A sensor, method of manufacture and system for monitoring arterial blood gas data

Abstract

The application provides a sensor, a preparation method and a system for monitoring arterial blood gas data, the sensor comprising: a substrate; and functional blocks adjacently arranged on the substrate, the plurality of functional blocks being capable of detecting pH, O2 and CO2 under excitation light of 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 layer, and the coating layer is capable of simultaneously loading O2 and pH fluorescent indicators. The application realizes sensitive detection of multiple biological amounts by constructing the first functional block and the second functional block, and especially, the coating layer on the first functional block is capable of simultaneously loading O2 fluorescent indicators and pH fluorescent indicators, the same polarity of the O2 fluorescent indicators and the pH fluorescent indicators is utilized, the detection of the three substances is realized by arranging the two functional blocks, the structural complexity of the entire detector is reduced, and the reliability of the detector is improved.

Description

Technical Field

[0001] This invention relates to the field of detection technology, specifically to a sensor, preparation method, and system for monitoring arterial blood gas data. Background Technology

[0002] In the treatment and recovery process of critically ill patients, specialized analyzers are typically used to display and record relevant blood information in real time during intensive care settings to improve the timeliness and targeting of treatment. By monitoring the blood, valuable information such as the patient's oxygenation status, gas exchange, acid-base homeostasis, and ventilation can be obtained in real time. Although various bioanalytical 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, and although these instruments have been used clinically 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 probes used in commonly used invasive real-time blood gas analyzers are tapered fiber optic probes. The purpose of these probes is to increase the energy of the excitation light entering the evanescent field, thereby improving detection sensitivity. However, the tapered structure of the fiber optic probe leads to a mismatch between the mode characteristic parameter V value in the detection region and the transmission region, resulting in signal loss. This is especially true in intensive care settings. Summary of the Invention

[0004] One objective of this invention is to achieve sensitive detection of a variety of biomass by constructing fluorescent nanoprobes, thereby providing 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] Specifically, the present invention provides a sensor for monitoring arterial blood gas data, comprising:

[0008] Matrix; and

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

[0010] The functional block includes a first functional block and a second functional block; wherein the first functional block is covered with a coating that 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 method comprising:

[0012] Provide a matrix;

[0013] The substrate is divided into adjacent first functional blocks and second functional blocks along a straight line;

[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 same wavelength of excitation light.

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

[0016] In this invention, sensitive detection of multiple biomass 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 O2 fluorescent indicator and pH fluorescent indicator. Taking advantage of the fact that O2 fluorescent indicator and pH fluorescent indicator have the same polarity, the detection of three substances can be achieved by setting two functional blocks, which reduces the structural complexity of the entire detector and thus improves the reliability of the detector.

[0017] In this invention, the coating is a fluorescent nanoparticle coating with polylysine on the surface. That is, an O2 fluorescent indicator and a pH fluorescent indicator are simultaneously loaded in a medium. Due to this mixed arrangement, the distribution area of ​​both the O2 and pH fluorescent indicators can be expanded, and the O2 and pH fluorescent indicators can continuously output fluorescent signals, thereby improving the fluorescence brightness and significantly improving the detection efficiency and sensitivity.

[0018] In this invention, for the second functional block, namely the CO2 sensitive detection area, the CO2 sensitive solution is fixed to the inner wall of the capillary by a gel method to form a gas-permeable but proton-permeable polymer sensing membrane; in the first functional block, namely the O2 and pH fluorescence sensitive detection area, O2 fluorescence indicator and pH fluorescence indicator are simultaneously coated with nanoparticles, and the O2 and pH fluorescence indicators are fixed in the first functional block by a Schiff base reaction assembly method of nanoparticles on the inner wall of the capillary; thereby obtaining a multifunctional fluorescent capillary probe with good sensitivity.

[0019] The above and other objects, advantages and features of the present invention will become more apparent to those skilled in the art from the following detailed description of specific embodiments of the invention in conjunction with the accompanying drawings. Attached Figure Description

[0020] The following sections will describe some specific embodiments of the invention in detail by way of example and not limitation, with reference to the accompanying drawings. The same reference numerals in the drawings denote the same or similar parts or portions. Those skilled in the art should understand that these drawings are not necessarily drawn to scale. In the drawings:

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

[0022] Figure 2 This is a schematic diagram of sensor fabrication steps according to an embodiment of the present invention;

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

[0024] In the picture:

[0025] 1 - First functional block, 2 - Second functional block, 100 - Sensor for monitoring arterial blood gas data.

