Quick-response potential type passive creatinine sensor based on molecularly imprinted polymer and preparation method and application of quick-response potential type passive creatinine sensor
By modifying molecular imprinting polymer MIPs on the electrode surface, the creatinine ion selection membrane is constructed, which solves the problems of poor specificity, complex detection process, high cost and difficulty in real-time detection of existing creatinine detection methods, and achieves rapid creatinine Accurate and portable detection.
Patent Information
- Application Number
- CN202411442128.3
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-10-16
- Publication Date
- 2025-02-21
AI Technical Summary
The existing creatinine detection methods have problems such as poor specificity, complex detection process, high cost and difficulty in real-time detection.
A potential passive creatinine sensor based on molecularly imprinted polymers is used to construct a creatinine ion selection membrane by modifying molecular imprinted polymer MIPs on the electrode surface to achieve selective identification and detection of creatinine.
It realizes rapid, accurate and portable detection of creatinine, improves the sensitivity and selectivity of detection, reduces the detection cost, and is suitable for on-site and home medical scenarios.
Smart Images
Figure CN119492793A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of sensors, and in particular relates to a potential-type passive creatinine sensor capable of rapid response based on molecular imprinting polymers, a preparation method thereof and applications thereof. Background Art
[0002] Creatinine, also known as creatinine, is a product of muscle metabolism in the human body. It is mainly filtered and excreted through the kidneys. Therefore, the concentration of creatinine in blood and urine is one of the important indicators for evaluating kidney function. Kidney disease is a common health problem worldwide, affecting the quality of life and life expectancy of a large number of people. As a marker of glomerular filtration function, changes in creatinine concentration can promptly reflect the degree of kidney damage. Therefore, accurate and rapid detection of creatinine levels is of vital importance for the diagnosis, treatment monitoring and health assessment of kidney disease.
[0003] At present, the commonly used creatinine detection methods in clinical practice mainly include the picric acid method and the enzyme method. The picric acid method is a classic chemical determination method, but it has disadvantages such as poor specificity and susceptibility to interference from other substances, resulting in inaccurate test results; although the enzyme method has high specificity and accuracy, the detection process is usually more complicated, requiring expensive reagents and sophisticated instruments and equipment, with high detection costs, and it is difficult to achieve point-of-care testing (POCT).
[0004] Compared with the above two creatinine detection methods, the potentiometric sensor has the advantages of simple operation, fast response and low cost. The working principle of the ion selective electrode is based on the response of the selective membrane on the electrode surface to specific ions. When creatinine ions interact with the selective membrane on the electrode surface, it will cause a change in the electrode potential. According to the Nernst equation, this potential change is proportional to the concentration of creatinine, thereby realizing the quantitative detection of creatinine. By measuring the potential difference between the working electrode and the reference electrode, the qualitative and quantitative detection of the target analyte, creatinine, can be achieved, and the reliability and sensitivity of the detection results can be ensured. Molecular imprinting (MIP) technology is a technology that simulates the recognition process of biological molecules. By forming holes in the polymer matrix that match the target molecule (template molecule) in spatial structure and binding site, molecularly imprinted polymers (MIPs) can specifically recognize and bind to the target molecule. Applying molecular imprinting technology to potentiometric sensors, especially using MIPs as selective creatinine carriers to construct ion-selective electrodes, can achieve potentiometric detection of creatinine, significantly improve the selectivity and specificity of the sensor, reduce the impact of interfering substances, and thus improve the accuracy of detection. This design enables the sensor to accurately identify creatinine and ensure reliable detection results in complex samples.
[0005] Therefore, the research on fast-response potential-type passive creatinine sensors based on molecular imprinting polymers has important clinical significance and application value. By developing this new type of sensor, it is expected to achieve rapid, accurate and portable detection of creatinine, providing strong support for the diagnosis and treatment of kidney diseases. Summary of the invention
[0006] The present invention aims to solve at least one of the problems existing in the above-mentioned prior art. To this end, the present invention provides a potential-type passive creatinine sensor based on molecular imprinting polymer with fast response, and a preparation method and application thereof.
