CN114873644A - Preparation method of molecular carrier for molecular detection - Google Patents
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- 238000001514 detection method Methods 0.000 title claims abstract description 21
- 238000002360 preparation method Methods 0.000 title claims description 12
- 239000002073 nanorod Substances 0.000 claims abstract description 50
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 38
- -1 modified sodium gadolinium tungstate Chemical class 0.000 claims abstract description 25
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 24
- 239000003999 initiator Substances 0.000 claims abstract description 22
- 239000000377 silicon dioxide Substances 0.000 claims abstract description 19
- 239000004088 foaming agent Substances 0.000 claims abstract description 17
- 239000000463 material Substances 0.000 claims abstract description 14
- 238000001125 extrusion Methods 0.000 claims abstract description 12
- 239000011159 matrix material Substances 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims abstract description 12
- 238000005469 granulation Methods 0.000 claims abstract description 6
- 230000003179 granulation Effects 0.000 claims abstract description 6
- 238000000465 moulding Methods 0.000 claims abstract description 6
- UZPIQWSRYNIAEI-UHFFFAOYSA-N gadolinium sodium Chemical compound [Na][Gd] UZPIQWSRYNIAEI-UHFFFAOYSA-N 0.000 claims description 25
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 20
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 20
- 239000008367 deionised water Substances 0.000 claims description 15
- 229910021641 deionized water Inorganic materials 0.000 claims description 15
- 238000003756 stirring Methods 0.000 claims description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 12
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 10
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 10
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 10
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 10
- 229910052786 argon Inorganic materials 0.000 claims description 10
- 238000005119 centrifugation Methods 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 10
- 239000006228 supernatant Substances 0.000 claims description 10
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 5
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 5
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 5
- 229920002101 Chitin Polymers 0.000 claims description 5
- 102000004190 Enzymes Human genes 0.000 claims description 5
- 108090000790 Enzymes Proteins 0.000 claims description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 5
- 239000005642 Oleic acid Substances 0.000 claims description 5
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 5
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 5
- 238000000605 extraction Methods 0.000 claims description 5
- 239000007789 gas Substances 0.000 claims description 5
- 230000005484 gravity Effects 0.000 claims description 5
- 238000010438 heat treatment Methods 0.000 claims description 5
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 5
- 239000007788 liquid Substances 0.000 claims description 5
- CCCMONHAUSKTEQ-UHFFFAOYSA-N octadecene Natural products CCCCCCCCCCCCCCCCC=C CCCMONHAUSKTEQ-UHFFFAOYSA-N 0.000 claims description 5
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 5
- 239000000843 powder Substances 0.000 claims description 5
- 239000011734 sodium Substances 0.000 claims description 5
- CMPGARWFYBADJI-UHFFFAOYSA-L tungstic acid Chemical compound O[W](O)(=O)=O CMPGARWFYBADJI-UHFFFAOYSA-L 0.000 claims description 5
- 238000011068 loading method Methods 0.000 abstract description 6
- 239000003814 drug Substances 0.000 abstract description 4
- 229940079593 drug Drugs 0.000 abstract description 3
- 230000035945 sensitivity Effects 0.000 abstract description 3
- 238000004557 single molecule detection Methods 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000000969 carrier Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000011896 sensitive detection Methods 0.000 description 2
- 238000001712 DNA sequencing Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000005842 biochemical reaction Methods 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000007877 drug screening Methods 0.000 description 1
- 238000013399 early diagnosis Methods 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000000329 molecular dynamics simulation Methods 0.000 description 1
- 239000002086 nanomaterial Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 238000000197 pyrolysis Methods 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
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- C01—INORGANIC CHEMISTRY
- C01G—COMPOUNDS CONTAINING METALS NOT COVERED BY SUBCLASSES C01D OR C01F
- C01G41/00—Compounds of tungsten
