at different positions of the array detection chip; the spectra of the light emitted by the first light source and the second light source are different, the spectral range of the light emitted by the first light source is within the spectral measurement range of the array detection chip, and the spectral range of the light emitted by the second light source overlaps with the fluorescence excitation spectrum of the coordination polymer.

[0012] Preferably, the biochemical sensor further comprises at least one filter, which is located at at least one light outlet of the light emitting device; the filter makes the spectrum of the incident light irradiated to the surface of the dispersion device have only one or two spectral peaks, and at the same time makes the peak wavelength of the spectral peak different from the peak wavelength of the emission peak of the coordination polymer; the filter also makes the peak of the spectrum of the incident light irradiated to the surface of the sensor device close to or overlap with the peak of the excitation spectrum of the coordination polymer.

[0013] Preferably, the sensor device and the dispersion device of the biochemical sensor are combined into a dispersion sensor device, and the dispersion sensor device has all the functions of the sensor device and the dispersion device.

[0014] Preferably, the coordination polymer of the biochemical sensor is a metal organic framework compound, namely, a MOF material; the metal organic framework compound (MOF material) is an ultra-porous nanomaterial, a crystal in which metal ions and organic ligands are connected by coordination bonds and extend in space in a certain pattern.

[0015] Preferably, the biochemical sensor also includes a filter or a light wavelength conversion component arranged between the sensor device and the array detection chip; the filter can completely or partially block the passage of light in the fluorescence excitation band of the coordination polymer, but cannot block the passage of light in the fluorescence emission band of the coordination polymer; the light wavelength conversion component includes at least one wavelength conversion optical material, the absorption spectrum band of the wavelength conversion optical material overlaps with the fluorescence emission band of the coordination polymer, and the emission spectrum band of the wavelength conversion optical material is within the detection band range of the array detection chip.

[0016] Preferably, the container of the biochemical sensor is a cylindrical container, or the container wall where the light enters the container is not parallel to the container wall where the light exits the container.

[0017] Preferably, the sensor device comprises a plurality of coordination polymers, the excitation light spectra of the plurality of coordination polymers do not overlap with each other, and the plurality of coordination polymers are mixedly distributed on the surface of the sensor device; a filtering device is provided at the light outlet of the light source of the light-emitting device of the biochemical sensor, and the filtering device is composed of a plurality of filters and a controller, and under the action of different control parameters of the controller, filters with different transmission spectra are respectively arranged in the light path between the light source and the sensor device in the light-emitting device at different times, so that different coordination polymers respectively emit fluorescence under the action of different control parameters of the controller, thereby successively sensing the concentration changes or physical property changes of different substances to be measured.

[0018] The present invention discloses a sensing method of a biochemical sensor with wide spectrum, high sensitivity and high throughput: the intensity of monochromatic light of different wavelengths at different pixel positions of the array detection chip after passing through the dispersion device is divided by the intensity of monochromatic light of different wavelengths at different pixel positions of the array detection chip without passing through the dispersion device and the sensor device, and the ratios obtained after the division are respectively substituted into the coefficient matrix C of the matrix equation, and the intensity of light of the light emitting device at different pixel positions in the array detection chip after passing through the dispersion device and the sensor device during the first sensing is respectively substituted into the augmented matrix Y0 of the matrix equation, and the calculation result X0 at the initial moment is obtained by solving the matrix equation CX0=Y0; during the sensing process, the coefficient matrix C is kept unchanged, and the intensity of light at each pixel in the array detection chip sensed each time is respectively substituted into different augmented matrices Y1, Y2...Y t In the above example, we solve the matrix equations CX1=Y1, CX2=Y2…CX t =Y t Then we get the calculation results X1, X2…X t , detect the calculation results X1, X2…X obtained by each sensing t Is there any change compared with X0, or detect the calculation results X1, X2...X obtained by each sensing t Whether there is a change between the two, the concentration change or physical property change of the substance to be tested is sensed according to the test results to achieve sensing, where t is a positive integer, Y t represents the augmented matrix corresponding to the t-th sensing, X t Represents the calculation result corresponding to the t-th sensing.

[0019] The present invention discloses the implementation steps of a sensing method of a wide spectrum, high sensitivity and high throughput biochemical sensor:

[0020] Step 1: Spectral band division: Divide the spectral band of light incident on the dispersion device or the light that can be received by the array detector into n central wavelengths λ1, λ2, ...λ n A wavelength band with a width of Δλ, where n is an integer greater than 3.

[0021] Step 2, calibration coefficient determination: Use a light emitting device and a monochromator or a tunable laser to obtain narrow-band calibration light with a central wavelength of λ j The light intensity of the narrow spectrum calibration light detected by the i-th pixel element of the array detection chip after passing through the dispersion device and other devices in front of the array detection chip is related to the central wavelength λ j The narrowband calibration light that has not passed through the dispersion device is detected by the light intensity. The ratio of these two measured light intensities minus the ambient noise is recorded as the calibration coefficient C. ij , where i=1,2…n, where j=1,2…n.

[0022] Step 3, solve the matrix equation: remove the monochromator or tunable laser, and the value of the light intensity detected by n pixels in the array detection chip minus the ambient noise is recorded as I m1 ,I m2 ,…I mn (where m is a natural number), solve the following matrix equation by regularization algorithm or other mathematical optimization methods to obtain the central wavelengths λ1, λ2, …λ n The intensity of the light component corresponding to the wavelength band I m (λ1),I m (λ j ),…I m (λ n ):

[0023]

[0024] The coefficient matrix of the above matrix equation is is the calibration coefficient matrix,

[0025] Each cell C in the calibration coefficient matrix C ij This is the calibration coefficient measured in step 2. Solving the above matrix equation can be divided into two situations: calibration and sensing. During calibration (m = 0), the concentration and refractive index of the solution to be measured do not change. At this time, the above matrix equation is solved by a mathematical optimization algorithm to obtain the central wavelengths λ1, λ2, ...λ n The intensity of the light components corresponding to the wavelength band is I0(λ1), I0(λ2),…I0(λ n ), for I0(λ1),I0(λ2),…I0(λ n) is linearly fitted and normalized to obtain the calibration recovery curve; when the mth sensing is performed (m = 1, 2...), the data in the calibration coefficient matrix is ​​kept unchanged, and the value I after the light intensity detected by the n pixels in the array detection chip minus the environmental noise is m1 ,I m2 ,…I mn Substitute them into the augmented matrix of the above matrix equation respectively, and solve the above matrix equation through mathematical optimization algorithm to obtain the central wavelengths λ1, λ2, …λ n The intensity of the light component corresponding to the band is I m (λ1),I m (λ2),…I m (λ n ), to I m (λ1),I m (λ2),…I m (λ n ) is linearly fitted and normalized to obtain a normalized restoration curve corresponding to the m-th sensing; the mathematical optimization algorithm makes the obtained normalized restoration curve closer to the normalized spectral curve of the light incident on the dispersion device, and the mathematical optimization algorithm can be a combination of one or more of a regularization algorithm, a simulated annealing algorithm, a machine learning algorithm, a convex optimization algorithm, a genetic algorithm, and a cross-direction multiplier algorithm, or it can be an improved algorithm after adding a smoothness coefficient optimization term on the basis of the above algorithm, and the smoothness coefficient optimization term can make the restoration curve continuous and smooth.

