JP-2026076068-A - Sensors using particles with molecularly imprinted polymers on their surface

Abstract

[Problem] To resolve the problem of reduced sensor sensitivity caused by silicone oil in a molecular imprint polymer paste, in a sensor that includes an electrode immobilized with a molecular imprint polymer paste. [Solution] A sensor that utilizes conductive carbon for wiring, wherein the sensor has (a) an working electrode, (b) a counter electrode, (c) a reference electrode, (d) a wiring section, and (e) a connection section to a measuring instrument, the working electrode is formed from a molecular imprint polymer paste containing conductive particles having molecular imprint polymers on their surface and silicone oil, and a portion of the wiring section between the connection section to the measuring instrument and the working electrode is replaced with a conductive and non-lipophilic substance. A sensor comprising an electrode substrate coated or filled with a molecular imprint polymer paste containing conductive particles having molecular imprint polymers on their surface and an amphiphilic substance. [Selection Diagram] None

Inventors

• 吉見 靖男

Assignees

• 学校法人 芝浦工業大学

Dates

Publication Date

20260511

Application Date

20241023

Claims (19)

1. A sensor that uses conductive carbon in its wiring, The sensor has (a) an working electrode, (b) a counter electrode, (c) a reference electrode, (d) a wiring section, and (e) a connection section for a measuring instrument. The working electrode is formed from a molecular imprint polymer paste containing conductive particles having molecular imprint polymers on their surface and silicone oil. A portion of the wiring between the connection point to the measuring instrument and the working electrode is replaced with a conductive and non-lipophilic substance. Sensor.
2. The sensor according to claim 1, wherein the conductive and non-lipophilic substance is silver and/or a silver salt.
3. The sensor according to claim 1, wherein the conductive particles are graphite particles.
4. The sensor according to claim 1, wherein the conductive particles having a molecularly imprinted polymer on their surface are obtained by polymerizing particles immobilized with an initiator by contacting a functional monomer, a crosslinkable monomer, and a measurement substance.
5. The sensor according to claim 1, wherein the substance to be measured is a hormone, an antibacterial agent, an anticoagulant, or a toxic substance or freshness indicator substance in food.
6. The sensor according to claim 1, wherein the substance to be measured is heparin, warfarin, serotonin, vancomycin, phenobarbital, theophylline, edoxaban, or histamine.
7. A method for measuring a substance, comprising contacting a sample containing the substance to be measured with a sensor according to any one of claims 1 to 6, and detecting a change in the signal.
8. A method for measuring a substance according to claim 7, comprising detecting a change in current as a change in signal.
9. The measurement method according to claim 7, wherein the sample is whole blood, blood components, or food.
10. A sensor comprising an electrode substrate coated or filled with a molecularly imprinted polymer paste containing conductive particles having molecularly imprinted polymers on their surface and an amphiphilic substance.
11. The sensor according to claim 10, wherein the molecularly imprinted polymer paste functions as the working electrode.
12. The sensor according to claim 10, wherein the amphiphilic substance is polyethylene glycol monoacrylate.
13. The sensor according to claim 10, wherein the conductive particles are graphite particles.
14. The sensor according to claim 10, wherein the conductive particles having a molecularly imprinted polymer on their surface are obtained by polymerizing particles immobilized with an initiator by contacting a functional monomer, a crosslinkable monomer, and a measurement substance.
15. The sensor according to claim 10, wherein the substance to be measured is a hormone, an antibacterial agent, an anticoagulant, or a toxic substance or freshness indicator substance in food.
16. The sensor according to claim 10, wherein the substance to be measured is heparin, warfarin, serotonin, vancomycin, phenobarbital, theophylline, edoxaban, or histamine.
17. A method for measuring a substance, comprising contacting a sample containing the substance to be measured with a sensor according to any one of claims 10 to 16, and detecting a change in the signal.
18. A method for measuring a substance according to claim 17, comprising detecting a change in current as a change in signal.
19. The measurement method according to claim 17, wherein the sample is whole blood, blood components, or food.

