Supramolecular fluorescence sensing array and its application in the detection of tyrosine kinase inhibitors

Abstract

This invention provides a supramolecular fluorescence sensing array and its application in detecting five tyrosine kinase inhibitors, belonging to the field of analytical chemistry detection technology. The supramolecular fluorescence sensing array is composed of three supramolecular fluorescent probes: 2NR@Q[8], 2AO@Q[8], and APFG@Q[8]. This invention uses a supramolecular fluorescence sensing array composed of three supramolecular fluorescent probes: 2NR@Q[8], 2AO@Q[8], and APFG@Q[8]. By utilizing the cross-fluorescence response signals generated by this supramolecular fluorescence sensing array for five TKIs, combined with classical pattern recognition algorithms, it is possible to perform qualitative and quantitative detection of five TKIs: GEF, EH, LD, AD, and DAC. Moreover, this supramolecular fluorescence sensing array has good anti-interference properties, and serum samples have demonstrated that the supramolecular fluorescence sensing array constructed in this invention can simultaneously analyze five TKIs in complex systems. Therefore, this invention provides a new method for detecting tyrosine kinase inhibitors, which is more intuitive and convenient than traditional detection techniques.

Description

Technical Field

[0001] This invention belongs to the field of analytical chemistry detection technology, specifically supramolecular fluorescence sensing arrays and their application in detecting five tyrosine kinase inhibitors. Background Technology

[0002] Tyrosine kinase inhibitors (TKIs) are small molecule drugs that inhibit tyrosine kinase activity, thereby promoting tumor cell apoptosis through inhibition of cell signal transduction, and are considered standard first- and second-line treatments for solid tumors. Severe skin toxicity is frequently observed in patients receiving TKI treatment, and some patients have even experienced fatal side effects such as pneumonia and liver damage. Monitoring TKI levels can more effectively limit toxicity risks. Furthermore, with the widespread development of TKI drugs, the simultaneous detection of multiple drugs is becoming increasingly important; therefore, establishing a detection technique capable of analyzing multiple TKIs is necessary for clinical and environmental toxicology studies.

[0003] High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS) is a commonly used technique for analyzing targeted drugs. While it offers high sensitivity and selectivity, it requires complex sample pretreatment, cumbersome equipment, high costs, and time-consuming experiments. Array sensing, on the other hand, combines the output signals of multiple sensing elements into each analyte, thus providing a new dimension to the detection signal. It is favored for its advantages of reduced signal interference, simplicity, sensitivity, and low cost; however, currently, no methods for identifying and detecting TKIs based on sensor arrays have been reported. Summary of the Invention

[0004] This invention provides a supramolecular fluorescence sensing array and its application in detecting five tyrosine kinase inhibitors. The purpose is to enable rapid identification and detection of five TKIs, GEF, EH, LD, AD, and DAC. It has the advantages of simple preparation, rapid and sensitive detection, and strong anti-interference ability.

[0005] The present invention provides the following technical solution to achieve the above objectives:

[0006] A supramolecular fluorescence sensing array, wherein the supramolecular fluorescence sensing array is composed of three supramolecular fluorescent probes 2NR@Q[8], 2AO@Q[8] and APFG@Q[8].

[0007] In the aforementioned supramolecular fluorescence sensing array, 2NR@Q[8] is a solution of NR and Q[8] with a molar ratio of 2:1; 2AO@Q[8] is a solution of AO and Q[8] with a molar ratio of 2:1; and APFG@Q[8] is a solution of APFG and Q[8] with a molar ratio of 1:1.

[0008] In the aforementioned supramolecular fluorescence sensing array, the concentrations of the supramolecular fluorescent probes 2NR@Q[8], 2AO@Q[8], and APFG@Q[8] are all 2×10⁻⁶. -5 mol / L.

[0009] The aforementioned supramolecular fluorescence sensing array is used to detect tyrosine kinase inhibitors, namely GEF, EH, LD, AD, and DAC.

[0010] The aforementioned supramolecular fluorescence sensing array is used to detect tyrosine kinase inhibitors. The detection method includes the following steps:

[0011] S1: Prepare supramolecular fluorescent probes 2NR@Q[8], 2AO@Q[8] and APFG@Q[8] respectively;

[0012] S2: Prepare separate solutions with a molar concentration of 1×10⁻⁶. -2 mol / L solutions of GEF, EH, LD, AD, and DAC;

[0013] S3: Add any of the solutions prepared in S2 to any of the supramolecular fluorescent probes prepared in S1 according to the molar ratio of supramolecular fluorescent probe and tyrosine kinase inhibitor of 1:1. Let stand for 10 min, measure the fluorescence emission spectrum of the mixed solution and observe the color change under a 365nm ultraviolet lamp for detection.