[0026] Step 4, comparison of restoration curves: the peak value of the normalized restoration curve obtained during sensing is called the sensing peak, and the peak value of the normalized restoration curve obtained during calibration is called the calibration peak. The sensing peak is compared with the calibration peak. If there is a change between the sensing peak and the calibration peak, it indicates that the refractive index, concentration or physical property of the substance to be measured has changed during sensing. Alternatively, the mth sensing peak obtained during the mth sensing is compared with the (m-1)th sensing peak obtained during the (m-1)th sensing. If there is a change between the mth sensing peak and the (m-1)th sensing peak, it indicates that the concentration or physical property of the substance to be measured has changed during the mth sensing.

[0027] Compared with the prior art, the sensor of the present invention adopts the above technical solution and has the following technical effects:

[0028] (1) High sensor sensitivity.

[0029] Traditional sensors basically sense by directly measuring the intensity or wavelength change of the spectral peak, but the fluorescence intensity required to be detected by traditional MOF sensors is relatively small, and it is difficult to sense directly by detecting the intensity change of the fluorescence spectrum peak, so the sensing sensitivity is low. The sensor in the present invention does not directly sense by measuring the change in the spectral emission peak intensity of the fluorescence emitted by the coordination polymer, but uses the change in the fluorescence spectrum emission peak intensity during sensing as a perturbation signal to the set standard signal with a stronger signal, and then senses by measuring the change in the standard signal restored spectrum caused by the change in the perturbation signal. This sensing technology can only be realized by the technology disclosed in the present invention. This is because the technology in the present invention performs spectral restoration by solving matrix equations, and any pixel element of the array detection chip used in this technology can receive signals of multiple wavelengths at the same time. During sensing, not only can the wavelength range of the standard signal be defined by itself, but it is also extremely sensitive to perturbation signals. To give a simple example, assume that there is such a matrix equation:

[0030]

[0031] It is easy to find that the exact solution of this matrix equation is x = [2,0] T , the exact solution is set as the standard signal. If a small change occurs in an element of the augmented matrix during the sensing process, the change can be regarded as a perturbation signal of the set standard signal. Therefore, the matrix equation obtained at a certain moment in the sensing is:

[0032]

[0033] At this time, the solution of the matrix equation is x = [1,1] T . It can be seen that 10 in the matrix element -7 A small change in will also lead to a huge difference in the solution of the equations. Therefore, making full use of this property for sensing can greatly improve the sensing sensitivity.

[0034] During actual sensing, the matrix equation obtained by spectral restoration has more rows and columns. Changes in the concentration of the object to be measured during the sensing process will cause changes in the light intensity detected by some pixels of the array detection chip. However, because there are too many data in the augmented matrix and there is no regularity, it is impossible to achieve sensing by comparing the data in the augmented matrix with the data during calibration one by one. Therefore, assuming that the coefficient matrix remains unchanged, sensing is achieved by comparing the spectral line peaks of the matrix equation solutions during sensing with the spectral line peaks of the matrix equation solutions during calibration. This can achieve higher sensing sensitivity than traditional methods.

[0035] (2) High sensing flux, enabling parallel sensing of multiple materials.

[0036] The detection element used in the traditional sensor is a traditional spectrometer, which has only one light signal input port. The single input port makes the traditional spectrometer unable to detect weak light signal changes. The detection element of the computational spectrum sensor is an array detection chip (such as CCD or CMOS), on which there are more than one million pixels that can detect many light signals at the same time, so the sensor system has a large light flux and a high signal-to-noise ratio. Since each pixel can receive light from different positions of the dispersion device, some pixels may just be in the position of constructive interference at the beginning of sensing, and when the concentration of the analyte changes slightly, the coordination polymer adsorbs the analyte to change the position of constructive interference to the position of other pixels. Therefore, the present invention can detect the tiny signal change that the traditional spectrometer cannot measure through the pixels at different positions, thereby improving the sensing sensitivity. At the same time, if different parts of the sensor device are sensitive to different substances to be tested, the same sensor can also perform high-throughput parallel sensing on multiple different substances at the same time.

[0037] (3) High sensing selectivity.

[0038] Almost all sensors that perform sensing detection based on spectral characteristic peaks will be interfered with or even unable to sense when the composition of the sensed substance is complex. Although some sensors have high universality, that is, they can sense relatively more types of substances, but in the presence of interference factors, the sensing sensitivity and signal-to-noise ratio for specific substances are relatively low. The present invention uses MOF materials to sense the adsorption properties and fluorescence emission properties of specific substances. MOF materials are formed by self-assembly of inorganic metal ions and organic ligands, and have ultra-high specific surface area, high porosity, adjustable pore size, and good stability. Biochemical sensors based on MOF materials have been widely used in clinical medicine, food safety and other fields. Therefore, the sensing detection method based on MOF materials adopted in the present invention has the advantages of high selectivity, high sensitivity, and low cost.

[0039] (4) It has the characteristics of rich detection objects and wide spectrum

[0040] Traditional sensors can only sense within the wavelength band that the spectrometer used can detect, so it is necessary to use spectrometers with different wavelength measurement ranges to sense and detect signals in the ultraviolet band and infrared band respectively. The present invention can expand the wavelength detection range of the sensor by placing low-cost up-conversion or down-conversion luminescent materials in front of the array detection chip, so that more substances can be sensed. Since the traditional spectrometer does not need to measure the calibration coefficient, the up-conversion and down-conversion luminescent materials cannot be directly used in traditional spectrometers, but are suitable for the sensing technology in the present invention. Since the excitation light band of many MOF materials is in the ultraviolet band range, the excitation light signal of the MOF material cannot be directly measured by a silicon-based detector. The inventor uses a down-conversion luminescent material to convert ultraviolet rays after passing through the MOF material into visible light that can be detected by a silicon-based CCD or CMOS, and then the spectrum of the standard signal with a stronger intensity is also set in the visible light band, so that the change in the spectrum of the converted standard signal restoration can be sensed by detecting the change in the perturbation signal.

[0041] (5) Simple structure and small size.

[0042] The sensor in the present invention has the characteristics of miniaturization, simple optical path design and low cost. Traditional sensors need to use large prisms or gratings, while the sensor devices and array detection chips in the present invention are small in size, which is conducive to integrating the entire device in a small volume. In addition, the array detection chip can use mature products such as CCD or CMOS, so the production cost is low and the preparation process is simple and mature. During detection, there is no need to adjust the optical path to meet the phase matching conditions, and the optical path construction is simple.

[0043] (6) Label-free detection and real-time sensing are possible.

[0044] Traditional sensors need to add markers when performing sensing detection, and sometimes cannot measure in real time. In contrast, the present invention does not need to add markers, will not pollute the original solution, and can monitor the substance to be tested in real time. BRIEF DESCRIPTION OF THE DRAWINGS

[0045] Figure 1 This is a schematic diagram of the structural principle of the biochemical sensor proposed in the present invention when the first light source and the second light source are used.

