Sensor for monitoring arterial blood gas data, preparation method and system

Abstract

The invention provides a sensor for monitoring arterial blood gas data, a preparation method and a system. The functional blocks are adjacently arranged on the base body, and the plurality of functional blocks can be used for detecting pH, O2 and CO2 under the excitation light with the same wavelength; wherein the functional blocks comprise a first functional block and a second functional block; wherein the first functional block is coated with a coating, and the coating can load O2 and a pH fluorescent indicator at the same time. By constructing the first functional block and the second functional block, sensitive detection of multiple biomass is realized, especially the O2 fluorescent indicator and the pH fluorescent indicator can be loaded at the same time through the coating on the first functional block, and the characteristic that the O2 fluorescent indicator and the pH fluorescent indicator have the same polarity is utilized; by arranging the two functional blocks, the detection of three substances can be realized, and the structural complexity of the whole detector is reduced, so that the reliability of the detector is improved.

Description

Technical Field

[0001] The present invention relates to the field of detection technology, and in particular to a sensor for monitoring arterial blood gas data, a preparation method and a system. Background Art

[0002] During the treatment and recovery process of critically ill patients, dedicated analyzers are usually used to display and record relevant blood information in real time during critical care scenarios to improve the timeliness and pertinence of treatment. By monitoring the blood, valuable information about the patient's oxygenation status, gas exchange, acid-base homeostasis, and ventilation can be obtained in real time. Although various bioanalyte sensor technologies have been developed, especially non-invasive real-time blood gas analyzers, such as finger pulse oximeters, CO2 analyzers, and transcutaneous blood gas analyzers, although these instruments have been clinically used for many years, their accuracy is affected by factors such as peripheral microcirculation and vasoactive drugs, and they still cannot completely replace traditional arterial blood gas analysis.

[0003] The biological probe used in the commonly used invasive real-time blood gas analyzer is a tapered fiber probe, which aims to improve the sensitivity of detection by increasing the energy of the excitation light entering the evanescent field. However, the tapered structure of the fiber probe will lead to a mismatch between the mode characteristic parameter V value in the detection area and the transmission area, resulting in the loss of the detection signal. This is especially true in critical care situations. Summary of the invention

[0004] One object of the present invention is to achieve sensitive detection of various biomass by constructing fluorescent nanoprobes, and further the present invention provides a sensor for monitoring arterial blood gas data.

[0005] A further object of the present invention is to provide a method for preparing a sensor for monitoring arterial blood gas data.

[0006] A further object of the present invention is to provide a system for monitoring arterial blood gas data.

[0007] In particular, the present invention provides a sensor for monitoring arterial blood gas data, comprising:

[0008] a substrate; and

[0009] Functional blocks are adjacently arranged on the substrate, and the plurality of functional blocks can detect pH, O2 and CO2 under the excitation light of the same wavelength;

[0010] The functional block includes a first functional block and a second functional block; the first functional block is covered with a coating, and the coating can simultaneously load an O2 fluorescent indicator and a pH fluorescent indicator.

[0011] In particular, the present invention also provides a method for preparing a sensor for monitoring arterial blood gas data, the preparation method comprising:

[0012] providing a substrate;

[0013] Dividing the substrate into adjacent first functional blocks and second functional blocks along a straight line direction;

[0014] A thin film for detecting CO2 is formed in the second functional block of the substrate, and nanoparticles for detecting O2 and pH are formed in the first functional block of the substrate. The first functional block and the second functional block can detect pH, O2 and CO2 under the excitation light of the same wavelength.

[0015] In particular, the present invention also provides a system for monitoring arterial blood gas data, comprising the sensor for monitoring arterial blood gas data.

[0016] In the present invention, sensitive detection of multiple biomasses is achieved by constructing a first functional block and a second functional block. In particular, the coating on the first functional block can simultaneously load an O2 fluorescent indicator and a pH fluorescent indicator, and the O2 fluorescent indicator and the pH fluorescent indicator have the same polarity. The two functional blocks are set to detect three substances, thereby reducing the structural complexity of the entire detector and improving the reliability of the detector.

