Potassium ion selective optical sensor and manufacturing method thereof

Abstract

An ion-selective optical sensor for detecting potassium (K +) ions and a method of manufacturing an ion-selective sensor comprising the steps of: treating a surface of the sensor with (3-aminopropyl) triethoxysilane (APTES) and then with glutaraldehyde (GA); coating the APTES-GA surface with a crown ether ionophore to produce a functionalized layer; wherein when the functionalized layer is in contact with a target ion in the sample, a complex is formed between the crown ether and the target ion, thus changing the material index of the functionalized layer, the change corresponding to the concentration of the target ion in the sample.

Description

Technical Field

[0001] The present invention generally relates to the detection of metal cations, and more particularly to sensors for detecting and measuring the potassium (K+) ion content in a sample and methods of manufacturing the sensors. Background Art

[0002] Measuring cation concentration is crucial in various fields. For example, quantifying the presence of cations plays a major role in the clinical and medical fields because some cations are essential for many intracellular activities. For example, potassium cations play an important role in information transmission in the nervous system and circulation in muscle tissues. Therefore, in the medical field, it is highly necessary to accurately, easily, and rapidly sense potassium ions because these characteristics can help quickly evaluate a patient's condition.

[0003] The choice of sensor depends on the type of ion concentration to be measured. It is understood that the sensor must be more sensitive to the activity of the target ion compared to the activities of other ions that may be present in the sample or test solution. There are several ways to detect the presence of ions in a sample, one of which is the binding of the target ion to a compound, which typically results in the formation of a strong binding complex that indicates the presence of the target ion in the sample and can be used for quantification. However, it should be noted that there are various conditions and variables that can affect cation recognition, stability, and selectivity in such sensors, such as cavity size, shape, substituent effects, conformational flexibility, type of donor atoms, and the solvent used.

[0004] There are several difficulties in measuring cation content, such as sustainability and cost, because most sensing devices and equipment require complex operation steps as well as complex sample pretreatment processes, which increase the manufacturing cost and are moreover not suitable for on-site or in-situ measurements, considering that most of these devices and equipment are laboratory-limited. Summary of the Invention

[0005] In one aspect, the present invention provides a method of forming an ion-selective optical sensor, the method comprising the steps of: treating the surface of the sensor with (3-aminopropyl)triethoxysilane (APTES) and then with glutaraldehyde (GA); and coating the APTES-GA surface with a crown ether ionophore to produce a functionalized layer; wherein when the ionophore functionalized layer contacts the target ion in the sample, a complex is formed between the crown ether and the target ion, thus changing the material index of the functionalized layer, the change corresponding to the concentration of the target ion in the sample.

[0006] Generally, the surface of the sensor comprises a resonant structure.

[0007] Generally, changing the material index shifts the resonant condition of the functionalized layer, thus enabling the measurement of ion concentration.

[0008] In one embodiment, the target ion is K + .

[0009] In another embodiment, before treating the surface with APTES and GA, the method further includes a pretreatment step to modify the surface of the sensor to enable hydroxylation.

[0010] In yet another embodiment, the pretreatment step includes plasma irradiation treatment with oxygen.

[0011] In one embodiment, the crown ether is benzo-18-crown-6. Typically, the crown ether compounds are carboxy-benzo-18-crown-6 and 4-aminobenzo-18-crown-6.

[0012] In one embodiment, the step of treating the surface with APTES and GA further includes diluting APTES in ethanol and diluting GA in deionized water, typically 2% (v / v) (volume / volume %) APTES and 0.1% (v / v) GA.

[0013] In one embodiment, the step of coating the APTES-GA surface with a crown ether ionophore includes diluting the crown ether compound in methanol.

[0014] In one embodiment, the method further includes diluting the crown ether compound in methanol.

[0015] In another aspect, the present invention provides an optical sensor for detecting ions in a sample, which includes a resonant structure having an ionophore layer prepared from a crown ether compound, wherein when the target ion contacts the functionalized ionophore layer, its material index changes due to the absorption of the target ion, thus enabling the determination of the concentration of the target ion in the sample.

[0016] In one embodiment, the resonant structure includes a pair of waveguides, in the form of a sensing arm coated with a functionalized ionophore layer and a reference arm including a barrier coating on (or not coated with a functionalized layer) the functionalized ionophore layer. Typically, the resonant structure is formed in silicon or silicon oxide.

[0017] Typically, the channel width of the waveguide is in the range of 15 to 1000 nm, and the length is in the range of 200 μm to 1 cm. Typically, the thickness of the waveguide is about 220 nm.