Description

This invention relates to a sensor using particles having a molecularly imprinted polymer on its surface, and a measurement method using the sensor. To effectively use drugs with strong side effects, therapeutic drug monitoring (TDM) is required to ensure that their blood concentrations remain within the effective range. However, due to the lack of appropriate sensing technologies, the widespread adoption of TDM in clinical practice is not progressing. Molecular imprinted polymers (MIPs) are molecular recognition elements obtained by copolymerizing a monomer (functional monomer) that has affinity for a target substance (template) with a crosslinkable monomer in the presence of the target substance. They are molecular recognition elements that can be prepared tailor-made for any target substance using a simple and economical process. The inventors have found that the oxidation-reduction current in an electrode grafted with MIP on its surface depends on the concentration of the template. This is thought to be due to a change in the accessibility of redox species to the substrate electrode (gate effect) caused by the specific interaction between the template and the MIP. By measuring this current, the template can be sensed simply and quickly. Based on this finding, Patent Document 1 describes a sensor for measuring anticoagulants composed of a substrate on which molecular imprinted polymers are immobilized. Patent Document 2 describes a sensor composed of a substrate on which molecular imprinted polymers are directly immobilized on its surface, wherein redox species are immobilized on the molecular imprinted polymer and/or the substrate. Furthermore, Patent Document 3 describes a sensor composed of conductive particles having a molecularly imprinted polymer grafted onto the surface of conductive particles on which a polymerization initiator is immobilized, and a support. International Publication No. WO2012/124800International Publication WO2016/140337International Publication WO2018/117067 Figure 1 illustrates the principle of molecular imprinting.Figure 2 shows an overview of the sensor chip substrate fabrication procedure. Figure 2(a) shows the fabrication procedure for a standard sensor chip substrate, and (b) shows the fabrication procedure for a sensor chip substrate in which part of the carbon ink is replaced with Ag/AgCl ink.Figure 3 shows the wiring of a typical sensor chip substrate. (a) shows the overall view of a screen made with carbon ink, and (b) shows the structure of one sensor substrate unit.Figure 4 shows a typical sensor chip substrate after (a) insulation treatment and (b) reference electrode formation.Figure 5 shows the ink replacement procedure for fabricating a sensor chip substrate in which a portion of the carbon ink is replaced with Ag/AgCl ink.Figure 6 shows a sensor completed using a standard sensor chip substrate.Figure 7 shows the relationship between vancomycin concentration in human serum and response current. The pie plot shows the results when using a substrate wired with carbon ink only, and the square plot shows the results when using a substrate with both Ag/AgCl.Figure 8 shows the relationship between histamine concentration in milk and reduction current. (a) shows the results when a histamine MIP-CP control containing silicone oil as a binder is used, and (b) shows the results when a histamine MIP-CP containing polyethylene glycol monomethacrylate as a binder is used. Embodiments of the present invention will be described below. The sensor of the present invention A sensor that uses conductive carbon in its wiring, The sensor has (a) an working electrode, (b) a counter electrode, (c) a reference electrode, (d) a wiring section, and (e) a connection section for a measuring instrument. The working electrode is formed from a molecular imprint polymer paste containing conductive particles having molecular imprint polymers on their surface and silicone oil. A portion of the wiring between the connection point to the measuring instrument and the working electrode is replaced with a conductive and non-lipophilic substance. It is a sensor. Furthermore, the sensor of the present invention is The sensor includes an electrode substrate coated or filled with a molecular imprint polymer paste containing conductive particles having molecular imprint polymers on their surface and an amphiphilic substance. By copolymerizing a functional monomer with a crosslinkable monomer in a self-assembled state consisting of a specific substance (template) and a functional monomer that reversibly binds to it, a molecularly imprinted polymer can be synthesized that memorizes the molecular structure of the template and specifically re-bonds to it (Figure 1). This molecularly imprinted polymer is more chemically and physically stable than biopolymers and can be prepared at low cost and in a short time. To use molecularly imprinted polymers as sensor elements, it is necessary to generate signals such a