WO2022173426A1 - Capteur chimique basé sur la fluorescence - Google Patents
Capteur chimique basé sur la fluorescence Download PDFInfo
- Publication number
- WO2022173426A1 WO2022173426A1 PCT/US2021/017437 US2021017437W WO2022173426A1 WO 2022173426 A1 WO2022173426 A1 WO 2022173426A1 US 2021017437 W US2021017437 W US 2021017437W WO 2022173426 A1 WO2022173426 A1 WO 2022173426A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- chemosensor
- ammonia
- microparticles
- network
- analyte
- Prior art date
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- 229910052720 vanadium Inorganic materials 0.000 description 1
- GPPXJZIENCGNKB-UHFFFAOYSA-N vanadium Chemical compound [V]#[V] GPPXJZIENCGNKB-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000002982 water resistant material Substances 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
- G01N33/582—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with fluorescent label
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/84—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving inorganic compounds or pH
Definitions
- the present disclosure relates to a fluorescence-based chemosensor, specifically real time analyte chemosensor in an aqueous medium such as real-time ammonia chemosensor, and a method of using the same.
- a fluorescence-based chemosensor includes a cross-linked polymer network, a plurality of microparticles embedded within the network and including at least one chemo sensing molecule, having a fluorophore, configured to react with an analyte, a surfactant including reverse micelles enveloping the plurality of microparticles, and a mixture of a buffer and a solvent concentrated within the reverse micelles.
- Each one of the reverse micelles may include a core and the core includes one of the plurality of microparticles.
- Each one of the reverse micelles may include a core and the core includes the mixture of the buffer and the solvent.
- the chemo sensing molecule may include a portion configured to react with ELfl.
- the chemosensor may be a real-time chemosensor.
- the network may be hydrophobic.
- the analyte may be ammonia. [0004] In another embodiment, an ammonia chemosensor is disclosed.
- the ammonia chemosensor includes a hydrophobic network forming a matrix housing a plurality of microparticles, a plurality of chemo sensing molecules, attached to the microparticles, configured to react with ammonia, a surfactant system including a plurality of reverse micelles, each reverse micelle having a hydrophilic core enclosing one of the plurality of microparticles, and a buffer system enclosed within the core of the reverse micelles.
- the chemo sensing molecules may include fluorophores.
- the surfactant system may include one or more non-ionic surfactants.
- the matrix may be hydrophobic.
- the hydrophobic network may be cross-linked.
- the ammonia chemosensor may be included in a multi-layer film.
- an ammonia chemosensor in yet another embodiment, includes a hydrophobic portion including a network, a plurality of microparticles embedded in the network, the microparticles having chemo sensing molecules configured to react with ammonia and re-emit light after the reaction with ammonia upon light excitation, and a plurality of reverse micelles with hydrophilic cores, the cores holding the plurality of microparticles and a solvent configured to chemically tune a dissociation constant of NHC.
- the ammonia chemosensor may further include a buffer.
- the reverse micelles may include one or more non-ionic surfactants.
- the network may be a multi-layered network.
- the network may be cross-linked.
- the microparticles may be spherical.
- the ammonia chemosensor may be included in a multi-layer film.
- FIG. 1 is a schematic depiction of the photoinduced electron transfer (PET) mechanism utilized in chemosensors
- Figure 2 is a combined graph typically used to predict unknown concentrations of the ion/analyte in an aqueous environment by measuring the fluorescence from a chemosensor;
- Figure 3A is a schematic depiction of a chemosensor structure including a matrix network with embedded microparticles and a surfactant system disclosed herein;
- Figure 3B shows a detailed view of a section of the chemosensor of Figure 3 A;
- Figure 3C shows a detailed view of the microparticle with the surfactant system of
- Figure 3D shows a non-limiting example of a chemo sensing molecule of the chemosensor disclosed herein;
- Figure 4 shows a non-limiting example of the chemosensor disclosed herein incorporated into a chemo sensing structure including multiple layers;
- Figure 5 displays a graph showing results of a real-time titration experiment using sea water as the aqueous medium, ammonia as the analyte, and the chemosensor disclosed herein to identify the analyte in the medium;
- Figure 6 shows a non-limiting example of an optical analytical system employing the chemosensor disclosed herein;
- Figure 7 shows another non-limiting example of the optical system having the chemosensor disclosed herein;
- Figure 8 shows a device using the optical and electrical system with the chemosensor disclosed herein.
- Figure 9 shows an exploded view of the compartment housing the chemosensor within the device shown in Figure 8.
- the term “substantially,” “generally,” or “about” means that the amount or value in question may be the specific value designated or some other value in its neighborhood. Generally, the term “about” denoting a certain value is intended to denote a range within ⁇ 5% of the value. As one example, the phrase “about 100” denotes a range of 100 ⁇ 5, i.e. the range from 95 to 105. Generally, when the term “about” is used, it can be expected that similar results or effects according to the disclosure can be obtained within a range of ⁇ 5% of the indicated value.
- the term “substantially” may modify a value or relative characteristic disclosed or claimed in the present disclosure. In such instances, “substantially” may signify that the value or relative characteristic it modifies is within ⁇ 0%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5% or 10% of the value or relative characteristic.
- integer ranges explicitly include all intervening integers.
- the integer range 1-10 explicitly includes 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10.
- the range 1 to 100 includes 1, 2, 3, 4. . . . 97, 98, 99, 100.
- intervening numbers that are increments of the difference between the upper limit and the lower limit divided by 10 can be taken as alternative upper or lower limits. For example, if the range is 1.1. to 2.1 the following numbers 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, and 2.0 can be selected as lower or upper limits.
- concentrations, temperature, and reaction conditions e.g., pressure, pH, flow rates, etc.
- concentrations, temperature, and reaction conditions can be practiced with plus or minus 30 percent of the values indicated rounded to or truncated to two significant figures of the value provided in the examples.
- concentrations, temperature, and reaction conditions e.g., pressure, pH, flow rates, etc.
- concentrations, temperature, and reaction conditions can be practiced with plus or minus 10 percent of the values indicated rounded to or truncated to two significant figures of the value provided in the examples.