[0017] In the present invention, the coating is a fluorescent nanoparticle coating with polylysine coated on the surface, that is, a medium is used to simultaneously load the O2 fluorescent indicator and the pH fluorescent indicator. Due to the use of such a mixed arrangement structure, the distribution areas of the O2 fluorescent indicator and the pH fluorescent indicator can be expanded, and the O2 fluorescent indicator and the pH fluorescent indicator can continuously output fluorescent signals, thereby improving the fluorescent brightness, thereby significantly improving the detection efficiency and sensitivity.

[0018] In the present invention, for the second functional block, that is, the CO2 sensitive detection area, the CO2 sensitive solution is fixed on the inner wall of the capillary by a gel method to form a polymer sensing membrane that is permeable to air but not permeable to protons; in the first functional block, that is, the O2 and pH fluorescence sensitive detection area, nanoparticles are used to simultaneously coat the O2 fluorescent indicator and the pH fluorescent indicator, and the O2 and pH fluorescent indicators are fixed on the first functional block by a Schiff base reaction assembly method of the nanoparticles on the inner wall of the capillary; thereby a multifunctional fluorescent capillary probe with good sensitivity is obtained.

[0019] Based on the following detailed description of specific embodiments of the present invention in conjunction with the accompanying drawings, those skilled in the art will become more aware of the above and other objects, advantages and features of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Hereinafter, some specific embodiments of the present invention will be described in detail in an exemplary and non-limiting manner with reference to the accompanying drawings. The same reference numerals in the accompanying drawings indicate the same or similar components or parts. It should be understood by those skilled in the art that these drawings are not necessarily drawn to scale. In the accompanying drawings:

[0021] Figure 1 is a schematic diagram of a sensor according to an embodiment of the present invention;

[0022] Figure 2 is a schematic diagram of sensor preparation steps according to one embodiment of the present invention;

[0023] Figure 3 FIG. 4 is a schematic diagram of a system for monitoring arterial blood gas data according to an embodiment of the present invention.

[0024] In the figure:

[0025] 1-first functional block, 2-second functional block, 100-sensor for monitoring arterial blood gas data,

[0026] 200-excitation light source, 300-fluorescence detection system, 400-fluid control system, 500-organism. DETAILED DESCRIPTION

[0027] In the description of this embodiment, it should be understood that the terms "first", "second", etc. are only used for descriptive purposes and cannot be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Therefore, the definition of "first", "second", etc. can explicitly or implicitly include at least one of the features, that is, include one or more of the features.

[0028] In the description of the present invention, "plurality" means at least two, such as two, three, etc., unless otherwise clearly and specifically limited. When a certain feature "includes or contains" one or some of the features it covers, unless otherwise specifically described, this indicates that other features are not excluded and other features may be further included.

[0029] Unless otherwise clearly defined and limited, the terms "installed", "connected", "connected", "fixed", "set" and the like should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integrated connection; it can be a mechanical connection or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium, it can be the internal connection of two elements or the interaction relationship between two elements, unless otherwise clearly defined. A person skilled in the art should be able to understand the specific meanings of the above terms in the present invention according to the specific circumstances.

[0030] like Figure 1 As shown, this embodiment provides a sensor 100 for monitoring arterial blood gas data, including: a substrate; and functional blocks, which are adjacently arranged on the substrate, and the multiple functional blocks can detect pH, O2 and CO2 under the excitation light of the same wavelength, wherein the functional blocks include a first functional block 1 and a second functional block 2, wherein the first functional block 1 is covered with a coating, and the coating can simultaneously load O2 and pH fluorescent indicators.