[0007] In order to achieve the above objectives, the specific technical solutions are as follows: A potential-type passive creatinine sensor based on molecular imprinting polymer with rapid response, the preparation method of which includes: using creatinine as a template molecule and acrylamide as a functional monomer to obtain molecular imprinting polymer MIPs through polymerization; modifying the molecular imprinting polymer MIPs on the surface of an electrode to obtain the sensor. The present invention uses molecular imprinting polymer MIPs as a creatinine ion carrier to prepare a creatinine ion selective membrane, and applies it to the construction of a creatinine ion selective electrode to form a creatinine ion selective electrode to achieve selective recognition and detection of creatinine, and finally obtains a LC wireless passive creatinine sensor with high sensitivity and selectivity.
[0008] Preferably, the molecular imprinting polymer preparation process further includes using divinylbenzene as a crosslinking agent and azobisisobutyronitrile as an initiator, the polymerization is carried out under sealed conditions, and nitrogen degassing treatment is carried out before the sealed polymerization reaction.
[0009] Furthermore, the polymerization reaction temperature is 60-80° C., the reaction time is 12-24 h, the mass ratio of creatinine to acrylamide is (1-2.4):(3.98-9.552), and the amount of the crosslinking agent and the initiator is adjusted according to the polymerization reaction.
[0010] Furthermore, after the polymerization reaction is completed, a washing process of the template molecules is also included; the washing process is specifically: firstly centrifugation washing is performed using a mixed solution of methanol and acetic acid, then suction filtration washing is performed using methanol and acetic acid in sequence, and finally suction filtration washing is performed using deionized water.
[0011] Furthermore, the modification process specifically comprises the following steps: (1) Dissolving molecular imprinting polymer, sodium tetraphenylborate (NaTPB), polyvinyl chloride (PVC) and 2-nitrophenyl octyl ether (o-NPOE) in tetrahydrofuran (THF) to obtain an ISM solution; (2) The ISM solution is coated on the electrode surface and dried to obtain the potential-type passive creatinine sensor.
[0012] Furthermore, the mixing ratio of the molecular imprinting polymer, sodium tetraphenylborate, polyvinyl chloride, 2-nitrophenyl octyl ether, and tetrahydrofuran is (0.7-0.945) mg: (0.1-0.135) mg: 4.8 mg: (8.8-9) mg: 3.3 mL.
[0013] The second aspect of the present invention provides a potential-type passive creatinine sensor based on molecular imprinting polymer with fast response obtained according to the above preparation method. The sensor has excellent creatinine detection performance, a sensitivity of 61.28mV / dec, and a response time of about 2 seconds.
[0014] The third aspect of the present invention provides an application of the above-mentioned molecular imprinting polymer-based potential-type passive creatinine sensor with rapid response in creatinine detection.
[0015] Furthermore, during the detection process, the sensor is first placed in a solution with a pH of 4.5 to 6.5 and a concentration of 10 -3 -10 -2 The sample was pretreated by soaking in a creatinine solution of M, and the soaking time was 6-12 h.
