Esophageal cell sampler

Abstract

The present invention provides an esophageal cell sampler, which solves the problem of lack of efficient and convenient sampling tools for collecting esophageal epithelial cells; an esophageal cell sampler, the sampler consists of a sampling part and a connecting part fixedly connected to the sampling part, part or all of the sampling part is made of shape memory material, the shape memory material is polycaprolactone or polycaprolactone diol, the sampling part has a first form and a second form, and the second form can restore the first form within a temperature range of 52°C-57°C or 48.3°C-50.1°C.

Description

Technical Field

[0001] The invention relates to the technical field of medical devices, and in particular to an esophageal cell sampler. Background Art

[0002] Esophageal cancer is a highly prevalent malignant tumor, with a large number of new cases and deaths every year, which makes early screening particularly important. Traditional screening methods such as digestive endoscopy combined with iodine staining of the esophageal mucosa are effective, but they are only promoted in high-risk groups due to their high cost and invasiveness. Although screening using gastroscopy alone is highly accurate, it is difficult to make an appointment, causes pain to patients, and uneven distribution of medical resources, all of which limit its widespread application.

[0003] Studies have shown that esophageal epithelial exfoliated cells can reflect the health of the esophagus and provide valuable information even for small lesions that are difficult to detect with gastroscopy. Although there are already some tools for collecting esophageal epithelial cells, their application is not yet popular and convenient. This suggests that these sampling tools need to be further developed and optimized to increase the coverage and convenience of screening, thereby achieving more effective early screening. Summary of the invention

[0004] The invention provides an esophageal cell sampler, which solves the problem of lack of efficient and convenient sampling tools for collecting esophageal epithelial cells.

[0005] To achieve the purpose of the present invention, the following technical solutions are adopted:

[0006] An esophageal cell sampler, the sampler consisting of a sampling part and a connecting part fixedly connected to the sampling part, part or all of the sampling part is made of shape memory material, the shape memory material is polycaprolactone or polycaprolactone diol, the sampling part has a first form and a second form, the second form can restore to the first form within a temperature range of 52°C-57°C or 48.3°C-50.1°C.

[0007] Furthermore, the preparation method of the sampling part is:

[0008] S1: a polycaprolactone wire with a molecular weight of 4000 is made into a first form and irradiated at a dose of 200 kGy;

[0009] S2: raising the temperature of the first form to between 70-85°C, maintaining the temperature, and compressing the first form into the second form;

[0010] S3: Keep the second form cooled to room temperature to fix the second form.

[0011] Optionally, the sampling portion is woven from polycaprolactone wire into a spherical structure with the center of the sphere as the weaving point, and the diameter of the first form is slightly larger than the diameter of the esophagus, and the diameter of the second form is smaller than the diameter of the esophagus.

[0012] Optionally, the sampling portion is a columnar sampling portion, which consists of a hollow cylindrical main body and a cell scraper arranged outwardly perpendicular to the surface of the main body, and the side of the cell scraper has a sample groove formed by an inward depression, and the sample groove is used to collect sample cells.

[0013] Optionally, the sampler is a safety sampler, which is composed of a support covered with a membrane and a connecting part connecting the inside and outside of the support, and the connecting part is a hollow connecting tube.

[0014] Furthermore, the film is prepared by the following method:

[0015] S11: Add 10% glucose powder by mass to 4% silk fibroin solution, stir evenly at 30°C and 500r / min, add 0.5% glycerol solution and continue stirring for 30min, print with electrospinning equipment, keep the solution flow rate at 0.2-0.5mL / h, voltage at 10-30kV, and distance at 15cm to obtain silk fibroin film;

[0016] S12: Dissolve the polyurethane particles in DMF solution to prepare a polyurethane solution with a mass fraction of 8%, apply the polyurethane solution on the outside of the silk fibroin membrane, place it in a drying oven at 35°C to form a membrane, take it out and soak it in deionized water for 8 hours, and then place it in an oven at 35°C to dry it to obtain a membrane.

[0017] Furthermore, in step S12, the following steps are added: after the polyurethane solution is coated, it is first placed in a drying oven at 35° C. for 0.5 h, taken out and knurled on the surface of the polyurethane film, and then put back into the drying oven until it is completely dry.

[0018] Furthermore, the side with the polyurethane layer is located on the outside of the bracket.

