CN113546232B - Therapeutic equipment and preparation method of cell filter membrane - Google Patents
Therapeutic equipment and preparation method of cell filter membrane Download PDFInfo
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- CN113546232B CN113546232B CN202010333713.5A CN202010333713A CN113546232B CN 113546232 B CN113546232 B CN 113546232B CN 202010333713 A CN202010333713 A CN 202010333713A CN 113546232 B CN113546232 B CN 113546232B
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D67/00—Processes specially adapted for manufacturing semi-permeable membranes for separation processes or apparatus
Abstract
The application discloses treatment equipment and a preparation method of a cell filter membrane, and belongs to the technical field of biochemical detection. The treatment apparatus includes: the cell filter comprises a sealing cavity, a cell filter membrane positioned in the sealing cavity, and a first pipeline and a second pipeline which are communicated with the sealing cavity. When the treatment equipment is used for treating a patient, one end of the first pipeline and one end of the second pipeline are communicated with blood vessels of the patient, so that blood of the patient enters the sealed cavity through the first pipeline, CTC cells in the blood of the patient are filtered through the cell filter membrane in the sealed cavity, and the blood with the CTC cells filtered can flow back into the patient through the second pipeline. CTC cells in the blood of a patient can be removed by the treatment apparatus, so that the treatment apparatus can exert a therapeutic effect on the patient.
Description
Technical Field
The application relates to the technical field of biochemical detection, in particular to treatment equipment and a preparation method of a cell filter membrane.
Background
Circulating tumor cells (English: circulating tumor cell; CTC for short) in the blood of cancer patients are one of the factors that lead to metastasis of cancer in patients. However, the current technology cannot remove CTC cells in the patient's blood, and thus, a therapeutic apparatus capable of removing CTC cells in the patient's blood is highly demanded.
Disclosure of Invention
The embodiment of the application provides a treatment device and a preparation method of a cell filter membrane. The problem that CTC cells in blood of a patient cannot be removed in the prior art can be solved, and the technical scheme is as follows:
in one aspect, there is provided a therapeutic apparatus comprising:
sealing the box body;
the cell filter membrane is positioned in the sealing box body, the sealing box body is separated by the cell filter membrane to obtain two cavities, and the two cavities comprise a first cavity and a second cavity;
a first pipeline with one end communicated with the first cavity of the sealing box body and a second pipeline with one end communicated with the second cavity of the sealing box body;
the first pipeline is far away from one end of the sealing box body, and the second pipeline is far away from one end of the sealing box body, and the first pipeline and the second pipeline are all ports communicated with blood vessels.
Optionally, the sealing box body includes: a first housing and a second housing detachably connected;
the edge of the cell filter membrane is detachably connected with the opening of the first shell or the opening of the second shell, one end of the first pipeline is communicated with the first shell, and one end of the second pipeline is communicated with the second shell.
Optionally, the cell filter membrane comprises: a laminated flexible layer, a functional layer, and a mask layer, the functional layer comprising: at least one of a conductive layer, a light shielding layer and a biochemical layer which can be modified by a modifying liquid.
Optionally, the therapeutic apparatus further comprises: a sensor located within the first conduit and/or the second conduit, and a processor connected to the sensor;
wherein the processor is configured to determine whether the cell filter membrane is clogged based on information of the fluid parameter detected by the sensor.
Optionally, the first pipeline is a liquid inflow pipeline, and the sensor in the first pipeline is a pressure sensor;
the second pipeline is a liquid outflow pipeline, and the sensor in the second pipeline is a flow rate sensor;
wherein the processor is configured to: when the pressure sensor detects that the pressure of the fluid in the first pipeline is greater than a pressure threshold value, determining that the cell filter membrane is blocked;
the processor is further configured to: and when the flow rate of the liquid in the second pipeline detected by the flow rate sensor is smaller than a flow rate threshold value, determining that the cell filter membrane is blocked.
Optionally, the direction of extension of the cell filter membrane is parallel to the direction of gravity.
In another aspect, a method of preparing a cell filter membrane is provided, the method comprising:
forming a thin film on a light-transmitting substrate;
patterning the film to form a cell filter film on the light-transmitting substrate;
and stripping the light-transmitting substrate to obtain the cell filter membrane.
Optionally, the film comprises: a flexible film, a functional film and a mask film which are sequentially laminated along a direction away from the light-transmitting substrate;
patterning the thin film to form a cell filter film on the light-transmitting substrate, comprising:
performing a patterning process on the mask film to form a mask layer;
performing first etching treatment on the functional film to form a functional layer with the mask layer;
and carrying out second etching treatment on the flexible film to form a flexible layer with the mask layer and the functional layer.