[0016] Compared with the prior art, the present invention has the following beneficial effects: The present invention uses creatinine as a template molecule and acrylamide as a functional monomer to obtain molecular imprinting polymers (MIPs) through polymerization, and uses the molecular imprinting polymers to obtain a fast-responding potential-type passive creatinine sensor based on molecular imprinting polymers, which has high sensitivity, short response time and low detection limit; in practical applications, the fast-responding sensor can provide test results in a short time, which helps to make timely diagnosis and treatment decisions. In addition, sensors with passive detection (i.e., no external power supply required) have higher portability and ease of use, and are suitable for scenarios such as on-site detection and home medical care. BRIEF DESCRIPTION OF THE DRAWINGS
[0017] Figure 1 a-1b are schematic diagrams of the creatinine sensor and its working principle of the present invention; Figure 2 This is a schematic diagram of the preparation and testing process of the creatinine sensor of the present invention; Figure 3 The open circuit voltage of the sensor in Example 1 changes with time; Figure 4 This is a sensitivity test diagram of the sensor in Example 1; Figure 5 a-5b are the response curves and sensitivity curves of the sensor of Example 1 to dimethylamine, glucose, and lysine, respectively; Figure 6 a is a response curve of the sensor in Example 1 to creatinine solutions of different concentrations; Figure 6 b is a response / recovery time test diagram of the sensor in Example 1; Figure 7 a and 7c are curves showing the change of the open circuit voltage of the sensor of Example 1 with time under the conditions of pH 4.5 and pH 7, respectively; Figure 7 b and 7d are the detection limit test graphs of the sensor under pH 4.5 and pH 7, respectively; Figure 8 a-8p are the open circuit voltage variation over time trend diagram and sensitivity test diagram of the sensor under pH conditions of 4.5, 5, 5.5, 6, 6.5, 7, 7.5, and 8, respectively; Fig. 9 a-9d are the open circuit voltage change trend graph and sensitivity curve of the creatinine sensor pretreated with creatinine solution with pH 4.5 and 7, respectively. DETAILED DESCRIPTION
[0018] The principles and features of the present invention are described below in conjunction with examples. The examples are only used to explain the present invention and are not used to limit the scope of the present invention. The experimental methods used in the following examples are conventional methods unless otherwise specified; the materials, reagents, etc. used in the following examples can be obtained from commercial channels unless otherwise specified.
[0019] like Figure 1 a-1b are schematic diagrams of the creatinine sensor and its working principle of the present invention; Figure 2 The figure is a schematic diagram of the preparation and testing process of the creatinine sensor of the present invention. Example 1
[0020] A method for preparing a fast-responding potential-type passive creatinine sensor based on molecular imprinting polymer comprises the following steps: MIP aggregation: (1) Dissolve 10 mg of creatinine powder in 200 μL of deionized water to prepare creatinine concentrate; (2) Add 39.8 mg acrylamide (AM), 937.5 μL divinylbenzene (DVB) and 10.6 mg azobisisobutyronitrile (AIBN) to a beaker, and then add 13 mL acetonitrile to the beaker; then, add 200 μL creatinine concentrate to the reaction mixture, stir the solution for 5 minutes, and sonicate for 10 minutes; (3) The obtained mixed solution was poured into a transparent glass vial and degassed by purging nitrogen gas for 15 minutes. After degassing, the glass vial was sealed and placed in a water bath at 60°C for 12 hours under heating and stirring to complete the MIP polymerization.
[0021] washing: (1) First, the MIPs were centrifuged and washed with 400 mL of a methanol / acetic acid mixture (1:1) at 3000 rpm for 5 min each time; (2) The polymer was then filtered and washed using 200 mL of methanol and 200 mL of acetic acid respectively; (3) Finally, use 300 mL of deionized water to filter and wash to remove acetic acid; after washing, place the MIPs in a dry environment and air-dry for 24 hours. After air-drying, grind the polymer.
[0022] Electrode preparation: (1) 26 mg of MIPs, 4.5 mg of NaTPB, 165 mg of PVC, and 304 mg of o-NPOE were dissolved in 3.3 mL of tetrahydrofuran, stirred for 10 min, and ultrasonicated for 15 min to obtain an ISM solution; (2) 15 μL of ISM solution was added dropwise onto the surface of the gold electrode and dried for 12 hours to form an ion selective electrode, thereby obtaining the potential-type passive creatinine sensor.