[0019] Optionally, the sampling portion is prepared from polycaprolactone diol, and the preparation method of the polycaprolactone diol is:

[0020] S21: Add tetrapropyl phthalate and polyethylene glycol with a molecular weight of 400 into a reactor, slowly heat to 180-220°C, gradually reduce the pressure to 10-50 mmHg, maintain the reaction temperature and vacuum, react for 4 hours and then cool to room temperature; wherein the molar ratio of tetrapropyl phthalate to polyethylene glycol is 1:3;

[0021] S22: Under the protection of nitrogen atmosphere, the initiator and the polycaprolactone monomer are added into the reactor in a molar ratio of 10:1, and the mixture is heated to 160° C. and reacted for 30 minutes to generate polycaprolactone diol.

[0022] Furthermore, the melting point of the polycaprolactone diol is 48.3°C-50.1°C.

[0023] Compared with the prior art, the present invention has the following beneficial effects:

[0024] The structure of the invention is simple and can be integrally formed in industrial manufacturing, which is more conducive to industrialization;

[0025] The structure of the present invention may optionally have a hollow structure, which allows saliva, gastric juice, etc. to flow, which is beneficial for sampling and keeping the sample clean;

[0026] The product of the present invention is easy to use, and can quickly restore to the first form by taking hot water, and the waiting time is short;

[0027] The present invention can have a variety of optional structures, such as adding auxiliary samplers and cell scrapers, etc., which can be suitable for uneven esophageal surfaces and esophagea of ​​different diameters, and can improve the integrity and effectiveness of sampling;

[0028] The present invention also takes into account the regulation of the recovery temperature. By modifying the polycaprolactone, the recovery temperature can be lowered, which is more friendly to the tester who may have mucosal damage. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 is a schematic diagram of the morphological structure of the first form and the second form of Example 1 in Embodiment 1 and the change between the forms;

[0030] Figure 2 is a schematic structural diagram of the sampling auxiliary unit of Example 1 in Embodiment 1;

[0031] Figure 3 is a schematic diagram of the structure of the columnar sampling portion of Example 2 in Embodiment 1;

[0032] Figure 4 is a schematic diagram of the structure of the sample tank in Example 2 of Embodiment 1;

[0033] Figure 5 It is a schematic diagram of the structure of the safety sampler of Example 3 in Example 1.

[0034] Among them, 11-bending part, 12-sampling auxiliary part, 121-inner line, 122-outer line, 123-recessed part, 13-columnar sampling part, 131-main body, 132-cell scraper, 133-sample slot, 14-safety sampler, 141-bracket, 142-membrane, 143-connecting tube. DETAILED DESCRIPTION

[0035] In order to more clearly illustrate the technical solution of the present invention, the detailed description of the embodiments of the accompanying drawings will be combined below to clearly and completely describe the technical solution of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. All other embodiments obtained by ordinary technicians in this field without creative work belong to the protection scope of the present invention.

[0036] The terms "first" and "second" in the present invention are only used for distinguishing descriptions and should not be understood as indicating or implying relative importance; the term "connection" refers to a fixed connection or an integrally formed connection.

[0037] In the prior art, common esophageal cell collection devices include the following:

[0038] The first is the structure disclosed in patent CN111557697A, which has a connecting line and a pull ring, as well as an expandable sampler; wherein, the expandable sampler needs to be pre-stored in a capsule shell and compressed and fixed, and it needs to be taken with cold water, and then warm water is used to accelerate the dissolution of the capsule shell, thereby releasing the expandable sampler inside. In this invention, the expandable sampler uses a sponge material. This patent has the advantages of relatively simple structure and easy use, but its manufacturing requires additional capsule packaging steps, which will increase the difficulty and cost of manufacturing. At the same time, this also means that sufficient time is required to ensure that the capsule shell dissolves, which usually takes 5-7 minutes; in addition, the expandable sampler made of sponge material will have the problem of not being able to uniformly collect cell samples during sampling, which is mainly because the sponge may miss certain parts or fail to fully contact certain parts when passing through the esophagus, and the foreign body sensation of the sponge is more obvious when it is taken out, and the patient's experience is poor.