- C01G41/006—Compounds containing tungsten, with or without oxygen or hydrogen, and containing two or more other elements
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- B82Y40/00—Manufacture or treatment of nanostructures
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- C01—INORGANIC CHEMISTRY
- C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
- C01P2004/00—Particle morphology
- C01P2004/10—Particle morphology extending in one dimension, e.g. needle-like
- C01P2004/16—Nanowires or nanorods, i.e. solid nanofibres with two nearly equal dimensions between 1-100 nanometer
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Abstract
本发明公开了一种用于分子检测的分子载体的制备方法，包括如下步骤：S1：选取基础材料，基础材料包括介孔二氧化硅、改性钨酸钆钠纳米棒和内容物；S2：将基础材料进行混合，然后加入相容剂、引发剂、生物亲和剂，投入单螺杆造粒机挤出造粒，然后加入发泡剂投入双螺杆挤出机挤压成型；S3：成型后进入高压室，高压空气控制在10‑13倍的大气压，持续30‑40min后迅速减压1‑2min至常压获得基体，然后将内容物投入离心机甩出渗入基体中。通过本方法制备的分子载体具有高药物负载能力，胶束结构稳定，靶点释放的pH敏感度高，生物相容性高，对分子检测的外在影响小，同时具有很好的负载能力。The invention discloses a method for preparing a molecular carrier for molecular detection, comprising the following steps: S1: selecting basic materials, the basic materials comprising mesoporous silica, modified sodium gadolinium tungstate nanorods and contents; S2: Mix the basic materials, then add compatibilizer, initiator, bioaffinity agent, put into single-screw granulator for extrusion and granulation, then add foaming agent and put into twin-screw extruder for extrusion molding; S3: After molding Enter the high-pressure chamber, and the high-pressure air is controlled at 10-13 times the atmospheric pressure. After 30-40 minutes, the pressure is rapidly reduced for 1-2 minutes to normal pressure to obtain the matrix, and then the contents are thrown into the centrifuge and infiltrated into the matrix. The molecular carrier prepared by the method has high drug loading capacity, stable micellar structure, high pH sensitivity of target release, high biocompatibility, little external influence on molecular detection, and good loading capacity.
Description
技术领域technical field
本发明涉及涉及分子检测技术领域，更具体地说，涉及一种用于分子检测的分子载体的制备方法。The present invention relates to the technical field of molecular detection, and more particularly, to a preparation method of a molecular carrier for molecular detection.
背景技术Background technique
单分子检测是近十年来迅速发展起来的一种超灵敏的检测技术，为分析化学工作者打开了一扇新的大门。单分子检测(SMD)及其分析是一个考察细胞系统内动力学变化以及物质相互作用的精妙方法。现在，人们不仅可以在溶液中对单个分子进行检测和成像，而且可以通过对单分子的光谱性质进行测量，从而对化学反应的途径进行实时监测，特别是能对生物大分子进行探测提分子结构与功能之间的信息。同时，单分子检测技术是一种超灵敏的检测技术，可以对单个分子进行检测，在化学分析、DNA测序、纳米材料分析、医学诊断、分子动力学机理、食品安全等领域应用广泛。与传统的分析方法相比，单分子检测法研究体系处于非平衡状态下的个体行为，或平衡状态下的波动行为，因此特别适合研究化学及生化反应动力学、生物分子的相互作用、结构与功能信息、重大疾病早期诊断、病理研究以及高通量药物筛选等。Single-molecule detection is an ultra-sensitive detection technology that has developed rapidly in the past decade, opening a new door for analytical chemists. Single-molecule detection (SMD) and its analysis are a sophisticated method to investigate dynamic changes and substance interactions within cellular systems. Now, it is not only possible to detect and image single molecules in solution, but also to monitor the pathways of chemical reactions in real time by measuring the spectroscopic properties of single molecules, especially biological macromolecules to detect and extract molecular structure. information between functions. At the same time, single-molecule detection technology is an ultra-sensitive detection technology that can detect single molecules, and is widely used in chemical analysis, DNA sequencing, nanomaterial analysis, medical diagnosis, molecular dynamics mechanism, food safety and other fields. Compared with traditional analytical methods, the single-molecule detection method studies the individual behavior of the system in a non-equilibrium state, or the fluctuating behavior in an equilibrium state, so it is especially suitable for studying the kinetics of chemical and biochemical reactions, the interaction of biomolecules, the structure and Functional information, early diagnosis of major diseases, pathological research, and high-throughput drug screening, etc.
目前在单分子检测技术中，一般是将待检测样品的检测物提取后放置在分子载体上进行检测，且检测时采用的分子载体大多采用硬质基底。在医药领域，高药物负载能力，胶束结构稳定，靶点释放的pH敏感性，生物相容性高这几项对因素是评判分子载体性能的重要因素，而现有的分子载体无法保证上述因素性能的稳定性，导致检测存在一定误差、增加检测复杂度和难度。At present, in the single-molecule detection technology, the detection substance of the sample to be detected is generally extracted and placed on a molecular carrier for detection, and the molecular carrier used in the detection mostly adopts a rigid substrate. In the field of medicine, high drug loading capacity, stable micellar structure, pH sensitivity of target release, and high biocompatibility are important factors for evaluating the performance of molecular carriers, while existing molecular carriers cannot guarantee the above The stability of the factor performance leads to certain errors in detection and increases the complexity and difficulty of detection.