[0031] According to one embodiment of the present invention, the substrate adopts a capillary. In this embodiment, the capillary is divided into two functional blocks, respectively named as the first functional block 1 and the second functional block 2. The first functional block 1 and the second functional block 2 are adjacent to each other. The first functional block 1 is covered with a coating, and the coating can simultaneously load O2 and pH fluorescent indicators. It can be understood that the first functional block 1 and the second functional block 2 are both continuous areas formed on the inner wall of the capillary. The first functional block 1 and the second functional block 2 can be irradiated with lasers of the same wavelength, but output three different peak fluorescence signals for computer processing. As is known to all, the principle of the fluorescent fiber optic sensor is to transmit the excitation light of the light source to the fluorescent probe through the excitation optical fiber, and the fluorescent probe is excited to emit fluorescence. At the same time, the detector detects the fluorescence signal transmitted by the emission optical fiber to achieve quantitative analysis of the object to be measured. In more embodiments, other forms of substrates, such as glass plates, can also be used.

[0032] According to one embodiment of the present invention, the first functional block 1 is coated with fluorescent nanoparticles whose main component is surface-coated polylysine, the nanoparticles are mixed particles of platinum (II) octaethylporphyrin (Platinum octaethylporphyrin, hereinafter referred to as PtOEP) and fluorescein isothiocyanate (English name Fluorescein isothiocyanate, referred to as FITC, hereinafter referred to as FITC), and the matrix of the nanoparticles is polystyrene. In some embodiments, the matrix of the nanoparticles can also be cellulose materials, polyvinyl alcohol, dextran, polyurethane, polyacrylamide, polyhydroxyalkyl acrylate, polyvinyl pyrrolidone, hydrophilic polyamide, polyester and any combination thereof. In some embodiments, the O2 fluorescent indicator is PtOEP, and the O2 fluorescent indicator can also use benzopyrene, polycyclic aromatic compounds and their derivatives.

[0033] In some embodiments, the available O2 fluorescent indicators include simple substances or complexes or compounds of elements such as ruthenium, osmium, iridium, rhodium, rhenium and chromium, wherein. In some embodiments, the available O2 fluorescent indicators also include complexes of cobalt, copper, platinum, palladium, zinc and porphyrin, protoporphyrin, tetraphenylporphyrin, tetrafluorophenylporphyrin, tetrabenzoporphyrin, tetrafluorobenzoporphyrin, tetrachlorobenzoporphyrin, mesoporphyrin IX diester, protoporphyrin IX dimethyl ester and octaethylporphyrin. It can be understood that PtOEP is a complex.

[0034] In some embodiments, the available pH fluorescent indicator can be phenolphthalein, fuchsin, bromocresol purple and other phenolic pigments, methyl pigments such as methyl yellow diphenylamine, indigo, alizarin, methyl red and / or various functionalized derivatives of the above species in addition to FITC. In this embodiment, the selection of platinum (II) octaethylporphyrin also takes into account its other properties, especially its ability to attach to a substrate after reacting with chemical substances, and the degree of stability of mixing with the pH fluorescent indicator (FITC in this embodiment). See below for details.

[0035] According to one embodiment of the present invention, the second functional block 2 is covered with a film for detecting CO2, and the composition of the film includes 8-hydroxypyrene-1,3,6-trisulfonic acid, trisodium salt (HTPS, hereinafter referred to as HPTS). It can be understood that in this embodiment, tetraoctylammonium bromide and ethyltriethoxysilane are used as the loading materials of the CO2 fluorescent indicator, and the actual CO2 fluorescent indicator is HPTS. In this embodiment, the HTPS is fixed in the film by a physical embedding method, that is, the film for detecting CO2 in the second functional block 2 is actually polymerized by multiple components covered with HPTS, and the membranes of these components have good water-proof and air-permeable properties. This method can be used to directly measure the CO2 concentration in the blood. See below for details.

[0036] In certain embodiments, available CO2 fluorescent indicator can also be fluorescein and its derivatives (for example), hemi-naphthol rhodan fluorescein or metal complexes.Consider that the method used for detecting CO2 concentration at present is generally obtained indirectly by the change of pH value, when CO2 molecule and medium effect, will change its pH value, and the emission fluorescence intensity of pH fluorescent indicator changes with the change of pH value, and the concentration of carbon dioxide gas in medium can be known by measuring the change of fluorescence intensity.Therefore, above-mentioned pH fluorescent indicator can also be used as CO2 fluorescent indicator.And in the present embodiment, consider that HPTS is closer to the Ka value of blood, high fluorescence quantum yield, good stability, available ratio method measurement and other advantages, select it as CO2 fluorescent indicator.