[0018] In another embodiment, the light source is configured to emit light of at least one wavelength, and after a predetermined exposure time, the light is guided through the pair of waveguides, thereby generating a corresponding pattern that can be compared to determine the concentration of the target ion. Typically, the light source emits light waves in the wavelength range of 1500 to 1600 nm.

[0019] In one embodiment, the exposure time for detecting ions is 20 seconds or more.

[0020] In a further embodiment, the sensor includes a spectroscopic interrogator for detecting and measuring ion concentration.

[0021] Typically, the target ion is K + .

[0022] In one embodiment, the concentration of the detected ions in the sample is determined based on the measurement of the shift of the resonant wavelength over time. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] The present invention will be better understood by reference to the following description in conjunction with the accompanying drawings:

[0024] Figure 1A A schematic diagram of the binding mechanism of potassium ions with carboxyl-functionalized benzo-18-crown-6 according to an embodiment of the present invention is provided;

[0025] Figure 1B A schematic diagram of the binding mechanism of potassium ions with 4-aminobenzo-18-crown-6 according to an embodiment of the present invention is provided;

[0026] Figure 2A A top view of a sensor chip according to an embodiment of the present invention is shown;

[0027] Figure 2B An example of a waveguide according to an embodiment of the present invention is provided;

[0028] Figure 3 A flowchart of a method according to an embodiment of the present invention is shown;

[0029] Figure 4 An example of the wavelength shift with respect to the change in the material index according to an embodiment of the present invention is shown;

[0030] Figure 5A – Figure 5B An example of the wavelength shift caused by the increased ion concentration is shown. DETAILED DESCRIPTION

[0031] Based on the above summary of the invention, the following description of a number of specific and alternative embodiments is provided to understand the inventive features of the present invention. However, it will be apparent to those skilled in the art that the present invention may be practiced without these specific details. Some details may not be described in detail so as not to obscure the present invention. For ease of reference, the same reference numerals are used in all the drawings when referring to the same or similar features common to the drawings.

[0032] Embodiments of the present invention are described by way of example. As will be appreciated, the present invention is capable of having other and different embodiments, and several details can be modified in various aspects, all without departing from the scope of the present invention. It should be noted that the drawings include flowcharts of how to perform the method according to the preferred embodiments. Standard devices or components may not be shown as they are known in the art.

[0033] The present invention provides a potassium ion-selective optical sensor that includes a functionalized ion carrier layer prepared with a macrocyclic compound, more particularly an amino- and carboxy-crown ether compound, such that as shown in FIG. 1, when a target ion contacts the amino- and carboxy-crown ether functionalized layer, due to the absorption kinetics of the target ion on the functional layer, the material index of the functionalized layer changes, and thus potassium ions in a sample can be detected. Accordingly, the ion concentration in the sample can be obtained by measuring the shift of the resonant wavelength over time. In a preferred embodiment, the sensor is an optical sensor that includes a resonant surface and waveguide portions of different widths.

[0034] Now referring Figure 2A , a light source (13) projects a light beam that passes through an input waveguide and then splits equally at a Y-junction and is then directed to propagate along a sensing exposure arm (10) and a reference arm (12) in the form of straight waveguides. In a preferred embodiment, the reference arm (12) is coated with a material that prevents sensing of potassium ions, thus providing a reference wavelength pattern corresponding to the condition of the absence of potassium ions, while the sensing arm (10) is coated with a functional layer to detect potassium ions and provide a wavelength pattern corresponding to the potassium ion concentration. The chemical reaction in the sensing arm (10) can be measured by the interference intensity at the output waveguide and then measured by a interrogator (15).

[0035] Accordingly, the sensor can be calibrated and optimized based on each different channel pair having different characteristics to provide a maximum shift at a specific or selected wavelength. Advantageously, this comparison allows for precise measurement of shifts of <500 pM, corresponding to a sensitivity of 10 ppb potassium ions.

[0036] In one embodiment, the functionalized layer can be provided on a surface in a waveguide-based sensor that includes a chip having a Mach-Zehnder interferometer (MZI) configuration. Figure 2BAn example of an MZI optical waveguide sensor of silicon-on-insulator (SOI) with a functionalized layer according to the present invention on an insulator platform is shown. In this embodiment, the sensing part (20) includes a waveguide with a silicon dioxide SiO2 cladding layer having a thickness of about 220 nm, a width of 15 - 1000 nm, and a length of about 200 μm - 1 cm. The coupling is a vertical grating coupler (11), preferably in a transverse mode. The wavelength range is 1500 - 1600 nm, and the resolution measurement is up to 1 picometer (pm). The interrogator (15) is connected to the output, where the interrogator (15) may include a pair of MMI-based reflectors (15A, 15B) and 2 pairs of microring resonators (16, 17, 18, 19). Appropriately, the readout parameter is in-phase or λ.