- values of the subscripts can be plus or minus 50 percent of the values indicated rounded to or truncated to two significant figures. For example, if CH2O is indicated, a compound of formula C(o.8-i.2)H(i.6-2.4)0(o.8-i.2). In a refinement, values of the subscripts can be plus or minus 30 percent of the values indicated rounded to or truncated to two significant figures. In still another refinement, values of the subscripts can be plus or minus 20 percent of the values indicated rounded to or truncated to two significant figures.
- the term “and/or” means that either all or only one of the elements of said group may be present.
- a and/or B means “only A, or only B, or both A and B”. In the case of “only A,” the term also covers the possibility that B is absent, i.e. “only A, but not B”.
- the term “one or more” means “at least one” and the term “at least one” means “one or more.”
- the terms “one or more” and “at least one” include “plurality” as a subset.
- the description of a group or class of materials as suitable for a given purpose in connection with one or more embodiments implies that mixtures of any two or more of the members of the group or class are suitable. Description of constituents in chemical terms refers to the constituents at the time of addition to any combination specified in the description, and does not necessarily preclude chemical interactions among constituents of the mixture once mixed.
- Ammonia is a nutritious, inorganic nitrogen compound that is found naturally in the air, soil, water, and living tissues. But ammonia may require regular monitoring. This is related to toxicity of ME in water adversely affecting living organisms. An increased level of ammonia in waste and reprocessed water is also of importance as it directly affects the yield of water treatment process efficiency. In sea water for aquaculture, ammonia directly affects the health and yield of the farm organisms. An improper level of ME can affect the entire aquaculture pond, potentially damaging the entire crop. In fresh water sources, e.g. in agriculture, over-fertilization increases the levels of ME, resulting in ground water pollution. It is also important to monitor the level of ME in drinking water due to health reasons. Hence, detection of ME is important in any type of water in various environments.
- ME detection in any aqueous media has been technically challenging. This is due to the presence of both ME and ME + forms in water.
- the chemical equilibrium of concentrations of ME and ME + depends mainly on different factors, including temperature, pH, and salinity of the aqueous medium NH3 and NH4 + may be present in.
- An ionized form of ammonia is not harmful, but it is difficult to separate NH4 + from NH3 during detection in water using conventional approaches.
- Ion sensing techniques have been employed in detecting ions in a fluid medium (e.g . water).
- a fluid medium e.g . water
- fluorescence-based detection methods have been utilized to sense ions, including heavy metal ions in water, where an ion binds to a detecting molecule (e.g. a chemosensor) to either generate or quench fluorescence. Measuring the fluorescence can subsequently determine concentration of the ion in the water.
- the conventional fluorescence-based detection methods may exhibit different sensitivities toward the sensing of different ions. Therefore, to accurately detect the presence of a target ion in a fluid medium, a detecting molecule needs to selectively bind to the target ion with a high sensitivity. The difficulty associated with separation of NH + from NFb during detection thus leads to difficulty during sensing as the NFLri may bind to the detecting molecule instead of the desired MB or vice versa.
- a receptor-spacer-fluorophore type of sensor may be used to identify ions/analytes.
- Such sensor may utilize photoinduced electron transfer (PET).
- PET photoinduced electron transfer
- An example chemosensor and the PET principle are shown in Fig. 1.
- the chemosensor 10 may include fluorophore 12.
- the fluorophore 12 is covalently linked to an ion/analyte receptor 14 via a non-conjugating spacer group 16.
- the unbound receptor 14 has a higher energy than the excited fluorophore 12. This energy difference, among other factors, drives rapid electron transfer from the receptor 14 to the excited-state fluorophore 12, thus quenching the fluorescence.
- the energy level of the receptor’s electron pair is lower than that of the excited fluorophore 12; the electron transfer is not energetically favoured, and thus, fluorescence is “switched on.”
- the change in the fluorescence intensity with respect to the ion/analyte concentration may be utilized to create a master curve, example of which is shown in Fig. 2, which may be used to predict unknown concentrations of the ion/analyte in the aqueous environment by measuring the fluorescence from the sensor.
- chemosensors have been used to realise a low cost, highly sensitive (ion concentration in ppm range), in-line, real-time sensors for water quality monitoring.
- atypical chemosensor design uses a hydrophilic cross-linked polymer matrix or hydrogel to contain the chemo sensing molecules. This not only facilitates PET effect essential for sensing, but also ensures smooth exchange of ions/analytes from water onto the sensor.
- sea water is a complex media with very high concentrations of interfering ions such as calcium (Ca), magnesium (Mg), potassium (K), and/or sodium (Na) ions.
- concentrations may be about 100-10000 ppm depending on the water source. Any specific chemo sensing reaction in the presence of such high concentrations of the interfering ions in less likely to happen.
- This system may be also susceptible to sensor hysteresis, where the sensor performance is not reliable.
- a chemosensor overcoming one or more drawbacks listed above is disclosed.
- the chemosensor is a chemical sensor.
- the chemosensor is arranged, designed, and/or configured to detect ammonia, NFb, in an aqueous environment including complex aqueous media.
- the aqueous environment/complex aqueous media may be fresh water, brackish water, sea water, recycled water, reservoir water, wastewater in a water treatment facility or other processing facility such as a meat packing plant, bodily fluid, animal fluid, blood, or the like.
- the chemosensor 100 may include a hydrophobic portion and a hydrophilic portion.
- the chemosensor may include a hydrophobic matrix or network 102.
- the matrix 102 may be a cross-linked matrix.
- the matrix 102 is a selective matrix.
- the matrix 102 is configured to allow entry of, entrap, enrich, and/or capture NFb species only, while rejecting entry of other hydrophilic species.
- the matrix 102 is configured to entrap the analyte, sensing molecules, or molecules to be detected, such as NFb.
- the matrix or network 102 is also configured to prevent influx or entry of other compounds such as any other compounds besides the analyte of interest.
- the matrix or network 102 is configured or structured to prevent entry of any non-ammonia species or compounds into the network 102.
- the matrix or network 102 may be configured to prevent influx of a sample matrix, that is any other compound besides the analyte in an aqueous sample.
- the matrix or network 102 may be configured to prevent influx or entry of interfering ions such as Ca, K, Na, or Mg.
- the matrix 102 further prevents entry of NFF until the NFF is deprotonated. When NFF is deprotonated, the matrix 102 is configured to accept NFb.
- the matrix or network 102 includes hydrophobic material.