[0014] The aforementioned supramolecular fluorescence sensing array is used to detect tyrosine kinase inhibitors. The fluorescence color of 2NR@Q[8] under ultraviolet light is weak. When a certain tyrosine kinase inhibitor is added to 2NR@Q[8], if the emission spectrum intensity at 624nm is slightly enhanced and the fluorescence is deep purple-red under ultraviolet light, then the tyrosine kinase inhibitor is DAC; if the emission spectrum at 624nm is enhanced and the color is purple-red under ultraviolet light, then the tyrosine kinase inhibitor is AD; if the emission spectrum at 624nm is enhanced and the color is pink under ultraviolet light, then the tyrosine kinase inhibitor is GEF; if the emission spectrum at 624nm is enhanced and the color is reddish-brown under ultraviolet light, then the tyrosine kinase inhibitor is LD; if the emission spectrum at 624nm is significantly enhanced and the color is carmine-red under ultraviolet light, then the tyrosine kinase inhibitor is EH.

[0015] The aforementioned supramolecular fluorescence sensing array is used to detect tyrosine kinase inhibitors. The fluorescence color of 2AO@Q[8] under ultraviolet light is deep yellow. When a certain tyrosine kinase inhibitor is added to 2AO@Q[8], if the emission spectrum at 536nm is slightly enhanced and the color under ultraviolet light is light yellow-green, then the tyrosine kinase inhibitor being tested is AD or DAC, and AD has a brighter fluorescence color than DAC. If the emission spectrum at 536nm is enhanced and the color under ultraviolet light is bright green, then the tyrosine kinase inhibitor being tested is EH or GEF, and EH has a brighter fluorescence color than GEF. If the emission spectrum at 536nm is significantly enhanced and the color under ultraviolet light is light green, then the tyrosine kinase inhibitor being tested is LD.

[0016] The aforementioned supramolecular fluorescence sensing array is used to detect tyrosine kinase inhibitors. The APFG@Q[8] has no fluorescence color under ultraviolet light. When a certain tyrosine kinase inhibitor is added to APFG@Q[8], if the emission spectrum does not change and the color is weak green under ultraviolet light, the tyrosine kinase inhibitor is LD. If the emission spectrum shifts from 591nm to 594nm, the emission spectrum is slightly enhanced and the color is deep red under ultraviolet light, the tyrosine kinase inhibitor is EH. If the emission spectrum shifts from 591nm to 599nm, the emission spectrum is enhanced and the color is deep pink under ultraviolet light, the tyrosine kinase inhibitor is GEF. If the emission spectrum shifts from 591nm to 599nm, the emission spectrum is enhanced and the color is orange-red under ultraviolet light, the tyrosine kinase inhibitor is DAC. If the emission spectrum shifts from 591nm to 604nm, the emission spectrum is significantly enhanced and the color is bright orange-red under ultraviolet light, the tyrosine kinase inhibitor is AD.

[0017] Beneficial effects

[0018] Compared with existing technologies, the present invention has the following advantages: The present invention proposes a supramolecular fluorescence sensing array composed of three supramolecular fluorescent probes 2NR@Q[8], 2AO@Q[8], and APFG@Q[8]. Using this supramolecular fluorescence sensing array to detect the cross-fluorescence response signals of five TKIs, combined with classical pattern recognition algorithms, the five TKIs, GEF, EH, LD, AD, and DAC, can be qualitatively and quantitatively detected. Moreover, the supramolecular fluorescence sensing array has good anti-interference properties, and serum samples have demonstrated that the supramolecular fluorescence sensing array constructed in this invention can simultaneously analyze five TKIs in complex systems. Therefore, the present invention provides a new method for detecting tyrosine kinase inhibitors, which is more intuitive and convenient than traditional detection techniques. Attached Figure Description

[0019] Figure 1The chemical structural formulas are Q[8], NR, AO and APFG;

[0020] Figure 2 The probes S1(a), S2(b), and S3(c) are used to target TKI (2×10⁻⁶). -5 Fluorescence emission spectrum of response (mol / L);