[0037] According to one embodiment of the present invention, it can be seen from the above that measuring CO2 is actually also measuring pH. Therefore, in order to avoid the influence of pH changes in the test liquid, in this embodiment, a matrix material that only transmits CO2 is selected to fix the CO2 fluorescent indicator, that is, the multiple membrane structures coated with HPTS on the film for detecting CO2 in the second functional block 2 only transmit CO2. This structure can be a gas-permeable and water-blocking silane polymer or a hydrophobic silicone isolation layer (liquid silicone rubber).

[0038] like Figure 2 As shown, in particular, the present invention also discloses a method for preparing a sensor for monitoring arterial blood gas data, the preparation method comprising the following steps:

[0039] S1. Provide a substrate.

[0040] S2, dividing the substrate into adjacent first functional blocks 1 and second functional blocks 2 along a straight line direction.

[0041] S3. A thin film for detecting CO2 is formed in the second functional block 2 of the substrate, and a nanoparticle coating for detecting O2 and pH is formed in the first functional block 1 of the substrate. The first functional block 1 and the second functional block 2 can detect pH, O2 and CO2 under the excitation light of the same wavelength.

[0042] According to one embodiment of the present invention, in the above step S3, two solutions need to be prepared, one is an O2 and pH sensitive solution, and the other is a CO2 sensitive solution. These two solutions are used to form a nanoparticle coating for detecting O2 and pH on the first functional block 1, and a film for detecting CO2 on the second functional block 2.

[0043] The configuration of CO2 sensitive solution includes:

[0044] S301. First, stir and mix tetra-n-octylammonium bromide and silver oxide methanol solution of a certain concentration, and take the supernatant for later use. It can be understood that tetra-n-octylammonium bromide (TPAB) is a commonly used phase transfer catalyst, which can help transfer reactants from one phase to another, thereby promoting the reaction. The silver oxide methanol solution contains silver particles, which can be used to enhance the mechanical strength of the sensing membrane and / or as a catalyst.

[0045] S302, then prepare a solution of HPTS dissolved in 0.1 mol / L sodium hydroxide, and place it in a dichloromethane solution of tetra-n-octylammonium bromide and ethyltriethoxysilane, and shake it thoroughly for 10 minutes. Extract the organic phase, wash it with distilled water 3 times, and obtain a yellow organic solution. It can be understood that the main function of this step is to convert HPTS into an organic phase.

[0046] S303. Finally, add the yellow solution into a hydrochloric acid solution with a pH of 2.0, stir for 1 hour, and then add it into the supernatant obtained in the first step, shake and mix, to obtain a CO2 sensitive solution.

[0047] The preparation of O2 and pH fluorescent sensitive nanoparticles adopts the reprecipitation method-coating method, and the detailed steps are as follows:

[0048] S311, first prepare a tetrahydrofuran mixed solution of oxygen fluorescence indicator PtOEP, FITC, polystyrene and trimethylsiloxane (DTS) in a certain mass ratio. It is understandable that trimethylsiloxane (DTS) is an organosilicon compound with hydrophobicity, commonly used in the preparation of hydrophobic coatings and as a surface modifier for nanoparticles. It is introduced in this embodiment for the preparation of silane polymers.

[0049] S302, the mixed solution is rapidly injected into deionized water containing polylysine under ultrasonic oscillation conditions, and the resulting suspension is allowed to stand for 2 hours. Under ultrasonic oscillation conditions, the mixed solution is injected into deionized water containing polylysine to form fluorescent nanoparticles that encapsulate the O2 fluorescent indicator and the pH fluorescent indicator and are coated with polylysine on the surface.

[0050] S303. Finally, dialyze in deionized water for 24 hours to obtain fluorescent nanoparticles with oxygen and pH fluorescent indicators encapsulated inside and poly-lysine coated on the surface.