- the matrix 102 may include cross-linked hydrophobic polymer(s).
- a non-limiting example hydrophobic material may include siloxane-based polymers such as polydimethoxy siloxane, silicone, polybutadiene, polyisoprene, the like, or a combination thereof.
- the matrix 102 may be a silicone cross-linked matrix.
- the matrix 102 may form or include a cross-linked network 103.
- the network 103 may include interconnected portions forming gaps 105 between the cross-linked material.
- the network 103 may form a single layer or be multi-layered.
- the gaps 105 between individual branches of the network may have the same or different dimensions.
- the gaps 105 may house other components of the chemosensor 100 such as microparticles 104, chemo sensing molecules 106, surfactant system 108, buffer system 114, co-solvent(s) 118, or a combination thereof.
- the chemosensor 100 includes microparticles 104 with the chemo sensing molecule
- the microparticles 104 may be arranged within the matrix 102, in the gaps 105, or both.
- the microparticles 104 have a smaller diameter than the gaps 105.
- the microparticles 104 may have the same or different size and/or shape.
- the microparticles 104 may have a regular, irregular, spherical, or another shape.
- the microparticles 104 may include the same or different material.
- the microparticles 104 may include a mixture of different microparticles.
- the microparticles 104 may include materials such as polymers, silica, cellulose, metal-organic frameworks, the like, or a combination thereof.
- the chemo sensing molecule 106 may include a fluorophore binding site, a fluorophore, a spacer, a receptor, a sidechain, or a combination thereof.
- the chemo sensing molecule 106/fluorophore may include two or more combined aromatic groups or planar or cyclic molecules with several p bonds.
- the chemo sensing molecule 106 may include and/or the fluorophore may be anthracene, benzene, carbazole, diphenylfurane, naphthalene, 1,8 naphthalimide, porphyrin, and/or pyrene.
- the fluorophore is a fluorescent compound configured to re-emit light upon light excitation.
- the spacer may include a secondary amine adjacent to the fluorophore, a hydrocarbon chain, and/or one or more organic rings.
- the sidechain may be optional.
- the sidechain may include one or more ether groups.
- the receptor may include one or more binding sites for the analyte, one or more ether groups, and/or amine groups.
- the receptor may form a crown-like structure.
- the chemo sensing molecule may utilize the PET principle described above. A schematic depiction of the chemo sensing molecule is shown in Fig. 3D while interacting with NFLri.
- the chemo sensing molecule 106 may be coated onto the surface of the microparticles
- the chemo sensing molecule 106 may be applied and/or covalently linked or bonded onto to the microparticles 104.
- the chemo sensing molecule 106 may be attached to at least a portion, a portion, or the entire surface of at least some of or all of the microparticles 104.
- the chemo sensing molecule 106 may be intermixed with the material the microparticles 104 are made from such that the chemo sensing molecule 106 is on the surface and/or in the interior of the microparticles 104.
- the chemosensor 100 further includes a surfactant system 108.
- the surfactant system 108 The surfactant system
- Non-ionic surfactants include a hydrophilic head group 110 and a hydrophobic tail 112.
- Non-ionic surfactants are neutral, do not carry an electric charge on their tails.
- the molecules combine together to form structures called micelles.
- the micelle forms in a hydrophobic macro-environment, the surfactant heads position themselves in such a way that they are exposed to water while the tails are grouped together in the center of the structure protected from water.
- the chemosensor 100 includes inverse or reverse micelles as part of the non-ionic surfactant system 108.
- Reverse micelles are thermodynamically stable assemblies of surfactant molecules organized around a hydrophilic core of water or dissolved solute that spontaneously form optically transparent solutions in low polarity liquids.
- Reverse micelles are micelles in which the nonpolar and polar phases have reversed their roles and the orientation of surfactant molecules are inverted so that the head groups 110 point into the enclosed volume containing the polar phase.
- the non-ionic based surfactant system 108 is configured to have stable reverse micelle structures due to its chemical synergy with the matrix or network 102.
- Non-limiting examples of the surfactant may include TritonTM (nonionic surfactant that has a hydrophilic polyethylene oxide chain and an aromatic hydrocarbon lipophilic or hydrophobic group), Polysorbate 20 (polyoxyethylene (20) sorbitan monolaurate), silicone-based surfactants, the like, or a combination thereof.
- TritonTM nonionic surfactant that has a hydrophilic polyethylene oxide chain and an aromatic hydrocarbon lipophilic or hydrophobic group
- Polysorbate 20 polyoxyethylene (20) sorbitan monolaurate
- silicone-based surfactants the like, or a combination thereof.
- the chemosensor 100 may optionally include a buffer or a buffer system 114.
- the micelles of the non-ionic surfactant have hydrophilic cores 116.
- the cores 116 may include a buffer. All of the cores, or just a portion of the cores, may include the buffer.
- the buffer may include one compound, a system of compounds, or a mixture of compounds.
- the buffer may have a relatively low concentration of about a few nM such as 0.5 to 2 nM or 1 nM.
- the buffer provides conductive environment for the ehemo sensing.
- the core is configured for a high pH of about 8 to 9 and low buffer capacity condition of about 1 to 10 nM by using the appropriate buffer arranged to assist protonation of incoming NH3 into NH4 + and back to NH3 when desired.
- the buffer may be arranged to keep the pH of the hydrophilic system close to pKa of
- the buffer helps maintain chemical dynamic equilibrium between NH4 + inside micelles and NH3 outside in the hydrophobic matrix phase.
- Non-limiting examples of the buffer may include Tris buffer
- the chemosensor 100 may optionally include a compound configured to tune the dissociation constant K d of H4 + binding at lower or higher concentration range.
- the compound may be a solvent, herein also referred to as a co-solvent.
- co-solvent is being used because the media or sample to be tested includes water, which is a solvent. The term co-solvent thus distinguishes between the water included in the tested media/sample and the compound configured to tune the dissociation constant. Since the tested medium is an aqueous medium, the aqueous medium may enclose the chemosensor when the chemosensor is submerged or otherwise put in contact with the medium. The medium may intermix with one or more liquid portions of the chemosensor.
- the co-solvent 118 may be present in the core(s) of the reverse micelles of the non ionic surfactant.
- the co-solvent may be configured to tune the dissociation constant of MTi + binding at lower or higher concentration range.