[0021] Figure 3 Probes S1 (first row), S2 (second row), and S3 (third row) are used to detect five types of TKIs (2×10⁻⁶). -5 Fluorescence color matrix of (mol / L) under a 365nm UV lamp;

[0022] Figure 4 This is an LDA score diagram of the fluorescence response of five TKIs in ultrapure water by a supramolecular fluorescence sensing array;

[0023] Figure 5 This is an LDA diagram of the fluorescence response of a supramolecular fluorescence sensing array to different concentrations of LD in ultrapure water;

[0024] Figure 6 This is an LDA score diagram of the response modes obtained by the supramolecular fluorescence sensing array to five TKIs and other interfering ions (100 μM);

[0025] Figure 7 This is an LDA score diagram of five TKIs at three concentrations in a serum system obtained by a supramolecular fluorescence sensing array.

[0026] Figure 8 In NR(1×10 -5 Fluorescence spectrum changes when Q[8] concentration is increased in (mol / L) (a); fluorescence intensity to molar ratio I 624nm -N Q[8] / N NR Relationship curve (b); Fluorescence Job plot obtained by continuously varying the mole fractions of NR and Q[8] (c);

[0027] Figure 9 In AO(1×10 -5 Fluorescence spectrum changes when Q[8] concentration is increased in (mol / L) (a); fluorescence intensity to molar ratio I 536nm -N Q[8] / N AO Relationship curve (b); Fluorescence Job plot obtained by continuously varying the mole fractions of AO and Q[8] (c);

[0028] Figure 10 It is APFG(1×10) -5 Fluorescence spectrum changes when Q[8] concentration is increased in (mol / L) (a); fluorescence intensity to molar ratio I602nm -N Q[8] / N APFG Relationship curve (b); Fluorescence Job plot obtained by continuously varying the mole fractions of APFG and Q[8] (c). Detailed Implementation

[0029] The present invention will now be described in further detail with reference to the accompanying drawings and embodiments.

[0030] Example 1: A supramolecular fluorescence sensing array.

[0031] Using three dyes with different emission wavelengths: Neutral Red (NR), Acridine Orange hydrochloride (AO), and Astrazon Pink FG (APFG), the method was successfully applied. Figure 1 ), respectively, with an octagonal cucurbit ring (Q[8]) to construct three supramolecular fluorescent probes: 2NR@Q[8] (abbreviated as S1), 2AO@Q[8] (abbreviated as S2), and APFG@Q[8] (abbreviated as S3), and used them as sensing elements to construct a supramolecular fluorescent sensing array. The preparation method is as follows:

[0032] 1. Preparation of Supramolecular probe S1 standard solution

[0033] 1) Take 13.28 mg of Q[8], dissolve it in ultrapure water, sonicate it, transfer it to a 100 mL volumetric flask and make up to volume to obtain a concentration of 1×10 -4 Solution A, mol / L, is ready for use;

[0034] 2) Dissolve NR 28.88 mg in ultrapure water, transfer to a 100 mL volumetric flask and dilute to volume to obtain a concentration of 1 × 10⁻⁶ mg / mL. - 3 Solution B, mol / L, is available for later use;

[0035] 3) Take 10 mL of solution A and 2 mL of solution B and mix them in a 100 mL volumetric flask. Make up to volume with ultrapure water to obtain NR to Q[8] with a molar ratio of 2:1 and a concentration of 2×10⁻⁶. -5 mol / L supramolecular probe S1.

[0036] 2. Preparation of Supramolecular probe S2 standard solution

[0037] 1) Take 13.28 mg of Q[8], dissolve it in ultrapure water, sonicate it, transfer it to a 100 mL volumetric flask and make up to volume to obtain a concentration of 1×10 -4 Solution A, mol / L, is ready for use;

[0038] 2) Dissolve 0.18 mg of AO in ultrapure water, transfer to a 100 mL volumetric flask and dilute to volume to obtain a concentration of 1 × 10⁻⁸ mg. - 3 Solution B, mol / L, is available for later use;

[0039] 3) Take 10 mL of solution A and 2 mL of solution B and mix them in a 100 mL volumetric flask. Make up to volume with ultrapure water to obtain a molar ratio of AO to Q[8] of 2:1 and a concentration of 2×10⁻⁶. -5 mol / L supramolecular probe S2.