[0026] 200 - Excitation source, 300 - Fluorescence detection system, 400 - Fluorescence control system, 500 - Organism. Detailed Implementation

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

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

[0029] Unless otherwise expressly specified and limited, the terms "installation," "connection," "linking," "fixing," and "setting," etc., should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral part; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; they can refer to the internal communication of two components or the interaction between two components, unless otherwise expressly limited. Those skilled in the art should be able to understand the specific meaning of the above terms in this 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 arranged adjacent to each other on the substrate. Multiple functional blocks can detect pH, O2 and CO2 under the same wavelength of excitation light. The functional blocks include a first functional block 1 and a second functional block 2. The first functional block 1 is coated with a coating that can simultaneously load O2 and pH fluorescent indicators.

[0031] According to one embodiment of the present invention, the substrate is a capillary tube. In this embodiment, the capillary tube is divided into two functional blocks, named the first functional block 1 and the second functional block 2, respectively. The first functional block 1 and the second functional block 2 are adjacent to each other. The first functional block 1 is coated with a coating that can simultaneously load O2 and pH fluorescent indicators. It is understood that the first functional block 1 and the second functional block 2 are both continuous regions formed on the inner wall of the capillary tube. The first functional block 1 and the second functional block 2 can receive laser irradiation of the same wavelength, but output three fluorescence signals with different peak values ​​for computer processing. As is well known, the principle of a fluorescent fiber optic sensor is to transmit excitation light from a light source to a fluorescent probe through an excitation fiber. The fluorescent probe is excited and emits fluorescence, while the detector detects the fluorescence signal transmitted through the emission fiber, thereby achieving quantitative analysis of the analyte. In other 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 polylysine coated on the surface. The nanoparticles are a mixture of platinum(II) octaethylporphyrin (hereinafter referred to as PtOEP) and fluorescein isothiocyanate (hereinafter referred to as FITC), and the matrix of the nanoparticles is polystyrene. In some embodiments, the matrix of the nanoparticles may also be cellulose material, polyvinyl alcohol, dextran, polyurethane, polyacrylamide, hydroxyalkyl polyacrylate, polyvinylpyrrolidone, hydrophilic polyamide, polyester, and any combination thereof. In some embodiments, the O2 fluorescent indicator is PtOEP, and the O2 fluorescent indicator may also be benzo[a]pyrene, polycyclic aromatic compounds, and their derivatives.

[0033] In some embodiments, available O2 fluorescent indicators include elemental forms of ruthenium, osmium, iridium, rhodium, rhenium, and chromium, or their complexes or compounds. In some embodiments, 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 is understood that PtOEP is one such complex.

[0034] In some embodiments, besides FITC, the pH fluorescent indicator that can be used can also be phenolic pigments such as phenolphthalein, fuchsin, and bromocresol purple, methyl pigments such as m-amine yellow diphenylamine, indigo, alizarin, and methyl red, and / or various functionalized derivatives of the above species. In this embodiment, the selection of platinum(II) octaethylporphyrin also takes into account its other properties, especially its ability to adhere to the matrix after reacting with chemicals, and its stability when mixed 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 coated with a membrane for detecting CO2. The membrane comprises trisodium 8-hydroxypyrene-1,3,6-trisulfonic acid (HTPS, hereinafter referred to as HPTS). It is understood that in this embodiment, tetra-n-octylammonium bromide and ethyltriethoxysilane are used as the loading materials for the CO2 fluorescent indicator, while the actual CO2 fluorescent indicator is HPTS. In this embodiment, HTPS is immobilized in the membrane using a physical embedding method. That is, the membrane for detecting CO2 in the second functional block 2 is actually polymerized from multiple components coated with HPTS. The membrane of these components has good water-resistant and air-permeable properties, and this method can be used to directly measure the CO2 concentration in the blood. See below for details.

[0036] In some embodiments, the available CO2 fluorescent indicators may also be fluorescein and its derivatives (e.g., semi-naphthol rhodane fluorescent compounds or metal complexes). Considering that current methods for detecting CO2 concentration generally obtain the result indirectly through changes in pH, when CO2 molecules interact with the medium, they change the pH value. The emission intensity of a pH fluorescent indicator changes with the pH value, and the concentration of carbon dioxide gas in the medium can be determined by measuring the change in fluorescence intensity. Therefore, the aforementioned pH fluorescent indicators can also be used as CO2 fluorescent indicators. In this embodiment, considering the advantages of HPTS (Highly Fiber Resonant Tolerancing Thyroid Sulfate) such as its closer Ka value to blood, high fluorescence quantum yield, good stability, and applicability to ratiometric methods, it is selected as the CO2 fluorescent indicator.