- the co-solvent thus chemically tunes the dissociation constant, Kd, which controls the binding energy between the analyte (NH3) and the binding site of the chemosensor.
- the co-solvent thus chemically tunes the overall sensitivity range of an analyte detection.
- the dissociation constant K d is related to the binding energy by the relationship:
- Kd coe AG/kT , [0063] where co is the standard reference concentration (1 molar),
- kT is the temperature in energy units.
- the binding free energy equals the free energy of the bound state minus the free energy of the unbound (solvated) state. Because of the ion charge, the solvation energy strongly depends on the solvent dielectric properties, i.e. the electrostatic interaction between the solvent and the charged ion. This changes with the co-solvent, allowing the co-solvent(s) to be used as a tuning knob for the binding energy and thus the sensitivity.
- a non-limiting example of the co-solvent(s) may include glycerol, ethylene glycol, sucrose, polyacrylic acid, polyvinyl alcohol, the like, or a combination thereof.
- the chemosensor may include a mixture of the buffer system and the co-solvent(s). In another embodiment, the chemosensor may be free of the buffer system, but include the co-solvent(s). In another embodiment, the chemosensor may be free of the co-solvent(s), but include the buffer system. In yet another embodiment, the chemosensor may be free of the buffer system and the co- solvents).
- the herein-disclosed chemosensor may include both the buffer and the co-solvent(s).
- the buffer and the co-solvent(s) may form a mixture.
- the resultant chemosensor is configured to facilitate 1) hydrophilic environment required for PET effect and thus chemo sensing, 2) dynamic equilibrium condition between NEE and NH + , and/or 3) tuning of the measurement range of NEE detection as per requirement without changing basic chemical architecture of NEE + -specific chemosensor molecule.
- the reverse micelles may enclose the microparticles 104. All, some, or at least one of the microparticles 104 may be enclosed by or trapped in a reverse micelle of the surfactant system 108.
- the surfactant reverse micelle heads may be oriented towards the core 116 including the microparticle 104.
- the matrix 102 may form a base for the microparticles 104, and the surfactant system 108 may envelop, surround, or enclose the individual microparticles 104 within the matrix 102.
- the MP from the tested medium encounters the chemosensor structure, enters the reverse micelle, gets protonated into NTri, and reacts with the chemo sensing molecule 106 present on the microparticle 104. Fluorescence of the chemo sensing molecule 106, caused by the interaction of the chemo sensing molecule 106 with the analyte, then indicates presence of NFb in the tested medium, upon light excitation.
- the chemosensor 102 interacts with the tested media, named herein such as sea water, wastewater, blood, etc .
- the chemosensor 102 may include water as a solvent present in the tested media.
- the chemosensor 102 may be incorporated within a more complex structure.
- a non limiting example of the structure 150 is shown in Fig. 4.
- the chemosensor 102 may be a part of a multi-layer structure or film 150.
- the chemosensor 102 may form a top layer 120 which is adhered to a transparent substrate 122. Adhesion may be provided via an adhesive layer 124.
- the chemosensor 102 may include a layer having a black tint such as carbon black to prevent incidences of random, unexpected sensor-light interaction coming from ambient light.
- the ammonium may be removed from the reverse micelle environment through chemical dynamic equilibrium by adjusting the concentration of NFb inside the micelle and outside, within the hydrophobic matrix phase to reset the chemosensor 100.
- a desired reset may be also accomplished by applying a pH increase to drive the MTi + -> MP + H + reaction.
- the pH increase may be applied through an electrochemical component such as by applying a voltage, injecting a buffer solution, or adding other solutes.
- the chemosensor described herein may be prepared by the following method.
- the microparticles with the covalently linked chemosensor molecules may be added into a container such as a glass bottle, followed by an optional addition of the co-solvent(s) and/or the buffer system.
- the mixture may be stirred well with a stirrer such as a magnetic stirrer for a first time period.
- the first time period may be, for example, about 15 minutes to 1 hour, 20 minutes to 45 minutes, or 30 to 40 minutes.
- the mixing may be followed by addition of hydrophobic matrix phase precursor to the solution and continued stirring of the suspension for a second time period.
- the second time period may be about 30 minutes to 5 hours, 1 hour to 4 hours, or 2 to 3 hours.
- the non-ionic surfactant system may be added.
- the addition may be accomplished, for example, by dissolving the surfactant(s) in a small amount of an organic compound such as ethyl acetate.
- the mixture or dispersion including the solvent may be stirred for a third time period.
- the third time period may be about 5 to 30 minutes, 10 to 25 minutes, or 15 to 20 minutes.
- a cross-linker and a small amount of inhibitor may be added.
- the dispersion may be stirred for a fourth time period.
- the fourth time period may be about 30 minutes to 3 hours, 45 minutes to 2 hours, or 1 to 1.5 hours.
- a catalyst may be added, and the mixture may be stirred for a fifth time period.
- the fifth time period may be about 2 to 10 minutes, 5 to 7 minutes, or 3 to 6 minutes.
- the dispersion may be cast onto a film to form a chemosensor layer.
- the film may be a transparent film such as a transparent PET layer.
- the casting may be performed with a knife coater or another suitable tool.
- the fabricated chemosensor layer may be stored for a sixth time period to achieve complete or substantially complete polymerization of the matrix phase.
- the sixth time period may be, for example, about 6 to 18 hours, 10 to 15 hours, or 12 to 14 hours.
- the storing may be provided under ambient conditions such as ambient temperature and humidity.
- chemosensor Among the advantages of the herein-described chemosensor is the ability of real-time measurement. “Real-time” relates to the capability of measurement or analysis which takes place and the results are available virtually immediately or in a very short period of time after the measurement or analysis takes place. A real-time sensor, device, or system, described herein, has the advantage of providing results at the measurement location in a very short period of time. Real-time may relate to several second to several minutes.
- typical crown ether-based sensor molecules without the presence of co- solvents would typically engage in binding reaction in the range of about 50-100 ppm MTf due to Kd of 80 ppm of the sensor molecule.
- the herein-disclosed chemosensor facilitates hydrophilic environment that is essential for PET effect and ensures shifting of measurement range down to about 0-5 ppm without structural changes to the chemo sensing molecule. The resulting measurement range is thus much lower.