[0051] According to one embodiment of the present invention, a capillary is used as the substrate of the sensor, and the first functional block 1 and the second functional block 2 are respectively arranged on the left and right parts of the capillary, so that the fluorescent indicators do not interfere with each other. For the CO2 sensitive detection area (i.e., the second functional block 2), one end of the pretreated capillary is soaked in a CO2 sensitive solution for 12 hours, taken out, cleaned with anhydrous ethanol, and blown dry, and the CO2 fluorescent indicator on the inner wall of the capillary is fixed. The assembly steps for the fluorescent sensitive detection area of ​​O2 and pH (i.e., the first functional block 1) include: injecting an aldehyde siloxane acetone solution into the other end of the capillary, thereby introducing an aldehyde group, and then fixing the O2 and pH sensitive materials on the inner wall of the capillary based on the condensation reaction of the amino group on the surface of the nanoparticles and the aldehyde group to form a Schiff base. This method actually uses covalent bonds to combine nanoparticles with carriers (aldehyde groups), and the nanoparticles are embedded in the active groups of the carrier. This method can ensure stable bonding between the nanoparticles and the carrier, prevent the fluorescent indicator in the nanoparticles from leaking easily, and make the CO2 fiber optic sensor unaffected by pH value, ion concentration, solvent differences and temperature differences.

[0052] like Figure 3As shown, in particular, the present invention also provides a system for monitoring arterial blood gas data, including the above-mentioned sensor 100 for monitoring arterial blood gas data, which is named as a capillary fluorescent probe in this embodiment in consideration of naming tradition, and also includes an excitation light source 200, a fluorescence detection system 300 and a fluid control system 400. The excitation light source 200, the fluorescence detection system 300 and the fluid control system 400 in this embodiment are all existing devices and will not be described in detail here. Figure 2 As shown, the excitation light emitted by the excitation light source 200 is coupled by the optical fiber and then excites the O2, CO2 and pH fluorescent indicators on the inner wall of the capillary through the evanescent field. The fluorescent indicators emit fluorescent signals, which are collected and processed by the fluorescence detection system 300.

[0053] According to one embodiment of the present invention, the fluorescent capillary probe is connected to a fixing seat, fixed and protected by the fixing seat, and the detection areas at the left and right ends of the fluorescent capillary probe are separated in space to prevent interference between different fluorescent signals. The detection optical fiber can move in the capillary fixing seat to obtain fluorescent signals of O2, CO2 and pH. The capillary inlet hose is connected to a small measuring meter or a subcutaneous injection needle hole to obtain samples such as blood to be tested. The system can analyze the changes in fluorescent signals caused by solutions of specific concentrations of O2, CO2 and pH flowing through the capillary probe, draw a fluorescence detection calibration curve, and flow the solution to be tested through the fluorescent capillary probe to monitor the changes in each biomass to be tested through changes in fluorescence intensity.

[0054] According to one embodiment of the present invention, the capillary is a quartz capillary. The quartz capillary has structural consistency with the optical fiber in terms of material. The quartz tube is hollow and can be fused with the optical fiber to achieve the integration of the two. The quartz capillary is used instead of the optical fiber as a sensor probe to achieve the dual functions of liquid transmission and data transmission, which can effectively reduce the amount of sample used. The fluorescent indicator is fixed to the inner wall of the capillary, and the performance is more stable under the protection of the tube wall. In addition, by loading pH, PO2 and PCO2 multifunctional fluorescent sensitive materials on the inner wall of the capillary at the same time, parallel detection of multiple parameters becomes possible.

[0055] According to one embodiment of the present invention, the intensity and position changes of the absorption peaks of the three probes are analyzed by absorption spectroscopy to determine that the excitation light source is about 480 nm.

[0056] The above is a detailed description of this embodiment. Those skilled in the art should understand that, without departing from the spirit and scope of the present invention, these steps may be appropriately changed or modified to adapt to different application scenarios or requirements.