[0046] Figure 2 The schematic diagram of the spectrum wavelength division of the biochemical sensor proposed in the present invention; wherein the abscissa represents the wavelength and the ordinate represents the light intensity; the wavelength range of the emission spectrum of the light emitting device is divided into n equal parts by the calculus method, and the central wavelength of each part is taken, and the wavelength width of each part is △λ,λ j is the central wavelength of any small rectangle, and its amplitude is I0(λ j ).

[0047] Figure 3 The peak value (sensing peak) of the normalized recovery curve of the biochemical sensor proposed in the present invention during sensing is compared with the peak value (calibration peak) of the normalized recovery curve during calibration; the solid line is the normalized recovery curve obtained during calibration, and the dotted line is the normalized recovery curve obtained when sensing the biochemical sensor after the concentration of picric acid changes.

[0048] Figure 4 This is a schematic diagram of the three-dimensional structural principle of the biochemical sensor proposed in the present invention when using a filter and a dispersion sensor device.

[0049] Figure 5 The biochemical sensor proposed in the present invention is Fe 3+ The normalized recovery curve obtained before the change in ion concentration (dashed line) is compared with the normalized recovery curve obtained after the change in concentration (solid line).

[0050] Figure 6 This is a schematic diagram of the three-dimensional structural principle of the biochemical sensor proposed in the present invention when a filtering device is used.

[0051] Figure 7 Spectral curve of the light transmitted by the first filter used to excite the first coordination polymer [Cd(BTBD)2(AIC)].

[0052] Figure 8 To excite the second coordination polymer [Eu(TDA)(BDC-NH2) 0.5 Figure 5. Spectral curve of the light transmitted by the second filter of (DMA)].

[0053] Fig. 9 This is a schematic diagram of the three-dimensional structural principle of the biochemical sensor proposed in the present invention when using a light wavelength conversion component.

[0054] Description of the drawings: 1 is a light-emitting device, 2 is a container, 3 is a dispersion device, 4 is a sensor device, 5 is an array detection chip, 6 is a micro-nano particle, 7 is a substance to be measured, 8 is light irradiated on the surface of the dispersion device, 9 is light irradiated on the surface of the sensor device, 10 is the fluorescence emitted by the sensor device, 11 is a first light source, 12 is a second light source, 13 is a tube, 14 is a filter, 15 is a filter, 16 is a filtering device, 17 is a filter mirror, 18 is a dispersion sensor device, 19 is light emitted from different parts of the dispersion device, 20 is a controller, 21 is a light source, and 22 is an optical wavelength conversion component. DETAILED DESCRIPTION

[0055] The purpose, advantages and features of the present invention will be illustrated and explained through the non-limiting description of the following preferred embodiments. These embodiments are only typical examples of the application of the technical solution of the present invention, and any technical solution formed by equivalent replacement or equivalent transformation falls within the scope of protection claimed by the present invention.

[0056] Embodiment 1:

[0057] Example 1 provides a biochemical sensor that can detect picric acid (PA) with high sensitivity and selectivity. Picric acid is a toxic pollutant and can be used as an explosive raw material. Therefore, it is necessary to perform sensor detection on picric acid to solve the current severe environmental protection and safety problems. The structure of the biochemical sensor is as follows: Figure 1 As shown, the sensor includes a light emitting device 1, a container 2, a dispersion device 3, a sensor device 4, an array detection chip 5, and a computing unit connected to the array detection chip. Figure 1 The dispersion device 3 includes a plurality of micro-nano particles 6 of different sizes or shapes and uneven distribution, the sensor device 4 is placed in the container 2, the solution to be tested 7 is a solution containing picric acid, which flows into the container 2 from one end through the tube 8 and flows out from the other end, the solution to be tested 7 contacts the sensor device 4, the light emitting device 1 irradiates the dispersion device 3 via the filter 14, the plurality of micro-nano particles 6 of different sizes or shapes and uneven distribution in the dispersion device 3 will cause the light 8 irradiated on the surface of the dispersion device to scatter or diffract, and the light 19 emitted from different parts of the dispersion device will interfere with each other; the light signal irradiated on the surface of the dispersion device is used as the standard signal, and the fluorescent signal emitted by the coordination polymer is used as the perturbation signal, the array detection chip 5 detects the light intensity of the standard signal and the perturbation signal at each pixel position, and performs sensing by restoring the spectral line of the standard signal and detecting whether the peak value of the restored spectral line of the standard signal with stronger light intensity under the influence of the perturbation signal at different times changes.

[0058] The sensing method comprises: dividing the intensity of monochromatic light of different wavelengths at different pixel positions after passing through the dispersion device by the intensity before the light is incident on the dispersion device, and substituting the ratios obtained after the division into the coefficient matrix C of the matrix equation, and substituting the intensity of light at different pixel positions in the array detection chip at the initial moment into the augmented matrix Y0 of the matrix equation corresponding to the initial moment, and obtaining the initial calculation result X by solving the matrix equation CX0=Y0 0，In the sensing process, the coefficient matrix C of the matrix equation used to obtain the initial calculation result is kept unchanged, and the light intensity at each pixel in the array detection chip at different times is substituted into different augmented matrices Y1, Y2…Y corresponding to different times. k In the test, the matrix equations CX1 = Y1, CX2 = Y2…CX are solved by these augmented matrices. k =Y k The calculated results X1, X2…X k Compared with the initial calculation result X0, whether there is a change, the refractive index change or physical property change of the substance to be tested is sensed according to the test result, where k is an integer greater than 3, Y k represents the k-th moment augmented matrix, X k Indicates the calculation result at the kth moment.

[0059] In this embodiment, the principles of scattering, diffraction and interference are used to produce the dispersion effect. These principles are briefly introduced below:

[0060] Scattering is when a light beam passes through a particle, part of the light beam will deviate from the original direction and spread out. Scattering mainly includes Rayleigh scattering and Mie scattering. When Rayleigh scattering occurs, the particles on the dispersion device are about one-tenth of the wavelength of the incident light, and the scattered light has the same wavelength as the incident light. The intensity of the scattered light is related to the scattering direction and is proportional to the fourth power of the wavelength. When the diameter of the micro-nano particles is equivalent to the wavelength of the light, the scattering that occurs is Mie scattering. The radiation intensity of Mie scattering is proportional to the square of the wavelength. The scattering is stronger in the forward direction of the light than in the backward direction, and the directionality is more obvious. Regardless of which type of scattering is used, the light incident on the MOF particles can be dispersed in all directions. Therefore, regardless of whether Rayleigh scattering or Mie scattering occurs, micro-nano particles of different sizes and shapes will form different angular distributions of scattered light intensity for incident light of the same wavelength, and micro-nano particles of the same size and shape will also form different angular distributions of scattered light intensity for incident light of different wavelengths.