[0037] In use, when implementing a test using the MZI system, the following sequence can be observed. First, a drop of distilled water is added as a blank sample to the surface of the MZI system. Second, the droplet of distilled water is removed from the surface. Third, a drop of a solution with a known concentration of K + is added to the surface. After 30 seconds to 2 minutes, the solution is removed from the surface. Then, another drop of distilled water is added to the surface. Last but not least, the laser is scanned from a wavelength of 1500 to 1600 nm, and the output of the sensor is measured.

[0038] The present invention further provides a method for manufacturing or forming the ion-selective sensor for determining the presence of ion species in a sample. More specifically, the present invention provides a method for manufacturing a sensor for detecting potassium (K + ) ions, wherein a functionalized ionophore prepared with an amino- and carboxy-crown ether compound is coated on the surface of the sensor such that it forms a layer on the surface of the sensor.

[0039] Generally, macrocyclic compounds such as crown ethers are known for their unique property of forming stable complexes with alkali metals due to the tight fit of the cation in the cavity and the almost planar oxygen atoms around the central cation. The crown ether compound synthesized according to the present invention contains a moiety that is usually selective for cations, namely potassium, and is thus capable of detecting these substances in a sample.

[0040] In one embodiment of the present invention, the binding mechanism of potassium ions with the crown ether compound, the resulting strongly bound complex, and the ion-dipole interaction are generated by including a cation in the cavity, where electrostatic interaction occurs with the partial negative charge on the oxygen atoms.

[0041] In a preferred embodiment, a method for manufacturing an ion-selective sensor includes the steps of treating the surface of the sensor with (3-aminopropyl)triethoxysilane (APTES) and then with glutaraldehyde (GA); coating the APTES-GA surface with a crown ether ionophore to produce a functionalized layer; wherein when the ionophore functionalized layer contacts the target ion, the material index of the functionalized crown ether ionophore layer changes, thus enabling the detection of the target ion in the sample.

[0042] Typically, the crown ether ionophores include benzo-18-crown-6, more particularly carboxy-benzo-18-crown-6 and 4-aminobenzo-18-crown-6; however, it is contemplated that other benzo crown ether compounds and derivatives having a moiety selective for potassium ions or capable of selectively binding potassium ions may be used in this method.

[0043] The method includes using non-toxic solvents such as water, ethanol, and methanol in the step of preparing the functionalized ionophore layer.

[0044] In a preferred embodiment, the surface is treated with (3-aminopropyl)triethoxysilane (APTES) and glutaraldehyde (GA) to initiate a chemical cross-linking reaction for covalent binding, and then carboxy-benzo-18-crown-6 and 4-aminobenzo-18-crown-6 ionophores are immobilized onto the sensor surface.

[0045] Figure 3 A flowchart depicting the steps of a method for manufacturing an ion-selective optical sensor is provided, the method including: using oxygen, pre-modifying the target surface of the sensor via plasma treatment to change the surface and enable a hydroxylation reaction (S201). After plasma treatment, the pre-modified sensor surface is treated with a 2% (v / v) APTES solution diluted in absolute ethanol at room temperature for 1 hour (S202), and subsequently the APTES-treated surface is dried at a high temperature such as 80 °C for 1 hour (S203). Then the dried APTES-treated surface is treated with a 0.1% (v / v) GA solution in deionized water at room temperature for 20 minutes (S204). The APTES-GA modified surface is further treated with 50 mL of 100 mM self-synthesized carboxy-benzo-18-crown-6 and 4-aminobenzo-18-crown-6 ionophores in methanol and allowed to stand to evaporate the solvent (S205).

[0046] The functionalized ionophore layer is heterogeneously integrated with the resonant surface of the sensor such that the resonant condition of the sensor is shifted accordingly according to the change in the material index due to the absorption of ions, and thus the concentration of ions in the sample can be measured and quantified by detecting the shift of the resonant wavelength curve relative to the time curve. The same technique can be used to train an artificial neural network to derive the ion concentration.

[0047] Figure 4 An example of the wavelength shift of an optical sensor integrated with a functionalized layer due to a change in the material index is shown. Thus, when the layer absorbs ions, the change in the material index causes a shift in the wavelength, which facilitates the measurement or quantification of the ion concentration in a sample. This is Figure 5A and Figure 5B clearly shown in, where the wavelength shifts as the functionalized layer absorbs more ions from the sample. The presence of potassium ions can be detected within a predetermined exposure time, for example, within 30 to 120 seconds, after which the change or wavelength shift essentially no longer changes after 120 seconds.

[0048] In a preferred embodiment, the target surface of the sensor includes a resonant surface or structure, where the functionalized ionophore prepared according to the method can be applied on the resonant structure or resonant surface of the sensor, such as a Mach-Zehnder interferometer, a mirror resonator, or applied on an integrated photonics platform, i.e., a III-V silicon photonics device.