[0039] The second is the structure disclosed in patent CN110882011A, which still continues the design structure of the disintegrable shell and the internal expandable part, and its expandable part adopts a combination of a fixed net and an expander, and its structure is more complicated, and the difficulty and cost of manufacturing will be higher.

[0040] The third is the structure disclosed in patent CN110448343A, which uses a collection ball composed of an air bag and a sponge layer, and the outside still needs to be encapsulated in a capsule. The capsule dissolves in the digestive juice. Although this structure solves the problem of easy removal, it still needs to be encapsulated in a capsule, and its structure is relatively complex. The structure and connection relationship of the air bag, the inflation tube and the sponge layer are relatively complex, which increases the difficulty and cost of manufacturing. Example 1

[0041] This embodiment provides an esophageal cell sampler that does not require capsule or disintegrable shell packaging and does not use sponge sampling. The esophageal cell sampler is connected by a connecting line and a sampling part. Preferably, the free end of the connecting line can also be connected to a ring member, and the ring member is for facilitating force when the sampler is pulled out.

[0042] The connecting wire in this embodiment can be made of nylon, cotton, linen and other materials in the prior art. The sampling part in this embodiment is the key, which has the characteristic of shape memory. The sampling part in this embodiment is made of polycaprolactone wire, and its manufacturing method is:

[0043] S1: polycaprolactone (molecular weight 4000) wire is made into the first form and irradiated at a dose of 200 kGy;

[0044] S2: raising the temperature of the first form to between 70-85°C, maintaining the temperature, and compressing the first form into the second form;

[0045] S3: Keep the second form cooled to room temperature to fix the second form.

[0046] The first form mentioned above has various structures, including but not limited to the following structures.

[0047] Example 1:

[0048] like Figure 1 As shown, the structure of the first form is a loose spherical structure woven with polycaprolactone wire with the center of the sphere as the origin, and the diameter of the first form is slightly larger than the diameter of the esophagus. In step S2, the first form is compressed to form a second form. Compared with the first form, the second form has a smaller spherical radius and its size can easily pass through the esophagus. After reaching the predetermined position, the second form is restored to the size and shape of the first form by drinking hot water (52-57°C). At this time, the connecting line connected to the sampling part is pulled, and the sampling part will contact and scrape the esophagus, so as to achieve the purpose of collecting esophageal cells.

[0049] Of course, in order to better collect esophageal cells, the following improvements can be made on the basis of the above:

[0050] One of the improvements is that the surface of the esophagus is not smooth and the diameter is not uniform, so the sampling part with a fixed diameter will have the risk of incomplete sampling. Therefore, in the first form, the polycaprolactone wires can be woven into spheres of different diameters. Some of the wires will have a larger diameter, while most of them will still have the diameter of Example 1. In this way, more esophageal cells can be collected during use to ensure the completeness of the sampling.

[0051] The second improvement is that the bending part 11 of the polycaprolactone is the key position for contacting the esophagus for sampling. In order to enhance the sampling effect, the polycaprolactone wire is thickened at part of the bending part 11. Alternatively, a sampling auxiliary part 12 is provided, such as Figure 2 As shown, the sampling auxiliary part 12 is in the shape of a "spoon", which is enclosed by an inner line 121 and an outer line 122. The enclosed internal area is a solid structure, which is concave inward to form a concave part 123; wherein the inner line 121 is the bending part 11 of the polycaprolactone wire in Example 1, and the outer line is a protruding bending part 11 that is separately arranged outward. In order to facilitate the realization of this structure, a 3D printing method can be used for integral molding. When this structure is in use, the protruding sampling auxiliary part 12 will preferentially contact the esophageal wall, collect esophageal cells in the concave part 123, and can also collect samples to the greatest extent.

[0052] The structure of this example is extremely simple, the sampling part is integrally formed, and no additional capsule is required for packaging. In addition, the structure of this example is a non-solid structure, which allows saliva or gastric juice to flow without remaining inside or on the surface of the sampling part. The advantage is that it is easy to collect the sampled cells, and the collected samples are relatively clean.

[0053] Example 2:

[0054] like Figure 3 and Figure 4 As shown, the structure of another esophageal cell sampler is shown, which is a columnar sampling part 13. The columnar sampling part 13 is composed of a main body 131 and a cell scraper 132 fixed on the surface of the main body 131. The number of cell scrapers 132 is at least three. The main body 131 is a hollow cylindrical structure. The cell scraper 132 is arranged perpendicular to the surface of the main body 131. The connection between the cell scraper 132 and the main body 131 has a smooth transition. The side of the cell scraper 132 is concave inward to form a sample groove 133. The sample groove 133 is used to collect cell samples.