发明内容SUMMARY OF THE INVENTION
本发明的目的在于提供一种用于分子检测的分子载体的制备方法，用以解决上述背景技术中存在的技术问题。The purpose of the present invention is to provide a preparation method of a molecular carrier for molecular detection, so as to solve the technical problems existing in the above-mentioned background art.
本发明技术方案提供一种用于分子检测的分子载体的制备方法，包括如下步骤：The technical solution of the present invention provides a method for preparing a molecular carrier for molecular detection, comprising the following steps:
S1：选取基础材料，基础材料包括介孔二氧化硅、改性钨酸钆钠纳米棒和内容物；S1: Select basic materials, including mesoporous silica, modified sodium gadolinium tungstate nanorods and contents;
S2：将基础材料进行混合，然后加入相容剂、引发剂、生物亲和剂，投入单螺杆造粒机挤出造粒，然后加入发泡剂投入双螺杆挤出机挤压成型；S2: Mix the basic materials, then add a compatibilizer, an initiator, and a bioaffinity agent, put it into a single-screw granulator for extrusion and granulation, and then add a foaming agent and put it into a twin-screw extruder for extrusion molding;
S3：成型后进入高压室，高压空气控制在10-13倍的大气压，持续30-40min后迅速减压1-2min至常压获得基体，然后将内容物投入离心机甩出渗入基体中。S3: After molding, enter the high pressure chamber, the high pressure air is controlled at 10-13 times the atmospheric pressure, and after 30-40 minutes, the pressure is rapidly reduced to normal pressure for 1-2 minutes to obtain the matrix, and then the contents are thrown into the centrifuge and infiltrated into the matrix.
在一个优选地实施例中，所述介孔二氧化硅、改性钨酸钆钠纳米棒、内容物、相容剂、引发剂、生物亲和剂、发泡剂的重量份数分别为：介孔二氧化硅60-70份、改性钨酸钆钠纳米棒30-40份、内容物20-30份、相容剂3-4份、引发剂3-4份、发泡剂2-4份、生物亲和剂2-3份。In a preferred embodiment, the parts by weight of the mesoporous silica, modified sodium gadolinium tungstate nanorods, content, compatibilizer, initiator, bioaffinity agent, and foaming agent are respectively: Mesoporous silica 60-70 parts, modified gadolinium sodium tungstate nanorods 30-40 parts, content 20-30 parts, compatibilizer 3-4 parts, initiator 3-4 parts, foaming agent 2- 4 parts, 2-3 parts of bioaffinity.
在一个优选地实施例中，所述内容物为活性酶内容物，所述引发剂为丙烯酸，所述比重剂为轻质碳酸钙，所述生物亲和剂为甲壳素。In a preferred embodiment, the content is active enzyme content, the initiator is acrylic acid, the specific gravity agent is light calcium carbonate, and the bioaffinity agent is chitin.