[0040] 3. Preparation of Supramolecular probe S3 standard solution

[0041] 1) Take 13.28 mg of Q[8], dissolve it in ultrapure water, sonicate it, transfer it to a 100 mL volumetric flask and make up to volume to obtain a concentration of 1×10 -4 Solution A, mol / L, is ready for use;

[0042] 2) Dissolve 38.94 mg of APFG in ultrapure water, transfer to a 100 mL volumetric flask and dilute to volume to obtain a concentration of 1 × 10⁻⁶ mg / mL. -3 Solution B, mol / L, is available for later use;

[0043] 3) Take 20 mL of solution A and 2 mL of solution B and mix them in a 100 mL volumetric flask. Make up to volume with ultrapure water to obtain APFG and Q[8] with a molar ratio of 1:1 and a concentration of 2×10⁻⁶. -5 mol / L supramolecular probe S3.

[0044] Example 2. The three supramolecular fluorescent probes S1, S2, and S3 obtained in Example 1 were used to detect five tyrosine kinase inhibitors (TKIs): gefitinib (GEF), erlotinib (EH), lapatinib (LD), afatinib (AD), and dacomitinib (DAC).

[0045] First, accurately weigh the required analytical grade standards of GEF, EH, LD, AD, and DAC, dissolve them in DMSO, and prepare a molar concentration of 1×10⁻⁶. -2 Standard solutions of each TKI at mol / L.

[0046] 1. Qualitative Analysis

[0047] The excitation wavelength of probe S1 was 540 nm, the voltage was 585 V, and the slit width was 10 nm; the excitation wavelength of probe S2 was 470 nm, the voltage was 540 V, and the slit width was 5 nm; the excitation wavelength of probe S3 was 530 nm, the voltage was 530 V, and the slit width was 10 nm. The three supramolecular probe solutions (all 2 × 10⁻⁶) were then subjected to [further testing / treatment]. -5Different TKI standard solutions (molar ratio of supramolecular probe to each drug was 1:1) were added to the solution (mol / L). After standing for 10 min, the solutions were subjected to fluorescence emission spectroscopy. The results showed that probe S1 had an emission peak at 624 nm. The presence of TKI enhanced the fluorescence emission spectrum of probe S1 system. For example, the presence of DAC slightly enhanced the fluorescence intensity at 624 nm, while the presence of AD, GEF, LD, and EH greatly enhanced the fluorescence intensity at 624 nm. Figure 2 (a)). For the S2 supramolecular probe, probe S2 has an emission peak at 536 nm. When five TKIs are added, the emission spectrum of the system shows different responses. For example, the presence of AD and DAC slightly enhances the fluorescence at 536 nm, the presence of GEF and EH significantly enhances the fluorescence at 536 nm, and the presence of LD greatly enhances the fluorescence at 536 nm. Figure 2 (b)). The fluorescence emission spectrum of the S2-drug mixture solution indicates that ( Figure 2 (c) Probe S3 has an emission peak at 591 nm. Adding EH, GEF, DAC and AD to the probe enhances the fluorescence intensity of the probe, and the degree of response increases in sequence. The emission wavelength gradually red-shifts from 591 nm to 602 nm. However, the fluorescence intensity hardly changes after adding LD.

[0048] The specific detection and judgment methods are as follows:

[0049] 1) Add GEF, EH, LD, AD, and DAC standard solutions (molar ratio of supramolecular probe to each drug is 1:1) to the prepared S1 supramolecular probe solution, let stand for 10 min, and measure the fluorescence emission spectrum of the solution respectively. Figure 2 (a) and observe the color change under a 365nm ultraviolet lamp. Figure 3 First line):

[0050] The probe S1 itself has very weak fluorescence, but its emission spectrum at 624 nm shows varying degrees of enhancement after the addition of the drug. A slight increase in emission intensity at 624 nm, turning into a deep purplish-red fluorescence under UV light, indicates that the drug is DAC; a significant increase in emission intensity at 624 nm, with the color changing from weak fluorescence to purplish-red, pink, and reddish-brown fluorescence under UV light, indicates that the drugs are AD, GEF, and LD, respectively; and an even greater increase in emission intensity at 624 nm, with a carmine-red fluorescence under UV light, indicates that the drug is EH.