- chemosensor 100 While the chemosensor 100 described herein has been focused on detection of ammonia, the principles of the chemosensor 100 may be applied to different analytes of interest.
- the chemosensor including the hydrophobic matrix 102 housing the microparticles 104 including the sensing molecule 106, further including the surfactant system 108, and optionally the buffer system 114 and/or co-solvent 118 may be applicable for detection, measuring, and/or monitoring of various analytes in the media described herein.
- the chemistry of the chemosensor 100, or its portions, may differ from that described herein based on the type of aqueous media, sample, analyte.
- Non-limiting example analytes to be detected by the chemosensor described herein may include toxic ions such as Pb, As, Cd, Cr; ions that create “hard water” such as Mg and Ca; sulphuric compounds such as EES and H2SO4; carbonic compounds such as CO2 and formic acid (HCOOH).
- toxic ions such as Pb, As, Cd, Cr
- ions that create “hard water” such as Mg and Ca
- sulphuric compounds such as EES and H2SO4
- carbonic compounds such as CO2 and formic acid (HCOOH).
- the analyte may be a part of an aqueous media or an aqueous sample.
- sample is used broadly including a small quantity intended to show what the whole of a tested medium is like as well as a larger volume of the tested medium.
- the sample includes the analyte and the remainder of the sample also called a sample matrix.
- the chemosensor disclosed herein is configured or structured to allow access of the analyte to the chemosensing molecules, but prevent entry of the sample matrix to the chemosensing molecules.
- samples including the analyte of interest may differ from one another due to the environment the samples come from.
- individual samples may differ from one another by their biological, biochemical, chemical, and/or physical properties such as pH, temperature, alkalinity, suspended solids, salinity, dissolved gasses, etc.
- the analyte may be an aquacultural analyte or an analyte present in an aquacultural sample.
- the analyte is to be detected by an aquacultural fluorescence-based chemosensor described herein.
- the aquacultural sample may originate from an aquacultural environment or media such as aquafarming of fish, crustaceans, molluscs, or the like.
- the aquacultural sample may contain biological, biochemical, chemical, and/or physical portions typical for the aquacultural farming.
- the biological portion may include presence of plankton, fish waste, uneaten food.
- the chemical portion may include pH between about 6.5 and 9.0 if the aquacultural site is healthy or a different pH if the site pH needs to be improved, dissolved gasses such as oxygen, carbon dioxide, nitrogen, ammonia, dissolved oxygen of at least 5 ppm, content of CO2 of about 0 ppm to 5-15 ppm for healthy aquafarming.
- the physical portion may include clay particles as suspended solids, or the like.
- the analyte may be a farming environment analyte or an analyte in a farming environment sample.
- the farming environment sample may be a sample originating from an aqueous media at a farm location.
- the farming environment sample may be a sample from an agricultural runoff or a sample from a water source used as a drinking water for the animals at the farm.
- the farm may be a location cultivating livestock such as cattle, sheep, horses, goats, poultry such as chickens, geese, ducks, turkeys, pigs, horses, or other animals.
- the farming environment sample may contain biological, biochemical, chemical, and/or physical portions typical for farming on land including agricultural contaminants.
- the agricultural contaminants may include nutrients such as nitrogen, phosphorus, pesticides, herbicides, insecticides, fungicides, ammonia, bacteria, and the like.
- the analyte may be a manufacturing analyte or an analyte present in a manufacturing sample.
- the manufacturing sample may include biological, biochemical, chemical, and/or physical portion typical for a specific manufacturing process conducted at a facility such as a factory.
- An example facility may be a meat packing plant or a slaughterhouse.
- the contaminants may include nitrate, nitrite, ammonia, fecal coliform, biproducts of the disinfection processes such as chlorine, etc.
- the analyte may be a wastewater analyte or an analyte present in a wastewater sample.
- the wastewater sample may be an industrial or domestic wastewater sample.
- the wastewater sample may include biological, biochemical, chemical, and/or physical portion typical for wastewater including, but not limited to, organic substances and sulphide compounds.
- a wastewater sample from petroleum industry may include petroleum, fuel oil, etc.
- a wastewater sample from chemical plants may include carbonates, hydroxides, sand, organic compounds, salts of acids such as sulfuric acid or hydrochloric acid.
- a wastewater sample may originate from washing of equipment or surfaces and include acids, ammonia, fluorides, nitrites, methenamine, sulphates, arsenic, vanadium, etc.
- the analyte may be a drinking water analyte or an analyte present in a drinking water sample.
- the drinking water sample may include a fresh water or reservoir water sample for human or animal consumption.
- the drinking water sample may include biological, biochemical, chemical, and/or physical portion typical for drinking water such as microbes, toxins produced by bacteria, nitrogen, salts, ammonia, pesticides, metals, drug components, etc.
- the analyte may be a bodily fluid analyte or an analyte present in a bodily fluid.
- An example bodily fluid sample may be blood, plasma, urine, sweat, saliva, mucus, etc.
- the bodily fluid sample may originate in a human or an animal.
- the bodily fluid sample may include biological, biochemical, chemical, and/or physical portion typical for individual bodily fluid, including water, salts, protein such as enzymes like amylase, ammonia, sugars, urea, uric acid, red blood cells, white blood cells, platelets, electrolytes such as potassium, phosphorus, etc.
- the analyte may be an aqueous analyte from an aqueous media to be reprocessed or which was reprocessed or converted for further use or an analyte from a sample including the same.
- the reprocessing sample may include a recycled water sample, brackish water sample, or sea water sample.
- the chemosensor may be used for indication of ammonia, measuring of NTk/NTfri content, and/or monitoring in various environments.
- the chemosensor may be used for real-time indication of ammonia in various aqueous media including fresh water, brackish water, sea water, recycled water, reservoir water, wastewater in a water treatment facility or processing facility, bodily fluid, animal fluid, blood, or the like.
- the chemosensor may be used in aquaculture such as farming of fish such as salmon, trout, crustaceans such as shrimp, lobster, crabs, crayfish, molluscs such as clams, oysters, mussels, scallops, the like, or a combination thereof.
- Aquaculture involves cultivating freshwater and saltwater populations under controlled conditions, and can be contrasted with commercial fishing, which is the harvesting of wild fish.
- the chemosensor may be used for indication and/or monitoring of the aquatic health of a reservoir.