[0061] When the particles in the dispersion device are large, the gaps between the particles will cause the light incident on the dispersion device to diffract, and the diffraction will also cause the incident light to deviate from the original propagation direction. In addition, particle gaps of different sizes will form different diffraction light intensity angular distributions for incident light of the same wavelength, and particle gaps of the same size will form different diffraction light intensity angular distributions for incident light of different wavelengths.

[0062] Interference will occur between the light that has been scattered or diffracted as mentioned above. Interference is the phenomenon of superposition or cancellation of two or more light waves of the same wavelength when they meet in space. When two light waves propagate in the same medium and overlap, the particles of the medium within the overlapping range are affected by the two light waves at the same time. If the amplitude of the wave is not large, the vibration displacement of the particles of the medium within the overlapping range is equal to the vector sum of the displacements caused by the individual waves. This is called the principle of wave superposition. If the crests (or troughs) of the two waves arrive at the same location at the same time, the two waves are said to be in phase at that point, and the interference wave will produce the largest amplitude, which is called constructive interference; if the crest of one of the two waves and the trough of the other wave arrive at the same location at the same time, the two waves are said to be in anti-phase at that point, and the interference wave will produce the smallest amplitude, which is called destructive interference.

[0063] According to the above physical principles, the dispersion device can cause a dispersion effect on the incident light from the light-emitting device to the surface of the dispersion device. The dispersion effect can cause incident light of different wavelengths and the same intensity to form different light intensity distributions on the surface of the array detection chip after passing through the same part of the dispersion device, and incident light of the same wavelength and the same intensity to form different light intensity distributions after passing through different parts of the dispersion device.

[0064] In this embodiment, the light emitting device 1 is two different LEDs. The first light source 11 of the light emitting device 1 is composed of a broadband visible light LED, which is used to generate a standard signal; the second light source 12 of the light emitting device 1 is composed of a broadband ultraviolet LED, which is used to generate a perturbation signal. There are two filters 14 at the exits of the first light source and the second light source, respectively, which are filters with a transmission center wavelength of 616nm at the exit of the visible light LED, and filters with a transmission center wavelength of 375nm at the exit of the ultraviolet LED. The purpose of setting the filter at the exit of the first light source is to make the spectrum of the transmitted light emitted from the light emitting device after passing through the filter have only one spectral peak, and filter out other spectral peaks. There are two reasons for setting only one spectral peak: one is that when restoring the spectrum by solving the matrix equation method, the restoration effect is better for the spectrum with only one spectral peak; the other is that when sensing, it is necessary to compare the sensing peak with the calibration peak. When there are more than one calibration peak and sensing peak, it will affect the sensing effect, thereby affecting the sensing sensitivity. At the same time, when selecting a filter, it should be noted that the peak wavelength of the spectral peak of the light emitted from the filter at the exit of the first light source cannot be the same as the peak wavelength of the emission peak of the coordination polymer. This is because if the two are the same, the peak wavelengths of the standard signal and the perturbation signal will overlap, so it is not easy to see the difference between the standard peak and the sensing peak, which will also affect the sensing effect. The purpose of setting a filter at the exit of the second light source is to allow light within the excitation band of the coordination polymer to pass as much as possible, so that the signal-to-noise ratio of the fluorescent signal (perturbation signal) emitted by the sensor device will be higher.

[0065] In this embodiment, the container 2 is a glass container. The dispersion device 3 can be made by alternately depositing polyelectrolytes and silica nanospheres on a transparent substrate by a self-assembly method, or frosted glass can be directly used. The array detection chip 4 is a silicon-based CMOS detector. For the coordination polymer in the sensor device 5, this embodiment uses N, N'-bis (3, 5-dicarboxylphenyl) -thiophene-2, 5-dimethylbenzene amide (L3) and CdCl2 to synthesize the coordination polymer CdL3 by a solvent thermal method. The material has excellent chemical stability, not only can it maintain skeleton integrity for a long time in water and air, but also can be stably present in an aqueous solution with a pH range of 2 to 11. The excitation spectrum of the coordination polymer CdL3 is within the spectral range of the light emitted by the second light source, and the light emitted by the second light source irradiates the coordination polymer CdL3, but does not directly irradiate the array detection device. The light from the first light source can irradiate the pixel elements at different positions of the array detection device after passing through the dispersion device, and the fluorescence excited by the light emitted by the second light source after irradiating the sensor device can irradiate the pixel elements at different positions of the array detection device. Figure 3 shown.

[0066] In this embodiment, the synthesis method of the coordination polymer CdL3 is as follows: CdCl2·2.5H2O (138.4 mg, 0.6 mmol), L3 (50 mg, 0.91 mmol), DMF (3 mL), H2O (3 mL), CH3OH (1 mL) and a few drops of HCl solution (0.2 M) are added to a 25 mL polytetrafluoroethylene liner, ultrasonicated for half an hour, loaded into a stainless steel shell, and then placed in an oven, the temperature is adjusted to 70°C, kept for 3 days, and after cooling, colorless crystals can be obtained, and the crystals are washed with pure water for multiple times and collected. The coordination polymer CdL3 crystal particles can be adhered to the surface of a transparent glass substrate by gluing, spin coating or scraping, thereby making a sensor device.

[0067] In this embodiment, the coordination polymer CdL3 emits fluorescence with a peak wavelength of 463 nm under the irradiation of light with a peak wavelength of 375 nm. CdL3 exhibits high sensitivity in detecting picric acid: when the concentration of picric acid is in the range of 0-40 μM, the fluorescence quenching constant is 3.2×10 4 M -1 , competitive absorption, resonance energy transfer and electrostatic interaction are the main mechanisms of the change in the fluorescence intensity of the material. Moreover, it can be used repeatedly with different concentrations of picric acid, so the coordination polymer CdL3 realizes the function of a sensor device.

[0068] The sensing method of Example 1 is implemented in the following steps:

[0069] Step 1: Spectral band division: The spectrum of the light from the first light source incident on the dispersion device is equally divided into n central wavelengths λ1, λ2, ...λ n The wavelength width is Δλ, such as Figure 2 As shown, n here is an integer greater than 3;

[0070] Step 2: Calibration coefficient determination: Use the first light source and a monochromator or a tunable laser to obtain narrow-band calibration light with a central wavelength of λ j The light intensity of the narrow spectrum calibration light detected by the i-th pixel element of the array detection chip after passing through the dispersion device and other devices before the array detection chip CMOS is related to the central wavelength λ j The narrowband calibration light that has not passed through the dispersion device is detected by the light intensity. The ratio of these two measured light intensities minus the ambient noise is recorded as the calibration coefficient C. ij (i=1,2…n; j=1,2…n);-

[0071] Step 3: Solve the matrix equation: Remove the monochromator, and the value of the light intensity detected by n pixels in the array detection chip minus the ambient noise is recorded as I m1 ,I m2 ,…I mn , solve the following matrix equation by regularization algorithm or other mathematical optimization methods to obtain the central wavelengths λ1, λ2, …λ n The intensity of the light component corresponding to the wavelength band I m (λ1),I m (λ j ),…I m (λ n ), where m = 0, 1, 2, ...:

[0072] in is the calibration coefficient matrix,

[0073] Each cell C in the calibration coefficient matrix C ij (i=1,2…n;j=1,2…n) is the calibration coefficient measured in step 2. Solving the above matrix equation is divided into two cases: calibration and sensing:

[0074] When calibrating (m=0), the concentration of picric acid in the test solution does not change. At this time, the above matrix equation is solved by mathematical optimization algorithm to obtain the central wavelengths λ1, λ2, ...λ n The intensity of the light components corresponding to the wavelength band is I0(λ1), I0(λ2),…I0(λ n ), for I0(λ1),I0(λ2),…I0(λ n ) was used for linear fitting and normalization to obtain the calibration recovery curve.