[0051] 2) Add GEF, EH, LD, AD, and DAC standard solutions (molar ratio of supramolecular probe to each drug is 1:1) to the prepared S2 supramolecular probe solution, let stand for 10 min, and then measure the fluorescence emission spectra of the solutions respectively. Figure 2(b) and observe the color change under a 365nm ultraviolet lamp. Figure 3 Second line):

[0052] The probe S2 itself exhibits a deep yellow fluorescence, and its emission spectrum at 536 nm shows varying degrees of enhancement after the addition of the drug. If the emission spectrum at 536 nm is slightly enhanced, and it shows a pale yellow-green fluorescence under a 365 nm UV lamp, the drug is either AD or DAC, with AD showing a slightly brighter fluorescence than DAC. If the emission spectrum at 536 nm is significantly enhanced, and it shows a bright green fluorescence under a 365 nm UV lamp, the drug is either EH or GEF, with EH showing a brighter fluorescence. If the emission spectrum at 536 nm is significantly enhanced, and it shows a pale green fluorescence under a 365 nm UV lamp, the drug is LD.

[0053] 3) Add GEF, EH, LD, AD, and DAC standard solutions (molar ratio of supramolecular probe to each drug is 1:1) to the prepared S3 supramolecular probe solution, let stand for 10 min, and then measure the fluorescence emission spectrum of the solution. Figure 2 (c) and observe the color change under a 365nm ultraviolet lamp. Figure 3 Third line):

[0054] The probe S3 itself is almost non-fluorescent. After the addition of the drug, the emission spectrum undergoes a slight red shift and shows varying degrees of enhancement. If the emission spectrum does not change, but the color under 365nm UV light is weak green, the drug is LD. If the emission spectrum redshifts from 591nm to 594nm, with a slight enhancement and a deep red color under 365nm UV light, the drug is EH. If the emission spectrum redshifts from 591nm to 599nm, with a significant enhancement and deep pink and orange-red colors under 365nm UV light, the drugs are GEF and DAC, respectively. If the emission spectrum redshifts from 591nm to 604nm, with the greatest enhancement and a bright orange-red color under 365nm UV light, the drug is AD.

[0055] 4) The color changes of S1, S2, and S3 obtained in steps 1), 2), and 3) under a 365nm UV lamp were plotted as a fluorescence color array of 3 sensing elements × 5 drugs. From this, we can clearly see that the above array has significantly different responses to the five TKIs: GEF, EH, LD, DAC, and AD. By comparing the matrix fluorescence colors, the five TKIs can be well distinguished, achieving the purpose of simultaneous qualitative analysis. Figure 3 ).

[0056] 2. Statistical Data Analysis

[0057] 1) Three supramolecular fluorescent probes, S1, S2, and S3 (each at 20 μM), were prepared in ultrapure water. Using a 96-well sterile black microtiter plate, 300 μL of each probe solution (S1, S2, and S3) was added to each well as a mixed sample solution of one of the five TKIs (20 μM). Each mixed sample was analyzed in triplicate. The fluorescence intensity of the samples at the detection wavelength was measured sequentially using a full-function microplate reader. This generated a data matrix consisting of 3 sensing elements × 5 TKIs × 5 parallel experiments. Linear discriminant analysis (LDA) was then performed on the data matrix using SPSS version 22.0. Figure 4 As shown, under the LDA discriminant model established using the Fisher function, the five parallel points of the same drug for the above five TKIs cluster together, which can be well separated from the points of other drugs, showing a very obvious distinguishability. Therefore, the results indicate that this sensor array can detect and identify five different drugs: GEF, EH, LD, AD, and DAC.

[0058] 2) Using the method described in 1), LD was selected as the model analyte, and the fluorescence response of seven different concentrations of LD (0 μM, 0.5 μM…7.5 μM) was measured. A data matrix consisting of 3 sensing elements × 7 LD concentrations × 5 parallel experiments was obtained, and LDA was used for data analysis. Figure 5 As shown in the LDA model diagram, LD concentrations exhibit a series of distinct clusters, with the distribution gradually transitioning from a positive factor to a negative factor along the X-axis. The data results demonstrate that this array can correctly classify the originally grouped cases with 100% accuracy, further illustrating the versatility of this sensor array. This sensor array can quantitatively detect and identify TKI concentrations.

[0059] 3) Accurately weigh K + Na + Ca 2+ Mg 2+ Cu 2+ Fe 3+ Cl − HCO3 − HPO4 2− SO4 2− Analytical grade standards (with tetrabutylammonium salt as the anion and perchlorate as the cation) were dissolved in ultrapure water to prepare a molar concentration of 1×10⁻⁶. -2 mol / L standard solutions of various ions.