[0037] According to one embodiment of the present invention, as can be seen from the above, measuring CO2 is actually also measuring pH. Therefore, to avoid the influence of pH changes in the test solution, this embodiment uses a matrix material that is only permeable to CO2 for fixing the CO2 fluorescent indicator. That is, the multiple HPTS-coated membrane structures on the membrane used for CO2 detection in the second functional block 2 are only permeable to CO2. This structure can be a gas-permeable and water-resistant silane polymer or a hydrophobic organosilicon 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 method comprising the following steps:

[0039] S1, Provide a matrix.

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

[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 same wavelength of excitation light.

[0042] According to one embodiment of the present invention, in step S3 above, two solutions are required: one is an O2 and pH-sensitive solution, and the other is a CO2-sensitive solution. These two solutions serve as the nanoparticle coating on the first functional block 1 for detecting O2 and pH, and the thin film on the second functional block 2 for detecting CO2.

[0043] The preparation of CO2-sensitive solutions specifically includes:

[0044] S301. First, a certain concentration of tetrapentylammonium bromide and silver oxide methanol solution are stirred and mixed, and the supernatant is taken for later use. It can be understood that tetrapentylammonium 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. Next, 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, shaking thoroughly for 10 minutes. Extract the organic phase, wash three times with distilled water, and obtain a yellow organic solution. It can be understood that the main function of this step is to convert HPTS into the organic phase.

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

[0047] The O2 and pH fluorescently sensitive nanoparticles were prepared using a reprecipitation-coating method, the detailed steps of which are as follows:

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

[0049] S302. The above 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. Injecting the mixed solution into deionized water containing polylysine under ultrasonic oscillation conditions can form fluorescent nanoparticles with internally encapsulated O2 fluorescent indicators and pH fluorescent indicators and surface coated with polylysine.

[0050] S303, and finally dialyzed in deionized water for 24 hours, to obtain fluorescent nanoparticles with internally encapsulated oxygen and pH fluorescent indicators and surface coated with polylysine.

[0051] According to one embodiment of the present invention, a capillary is used as the substrate of the sensor. By setting a first functional block 1 and a second functional block 2 in the left and right parts of the capillary respectively, 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 immersed in a CO2-sensitive solution for 12 hours, then removed, cleaned with anhydrous ethanol, and dried, thus completing the fixation of the CO2 fluorescent indicator on the inner wall of the capillary. The assembly steps for the O2 and pH-sensitive detection areas (i.e., the first functional block 1) include: injecting an aldehyde-based siloxane acetone solution into the other end of the capillary to introduce aldehyde groups, and then fixing the O2 and pH-sensitive materials on the inner wall surface of the capillary based on the condensation reaction of the amino groups on the surface of the nanoparticles with the aldehyde groups to form a Schiff base. This method actually uses covalent bonds to bind nanoparticles to a carrier (aldehyde group). The nanoparticles are embedded in the active groups of the carrier. This method can make the nanoparticles and the carrier stably bonded, prevent the fluorescent indicator in the nanoparticles from easily leaking, and make the CO2 fiber optic sensor unaffected by pH value, ion concentration, solvent, 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 aforementioned sensor 100 for monitoring arterial blood gas data. Considering naming conventions, this embodiment names it a capillary fluorescent probe. It also includes an excitation light source 200, a fluorescence detection system 300, and a fluid control system 400. In this embodiment, the excitation light source 200, the fluorescence detection system 300, and the fluid control system 400 are all existing devices and will not be described in detail here. Figure 2 As shown, the excitation light emitted by the excitation source 200 is coupled through an optical fiber and then passes through an evanescent field to excite the O2, CO2 and pH fluorescent indicators on the inner wall of the capillary. The fluorescent indicators emit fluorescent signals, which are then collected and processed by the fluorescence detection system 300.

[0053] According to one embodiment of the present invention, a fluorescent capillary probe is connected to a fixing base for fixation and protection. The detection areas at both ends of the fluorescent capillary probe are spatially separated to prevent interference between different fluorescence signals. The detection optical fiber can move within the capillary fixing base to acquire fluorescence signals of O2, CO2, and pH. The capillary inlet tubing is connected to a small measuring instrument or a hypodermic needle to acquire samples such as blood. This system can analyze the changes in fluorescence signals caused by solutions of specific concentrations of O2, CO2, and pH flowing through the capillary probe, plot fluorescence detection calibration curves, and monitor changes in various biomass samples by passing the test solution through the fluorescent capillary probe and observing changes in fluorescence intensity.