[0075] When the mth (m is a positive integer) sensing is performed, the data in the calibration coefficient matrix is ​​kept unchanged, and the value I after subtracting the ambient noise from the light intensity detected by the n pixels in the array detection chip is calculated. m1 ,I m2 ,…I mn Substitute them into the augmented matrix of the above matrix equation respectively, and solve the above matrix equation through mathematical optimization algorithm to obtain the central wavelengths λ1, λ2, …λ n The intensity of the light component corresponding to the band is I m (λ1),I m (λ2),…I m (λ n ), to I m (λ1),I m (λ2),…I m (λ n ) is linearly fitted and normalized to obtain a normalized restoration curve corresponding to the m-th sensing; the mathematical optimization algorithm makes the obtained normalized restoration curve closer to the normalized spectral curve of the light incident on the dispersion device, and the mathematical optimization algorithm can be a combination of one or more of a regularization algorithm, a simulated annealing algorithm, a machine learning algorithm, a convex optimization algorithm, a genetic algorithm, and a cross-direction multiplier algorithm, or it can be an improved algorithm after adding a smoothness coefficient optimization term on the basis of the above algorithm, and the smoothness coefficient optimization term can make the restoration curve continuous and smooth.

[0076] Step 4: Comparison of recovery curves: The peak value of the normalized recovery curve obtained during the m-th sensing is called the sensing peak, and the peak value of the normalized recovery curve obtained during calibration is called the calibration peak. The sensing peak is compared with the calibration peak. If there is a change, it indicates that the refractive index or physical property of the substance to be measured has changed during the m-th sensing.

[0077] Using the above sensing method, the normalized restoration curve obtained during calibration is as follows: Figure 3 The solid line shows that during a certain sensing, the concentration of picric acid changes from 0 M at the time of calibration to 40 μM. The normalized recovery curve obtained at this time is shown as Figure 3 As shown by the dotted line. It can be clearly seen that the sensing peak is at a different position from the calibration peak, so a slight change in the concentration of picric acid can be detected by the above sensing method. It can be seen that the biochemical sensor has a high sensitivity.

[0078] Embodiment 2:

[0079] As the most abundant transition metal element in biological cells, Fe 3+ Ions are widely present in many enzymes and proteins and are involved in processes such as DNA transcription. 3+Ions play an integral role in many biological processes. Fe in natural water and most plants 3+ Ions can enter the human body through drinking water and food. However, Fe 3+ Excess or insufficient ions are very harmful to human health, and in severe cases can cause damage to nucleic acids and proteins. Based on the above application requirements, Example 2 discloses a method for efficiently and quickly detecting trace Fe 3+ In this embodiment, the coordination polymer uses 3D MOF ZnL2·0.5H2O·0.75DMF based on 9-(pyridine-4-yl)-9H-carbazole-3,6-dicarboxylic acid ligand, which is a kind of Fe in pure water or even acidic or alkaline solution. 3+ The metal organic framework material has high selectivity and good stability for ions. In this embodiment, we use the metal organic framework material to make a dispersion sensor device, which can achieve the performance of a sensor device and a dispersion device at the same time.

[0080] The fabrication process of the dispersion sensor device is as follows: 4-iodopyridine and 3,6-diiodo-9H-carbazole (4.2 g, 10.0 mmol), 4-iodopyridine (2.1 g, 10.0 mmol), cuprous iodide (190 mg, 1.0 mmol), L-proline (230 mg, 2.0 mmol) and K2CO3 (276 mg, 2.0 mmol) were placed in a Schlenk flask and 20 mL of DMSO was added. Then, the flask was placed in a vacuum for degassing and backfilled with argon, heated to 90 ° C, and reacted for 24 hours. After cooling to room temperature in air, the reaction mixture was poured into H2O and extracted and purified. Then, it was dried with Na2SO4 and the solvent in the organic phase was removed. Finally, the residue was purified by flash chromatography to obtain a light yellow solid product 4-(3,6-diiodo-9H-carbazole-9-yl)pyridine. A mixture of 4-(3,6-diiodo-9H-carbazole-9-yl)pyridine (0.49 g, 1.0 mmol) and dried cuprous cyanide (0.45 g, 5.0 mmol) was placed in anhydrous NMP (5 mL) and placed in a sealed tube and reacted at 140°C overnight. After the reaction mixture was cooled to room temperature, a mixture of H2O (18 mL), HCl (6 mL) and FeCl3 (1.45 g, 9.0 mmol) was poured into the above reaction mixture and stirred for 1 hour. The brown precipitate was then filtered out and washed with H2O. The solid was redissolved in DCM and washed with H2O. The organic phase was dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure to obtain a crude product. The crude product was further purified and cleaned by flash chromatography to obtain a white solid product (3,6-dicyano-9H-carbazole-9-yl)pyridine. A mixture of (3,6-dicyano-9H-carbazole-9-yl)pyridine (59 mg, 0.2 mmol) and KOH (0.22 g, 4.0 mmol) was added to H2O (1 mL) and EtOH (5 mL), heated and refluxed for 3 days. The reaction mixture was then cooled to room temperature in air, diluted with 20 mL of H2O, and acidified to pH = 1 with 2 M HCl. Finally, the resulting precipitate was filtered, washed with H2O and crystallized from ethanol to obtain pure off-white solid H2L2. A mixture of H2L2 (3.2 mg, 0.01 mmol), Zn(NO3)2·6H2O (5.8 mg, 0.02 mmol), DMF (2 ml), ethanol (1 ml), H2O (1 ml) and concentrated hydrochloric acid (50 μl) was placed in a 15 ml polytetrafluoroethylene reactor and reacted at 75 ° C for 2 days. Subsequently, the reaction mixture was slowly cooled to room temperature. The mixture is then filtered, the colorless block crystals are collected, and dried under vacuum conditions. The obtained crystals are ground into particles of different sizes and adhered to the surface of a glass sheet to produce a dispersion sensor device based on the coordination polymer ZnL2·0.5H2O·0.75DMF.The dispersion sensor device can emit strong blue-green light under the excitation of ultraviolet light with a peak wavelength of 385nm, and the spectrum of the emitted light is located near 460nm. Since the particles of the coordination polymer ZnL2·0.5H2O·0.75DMF are of different sizes and uneven distribution, these coordination polymer particles are glued to a transparent substrate to produce dispersion effects such as scattering and diffraction on the incident light. At the same time, since each Zn2(COO)2 binuclear unit is double-bridged with the other two binuclear units through the carbazole part to form a 1D chain, and is further connected together through the pyridine part to form a 3D skeleton, the coordination polymer has high structural stability and good fluorescence stability in aqueous solution with a pH of 4 to 10, and Fe in aqueous solution. 3+ Ions have a fluorescence quenching effect on the coordination polymer. 3+ When the concentration of Fe ions is in the range of 0 to 0.1 mM, the fluorescence intensity of the coordination polymer is similar to that of Fe 3+ The concentrations of K sv Equation, fluorescence quenching constant K sv 10800M -1 , so the coordination polymer has the ability to 3+ Perform sensing function.