[0057] At this point, those skilled in the art should recognize that, although multiple exemplary embodiments of the present invention have been shown and described in detail herein, many other variations or modifications that conform to the principles of the present invention can still be directly determined or derived based on the content disclosed in the present invention without departing from the spirit and scope of the present invention. Therefore, the scope of the present invention should be understood and recognized as covering all these other variations or modifications.

Claims

1. A sensor for monitoring arterial blood gas data, characterized in that: include: matrix; as well as Functional blocks are adjacently arranged on the substrate, and the plurality of functional blocks can detect pH, O2 and CO2 under the excitation light of the same wavelength; The functional block includes a first functional block and a second functional block; the first functional block is covered with a coating, and the coating can simultaneously load an O2 fluorescent indicator and a pH fluorescent indicator.

2. The sensor for monitoring arterial blood gas data according to claim 1, characterized in that: The second functional block is covered with a film for detecting CO2.

3. The sensor for monitoring arterial blood gas data according to claim 2, characterized in that: The film comprises 8-hydroxypyrene-1,3, trisulfonic acid trisodium salt.

4. The sensor for monitoring arterial blood gas data according to claim 1, characterized in that: The coating is a fluorescent nanoparticle coating with poly-lysine coated on the surface.

5. The sensor for monitoring arterial blood gas data according to claim 4, characterized in that: The nanoparticles are mixed particles of platinum (II) octaethylporphyrin and fluorescein isothiocyanate; and / or the matrix of the nanoparticles is polystyrene.

6. The sensor for monitoring arterial blood gas data according to claim 1, characterized in that: The first functional block is a whole.

7. A method for preparing a sensor for monitoring arterial blood gas data, characterized in that: The preparation method comprises: providing a substrate; Dividing the substrate into adjacent first functional blocks and second functional blocks along an extension direction of the substrate; Nanoparticles for detecting O2 and pH are formed in the first functional block of the substrate, and a thin film for detecting CO2 is formed in the second functional block of the substrate. The first functional block and the second functional block can detect pH, O2 and CO2 under the same wavelength of excitation light.

8. The method for preparing a sensor for monitoring arterial blood gas data according to claim 7, characterized in that: The step of forming the second functional block comprises: Stir and mix tetra-n-octylammonium bromide and silver oxide methanol solution, and take the supernatant for later use; Prepare a solution of 8-hydroxypyrene-1,3, trisulfonic acid trisodium salt dissolved in sodium hydroxide, and place it in a mixed solution of tetra-n-octylammonium bromide, ethyltriethoxysilane and dichloromethane, shake for a first set time, and extract the organic phase; Add the organic phase to the hydrochloric acid solution, stir for a second set time, then add it to the supernatant, shake and mix, to obtain a CO2 sensitive solution; The second functional block of the substrate is immersed in the CO2 sensitive solution for a third set time, taken out, cleaned with anhydrous ethanol, and then blown dry to form a film.

9. The method for preparing a sensor for monitoring arterial blood gas data according to claim 8, characterized in that: The step of forming the first functional block comprises: Platinum (II) octaethylporphyrin, fluorescein isothiocyanate, polystyrene and trimethylsiloxane are mixed in a tetrahydrofuran mixed solution to form a first mixed solution; Injecting the first mixed solution into deionized water containing poly-lysine under ultrasonic vibration conditions to form a second mixed solution; The second mixed solution is allowed to stand for a fourth set time, and finally dialyzed in deionized water for a fifth set time, thereby obtaining fluorescent nanoparticles with O2 and pH fluorescent indicators encapsulated inside and poly-lysine coated on the surface; The second functional block is injected into an aldehyde siloxane acetone solution to introduce aldehyde groups, and then the fluorescent nanoparticles are fixed on the inner wall surface of the capillary based on the condensation reaction of the amino groups on the surface of the nanoparticles and the aldehyde groups to form a Schiff base.

10. A system for monitoring arterial blood gas data, characterized in that: The invention comprises a sensor for monitoring arterial blood gas data as claimed in any one of claims 1 to 7.

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