- the chemosensor may be also used for detection of ammonia in drinking water, wastewater, treatment water, sewage, household wastewater, municipal water sources.
- the chemosensor may be used in agriculture such as animal farming.
- the chemosensor may be used in industrial environments such as chemical plants, farm animal processing plants, or the like.
- the chemosensor 100 may be incorporated into a device configured to detect the analyte.
- the device may be an optical device or optical system.
- optical systems designed to identify analytes include complicated arrangements, but are faced with many drawbacks. For example, many optical systems struggle with providing and preserving a sufficient amount of light, a strong enough signal for detection, and loss of sensitivity.
- optical chemosensor systems for example utilizing fluorescence.
- a fluorescence-based sensing of an analyte requires a minimum irradiance with a maximum signal which is as strong and non-noisy as possible. If the irradiance of the input light is too strong, it contributes to degradation of the chemosensor. The irradiance may photobleach the molecules by creating unwanted side reactions that damage the ability of the molecules to fluoresce. Additionally, hydrolysis or chemical stress may cause a failure resulting in degradation of the sensor phase from the film.
- the sensor molecules or microparticles may detach from the sensing layer, reducing overall concentration of the sensing molecules in the light path and decreasing the output signal and damaging the calibration.
- Some of the optical systems try to overcome drawbacks by introducing signal strengthening items such as fiber optic cables for signal multiplication. Other systems may incorporate multiple detectors. Some of the systems also implement waveguides for light transmission. All of these items make the traditional systems more complex, expensive, and sensitive to transportation. As a result, the optical systems are quite large in dimensions and traditionally stationary.
- an analytical optical detection system may be designed as a portable or point-of-use system.
- the terms portable and point-of-use relate to the system which is not bound to a single location such as a laboratory, a system which does not need to be secured to a table or another working surface in a laboratory, building, or a vehicle, a system which may be carried to a testing site and used at the site.
- the portable or point-of-use system may be easily transported from one location to another.
- the portability makes the system suitable for various applications and locations. The portability further allows faster and more economical analyses than traditional systems because an analysis may be conducted at the location where results are needed instead of transportation of samples to a lab.
- the portable system is designed to analyze one or more analytes.
- An example analyte may include ammonia.
- Other analytes, especially those named above, are contemplated.
- the system may thus be an ammonia analytical system.
- Non-limiting examples of the system 200, 200’ are shown in Figs. 6 and 7.
- the system 200, 200’ may be incorporated into a device, non-limiting example of which is shown in Figs. 8 and 9.
- the optical system and sensing device disclosed herein may include structural differences to reflect the environment the optical system and sensing device would be used in.
- the housing for the aquacultural chemosensor and sensing device for the aquacultural environment/analyte would be made to withstand the aquacultural environment.
- An example of such features may include a water-proof, anti-corrosive housing, and/or seals, gaskets preventing seawater ingress into the optical system.
- the optical system 200 includes a source of light 202.
- the light source 202 may be an LED such as a blue LED, laser, modulatable lamp, or modulatable light device.
- the light source 202 may be a modulated LED light source 202.
- the light source 202 may be a direct optical modulator.
- the light source 202 emits light having a wavelength depending on or in response to the excitation wavelength of the chemosensor included in the system 200.
- a non-limiting example wavelength may be about 450 to 490, 460 to 480, or 470 to 475 nm. Other wavelengths are contemplated.
- the wavelength emitted by the light source 202 may be a first wavelength.
- the light source 202 may be a monochromatic light source.
- the light source 202 may be an excitation source.
- the light source 202 is modulated at a certain frequency (f m ) which causes intensity of the excitation light to be modulated.
- the modulated excitation intensity gives rise to emissions at the chemosensor that are modulated at the same frequency (fm).
- the modulated light source 202 generates a beam of light carried over free space. The light is thus not propagated through an optical waveguide such as optical fibres.
- the system 200 further includes a lens 204.
- the lens 204 may be a collimating lens or a collimator. Collimating is the process of accurately aligning light or particles in a parallel fashion. A collimating lens 204 may ensure that the incoming light has minimal spread as it propagates.
- the lens 204 may be an aspheric condenser lens.
- the lens 204 may include a diffuser.
- the lens 204 is configured to collimate and/or diffuse the light from the light source 202.
- the lens 204 collimates the light beam to maximize the beam diameter of the excitation light on the chemosensor included in the system 200.
- the lens 204 is arranged downstream from the light source 202.
- the lens 204 may be located adjacent to the light source 202.
- the system 200 may further include one or more filters.
- the one or more filters may be colored filters.
- An example filter may be a first filter 206.
- the first filter 206 may be an excitation filter.
- the excitation filter 206 may limit the irradiance to the spectroscopic window that causes florescence.
- the filter 206 may be placed downstream from the lens 204 and the light source 202.
- the filter 206 is arranged between the lens 204 and the mirror 208. In one or more embodiments, the filter 206 is omitted.
- the system 200 includes a mirror 208.
- the mirror may be a dichroic mirror.
- the mirror 208 may be a high or long pass dichroic mirror or beam splitter.
- a dichroic mirror allows a light of certain wavelength(s) to pass through while light of other wavelength(s) is reflected.
- the excitation light After passing through the lens 204 and/or the excitation filter 206, the excitation light is directed to the dichroic mirror 208. The light is reflected at an angle downward to the chemosensor 210. The reflection angle may be 45 degrees.
- the chemosensor 210 may be the chemosensor 100 described above and shown in Figs. 3 A-4.
- the chemosensor 210 may be applied onto a film or layer(s).
- the film or layer(s) may include a dark portion, for example including carbon black, or a layer to prevent ambient light from entering the optical system 200.
- the film or layer(s) may allow ingress of water to the chemo sensing portion of the chemosensor 210.
- the chemosensor 210 is in contact with the liquid media to be analyzed.
- the chemosensor 210 reacts with the media, and if the analyte is present in the media, the chemosensor 210 causes fluorescence as the chemo sensing molecule reacts with the analyte.
- the chemosensor 210 may give rise to fluorescence in proportion to the concentration of the analyte in the media.
- Fluorescence generated by the chemosensor has a different wavelength than the excitation light which arrived at the chemosensor via reflection at the mirror 208.