[0081] In Example 1, the first light source and the second light source are at different positions, but in Example 2, light sources at different positions are not used. In Example 2, the light emitting device of the biochemical sensor is composed of only one LED, and the LED has two spectral peaks, and the peak wavelengths of the two spectral peaks are 385nm and 493nm. The sensor also includes a filter 18 arranged between the sensor device and the array detection chip, and the filter can completely or partially block the light in the fluorescence excitation band of the coordination polymer from passing through, but cannot block the light in the fluorescence emission band of the coordination polymer from passing through. In this embodiment, the filter can filter out 90% of the light intensity of light with a wavelength below 400nm. The container is in the shape of a cylindrical barrel, and the dispersion sensor device is placed in the container. The solution to be tested flows from one bottom surface of the cylindrical barrel container to the other through a tube. The use of a cylindrical container can ensure that when light enters from one side of the cylindrical container and passes through the dispersion sensor device and then exits from the other side, no Fabry-Perot resonant cavity will be formed between the sides of the cylindrical container, so that the spectrum of light emitted from the sensor device will not form a Fabry-Perot interference peak. Multiple interference peaks will affect the detection of changes in the peak value of the standard signal spectrum restoration spectrum line. The optical path composed of the light emitting device, the container, the dispersion sensor device, the filter, and the array detection chip is as follows: Figure 4 shown.

[0082] The sensing process is as follows: the intensity of monochromatic light of different wavelengths at different pixel positions of the array detection chip after passing through the dispersion device is divided by the intensity at different pixel positions of the array detection chip without passing through the dispersion device and the sensor device, and the ratios obtained after the division are respectively substituted into the coefficient matrix C of the matrix equation, and the intensity of the light of the light-emitting device at different pixel positions in the array detection chip after passing through the dispersion device and the sensor device during the first sensing is respectively substituted into the augmented matrix Y0 of the matrix equation, and the calculation result X0 at the initial moment is obtained by solving the matrix equation CX0=Y0; during the sensing process, the coefficient matrix C is kept unchanged, and the intensity of the light at each pixel in the array detection chip of each sensing is respectively substituted into the different augmented matrices Y1, Y2...Y t In the above example, we solve the matrix equations CX1=Y1, CX2=Y2…CX t =Y t Then we get the calculation results X1, X2…X t . It was found that according to the calculation results X1 and X2, the same spectrum was obtained, such as Figure 5 As shown by the dotted line. According to the calculation results X3, X4…X t The same spectrum is obtained, such as Figure 4 As shown by the solid line. Figure 5 The difference between the peak values ​​of the dashed line and the solid line shows that the Fe content in the solution to be tested increased significantly during the time period between the second and third tests. 3+ The concentration of ions changes slightly.

[0083] Embodiment 3:

[0084] A biochemical sensor disclosed in Example 3 can be used to sense Al 3+ and F - The sensor element of the biochemical sensor comprises two coordination polymers. The two coordination polymers are mixed and distributed on the surface of the sensor element, and their excitation light spectra do not overlap each other, and can be used to detect Al 3+ and F - The following are two types of coordination polymers:

[0085] The first coordination polymer is a Cd-MOF complex [Cd(BTBD)2(AIC)] prepared with BTBD (BTBD = 4,7-di(1H-1,2,4-triazolyl)-2,1,3-benzothiadiazole) and H2AIC (H2AIC = 5-aminoisophthalic acid) as ligand raw materials. The luminescence of this material mainly comes from the BTBD ligand and is transmitted through Al 3+ The interaction between the complex and the framework induces fluorescence enhancement to detect Al 3+The material can emit cyan fluorescence when excited by ultraviolet light at a wavelength of 365nm.

[0086] The second coordination polymer is based on Eu 3+ A three-dimensional Eu-MOF was synthesized with metal center, BDC-NH2 and TDA, and [Eu(TDA)(BDC-NH2) 0.5 (DMA)] (BDC-NH2 = 2-aminoterephthalic acid, TDA = 2,5-thiophenedicarboxylic acid), this material is reacted with F - The hydrogen bonds formed by the interactions are used to detect F - The material is exposed to ultraviolet light with a wavelength of 254nm. - As the concentration increases, the emitted fluorescence spectrum will blue-shift, and the detection limit is as low as 0.46μmol / L.

[0087] Example 3 uses Figure 6 The optical path shown. There is a filter 15 between the sensor device 4 and the array detection chip 5, and the filter 15 can prevent the light in the fluorescence excitation band of the coordination polymer from passing through, but cannot prevent the light in the fluorescence emission band of the coordination polymer from passing through. In this embodiment, the filter 15 can filter out light with a wavelength below 400nm. A filtering device 16 is provided at the light outlet of the light source 21 of the light-emitting device, and the filtering device 16 is composed of two filters 17 and a controller 20. In this embodiment, the controller 20 is an electric disk with a transparent substrate and its electric control device. Under the action of different control parameters, the electric disk with a transparent substrate enables the two filters 17 to be respectively arranged in the optical path between the light source 21 in the light-emitting device 1 and the sensor device 4 at different times. Figure 7 and Figure 8 They are the spectral curves of the light transmitted from the two filters respectively.

[0088] When Al needs to be detected 3+ When the concentration is Figure 7 The filter shown is arranged in the light path between the light source and the sensor device in the light emitting device. Figure 7The spectral curve in has two spectral peaks, which are 365.3nm and 562.3nm. The light component with a wavelength near 365.3nm can excite the first coordination polymer [Cd(BTBD)2(AIC)] in the sensor device. The fluorescence signal emitted by the first coordination polymer is the perturbation signal. When the light component with a wavelength near 365.3nm transmitted by the sensor device is filtered out by the filter 15, the light with a wavelength near 562.3nm (standard signal) is irradiated on the surface of the dispersion device 3, and then the dispersion effect occurs, and finally irradiates each pixel element of the array detection chip. The same sensing method as in Example 2 is used to restore the spectral spectrum lines of the standard signal with stronger light intensity under the influence of the perturbation signal, and the Al at different times are obtained according to the results detected by the array detection chip at different times. 3+ The corresponding spectral restoration line detects the Al 3+ The corresponding spectral restoration line changes to detect Al 3+ Is there any change in the concentration?