[0049] The concentration of potassium ions can be adjusted to optimize the detection range, where a higher detection range of ions can be achieved by increasing the concentration of ions and the sensitivity of the sensor. In one embodiment, the sensor can detect and measure ion concentrations from 10 ppb to 200 ppm.

[0050] Compared with conventional methods or devices that require complex sample pretreatment and highly skilled personnel to operate, such as ICP-MS / OES, the integration of the functionalized surface and the resonant surface of the sensor enables less complex in-situ measurements because the sensor can be implemented in a compact and portable form.

[0051] The sensor can be mass-produced by changing the concentration of the crown ether and its linker on a single sensor area, thus providing sensors that can be deployed in any system or environment.

[0052] Although the present invention has been described in terms of preferred embodiments and specific operating ranges and conditions as required, those skilled in the art will understand that the invention described herein is susceptible to variations and modifications other than those specifically described.

Claims

1. A method for forming an optical ion selective sensor, the method comprising the steps of: treating the surface of the sensor with (3-aminopropyl)triethoxysilane (APTES) and then with glutaraldehyde (GA); and coating the APTES-GA surface with a crown ether ionophore to produce a functionalized layer; wherein when the functionalized layer contacts the target ion in the sample, a complex is formed between the crown ether and the target ion, thus changing the material index of the functionalized layer, and the change corresponds to the concentration of the target ion in the sample.

2. The method according to claim 1, wherein, The surface of the sensor includes a resonant structure.

3. The method according to claim 1 or 2, wherein Changing the material index shifts the resonance condition of the layer, thus enabling the measurement of ion concentration.

4. The method according to any one of the preceding claims, wherein, The target ion is K + .

5. The method according to any one of the preceding claims 1, wherein, Before treating the surface with APTES and GA, the method further includes a pretreatment step to modify the surface of the sensor to enable hydroxylation.

6. The method according to claim 5, wherein The pretreatment step includes treatment with plasma irradiation of oxygen.

7. The method according to any one of the preceding claims, wherein The crown ether ionophore includes benzo-18-crown-16.

8. The method according to any one of the preceding claims, wherein, The crown ether ionophore includes carboxy-benzo-18-crown-6 and 4-aminobenzo-18-crown-6.

9. The method according to any one of the preceding claims, wherein, The step of treating the surface with APTES and GA further includes diluting APTES in ethanol and diluting GA in deionized water.

10. The method according to any one of the preceding claims, wherein, The step of coating the APTES-GA surface with the crown ether ionophore includes diluting the crown ether compound in methanol.

11. The method according to any one of the preceding claims, wherein, Treat the surface with a 2% (v / v) APTES solution diluted in ethanol and a 0.1% (v / v) GA solution in deionized water.

12. An optical sensor for detecting ions in a sample, comprising a resonant structure having a functionalized ionophore layer prepared from a crown ether compound, wherein when a target ion contacts the functionalized ionophore layer, its material index changes due to the absorption of the target ion, thus enabling the determination of the concentration of the target ion in the sample.

13. The optical sensor according to claim 12, wherein, The resonant structure further includes a waveguide to form a sensing arm coated with the functionalized ionophore layer and a reference arm including a barrier coating on the functionalized ionophore layer.

14. The optical sensor according to claim 13, wherein, The channel width of the waveguide is in the range of 15 to 1000 nm, and the length is in the range of 200 μm to 1 cm.

15. The optical sensor according to claim 13, wherein, A light source is configured to emit light of at least one wavelength; after a predetermined exposure time, the light of the at least one wavelength is guided through the waveguide pair, thereby generating a corresponding pattern, and the corresponding pattern can be compared to determine the concentration of the target ion.

16. The optical sensor according to claim 15, wherein, The light source emits light in the wavelength range of 1500 to 1600 nm.

17. The optical sensor according to any one of claims 12-16, wherein, The concentration of the detected ion in the sample is obtained based on the measurement of the shift of the resonant wavelength over time.

18. The optical sensor according to claim 12, wherein, The exposure time for detecting ions is 20 seconds or more.

19. The optical sensor according to claim 12, wherein, The sensor further includes a spectral interrogator for detecting and measuring ion concentration.

20. The sensor according to claim 12, wherein, The target ion is K + .

21. The sensor according to claim 12, wherein, The crown ether ionophore layer includes carboxy-benzo-18-crown-6 and 4-aminobenzo-18-crown-6.

22. The sensor according to any one of claims 12-21, wherein, Based on the measurement of the shift of the resonant wavelength over time, the concentration of the detected ion in the sample is obtained.

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