在一个优选地实施例中，所述改性钨酸钆钠纳米棒的制备方法为：In a preferred embodiment, the preparation method of the modified sodium gadolinium tungstate nanorods is:
A1：将油酸、十八烯和GdCl3·6H2O粉末混合，通氩气后升温至150-160℃搅拌，获得淡黄色澄清液，然后停止加热使体系自然降至室温；A1: Mix oleic acid, octadecene and GdCl 3 ·6H 2 O powder, pass argon and heat up to 150-160°C and stir to obtain a pale yellow clear liquid, then stop heating and let the system naturally drop to room temperature;
A2：缓慢滴加含Na2WO4·2H2O的氨水溶液，在室温下密封搅拌，溶液呈黄白色；A2: Slowly add aqueous ammonia solution containing Na 2 WO 4 ·2H 2 O dropwise, seal and stir at room temperature, the solution is yellowish white;
A3：通氩气，40-60℃保持50-80min后，在80-85℃下保持60-70min，然后在110-130℃下保持50-60min除去氨水，除完之后，接好冷凝管，体系升温至260-280℃，并保持40-50min，然后自然降至室温；A3: Pour argon gas, keep at 40-60°C for 50-80min, keep at 80-85°C for 60-70min, then keep at 110-130°C for 50-60min to remove ammonia water, after removing, connect the condenser tube, The system is heated to 260-280°C and kept for 40-50min, and then naturally lowered to room temperature;
A4：离心后丢弃上液，然后加入环己烷并超声分散，再加入酒精，超声分散，离心收集后丢弃上液，得到钨酸钆钠纳米棒的环己烷溶液，经提取即得到钨酸钆钠纳米棒；A4: Discard the supernatant after centrifugation, then add cyclohexane and ultrasonically disperse, then add alcohol, ultrasonically disperse, discard the supernatant after centrifugation to obtain a cyclohexane solution of gadolinium sodium tungstate nanorods, and obtain tungstic acid after extraction Gadolinium sodium nanorods;
A5：将钨酸钆钠纳米棒的环己烷溶液加入到去离子水中，然后滴加浓盐酸，密封搅拌，钨酸钆钠纳米棒便从上层的环己烷转移到去离子水中；离心收集，用去离子水清洗并超声分散、干燥，得到改性后的钨酸钆钠纳米棒。A5: Add the cyclohexane solution of gadolinium sodium tungstate nanorods into deionized water, then dropwise add concentrated hydrochloric acid, seal and stir, and the gadolinium sodium tungstate nanorods will be transferred from the upper cyclohexane to deionized water; centrifuged to collect , washed with deionized water, ultrasonically dispersed and dried to obtain modified sodium gadolinium tungstate nanorods.
在一个优选地实施例中，所述单螺杆造粒机的各分区温度为：一区150-170℃，二区160-175℃，三区180-190℃，四区190-200℃；所述双螺杆挤出机的各分区温度一区180-190℃，二区185-195℃，三区190-200℃，四区190-200℃。In a preferred embodiment, the temperature of each zone of the single-screw granulator is: 150-170°C in the first zone, 160-175°C in the second zone, 180-190°C in the third zone, and 190-200°C in the fourth zone; The temperature of each zone of the twin-screw extruder is 180-190°C in the first zone, 185-195°C in the second zone, 190-200°C in the third zone, and 190-200°C in the fourth zone.
本发明技术方案的有益效果是：The beneficial effects of the technical solution of the present invention are:
通过本方法制备的分子载体具有高药物负载能力，胶束结构稳定，靶点释放的pH敏感度高，生物相容性高，对分子检测的外在影响小，同时具有很好的负载能力。The molecular carrier prepared by the method has high drug loading capacity, stable micellar structure, high pH sensitivity of target release, high biocompatibility, little external influence on molecular detection, and good loading capacity.
以介孔二氧化硅、改性钨酸钆钠纳米棒和内容物为基础材料，以相容剂、引发剂、生物亲和剂、发泡剂作为辅料。其中通过热解法制备的钨酸钆钠纳米棒是亲油性的，为了在其表面包覆介孔二氧化硅，需对钨酸钆钠纳米棒进行亲水改性。先用浓盐酸处理钨酸钆钠纳米棒NaxGdWO3，再进行微波改性，可以使后续的介孔二氧化硅吸附率提高,增加分子载体的负载能力。It is based on mesoporous silica, modified sodium gadolinium tungstate nanorods and the contents, and uses compatibilizer, initiator, bioaffinity agent and foaming agent as auxiliary materials. The gadolinium sodium tungstate nanorods prepared by pyrolysis are lipophilic. In order to coat the mesoporous silica on the surface, the gadolinium sodium tungstate nanorods need to be hydrophilically modified. The gadolinium sodium tungstate nanorod NaxGdWO3 was first treated with concentrated hydrochloric acid, and then modified by microwave, which can improve the subsequent adsorption rate of mesoporous silica and increase the loading capacity of the molecular carrier.
具体实施方式Detailed ways
下面具体实施方式对本发明作进一步详细的说明。本发明的实施例是为了示例和描述方便起见而给出的，而并不是无遗漏的或者将本发明限于所公开的形式。很多修改和变化对于本领域的普通技术人员而言是显而易见的。选择和描述实施例是为了更好说明本发明的原理和实际应用，并且使本领域的普通技术人员能够理解本发明从而设计适于特定用途的带有各种修改的各种实施例。The following specific embodiments will further describe the present invention in detail. The embodiments of the present invention are presented for convenience of illustration and description, and are not intended to be exhaustive or to limit the invention to the form disclosed. Many modifications and variations will be apparent to those of ordinary skill in the art. The embodiment was chosen and described in order to better explain the principles of the invention and the practical application, and to enable others of ordinary skill in the art to understand the invention for various embodiments with various modifications as are suited to the particular use.