[0054] According to one embodiment of the present invention, the capillary is a quartz capillary. The quartz capillary shares structural similarities with optical fibers in terms of material. The hollow quartz tube allows for fusion splicing with the optical fiber, thus achieving integration of the two. Using the quartz capillary instead of the optical fiber as a sensor probe simultaneously realizes both liquid and data transmission functions, effectively reducing the amount of sample required. The fluorescent indicator is fixed to the inner wall of the capillary, and its performance is more stable under the protection of the tube wall. Furthermore, by simultaneously loading multifunctional fluorescent sensitive materials for pH, PO2, and PCO2 onto the inner wall of the capillary, parallel detection of multiple parameters becomes possible.

[0055] According to one embodiment of the present invention, the excitation source is determined to be around 480 nm by analyzing the intensity and position changes of the absorption peaks of the three probes using absorption spectroscopy.

[0056] The above is a detailed description of this embodiment. Those skilled in the art should understand that appropriate changes or modifications can be made to these steps without departing from the spirit and scope of the invention to adapt to different application scenarios or needs.

[0057] Therefore, those skilled in the art should recognize that although numerous exemplary embodiments of the present invention have been shown and described in detail herein, many other variations or modifications conforming to the principles of the present invention can be directly determined or derived from the disclosure of the present invention without departing from the spirit and scope of the invention. Thus, the scope of the present invention should be understood and construed as covering all such other variations or modifications.

Claims

1. A method for preparing a sensor for monitoring arterial blood gas data, characterized in that, The preparation method includes: Provide a matrix; Along the extension direction of the substrate, the substrate is divided into adjacent first functional blocks and second functional blocks; 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. The steps for forming the first functional block include: Platinum(II) octaethylporphyrin, fluorescein isothiocyanate, polystyrene and trimethylsiloxane are mixed in a tetrahydrofuran mixed solution to form a first mixed solution; The first mixed solution was injected into deionized water containing polylysine under ultrasonic vibration to form a second mixed solution; The second mixed solution was allowed to stand for a fourth set time, and then dialyzed in deionized water for a fifth set time to obtain fluorescent nanoparticles with internal encapsulation of O2 and pH fluorescent indicator and surface coating of polylysine. The first functional block is injected into an aldehyde-based siloxane acetone solution to introduce aldehyde groups. Then, based on the condensation reaction of the amino groups on the surface of the nanoparticles and the aldehyde groups to form Schiff bases, fluorescent nanoparticles are fixed on the inner wall surface of the capillary.

2. The method for preparing a sensor for monitoring arterial blood gas data according to claim 1, characterized in that, The steps for forming the second functional block include: Mix tetraoctylammonium bromide and silver oxide methanol solution by stirring, and keep the supernatant for later use; Prepare a solution of trisodium 8-hydroxypyrene-1,3-trisulfonate 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 to extract the organic phase. The organic phase is added to the hydrochloric acid solution and stirred for a second set time. Then, it is added to the supernatant and shaken to mix, thus obtaining a CO2-sensitive solution. The second functional block of the substrate was immersed in a CO2-sensitive solution for a third set time, then removed, cleaned with anhydrous ethanol, and dried to form a film.

3. A sensor for monitoring arterial blood gas data, characterized in that, The sensor is prepared by the method for preparing a sensor for monitoring arterial blood gas data according to any one of claims 1 to 2, comprising: Matrix; and Functional blocks are arranged adjacently on the substrate, and multiple functional blocks can detect pH, O2 and CO2 under the same wavelength of excitation light; The functional block includes a first functional block and a second functional block; wherein the first functional block is covered with a coating that can simultaneously load an O2 fluorescent indicator and a pH fluorescent indicator; The coating is a fluorescent nanoparticle coating with polylysine coated on its surface; The nanoparticles are a mixture of platinum(II) octaethylporphyrin and fluorescein isothiocyanate; and / or the matrix of the nanoparticles is polystyrene; The substrate is a capillary; The nanoparticles are covalently fixed to the inner wall of the capillary via a condensation reaction in which amino and aldehyde groups form Schiff bases.

4. The sensor for monitoring arterial blood gas data according to claim 3, characterized in that, The second functional block is covered with a thin film for detecting CO2.

5. The sensor for monitoring arterial blood gas data according to claim 4, characterized in that, The film is composed of 8-hydroxypyrene-1,3-trisulfonate trisodium salt.

6. The sensor for monitoring arterial blood gas data according to claim 3, characterized in that, The first functional block is a whole.

7. A system for monitoring arterial blood gas data, characterized in that, Includes the sensor for monitoring arterial blood gas data as described in any one of claims 3 to 6.

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