[0089] When it is necessary to detect F - When the concentration is Figure 8 The filter shown is arranged in the light path between the light source 21 and the sensor device 4 in the light emitting device 1 . Figure 8 The spectrum curve in has two spectral peaks, which are 253.9nm and 536.9nm. The light component with a wavelength near 365.3nm can excite the second coordination polymer [Eu(TDA)(BDC-NH2) 0.5 (DMA)]. The fluorescence signal emitted by the second coordination polymer is the perturbation signal. When the light component with a wavelength near 253.9nm is filtered out by the filter 15, the light with a wavelength near 536.9nm (standard signal) is irradiated on the surface of the dispersion device 3, and then the dispersion effect occurs, and finally irradiates each pixel element of the array detection chip. The same sensing method as in Example 2 is used to restore the spectral line of the standard signal with a stronger light intensity under the influence of the perturbation signal, and the F at different times is obtained according to the results detected by the array detection chip at different times. - The corresponding spectrum restoration line detects F at different times - The corresponding spectral restoration line is changed to detect whether F - Is there any change in the concentration?

[0090] Embodiment 4:

[0091] Since the excitation light band of many MOF materials is in the ultraviolet band, the perturbation signal emitted by the MOF material cannot be directly measured by a silicon-based detector, or the fluorescence emitted by the MOF material is too weak to affect the signal-to-noise ratio of the sensor. For this reason, a conversion luminescent material is used to convert the light that cannot be detected by the array detection chip after passing through the MOF material into visible light that can be detected by the array detection chip, so that sensing detection can be performed. Wavelength conversion materials are generally divided into up-conversion luminescent materials or down-conversion luminescent materials. Here is an explanation of what up-conversion luminescent materials and down-conversion luminescent materials are: Stokes' law states that some materials can be excited by high-energy light and emit low-energy light. In other words, short-wavelength and high-frequency light excites long-wavelength and low-frequency light. For example, ultraviolet light excites the material to emit visible light, and such a material is a down-conversion luminescent material. On the contrary, some materials can achieve a luminescence effect that is exactly the opposite of the above law, so we call it anti-Stokes luminescence, also known as up-conversion luminescence, and such materials are called up-conversion luminescent materials.

[0092] In this embodiment, when the coordination polymer is Eu2(OH-BDC)3 (OH-BDC = 2-hydroxyterephthalic acid), the substance to be tested is Fe 3+ When the coordination polymer emits a fluorescence signal of ultraviolet light with a peak wavelength of 327 nm, the fluorescence signal is difficult to be detected by the silicon-based CCD, that is, the array detection chip in this embodiment. Fig. 9 As shown in the optical path diagram, a light wavelength conversion component is inserted between the sensor device and the array detection chip. The light wavelength conversion component uses a Lumitek transmission type ultraviolet photosensitive card made of down-conversion luminescent material, which can convert 327nm ultraviolet light into 650nm red visible light, which can be detected by the silicon-based CCD. Then, the sensing implementation steps similar to those in Example 1 can be used to detect the substance Fe 3+ Perform sensor detection.

[0093] The present invention has many embodiments, for example, the coordination polymer can also effectively identify Cu 2+ 、UO2 2+ , Pd 2+ Other metal cations and Cl - Br - 、SCN - and N3 - The invention can also sense and detect pH value, volatile organic matter, energetic organic matter, mycotoxins, antibiotics, biological molecules and various gases. All technical solutions formed by equivalent transformation or equivalent transformation fall within the protection scope of the present invention.

Claims

1. A biochemical sensor with high sensitivity, high throughput and high selectivity, characterized in that: It includes a light emitting device, a container, a dispersion device, a sensor device, an array detection chip, and a computing unit connected to the array detection chip; The light emitting device comprises at least one light source; The container contains at least one substance to be tested; The dispersion device can cause the incident light from the light emitting device to the surface of the dispersion device to produce a dispersion effect. The dispersion effect can cause incident light of different wavelengths and the same intensity to form different light intensity distributions on the surface of the array detection chip after passing through the same part of the dispersion device, and incident light of the same wavelength and the same intensity to form different light intensity distributions after passing through different parts of the dispersion device. The sensor device comprises at least one coordination polymer, which is a compound in which metal ions and organic ligands are connected by coordination bonds and has adsorption properties or fluorescence emission properties for specific substances; the fluorescence excitation band of the coordination polymer in the sensor device partially or completely overlaps with the spectral wavelength range of the emission light of any light source in the light-emitting device; the coordination polymer in the sensor device is placed in the container and is in full contact with the substance to be detected; when the concentration or physical property of the substance to be detected changes, the fluorescence property of the corresponding coordination polymer will also change; Each different pixel element of the array detection chip detects the light emitted from each part of the dispersion device and irradiated at each pixel element position after the dispersion effect, and the fluorescence emitted from each part of the sensor device and irradiated at each pixel element position; The calculation unit uses the light signal irradiated on the surface of the dispersion device as the standard signal and the fluorescence signal emitted by the coordination polymer as the perturbation signal, restores the spectral line of the standard signal with stronger light intensity under the influence of the perturbation signal, and obtains the spectral restoration lines corresponding to the substance to be tested at different times according to the results detected by the array detection chip at different times, detects whether the spectral restoration lines corresponding to the substance to be tested at different times change, and judges the concentration change or physical property change of the substance to be tested according to the detection results.

2. A biochemical sensor with high sensitivity, high throughput and high selectivity according to claim 1, characterized in that: The light emitting device of the biochemical sensor comprises a first light source and a second light source; The light emitted by the first light source can irradiate the pixel elements at different positions of the array detection device after passing through the dispersion device but does not directly irradiate the sensor device; The light emitted by the second light source irradiates the sensor device but does not directly irradiate the array detection device. However, the fluorescence excited by the light emitted by the second light source on the sensor device irradiates the pixel elements at different positions of the array detection chip. The spectra of the light emitted by the first light source and the second light source are different. The spectral range of the light emitted by the first light source is within the spectral measurement range of the array detection chip, and the spectral range of the light emitted by the second light source overlaps with the fluorescence excitation spectrum of the coordination polymer.

3. A biochemical sensor with high sensitivity, high throughput and high selectivity according to claim 1, characterized in that: The biochemical sensor further comprises at least one filter; The at least one filter is located at at least one light outlet of the light emitting device; The filter makes the spectrum of the incident light irradiated to the surface of the dispersion device have only one or two spectrum peaks, the peak wavelengths of the spectrum peaks are different from the peak wavelengths of the emission peaks of the coordination polymer, and the filter also makes the peak of the spectrum of the incident light irradiated to the surface of the sensor device close to or overlap with the peak of the excitation spectrum of the coordination polymer.

4. A biochemical sensor with high sensitivity, high throughput and high selectivity according to claim 1, characterized in that: The sensor device and the dispersion device of the biochemical sensor are combined into a dispersion sensor device; the dispersion sensor device has all the functions of the sensor device and the dispersion device.

5. The biochemical sensor with high sensitivity, high throughput and high selectivity according to claim 1, characterized in that: The coordination polymer in the sensor element of the biochemical sensor is a metal organic framework compound; the metal organic framework compound is an ultra-porous nanomaterial, a crystal in which metal ions and organic ligands are connected by coordination bonds and extend in space according to a certain rule.