实施例1Example 1
本发明技术方案提供一种用于分子检测的分子载体的制备方法，包括如下步骤：The technical solution of the present invention provides a method for preparing a molecular carrier for molecular detection, comprising the following steps:
S1：选取基础材料，基础材料包括介孔二氧化硅、改性钨酸钆钠纳米棒和内容物；S1: Select basic materials, including mesoporous silica, modified sodium gadolinium tungstate nanorods and contents;
S2：将基础材料进行混合，然后加入相容剂、引发剂、生物亲和剂，投入单螺杆造粒机挤出造粒，然后加入发泡剂投入双螺杆挤出机挤压成型；S2: Mix the basic materials, then add a compatibilizer, an initiator, and a bioaffinity agent, put it into a single-screw granulator for extrusion and granulation, and then add a foaming agent and put it into a twin-screw extruder for extrusion molding;
S3：成型后进入高压室，高压空气控制在13倍的大气压，持续30min后迅速减压1min至常压获得基体，然后将内容物投入离心机甩出渗入基体中。S3: After molding, enter the high pressure chamber, the high pressure air is controlled at 13 times the atmospheric pressure, and after 30 minutes, the pressure is rapidly reduced to normal pressure for 1 minute to obtain the matrix, and then the contents are thrown into the centrifuge and infiltrated into the matrix.
在一个优选地实施例中，所述介孔二氧化硅、改性钨酸钆钠纳米棒、内容物、相容剂、引发剂、生物亲和剂、发泡剂的重量份数分别为：介孔二氧化硅60-70份、改性钨酸钆钠纳米棒30-40份、内容物20-30份、相容剂3-4份、引发剂3-4份、发泡剂2-4份、生物亲和剂2-3份。In a preferred embodiment, the parts by weight of the mesoporous silica, modified sodium gadolinium tungstate nanorods, content, compatibilizer, initiator, bioaffinity agent, and foaming agent are respectively: Mesoporous silica 60-70 parts, modified gadolinium sodium tungstate nanorods 30-40 parts, content 20-30 parts, compatibilizer 3-4 parts, initiator 3-4 parts, foaming agent 2- 4 parts, 2-3 parts of bioaffinity.
在一个优选地实施例中，所述内容物为活性酶内容物，所述引发剂为丙烯酸，所述比重剂为轻质碳酸钙，所述生物亲和剂为甲壳素。In a preferred embodiment, the content is active enzyme content, the initiator is acrylic acid, the specific gravity agent is light calcium carbonate, and the bioaffinity agent is chitin.
在一个优选地实施例中，所述改性钨酸钆钠纳米棒的制备方法为：In a preferred embodiment, the preparation method of the modified sodium gadolinium tungstate nanorods is:
A1：将油酸、十八烯和GdCl3·6H2O粉末混合，通氩气后升温至150-160℃搅拌，获得淡黄色澄清液，然后停止加热使体系自然降至室温；A1: Mix oleic acid, octadecene and GdCl 3 ·6H 2 O powder, pass argon and heat up to 150-160°C and stir to obtain a pale yellow clear liquid, then stop heating and let the system naturally drop to room temperature;
A2：缓慢滴加含Na2WO4·2H2O的氨水溶液，在室温下密封搅拌，溶液呈黄白色；A2: Slowly add aqueous ammonia solution containing Na 2 WO 4 ·2H 2 O dropwise, seal and stir at room temperature, the solution is yellowish white;
A3：通氩气，40℃保持50min后，在80℃下保持60min，然后在110-130℃下保持50min除去氨水，除完之后，接好冷凝管，体系升温至260℃，并保持40min，然后自然降至室温；A3: Pour argon gas, keep at 40°C for 50min, keep at 80°C for 60min, then keep at 110-130°C for 50min to remove ammonia water. and then naturally cooled to room temperature;
A4：离心后丢弃上液，然后加入环己烷并超声分散，再加入酒精，超声分散，离心收集后丢弃上液，得到钨酸钆钠纳米棒的环己烷溶液，经提取即得到钨酸钆钠纳米棒；A4: Discard the supernatant after centrifugation, then add cyclohexane and ultrasonically disperse, then add alcohol, ultrasonically disperse, discard the supernatant after centrifugation to obtain a cyclohexane solution of gadolinium sodium tungstate nanorods, and obtain tungstic acid after extraction Gadolinium sodium nanorods;
A5：将钨酸钆钠纳米棒的环己烷溶液加入到去离子水中，然后滴加浓盐酸，密封搅拌，钨酸钆钠纳米棒便从上层的环己烷转移到去离子水中；离心收集，用去离子水清洗并超声分散、干燥，得到改性后的钨酸钆钠纳米棒。A5: Add the cyclohexane solution of gadolinium sodium tungstate nanorods into deionized water, then dropwise add concentrated hydrochloric acid, seal and stir, and the gadolinium sodium tungstate nanorods will be transferred from the upper cyclohexane to deionized water; centrifuged to collect , washed with deionized water, ultrasonically dispersed and dried to obtain modified sodium gadolinium tungstate nanorods.