- the excitation wavelength is thus very different from the detection wavelength. Fluorescence is thus not reflected by the dichroic mirror 208, but instead, fluorescence passes through the dichroic mirror 208 as it travels upward and is transmitted through the dichroic mirror 208 into a detection/photodetection portion 212 of the system 200.
- An example detection wavelength may be about 520 to 550 nm, 525 to 545, or 530 to 535 nm. Other wavelengths are contemplated.
- Fluorescence may be a light having a second wavelength. The second wavelength is different from the first wavelength.
- the detection portion 212 may include a second filter 214.
- the second filter 214 may be an emission filter configured to reject any excitation light.
- the second filter 214 may be a detection filter.
- the detection filter may limit the detection of the excitation signal, reduce noise, or both.
- the filter 206 may be located between the mirror 208 and the second lens 216.
- the system 200 includes a second lens 216.
- the lens 216 may be an asymmetric lens.
- the second lens 216 may be a plano-convex lens.
- a plano-convex lens is flat on one side and outward- curved on the other side.
- a plano-convex lens is configured to focus parallel rays of light to a single point.
- the lens 216 may collect the light.
- the lens 216 may focus the fluorescent light onto a photodetector 218.
- the lens 216 is located upstream from the filter 206, the mirror 208, and downstream from the photodetector 218.
- the photodetector 218 is configured to convert light photons into current.
- the photodetector 218 may be a photodiode or a phototransistor.
- the photodiode is a semiconductor device that converts light into an electrical current. The current is generated when photons are absorbed in the photodiode.
- the phototransistor is a semiconductor device configured to sense light levels and alter the current flowing between an emitter and a collector according to the level of light it receives.
- the photodetector 218 may include one or more optical filters, built-in lenses, or the like.
- the system 200 may include a single photodetector 218.
- the system 200’ shown in Fig. 7 may include the same components as the system 200, but further includes an electrical device or an electronic system 220.
- the electrical device 220 may include one or more controllers.
- the electrical device 220 may be a printed circuit board (PCB) 220.
- the electrical device 220 may include one or more microprocessors enabling data processing, signal amplification, a timing circuit, electrical or electronic components, conductive tracks, conductive pads, data register, and/or other parts.
- the electrical device 220 is configured or programmed to control the light source 202, receive input such as detect signal from the photodetector 218 and/or the photodetection portion 212, provide input to one or more portions of the system 200, provide output to another device, or a combination thereof.
- the input the electrical device provides to the light source 202 may include a command to initiate analysis, stop the analysis, initiate excitation of light, stop excitation of light, the like, or a combination thereof.
- the input the electrical device may receive from the photodetector 218 may include a signal.
- the output the electrical device provides may be a number and/or data associated with the analyte, its quantity, or other information related to the analysis.
- the system 200 and/or 200’ may also include one or more additional devices such as a differential amplifier, high pass filter, or the like.
- the additional devices may filter out the DC and low frequency component of light.
- the additional devices may allow only the modulated, high frequency emissions to pass through and be amplified. This ensures that any ambient light or stray light picked up by the photodetector is not amplified. This leads to an improvement in the signal to noise ratio of the fluorescence signal generated by the chemosensor 210.
- the system 200 and/or 200’ may be compatible with various devices and systems.
- the system may be compatible with a computer and include a converter pluggable into one or more devices including a computer.
- the system may be wired or wireless, utilizing communication via Bluetooth, WiFi, Zigby, GSM, RFID, or another form of communication to transmit the signal out of the system 200, 200’.
- the system disclosed herein may be incorporated in a housing.
- a non-limiting example of the housing is schematically shown in Fig. 7.
- An alternative view of the housing is shown in Fig. 8.
- the housing 250, the system 200 and/or 200’, and additional items disclosed herein, may form an analytical or sensing device 300.
- the housing 250 may be compact, allowing for portability of the analytical device 300.
- the housing 250 may be modulated, molded, injected, extruded, 3D-printed, or otherwise formed around one or more components of the device 300.
- the housing 250 is designed to carry, protect, or enclose the optical and electrical components of the device system 200 and/or 200’ and the device 300.
- the housing 250 may have one or more layers.
- the housing 250 may have a first or inner layer 252 enclosing the system 200’, including or excluding the electrical device 220.
- the first layer 252 may form an inner portion or layer of the housing 250.
- the housing 250 may also include an outer layer 254 enclosing all internal components, including the system 200’ having the optical components and the electrical device 220 together.
- the optical components and the electrical device may be mounted or otherwise attached in the housing 250. The attachment may be permanent or temporary, allowing for an exchange of components.
- the outer layer 254 may be waterproof and corrosion resistant.
- the waterproof feature makes the system 200, 200’, and/or device 300 submersible in an aquatic medium.
- the outer layer 254 may be made from a corrosion-resistant and water-resistant material.
- a coating having the desired qualities may be applied onto the outer layer 254.
- a non-limiting example coating may be a hydrophobic coating.
- the outer layer 254 and the housing 250 may be water-resistant according to IP67, referring to the Ingress Protection Code, sometimes referred to as International Protection Code, IEC standard 60529 which classifies and rates the degree of protection provided by mechanical casings and electrical enclosures against intrusion, dust, accidental contact, and water.
- IP67 rating means that the device disclosed herein can be dropped into a body of water up to a meter deep for half an hour without any changes to the function or durability of the device.
- the chemosensor 210 is housed separately.
- the housing 250 is waterproof, protecting the optical and electrical components while the chemosensor 210 has access to the medium to be tested.
- the waterproof feature makes the system 200, 200’, and/or device 300 submersible in an aquatic medium.
- the chemosensor 210 may be placed in a compartment 260.
- the compartment 260 may be a barrel, pocket, cylinder, receptable, vessel, enclosure, or a container attached or attachable to the housing 250.
- the connection between the housing 250 and the compartment 260 is such that the integrity and water-proof quality of the housing and its internal components is not compromised.
- the connection may include one or more sealing components 262 ensuring water-tight seal, for example one or more O-rings, gaskets, or a combination thereof.
- a non-limiting example of the compartment 260 is shown in Fig. 9.
- the compartment 260 may have an upper portion 266 and a lower portion 268.
- the upper portion 266 may be attachable, permanently or temporarily, to the housing 250, and to the lower portion 268.
- the upper portion 266 may house the sealing component(s) 262 and the chemosensor 210.