Optionally, a patterning process is performed on the mask film to form a mask layer, including:
forming a photoresist film on the mask film;
performing exposure treatment and development treatment on the photoresist film to form a mask film with a photoresist pattern;
performing third etching treatment on the mask film with the photoresist pattern to form a mask layer with the photoresist pattern;
and removing the photoresist pattern to form the mask layer.
Optionally, the functional film includes: at least one of a conductive film, a light shielding film, and a biochemical film that can be modified by a modifying liquid.
The technical scheme provided by the embodiment of the application has the beneficial effects that at least:
when the treatment equipment provided by the application is used for treating a patient, one end of the first pipeline and one end of the second pipeline are communicated with the blood vessel of the patient, so that blood of the patient enters the sealed cavity through the first pipeline, CTC cells in the blood of the patient are filtered through the cell filter membrane in the sealed cavity, and the blood with the CTC cells filtered can flow back into the patient through the second pipeline. CTC cells in the blood of a patient can be removed by the treatment apparatus, so that the treatment apparatus can exert a therapeutic effect on the patient. In addition, the cell filter membrane in the treatment equipment can be used for capturing a large amount of CTC cells, so that the accuracy of detecting the CTC cells captured by the cell filter membrane can be ensured.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings required for the description of the embodiments will be briefly described below, and it is apparent that the drawings in the following description are only some embodiments of the present application, and other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
Fig. 1 is a schematic structural view of a therapeutic apparatus according to an embodiment of the present application;
FIG. 2 is an effect graph of removing CTC cells in a patient using the treatment apparatus shown in FIG. 1;
FIG. 3 is a schematic view of another therapeutic apparatus according to an embodiment of the present application;
FIG. 4 is a schematic view of another therapeutic apparatus according to an embodiment of the present application;
FIG. 5 is a graph showing the effect of the cell filter provided by the embodiment of the application on capturing CTC cells for detection;
FIG. 6 is a graph showing the distribution of the number of CTC cells captured by the cell filter on the cell filter according to the example of the present application;
FIG. 7 is a top view of a provided cell filter according to an embodiment of the present application;
FIG. 8 is a cross-sectional view of the cell filter membrane shown in FIG. 7 at A-A';
FIG. 9 is a flowchart of a method for preparing a cell filter according to an embodiment of the present application;
FIG. 10 is a flowchart of another method for preparing a cell filter according to an embodiment of the present application;
FIG. 11 is a schematic diagram of sequentially forming a flexible film, a functional film and a mask film on a transparent substrate according to an embodiment of the present application;
FIG. 12 is a schematic diagram of forming a photoresist film on a mask film according to an embodiment of the present application;
FIG. 13 is a schematic illustration of a method for forming a mask film with a photoresist pattern according to an embodiment of the present application;
FIG. 14 is a schematic diagram of forming a mask layer with a photoresist pattern according to an embodiment of the present application;
FIG. 15 is a schematic diagram of forming a mask layer according to an embodiment of the present application;
FIG. 16 is a schematic illustration of forming a functional layer with a mask layer according to an embodiment of the present application;
FIG. 17 is a schematic illustration of forming a flexible layer with a mask layer and a functional layer according to an embodiment of the present application;
FIG. 18 is a schematic diagram of a cell filter obtained by peeling off a transparent substrate with glass according to an embodiment of the present application.
Detailed Description
For the purpose of making the objects, technical solutions and advantages of the present application more apparent, the embodiments of the present application will be described in further detail with reference to the accompanying drawings.
Referring to fig. 1, fig. 1 is a schematic structural diagram of a therapeutic apparatus according to an embodiment of the present application. The therapeutic apparatus 00 may include:
sealing the cartridge 100, and a cell filter membrane 200 positioned within the sealing cartridge 100. The cell filter 200 can divide the sealed case 100 into two chambers. The two cavities include a first cavity 100a and a second cavity 100b. In the present application, the cell filter 200 is capable of filtering out larger volume cells, whereas CTC cells are generally larger in volume, so the cell filter 200 is capable of filtering out CTC cells. The cell filter 200 has a plurality of filter holes, and CTC cells can be captured through the filter holes, so as to achieve the purpose of filtering CTC cells.