[0055] In this example, at least the main body 131 is made of polycaprolactone and the method in the embodiment, and the cell scraper 132 can also be made of polycaprolactone material. The hollow internal structure is also conducive to the collection and storage of samples, and is also conducive to obtaining clean cell samples.

[0056] Of course, the structure of this example can also be improved as follows:

[0057] In order to reduce the amount of polycaprolactone used and speed up the structural recovery of the sampler, the main body 131 can be designed as a hollow structure with intervals. The advantage of this is that it is conducive to compression shaping in the diameter direction and reduces the size of the second form.

[0058] Example 3:

[0059] In this embodiment, drinking hot water (52-57°C) is required to restore the sampler from the second form to the first form. Generally, water above 60°C will feel hot and may damage the mucosa; but in esophageal cancer patients, the esophageal mucosa is likely to have been damaged to a certain extent, so they will be more intolerant to hot water. In order to solve this problem, this example has been improved and optimized from a structural perspective, making it safer to use, while still having a simple structure.

[0060] like Figure 5 As shown, the safety sampler 14 is composed of a bracket covered with a membrane 142 and a connecting tube 143 connected to the inside of the bracket. The bracket 141 is still made of polycaprolactone material and is spherical as a whole. The gap of the bracket 141 is wrapped with a membrane 142, and the membrane 142 is prepared by the following method:

[0061] S11: Add 10% glucose powder by mass to 4% silk fibroin solution, stir evenly at 30°C and 500r / min, add 0.5% glycerol solution and continue stirring for 30min, print with electrospinning equipment, keep the solution flow rate at 0.2-0.5mL / h, voltage at 10-30kV, and distance at 15cm to obtain silk fibroin film;

[0062] S12: The polyurethane particles were dissolved in DMF solution to prepare a polyurethane solution with a mass fraction of 8%, the polyurethane solution was coated on the outside of the silk fibroin membrane, and the membrane was placed in a 35°C drying oven to form a membrane. After taking it out, it was soaked in deionized water for 8 hours, and then placed in a 35°C oven to dry to obtain membrane 142.

[0063] As one improvement, a step can be added in step S12. After the polyurethane solution is coated, it is first placed in a drying oven at 35°C for 0.5 hours, taken out and knurled on the surface of the polyurethane film, and then put back into the drying oven until it is completely dry. The advantage of adding this step is that the roughness of the surface of the film 142 is increased, making it more conducive to the sampling and collection of cells.

[0064] The outer side (the side with polyurethane) of the membrane 142 prepared by the above method is placed on the outer side of the bracket 141. The outer side of the membrane 142 makes it waterproof and impermeable, and the inner silk protein membrane layer has high water absorption. The connecting tube 143 is a hollow tubular structure. Hot water enters the sampling part (bracket and membrane) through the connecting tube 143. The membrane 142 has good water absorption performance and quickly absorbs hot water. Therefore, the bracket 141 in close contact with the membrane 142 can be heated more quickly so that the shape is restored; and the waterproof effect on the outside can also prevent the outflow of hot water; in addition, because of the existence of the membrane 142, it has a certain thickness, so it also has a certain heat insulation performance and will not damage the mucosa. After the water is placed, the sampling part has a certain weight and temperature. In the process of collecting cells, the progress of sampling and the resistance of dragging can also be felt, and adjustments can be made in time to ensure the sampling effect. Example 2

[0065] On the basis of Example 1, polycaprolactone is modified to lower its melting point so that it has temperature-dependent properties at lower temperatures. At this time, warm water below 55°C can be used to help it recover its shape, making it safer to use and more comfortable to the body.

[0066] The modification method is as follows:

[0067] S21: Add tetrapropyl phthalate and polyethylene glycol with a molecular weight of 400 into a reactor, slowly heat to 180-220°C, gradually reduce the pressure to 10-50 mmHg, maintain the reaction temperature and vacuum, react for 4 hours and then cool to room temperature; wherein the molar ratio of tetrapropyl phthalate to polyethylene glycol is 1:3;

[0068] S22: Under the protection of nitrogen atmosphere, the initiator and the polycaprolactone monomer are added into the reactor in a molar ratio of 10:1, and the mixture is heated to 160° C. and reacted for 30 minutes to generate polycaprolactone diol.