在一个优选地实施例中，所述单螺杆造粒机的各分区温度为：一区150℃，二区160℃，三区180℃，四区190℃；所述双螺杆挤出机的各分区温度一区180℃，二区185℃，三区190℃，四区190℃。In a preferred embodiment, the temperature of each zone of the single-screw granulator is: 150°C in the first zone, 160°C in the second zone, 180°C in the third zone, and 190°C in the fourth zone; The zone temperature is 180°C for the first zone, 185°C for the second zone, 190°C for the third zone, and 190°C for the fourth zone.
实施例2Example 2
本发明技术方案提供一种用于分子检测的分子载体的制备方法，包括如下步骤：The technical solution of the present invention provides a method for preparing a molecular carrier for molecular detection, comprising the following steps:
S1：选取基础材料，基础材料包括介孔二氧化硅、改性钨酸钆钠纳米棒和内容物；S1: Select basic materials, including mesoporous silica, modified sodium gadolinium tungstate nanorods and contents;
S2：将基础材料进行混合，然后加入相容剂、引发剂、生物亲和剂，投入单螺杆造粒机挤出造粒，然后加入发泡剂投入双螺杆挤出机挤压成型；S2: Mix the basic materials, then add a compatibilizer, an initiator, and a bioaffinity agent, put it into a single-screw granulator for extrusion and granulation, and then add a foaming agent and put it into a twin-screw extruder for extrusion molding;
S3：成型后进入高压室，高压空气控制在10倍的大气压，持续40min后迅速减压2min至常压获得基体，然后将内容物投入离心机甩出渗入基体中。S3: After molding, enter the high-pressure chamber, and the high-pressure air is controlled at 10 times the atmospheric pressure. After 40 minutes, the pressure is quickly reduced to normal pressure for 2 minutes to obtain the matrix, and then the contents are thrown into the centrifuge and infiltrated into the matrix.
在一个优选地实施例中，所述介孔二氧化硅、改性钨酸钆钠纳米棒、内容物、相容剂、引发剂、生物亲和剂、发泡剂的重量份数分别为：介孔二氧化硅70份、改性钨酸钆钠纳米棒40份、内容物30份、相容剂4份、引发剂4份、发泡剂4份、生物亲和剂3份。In a preferred embodiment, the parts by weight of the mesoporous silica, modified sodium gadolinium tungstate nanorods, content, compatibilizer, initiator, bioaffinity agent, and foaming agent are respectively: 70 parts of mesoporous silica, 40 parts of modified sodium gadolinium tungstate nanorods, 30 parts of contents, 4 parts of compatibilizer, 4 parts of initiator, 4 parts of foaming agent, and 3 parts of bioaffinity.
在一个优选地实施例中，所述内容物为活性酶内容物，所述引发剂为丙烯酸，所述比重剂为轻质碳酸钙，所述生物亲和剂为甲壳素。In a preferred embodiment, the content is active enzyme content, the initiator is acrylic acid, the specific gravity agent is light calcium carbonate, and the bioaffinity agent is chitin.