The therapeutic apparatus 00 may further include: a first pipe 300 having one end communicating with the first chamber 100a, and a second pipe 400 having one end communicating with the second chamber 100b. The end of the first pipeline 300 away from the sealing box 100 and the end of the second pipeline 400 away from the sealing box 100 are all ports communicated with blood vessels.
It should be noted that fig. 1 is schematically illustrated by taking an example in which the treatment apparatus 00 comprises a cell filter 100. In other alternative implementations, the treatment apparatus 00 may also include a plurality of cell filters arranged in parallel. When the treatment apparatus 00 includes a plurality of parallel-arranged cell membranes, the parallel-arranged cell membranes can divide the sealing case 100 into three or more chambers, but the chambers always include a first chamber 100a communicating with the first pipeline 300 and a second chamber 100b communicating with the second pipeline 400.
In an embodiment of the present application, when CTC cells are contained in the blood of a patient, the treatment apparatus 00 may be employed to remove CTC cells in the blood of the patient. For example, referring to fig. 2, fig. 2 is an effect diagram of removing CTC cells in a patient using the treatment apparatus shown in fig. 1. One end of the first pipeline 300 and one end of the second pipeline 400 may be both communicated with the blood vessel of the patient, so that the blood of the patient flows into the sealing box body 100 through the first pipeline 300, CTC cells a in the blood are removed through the cell filter membrane 200 in the sealing box body 100, and other normal cells b such as red blood cells and white blood cells in the blood can normally pass through the cell filter membrane 200 due to the small volume thereof and are not filtered by the cell filter membrane. The blood having CTC cells a filtered through the cell filter 200 may be returned to the blood vessel of the patient through the second line 400. Therefore, CTC cells in the blood of the patient can be removed by the treatment apparatus 00, so that the treatment apparatus 00 can exert a therapeutic effect on the patient.
In the related art, when CTC cells are detected in a patient, it is necessary to collect a blood sample of the patient and pass the blood sample through a cell filter so that CTC cells in the blood sample are captured by the cell filter. However, since the concentration of CTC cells in the patient's blood is low and the volume of blood sample taken from the patient is limited, the number of CTC cells captured by the current cell filter is low, resulting in low accuracy in detecting CTC cells captured by the cell filter.
In the embodiment of the present application, when CTC cells are detected on a patient, CTC cells in the blood of the patient can be captured by the cell filter 200 in the treatment apparatus 00 while the patient is being treated by the treatment apparatus 00. When a patient is treated by the treatment apparatus 00, a large amount of blood is required to flow into the treatment apparatus 00, CTC cells are filtered out by the cell filter 200 in the treatment apparatus 00, and then the blood flows back into the blood vessel of the patient from the treatment apparatus 00. Because a great amount of blood of a patient can pass through the cell filter membrane 200, the difficulty of capturing CTC cells by the cell filter membrane 200 is effectively reduced, and the number of CTC cells captured by the cell filter membrane 200 is further increased, so that the accuracy of detecting the CTC cells captured by the cell filter membrane 200 is effectively improved.
In summary, the treatment apparatus provided in the embodiment of the present application includes: the cell filter comprises a sealing cavity, a cell filter membrane positioned in the sealing cavity, and a first pipeline and a second pipeline which are communicated with the sealing cavity. When the treatment equipment is used for treating a patient, one end of the first pipeline and one end of the second pipeline are communicated with blood vessels of the patient, so that blood of the patient enters the sealed cavity through the first pipeline, CTC cells in the blood of the patient are filtered through the cell filter membrane in the sealed cavity, and the blood with the CTC cells filtered can flow back into the patient through the second pipeline. CTC cells in the blood of a patient can be removed by the treatment apparatus, so that the treatment apparatus can exert a therapeutic effect on the patient. In addition, the cell filter membrane in the treatment equipment can be used for capturing a large amount of CTC cells, so that the accuracy of detecting the CTC cells captured by the cell filter membrane can be ensured.
Optionally, referring to fig. 3, fig. 3 is a schematic structural diagram of another therapeutic apparatus according to an embodiment of the present application. The sealing case 100 in the therapeutic apparatus 00 may include: a first housing 101 and a second housing 102 detachably connected. One end of a first tube 300 in the treatment apparatus 00 communicates with the first housing 101, and one end of a second tube 400 in the treatment apparatus 00 communicates with the second housing 102.