[0069] Because the addition of polyethylene glycol further lowers the melting point, after testing, the melting point remains between 48.3-50.1, which is safer and more comfortable for the sampler.

[0070] The method for preparing the sampler in this embodiment is the same as that in Example 1, and its structure can also be the same as the example, the only difference is that the polycaprolactone in Example 1 is replaced by the polycaprolactone diol in this embodiment.

Claims

1. An esophageal cell sampler, characterized in that: The sampler is composed of a sampling part and a connecting part fixedly connected to the sampling part, part or all of the sampling part is made of shape memory material, the shape memory material is polycaprolactone or polycaprolactone diol, the sampling part has a first form and a second form, and the second form can restore the first form within a temperature range of 52°C-57°C or 48.3°C-50.1°C; the sampler is a safety sampler, the sampler is composed of a support covered with a membrane and a connecting part connecting the inside and outside of the support, the connecting part is a hollow connecting tube, and the membrane is prepared by the following method: S11: Add 10% glucose powder by mass to 4% silk fibroin solution, stir evenly at 30°C and 500r / min, add 0.5% glycerol solution and continue stirring for 30min, print with electrospinning equipment, keep the solution flow rate at 0.2-0.5mL / h, voltage at 10-30kV, and distance at 15cm to obtain silk fibroin film; S12: Dissolve the polyurethane particles in DMF solution to prepare a polyurethane solution with a mass fraction of 8%, apply the polyurethane solution on the outside of the silk fibroin membrane, place it in a drying oven at 35°C to form a membrane, take it out and soak it in deionized water for 8 hours, and then place it in an oven at 35°C to dry it to obtain a membrane.

2. An esophageal cell sampler according to claim 1, characterized in that: The preparation method of the sampling part is: S1: a polycaprolactone wire with a molecular weight of 4000 is made into a first form and irradiated at a dose of 200 kGy; S2: raising the temperature of the first form to between 70-85°C, maintaining the temperature, and compressing the first form into the second form; S3: Keep the second form cooled to room temperature to fix the second form.

3. An esophageal cell sampler according to claim 1 or 2, characterized in that: The sampling part is woven from polycaprolactone wires into a spherical structure with the sphere center as the weaving point. The diameter of the first form is slightly larger than the diameter of the esophagus, and the diameter of the second form is smaller than the diameter of the esophagus.

4. An esophageal cell sampler according to claim 1 or 2, characterized in that: The sampling part is a columnar sampling part, which consists of a hollow cylindrical main body and a cell scraper arranged outwardly perpendicular to the surface of the main body. The side of the cell scraper has a sample groove formed by an inward depression, and the sample groove is used to collect sample cells.

5. The esophageal cell sampler according to claim 1, characterized in that: In step S12, the following steps are added: after the polyurethane solution is coated, it is first placed in a drying oven at 35°C for 0.5h, taken out and knurled on the surface of the polyurethane film, and then put back into the drying oven until it is completely dry.

6. An esophageal cell sampler according to claim 5, characterized in that: The side with the polyurethane layer is located on the outside of the bracket.

7. An esophageal cell sampler according to claim 1 or 2, characterized in that: The sampling part is prepared from polycaprolactone diol, and the preparation method of the polycaprolactone diol is as follows: S21: Add tetrapropyl phthalate and polyethylene glycol with a molecular weight of 400 into a reactor, slowly heat to 180-220°C, gradually reduce the pressure to 10-50 mmHg, maintain the reaction temperature and vacuum, react for 4 hours and then cool to room temperature; wherein the molar ratio of tetrapropyl phthalate to polyethylene glycol is 1:3; S22: Under the protection of nitrogen atmosphere, the initiator and the polycaprolactone monomer are added into the reactor in a molar ratio of 10:1, and the mixture is heated to 160° C. and reacted for 30 minutes to generate polycaprolactone diol.

8. An esophageal cell sampler according to claim 7, characterized in that: The melting point of the polycaprolactone diol is 48.3°C-50.1°C.

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