在一个优选地实施例中，所述改性钨酸钆钠纳米棒的制备方法为：In a preferred embodiment, the preparation method of the modified sodium gadolinium tungstate nanorods is:
A1：将油酸、十八烯和GdCl3·6H2O粉末混合，通氩气后升温至150-160℃搅拌，获得淡黄色澄清液，然后停止加热使体系自然降至室温；A1: Mix oleic acid, octadecene and GdCl 3 ·6H 2 O powder, pass argon and heat up to 150-160°C and stir to obtain a pale yellow clear liquid, then stop heating and let the system naturally drop to room temperature;
A2：缓慢滴加含Na2WO4·2H2O的氨水溶液，在室温下密封搅拌，溶液呈黄白色；A2: Slowly add aqueous ammonia solution containing Na 2 WO 4 ·2H 2 O dropwise, seal and stir at room temperature, the solution is yellowish white;
A3：通氩气，60℃保持80min后，在85℃下保持70min，然后在130℃下保持60min除去氨水，除完之后，接好冷凝管，体系升温至280℃，并保持50min，然后自然降至室温；A3: Pour argon gas, keep at 60°C for 80min, keep at 85°C for 70min, then keep at 130°C for 60min to remove ammonia water, after removing, connect the condenser tube, heat the system to 280°C, keep it for 50min, and then naturally to room temperature;
A4：离心后丢弃上液，然后加入环己烷并超声分散，再加入酒精，超声分散，离心收集后丢弃上液，得到钨酸钆钠纳米棒的环己烷溶液，经提取即得到钨酸钆钠纳米棒；A4: Discard the supernatant after centrifugation, then add cyclohexane and ultrasonically disperse, then add alcohol, ultrasonically disperse, discard the supernatant after centrifugation to obtain a cyclohexane solution of gadolinium sodium tungstate nanorods, and obtain tungstic acid after extraction Gadolinium sodium nanorods;
A5：将钨酸钆钠纳米棒的环己烷溶液加入到去离子水中，然后滴加浓盐酸，密封搅拌，钨酸钆钠纳米棒便从上层的环己烷转移到去离子水中；离心收集，用去离子水清洗并超声分散、干燥，得到改性后的钨酸钆钠纳米棒。A5: Add the cyclohexane solution of gadolinium sodium tungstate nanorods into deionized water, then dropwise add concentrated hydrochloric acid, seal and stir, and the gadolinium sodium tungstate nanorods will be transferred from the upper cyclohexane to deionized water; centrifuged to collect , washed with deionized water, ultrasonically dispersed and dried to obtain modified sodium gadolinium tungstate nanorods.
在一个优选地实施例中，所述单螺杆造粒机的各分区温度为：一区170℃，二区175℃，三区190℃，四区200℃；所述双螺杆挤出机的各分区温度一区190℃，二区195℃，三区200℃，四区200℃。In a preferred embodiment, the temperature of each zone of the single-screw granulator is: 170°C in the first zone, 175°C in the second zone, 190°C in the third zone, and 200°C in the fourth zone; The zone temperature is 190°C for the first zone, 195°C for the second zone, 200°C for the third zone, and 200°C for the fourth zone.
实施例3Example 3
本发明技术方案提供一种用于分子检测的分子载体的制备方法，包括如下步骤：The technical solution of the present invention provides a method for preparing a molecular carrier for molecular detection, comprising the following steps:
S1：选取基础材料，基础材料包括介孔二氧化硅、改性钨酸钆钠纳米棒和内容物；S1: Select basic materials, including mesoporous silica, modified sodium gadolinium tungstate nanorods and contents;
S2：将基础材料进行混合，然后加入相容剂、引发剂、生物亲和剂，投入单螺杆造粒机挤出造粒，然后加入发泡剂投入双螺杆挤出机挤压成型；S2: Mix the basic materials, then add a compatibilizer, an initiator, and a bioaffinity agent, put it into a single-screw granulator for extrusion and granulation, and then add a foaming agent and put it into a twin-screw extruder for extrusion molding;
S3：成型后进入高压室，高压空气控制在12倍的大气压，持续35min后迅速减压1-2min至常压获得基体，然后将内容物投入离心机甩出渗入基体中。S3: After molding, enter the high pressure chamber, and the high pressure air is controlled at 12 times the atmospheric pressure. After 35 minutes, the pressure is rapidly reduced for 1-2 minutes to normal pressure to obtain the matrix, and then the contents are thrown into the centrifuge and infiltrated into the matrix.
在一个优选地实施例中，所述介孔二氧化硅、改性钨酸钆钠纳米棒、内容物、相容剂、引发剂、生物亲和剂、发泡剂的重量份数分别为：介孔二氧化硅65份、改性钨酸钆钠纳米棒35份、内容物25份、相容剂3.5份、引发剂3.4份、发泡剂3份、生物亲和剂2.5份。In a preferred embodiment, the parts by weight of the mesoporous silica, modified sodium gadolinium tungstate nanorods, content, compatibilizer, initiator, bioaffinity agent, and foaming agent are respectively: 65 parts of mesoporous silica, 35 parts of modified sodium gadolinium tungstate nanorods, 25 parts of contents, 3.5 parts of compatibilizer, 3.4 parts of initiator, 3 parts of foaming agent, and 2.5 parts of bioaffinity.