[0060] Using the method described in 1), add the prepared standard ion solution (K). + Na + Ca 2+ Mg 2+ Cu 2+Fe 3+ Cl − HCO3 − HPO4 2− SO4 2− The fluorescence responses of 10 ions and five TKIs were measured. The obtained data matrix was analyzed using LDA, such as... Figure 6 As shown in the LDA model, the five groups of TKIs each form a non-overlapping cluster, while the 10 common interfering ions in biological systems cluster together, indicating that the sensing array has good anti-interference capabilities.

[0061] 4) Using the method described in 1), five TKIs at different concentrations (5 μM, 10 μM, and 20 μM) were added to guinea pig serum using the standard additive method. The fluorescence response of the array to the five TKIs at different concentrations in a complex system was measured, and the fluorescence data were analyzed by LDA: (e.g.) Figure 7 As shown in the LDA model diagram, the five TKIs at concentrations of 5 μM, 10 μM, and 20 μM all exhibit five non-overlapping clusters. This data demonstrates that the sensor array can simultaneously detect, identify, and differentiate five TKIs even in complex systems.

[0062] In order to study this invention, the inventors conducted a large number of experiments, including:

[0063] In order to determine the interaction ratio of Q[8] with NR, AO and APFG to form probes, the inventors used fluorescence emission spectroscopy to study the interaction between Q[8] and NR, AO and APFG respectively.

[0064] For example: Dilute solution B (NR) obtained in Experiment Case 1 with water to 1×10 -5 The concentration of Q[8] was gradually increased by mol / L using the molar ratio method, and its fluorescence emission spectrum was measured. The excitation wavelength was fixed at 540 nm, the voltage at 585 V, and the slit width at 10 nm. NR has a characteristic emission peak at 624 nm. As the concentration of Q[8] (0-15 μM) in the system gradually increases, the fluorescence intensity of the system gradually decreases. Figure 8 (a)); The ratio of fluorescence intensity at 624 nm to the molar ratio of Q[8] and NR I 624nm -N Q[8] / N NR Relationship curve ( Figure 8 (b) and Job chart ( Figure 8 (c) It can be seen that the ratio of NR to Q[8] is 2:1. Therefore, 10 mL of solution A and 2 mL of solution B from experimental case 1 can be mixed in a 100 mL volumetric flask, and water can be added to make up to the final volume to obtain 2×10 -5 mol / L supramolecular fluorescent probe S1.

[0065] The interaction between Q[8] and AO, APFG was performed using the same experimental method as that between Q[8] and NR. When testing the fluorescence emission spectrum, the AO excitation wavelength was 470 nm, the voltage was 540 V, and the slit width was 5 nm. The APFG excitation wavelength was 530 nm, the voltage was 530 V, and the slit width was 10 nm. It was found that the interaction ratio between Q[8] and AO was also 2:1 (…). Figure 9 The ratio of Q[8] to APFG is 1:1 ( Figure 10 Then, concentrations of 2×10⁻⁶ can be obtained. -5 S2 supramolecular probe solution with a concentration of 2×10 mol / L -5 mol / L S3 supramolecular probe solution.

[0066] The above are merely preferred embodiments of the present invention and are not intended to limit the present invention. Those skilled in the art can understand the specific meaning of the above terms in the present invention according to the specific circumstances. Furthermore, there may be other modifications and variations in the implementation methods. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A supramolecular fluorescence sensing array, characterized in that: The supramolecular fluorescent sensing array is composed of three supramolecular fluorescent probes: 2NR@Q[8], 2AO@Q[8], and APFG@Q[8]. Among them, NR refers to Neutral Red, AO refers to Acridine Orange, APFG refers to Cationic Peach Red FG, Q[8] refers to an octagonal cucurbit ring, 2NR@Q[8] refers to a supramolecular fluorescent probe constructed from Neutral Red and an octagonal cucurbit ring, 2AO@Q[8] refers to a supramolecular fluorescent probe constructed from Acridine Orange and an octagonal cucurbit ring, and APFG@Q[8] refers to a supramolecular fluorescent probe constructed from Cationic Peach Red FG and an octagonal cucurbit ring.