[0023] The sensitivity of the potential-type passive creatinine sensor was tested under the environmental condition of pH 4.5. Figure 3 It can be obtained that the open circuit voltage (OCP) changes with time in a step-like manner. Figure 4It can be seen that its sensitivity (slope) reaches 61.28mV / dec. Figure 5 As shown in a-5b, the creatinine sensor was selectively tested, mainly testing some pathological substances in urine, dimethylamine (DMA), glucose (Glu) and lysine (Lys). According to 5a, it can be obtained that the response curve of the sensor to different concentrations of dimethylamine, glucose and lysine has no obvious change, and according to 5b, it can be obtained that the response sensitivity of the sensor to dimethylamine, glucose and lysine is between ±1.5.
[0024] like Figure 6 As shown in a-6b, in order to test the response time of the sensor, a real-time solution test was performed on the creatinine sensor (i.e., adding a high concentration solution to a low concentration solution), and it was finally concluded that the sensor response time was about 2s. Figure 7 As shown in a-7d, the sensor is moved from a concentration of 10 -7 The creatinine solution was measured to 10 -1 M, thus obtaining the lower detection limit of the sensor; under the condition of environmental pH of 4.5, the detection limit of the sensor is 10 -5.038 M; under the condition of environmental pH of 7, its detection limit is 10 -4.896 M. According to Figure 8 A-8p shows that as the pH increases, the sensitivity (slope) of the sensor gradually decreases. Within the physiological pH range (4.5-7), the best sensitivity is 61.28 mV / dec at pH 4.5, and the worst sensitivity is 13.63 mV / dec at pH 8.
[0025] like Fig. 9 As shown in a-9d, in order to verify the effect of the pH of the pretreatment solution on the sensor, creatinine solutions with pH values of 4.5 and 7 (concentration of 10 -2 The response change of the creatinine sensor pretreated with creatinine solution (M, immersion time 12 h) can be seen from the figure. The pH of the pretreatment solution has a significant effect on the sensitivity of the sensor. The lower the pH, the higher the sensitivity. However, too low a pH will affect the adsorption of molecular imprinting (MIP), thereby affecting its detection performance.
[0026] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims
1. A method for preparing a fast-response potential-type passive creatinine sensor based on molecular imprinting polymer, characterized in that: The preparation method comprises the following steps: using creatinine as a template molecule and acrylamide as a functional monomer to obtain molecular imprinting polymer MIPs through polymerization; and modifying the molecular imprinting polymer MIPs on an electrode surface to obtain the sensor.
2. The preparation method according to claim 1, characterized in that: The molecular imprinting polymer preparation process also includes using divinylbenzene as a crosslinking agent and azobisisobutyronitrile as an initiator.
3. The preparation method according to claim 2, characterized in that: The mass ratio of creatinine to acrylamide is (1-2.4):(3.98-9.552).
4. The preparation method according to claim 1, characterized in that: The polymerization reaction temperature is 60-80° C., and the reaction time is 12-24 hours.
5. The preparation method according to claim 1, characterized in that: The modification process specifically comprises the following steps: (1) Dissolving molecular imprinting polymer, sodium tetraphenylborate (NaTPB), polyvinyl chloride (PVC) and 2-nitrophenyl octyl ether (o-NPOE) in tetrahydrofuran (THF) to obtain an ISM solution; (2) The ISM solution is coated on the electrode surface and dried to obtain the potential-type passive creatinine sensor.
6. The preparation method according to claim 5, characterized in that: The mixing ratio of the molecular imprinting polymer, sodium tetraphenylborate, polyvinyl chloride, 2-nitrophenyl octyl ether and tetrahydrofuran is (0.7-0.945) mg: (0.1-0.135) mg: 4.8 mg: (8.8-9) mg: 3.3 mL.
7. A potential-type passive creatinine sensor prepared according to any of the preparation methods described in claims 1-6.
8. Use of the potential-type passive creatinine sensor according to claim 7 in creatinine detection.
9. The use according to claim 8, characterized in that: During the detection process, the sensor was first placed in a solution with a pH of 4.5-6.5 and a concentration of 10 -3 - 10 -2 The samples were pre-treated by soaking in creatinine solution of M before creatinine detection.