在一个优选地实施例中，所述内容物为活性酶内容物，所述引发剂为丙烯酸，所述比重剂为轻质碳酸钙，所述生物亲和剂为甲壳素。In a preferred embodiment, the content is active enzyme content, the initiator is acrylic acid, the specific gravity agent is light calcium carbonate, and the bioaffinity agent is chitin.
在一个优选地实施例中，述改性钨酸钆钠纳米棒的制备方法为：In a preferred embodiment, the preparation method of the modified sodium gadolinium tungstate nanorod is:
A1：将油酸、十八烯和GdCl3·6H2O粉末混合，通氩气后升温至155℃搅拌，获得淡黄色澄清液，然后停止加热使体系自然降至室温；A1: Mix oleic acid, octadecene and GdCl 3 ·6H 2 O powder, pass argon and heat up to 155°C and stir to obtain a light yellow clear liquid, then stop heating to allow the system to naturally drop to room temperature;
A2：缓慢滴加含Na2WO4·2H2O的氨水溶液，在室温下密封搅拌，溶液呈黄白色；A2: Slowly add aqueous ammonia solution containing Na 2 WO 4 ·2H 2 O dropwise, seal and stir at room temperature, the solution is yellowish white;
A3：通氩气，50℃保持75min后，在85℃下保持70min，然后在120℃下保持55min除去氨水，除完之后，接好冷凝管，体系升温至270℃，并保持45min，然后自然降至室温；A3: Pour argon gas, keep at 50°C for 75min, keep at 85°C for 70min, then keep at 120°C for 55min to remove ammonia water, after removing, connect the condenser tube, heat the system to 270°C, keep it for 45min, and then naturally to room temperature;
A4：离心后丢弃上液，然后加入环己烷并超声分散，再加入酒精，超声分散，离心收集后丢弃上液，得到钨酸钆钠纳米棒的环己烷溶液，经提取即得到钨酸钆钠纳米棒；A4: Discard the supernatant after centrifugation, then add cyclohexane and ultrasonically disperse, then add alcohol, ultrasonically disperse, discard the supernatant after centrifugation to obtain a cyclohexane solution of gadolinium sodium tungstate nanorods, and obtain tungstic acid after extraction Gadolinium sodium nanorods;
A5：将钨酸钆钠纳米棒的环己烷溶液加入到去离子水中，然后滴加浓盐酸，密封搅拌，钨酸钆钠纳米棒便从上层的环己烷转移到去离子水中；离心收集，用去离子水清洗并超声分散、干燥，得到改性后的钨酸钆钠纳米棒。A5: Add the cyclohexane solution of gadolinium sodium tungstate nanorods into deionized water, then dropwise add concentrated hydrochloric acid, seal and stir, and the gadolinium sodium tungstate nanorods will be transferred from the upper cyclohexane to deionized water; centrifuged to collect , washed with deionized water, ultrasonically dispersed and dried to obtain modified sodium gadolinium tungstate nanorods.
在一个优选地实施例中，所述单螺杆造粒机的各分区温度为：一区150-170℃，二区160-175℃，三区180-190℃，四区190-200℃；所述双螺杆挤出机的各分区温度一区180-190℃，二区185-195℃，三区190-200℃，四区190-200℃。In a preferred embodiment, the temperature of each zone of the single-screw granulator is: 150-170°C in the first zone, 160-175°C in the second zone, 180-190°C in the third zone, and 190-200°C in the fourth zone; The temperature of each zone of the twin-screw extruder is 180-190°C in the first zone, 185-195°C in the second zone, 190-200°C in the third zone, and 190-200°C in the fourth zone.
显然，所描述的实施例仅仅是本发明的一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域及相关领域的普通技术人员在没有作出创造性劳动的前提下所获得的所有其他实施例，都应属于本发明保护的范围。本发明中未具体描述和解释说明的结构、装置以及操作方法，如无特别说明和限定，均按照本领域的常规手段进行实施。Obviously, the described embodiments are only some, but not all, embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art and related fields without creative work shall fall within the protection scope of the present invention. The structures, devices and operation methods that are not specifically described and explained in the present invention are implemented according to conventional means in the art unless otherwise specified and limited.
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