2. The supramolecular fluorescence sensing array according to claim 1, characterized in that: The 2NR@Q[8] is a solution formed by NR and Q[8] in a molar ratio of 2:1; the 2AO@Q[8] is a solution formed by AO and Q[8] in a molar ratio of 2:1; the APFG@Q[8] is a solution formed by APFG and Q[8] in a molar ratio of 1:

1.

3. The supramolecular fluorescence sensing array according to claim 2, characterized in that: The concentrations of the supramolecular fluorescent probes 2NR@Q[8], 2AO@Q[8], and APFG@Q[8] are all 2×10⁻⁶. -5 mol / L.

4. The application of the supramolecular fluorescence sensing array according to claim 3 for detecting tyrosine kinase inhibitors, characterized in that: The tyrosine kinase inhibitors detected were GEF, EH, LD, AD, and DAC.

5. The application of the supramolecular fluorescence sensing array according to claim 4 for detecting tyrosine kinase inhibitors, characterized in that: The detection method includes the following steps: S1: Prepare supramolecular fluorescent probes 2NR@Q[8], 2AO@Q[8] and APFG@Q[8] respectively; S2: Prepare separate solutions with a molar concentration of 1×10⁻⁶. -2 mol / L solutions of GEF, EH, LD, AD, and DAC; S3: Add any of the solutions prepared in S2 to any of the supramolecular fluorescent probes prepared in S1 according to the molar ratio of supramolecular fluorescent probe and tyrosine kinase inhibitor of 1:

1. Let stand for 10 min, measure the fluorescence emission spectrum of the mixed solution and observe the color change under a 365nm ultraviolet lamp for detection.

6. The application of the supramolecular fluorescence sensing array according to claim 5 for detecting tyrosine kinase inhibitors, characterized in that: The fluorescence color of 2NR@Q[8] under ultraviolet light is weak fluorescence. When a certain tyrosine kinase inhibitor is added to 2NR@Q[8], if the emission spectrum intensity at 624nm is slightly enhanced and the fluorescence is deep purple-red under ultraviolet light, then the measured tyrosine kinase inhibitor is DAC; if the emission spectrum at 624nm is enhanced and the color is purple-red under ultraviolet light, then the measured tyrosine kinase inhibitor is AD; if the emission spectrum at 624nm is enhanced and the color is pink under ultraviolet light, then the measured tyrosine kinase inhibitor is GEF; if the emission spectrum at 624nm is enhanced and the color is reddish-brown under ultraviolet light, then the measured tyrosine kinase inhibitor is LD; if the emission spectrum at 624nm is significantly enhanced and the color is carmine-red under ultraviolet light, then the measured tyrosine kinase inhibitor is EH.

7. The application of the supramolecular fluorescence sensing array according to claim 5 for detecting tyrosine kinase inhibitors, characterized in that: The fluorescence color of 2AO@Q[8] under ultraviolet light is deep yellow; when a certain tyrosine kinase inhibitor is added to 2AO@Q[8], if the emission spectrum at 536nm is slightly enhanced and the color under ultraviolet light is light yellow-green, then the measured tyrosine kinase inhibitor is AD or DAC, and AD is brighter than DAC; if the emission spectrum at 536nm is enhanced and the color under ultraviolet light is bright green, then the measured tyrosine kinase inhibitor is EH or GEF, and EH is brighter than GEF; if the emission spectrum at 536nm is significantly enhanced and the color under ultraviolet light is light green, then the measured tyrosine kinase inhibitor is LD.

8. The application of the supramolecular fluorescence sensing array according to claim 5 for detecting tyrosine kinase inhibitors, characterized in that: The APFG@Q[8] showed no fluorescence under ultraviolet light. When a certain tyrosine kinase inhibitor was added to APFG@Q[8], if the emission spectrum did not change and the color was weak green under ultraviolet light, the tyrosine kinase inhibitor was LD. If the emission spectrum shifted from 591nm to 594nm, the emission spectrum slightly increased and the color was deep red under ultraviolet light, the tyrosine kinase inhibitor was EH. If the emission spectrum shifted from 591nm to 599nm, the emission spectrum increased and the color was deep pink under ultraviolet light, the tyrosine kinase inhibitor was GEF. If the emission spectrum shifted from 591nm to 599nm, the emission spectrum increased and the color was orange-red under ultraviolet light, the tyrosine kinase inhibitor was DAC. If the emission spectrum shifted from 591nm to 604nm, the emission spectrum significantly increased and the color was bright orange-red under ultraviolet light, the tyrosine kinase inhibitor was AD.

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