- the lower portion 268 is attachable to the upper portion 266.
- the lower portion 268 may have an opening and closing mechanism 270 allowing for ingress of the tested medium into the device.
- the mechanism 270 may feature, for example, one or more slidable portions 272.
- the housing 250, the first layer 252, the second layer 254, the compartment 260, or a combination thereof may be made from the same or different material.
- the material may include steel such as stainless steel, plastic such as thermoplastic or thermoset, composite material, ceramic, or a combination thereof.
- the housing 250, the first layer 252, or both may be black in color.
- a lead/plug 222 from the electrical device 220 may extend from the housing 250 to accommodate wires such as a data cable.
- the device and the system disclosed herein may be free from fiber optic cable(s), waveguide(s), secondary detector(s), and/or one or more objective(s) configured to focus the light.
- the system, and thus the device are thus less complex than traditional systems, more economical, and may be incorporated into devices of smaller dimensions than traditional optical analytical systems.
- the device and other devices in which the system may be employed may have such dimensions that the device may be portable and/or handheld.
- the system and the device disclosed herein may be used as an analytical optical instrument for complex media named above in environments named above for identification, monitoring, quantitative and/or qualitative analysis of analytes named herein.
- a method of using the disclosed chemosensor, system, and device may include bringing the chemosensor in contact with the media/sample to be tested. Upon contact with the media/sample, the chemosensor may prevent influx of one or more types of interfering ions. The method may include allowing influx of the analyte to the matrix such that microparticles, embedded in the matrix, carrying the chemo sensing molecules with the surfactant system may react with the analyte, generating fluorescence, upon light excitation.
- the method may include initiating excitation from the light source.
- the method may include passing the light beam via free space.
- the method may include passing the light beam via a lens and/or a first filter.
- the method may include reflecting the light via a mirror such as a dichroic mirror onto the chemosensor.
- the method may also include generating fluorescence via the reaction of the analyte with the chemo sensing molecule.
- the method may include transmitting the fluorescent light via the mirror, a second filter, and a second lens to a photodetector.
- the method may also include converting the light photons in the photodetector into electrical current or signal.
- the method may further include modulating, collimating, reflecting, transmitting, filtering, rejecting, and/or focusing the excitation or fluorescent light, reducing noise via one or more items of the disclosed system, or a combination thereof.
- the method may also include forwarding or transmitting the electrical signal into another device via an electrical device, electronic system, or wirelessly.
- the method may include controlling the optical system and/or the device via the electrical device.
- the method may include controlling or commanding the source of light and/or one or more items of the system and/or device via the electrical device.
- the method may include transmitting the electrical signal wirelessly or via one or more wires into a different device, system, or a database.
- the processes, methods, or algorithms disclosed herein may be deliverable to or implemented by a processing device, controller, or computer, which may include any existing programmable electronic control unit or dedicated electronic control unit.
- the processes, methods, or algorithms may be stored as data and instructions executable by a controller or computer in many forms including, but not limited to, information permanently stored on non-writable storage media such as ROM devices and information alterably stored on writeable storage media such as floppy disks, magnetic tapes, CDs, RAM devices, and other magnetic and optical media.
- the processes, methods, or algorithms may also be implemented in a software executable object.
- the processes, methods, or algorithms may be embodied in whole or in part using suitable hardware components, such as Application Specific Integrated Circuits (ASICs), Field- Programmable Gate Arrays (FPGAs), state machines, controllers or other hardware components or devices, or a combination of hardware, software and firmware components.
- suitable hardware components such as Application Specific Integrated Circuits (ASICs), Field- Programmable Gate Arrays (FPGAs), state machines, controllers or other hardware components or devices, or a combination of hardware, software and firmware components.
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Abstract
Un capteur chimique basé sur la fluorescence comprend un réseau polymère réticulé, une pluralité de microparticules incorporées dans le réseau et comprenant au moins une molécule de détection chimique, comprenant un fluorophore conçu pour réagir avec un analyte, un tensioactif comprenant des micelles inverses enveloppant la pluralité de microparticules, et un mélange d'un tampon et d'un solvant concentré à l'intérieur des micelles inverses.
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PCT/US2021/017437 WO2022173426A1 (fr) | 2021-02-10 | 2021-02-10 | Capteur chimique basé sur la fluorescence |
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Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6521185B1 (en) * | 1995-10-23 | 2003-02-18 | American Research Corporation Of Virginia | Fluorescent probes based on the affinity of a polymer matrix for an analyte of interest |
US20110221425A1 (en) * | 2010-03-09 | 2011-09-15 | Nokia Corporation | Apparatus and associated methods |
US20120135141A1 (en) * | 2007-08-23 | 2012-05-31 | Agency For Science, Technology And Research | Polymerization on particle surface with reverse micelle |
KR20150051249A (ko) * | 2013-11-01 | 2015-05-12 | 한국과학기술원 | 금속 촉매의 전사 방법에 의해 결착된 라즈베리 중공 구조의 금속 산화물 소재, 그 제조방법 및 이를 이용한 고감도 센서 |
US20170373232A1 (en) * | 2016-06-27 | 2017-12-28 | Nanosys, Inc. | Methods for Buffered Coating of Nanostructures |
-
2021
- 2021-02-10 CN CN202180096892.8A patent/CN117178183A/zh active Pending
- 2021-02-10 WO PCT/US2021/017437 patent/WO2022173426A1/fr active Application Filing
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6521185B1 (en) * | 1995-10-23 | 2003-02-18 | American Research Corporation Of Virginia | Fluorescent probes based on the affinity of a polymer matrix for an analyte of interest |
US20120135141A1 (en) * | 2007-08-23 | 2012-05-31 | Agency For Science, Technology And Research | Polymerization on particle surface with reverse micelle |
US20110221425A1 (en) * | 2010-03-09 | 2011-09-15 | Nokia Corporation | Apparatus and associated methods |
KR20150051249A (ko) * | 2013-11-01 | 2015-05-12 | 한국과학기술원 | 금속 촉매의 전사 방법에 의해 결착된 라즈베리 중공 구조의 금속 산화물 소재, 그 제조방법 및 이를 이용한 고감도 센서 |
US20170373232A1 (en) * | 2016-06-27 | 2017-12-28 | Nanosys, Inc. | Methods for Buffered Coating of Nanostructures |
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