6. A biochemical sensor with high sensitivity, high throughput and high selectivity according to claim 1, characterized in that: The biochemical sensor further comprises a filter or a light wavelength conversion component disposed between the sensor device and the array detection chip; The filter can completely or partially block the light in the fluorescence excitation band of the coordination polymer from passing through, but cannot block the light in the fluorescence emission band of the coordination polymer from passing through; The optical wavelength conversion component includes at least one wavelength conversion optical material, the absorption spectrum band of the wavelength conversion optical material overlaps with the fluorescence emission band of the coordination polymer, and the emission spectrum band of the wavelength conversion optical material is within the detection band range of the array detection chip.

7. A biochemical sensor with high sensitivity, high throughput and high selectivity according to claim 1, characterized in that: The container of the biochemical sensor is a cylindrical container, or the container wall where the light enters the container is not parallel to the container wall where the light exits the container.

8. The biochemical sensor with high sensitivity, high throughput and high selectivity according to claim 1, characterized in that: The sensor device of the biochemical sensor comprises a plurality of coordination polymers, the excitation light spectra of the plurality of coordination polymers do not overlap each other, and the plurality of coordination polymers are mixedly distributed on the surface of the sensor device; a filtering device is provided at the light outlet of the light source of the light emitting device of the biochemical sensor, and the filtering device is composed of a plurality of filters and a controller. Under the action of different control parameters of the controller, filters with different transmission spectra are respectively arranged in the light path between the light source and the sensor device in the light emitting device at different times, so that different coordination polymers respectively emit fluorescence under the action of different control parameters of the controller, thereby successively sensing the concentration changes or physical property changes of different substances to be measured.

9. A sensing method using the high-sensitivity, high-throughput, high-selectivity biochemical sensor according to any one of claims 1 to 8, characterized in that: In advance, the intensity of monochromatic light of different wavelengths at different pixel positions of the array detection chip after passing through the dispersion device is divided by the intensity of light at different pixel positions of the array detection chip without passing through the dispersion device and the sensor device, and the ratios obtained after the division are respectively substituted into the coefficient matrix C of the matrix equation, and the intensity of the light of the light-emitting device at different pixel positions in the array detection chip after passing through the dispersion device and the sensor device is respectively substituted into the augmented matrix Y0 of the matrix equation, and the calculation result X0 at the initial moment is obtained by solving the matrix equation CX0=Y0; during the sensing process, the coefficient matrix C is kept unchanged, and the intensity of the light at each pixel in the array detection chip sensed each time is respectively substituted into the different augmented matrices Y1, Y2...Y corresponding to this sensing. t In the above example, we solve the matrix equations CX1=Y1, CX2=Y2…CX t =Y t Then we get the calculation results X1, X2…X t , detect the calculation results X1, X2…X obtained by each sensing t Is there any change compared with X0, or detect the calculation results X1, X2...X obtained by each sensing t Whether there is a change between the two, the concentration change or physical property change of the substance to be tested is sensed according to the test results to achieve sensing, where t is a positive integer, Y t represents the augmented matrix corresponding to the t-th sensing, X t Represents the calculation result corresponding to the t-th sensing.

10. The sensing method according to claim 9, characterized in that The method comprises the following implementation steps: Step 1: Spectral band division: Divide the spectral band of light incident on the dispersion device or the light that can be received by the array detector into n central wavelengths λ1, λ2, ...λ n A band with a wavelength width of Δλ, where n is an integer greater than 3; Step 2, calibration coefficient determination: Use a light emitting device and a monochromator or a tunable laser to obtain narrow-band calibration light with a central wavelength of λ j The light intensity of the narrow spectrum calibration light detected by the i-th pixel element of the array detection chip after passing through the dispersion device and other devices in front of the array detection chip is related to the central wavelength λ j The narrowband calibration light that has not passed through the dispersion device is detected by the light intensity. The ratio of these two measured light intensities minus the ambient noise is recorded as the calibration coefficient C. ij , where i = 1, 2…n, where j = 1, 2…n; Step 3, solve the matrix equation: remove the monochromator or tunable laser, and the value of the light intensity detected by n pixels in the array detection chip minus the ambient noise is recorded as I m1 ,I m2 ,…I mn (where m is a natural number), solve the following matrix equation by regularization algorithm or other mathematical optimization methods to obtain the central wavelengths λ1, λ2, …λ n The intensity of the light component corresponding to the wavelength band I m (λ1),I m (λ j ),…I m (λ n ): The coefficient matrix of the above matrix equation is is the calibration coefficient matrix, Each unit C in the calibration coefficient matrix C ij This is the calibration coefficient measured in step 2. Solving the above matrix equation can be divided into two situations: calibration and sensing. During calibration (m = 0), the concentration and refractive index of the solution to be measured do not change. At this time, the above matrix equation is solved by a mathematical optimization algorithm to obtain the central wavelengths λ1, λ2, ...λ n The intensity of the light components corresponding to the wavelength band is I0(λ1), I0(λ2),…I0(λ n ), for I0(λ1),I0(λ2),…I0(λ n ) is linearly fitted and normalized to obtain the calibration recovery curve; when the mth sensing is performed (m = 1, 2...), the data in the calibration coefficient matrix is ​​kept unchanged, and the value I after the light intensity detected by the n pixels in the array detection chip minus the environmental noise is m1 ,I m2 ,…I mn Substitute them into the augmented matrix of the above matrix equation respectively, and solve the above matrix equation through mathematical optimization algorithm to obtain the central wavelengths λ1, λ2, …λ n The intensity of the light component corresponding to the band is I m (λ1),I m (λ2),…I m (λ n ), to I m (λ1),I m (λ2),…I m (λ n ) to perform linear fitting and normalization, so as to obtain a normalized restoration curve corresponding to the m-th sensing; the mathematical optimization algorithm makes the obtained normalized restoration curve closer to the normalized spectrum curve of the light incident on the dispersion device, and the mathematical optimization algorithm can be a regularization algorithm, a simulated annealing algorithm, a machine learning algorithm, a convex optimization algorithm, a genetic algorithm, a cross-direction multiplier algorithm or one or more of the combined algorithms, or can be an improved algorithm after adding a smoothness coefficient optimization term on the basis of the above algorithms, and the smoothness coefficient optimization term can make the restoration curve continuous and smooth; Step 4, comparison of recovery curves: the peak value of the normalized recovery curve obtained during sensing is called the sensing peak, and the peak value of the normalized recovery curve obtained during calibration is called the calibration peak. The sensing peak is compared with the calibration peak. If there is a change between the sensing peak and the calibration peak, it indicates that the concentration or physical property of the substance to be measured has changed during sensing. Alternatively, the mth sensing peak obtained during the mth sensing is compared with the (m-1)th sensing peak obtained during the (m-1)th sensing. If there is a change between the mth sensing peak and the (m-1)th sensing peak, it indicates that there is a concentration or physical property change of the substance to be measured during the mth sensing.

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