The first housing 101 and the second housing 102 each have an opening, and the opening of the first housing 101 and the opening of the second housing 102 can be detachably connected. In the present application, the edge of the cell filter membrane 200 in the treatment apparatus 00 may be detachably coupled with the opening of the first housing 101 or the opening of the second housing 102. In this way, the cell filter 200 can be taken out from the sealing box 100, so that CTC cells captured by the cell filter 200 can be detected later, and when the cell filter 200 is blocked, a new cell filter can be replaced by the treatment device 00.
By way of example, the first housing 101 has a first connector 1011 and the second housing 102 has a second connector 1012 detachably connected to the first connector 1011. The detachable connection of the first housing 101 and the second housing 102 can be achieved by the engagement of the first connector 1011 and the second connector 1012. For example, the first connector 1011 and the second connector 1012 are two magnets with opposite magnetic properties, respectively, or the first connector 1011 and the second connector 1012 are a bolt and a nut, respectively.
Optionally, the sealing case 100 may further include: a sealing ring (not shown in fig. 3) between the first housing 101 and the second housing 102, through which the sealability of the sealing case 100 can be ensured, thereby ensuring the reliability of the use of the therapeutic apparatus 00.
Optionally, referring to fig. 4, fig. 4 is a schematic structural diagram of another therapeutic apparatus according to an embodiment of the present application. The therapeutic apparatus 00 may further include: a sensor 500 located within the first conduit 300 and/or the second conduit 400, and a processor 600 coupled to the sensor 500. It should be noted that, the sensor 500 needs to be fixedly connected to the inner wall of the first pipeline 300 and/or the second pipeline 400, so that the sensor 500 can detect the parameter of the fluid, and meanwhile, the problem that the therapeutic equipment 00 fails due to the falling of the sensor 500 is avoided.
Wherein the sensor 500 is configured to detect information of a fluid parameter in the first conduit 300 and/or the second conduit 400 and to send the detected information of the fluid parameter to the processor 600. The processor 600 is configured to receive information of the fluid parameter transmitted from the sensor 500 and determine whether the cell filter 200 is clogged based on the information of the fluid parameter.
By way of example, the first line 300 may be a liquid inflow line and the sensor 500 within the first line 300 is a pressure sensor 501. The pressure sensor 501 is configured to: the pressure of the fluid in the first line 300 is detected and the pressure of the fluid detected thereby is transmitted to the processor 600. The processor 600 is configured to: when the pressure of the fluid sent from the pressure sensor 501 is received, it is detected whether the pressure of the fluid is greater than a pressure threshold, and when it is detected that the pressure of the fluid is greater than the pressure threshold, it is determined that clogging of the cell filter 200 occurs.
The second line 400 may be a liquid outflow line and the sensor 500 within the second line 400 is a flow rate sensor 502. The flow rate sensor 502 is configured to: the flow rate of the fluid in the second pipe 400 is detected and the detected flow rate of the fluid is transmitted to the processor 600. The processor 600 is configured to: when the flow rate of the fluid sent from the flow rate sensor 502 is received, it is detected whether the flow rate of the fluid is less than a flow rate threshold, and it is determined that clogging of the cell filter 200 occurs when it is detected that the flow rate of the fluid is less than the flow rate threshold.
In the embodiment of the present application, as shown in fig. 3 and 4, when the therapeutic apparatus 00 is used to treat a patient, the direction of extension of the cell filter membrane 200 in the therapeutic apparatus 00 is parallel to the direction of gravity, that is, the cell filter membrane 200 is vertically disposed during use. Thus, when the cell filter 200 filters CTC cells in blood, the number of CTC cells captured by the cell filter 200 gradually decreases from bottom to top under the influence of gravity.
As shown in fig. 5 and 6, fig. 5 is a graph showing the effect of capturing CTC cells by using the cell filter according to the embodiment of the present application, and fig. 6 is a graph showing the number of CTC cells captured by using the cell filter according to the embodiment of the present application distributed on the cell filter. The left end of the cell filter 200 shown in fig. 5 is the end thereof near the lower side when the inside of the cartridge is sealed, and the right end of the cell filter 200 shown in fig. 5 is the end thereof near the upper side when the inside of the cartridge is sealed. The number of CTC cells a on the cell filter 200 may be detected in the left-to-right direction x using a detection device 01 such as a microscope, so that a number distribution graph shown in fig. 6 may be obtained. The abscissa in fig. 6 represents different positions in the cell filter 200 in fig. 5, and the ordinate in fig. 6 represents the number of CTC cells a captured by the cell filter 200 at the corresponding positions. Based on this graph, the number of CTC cells a captured by the cell filter 200 decreases sequentially from left to right in fig. 5. Thus, when determining the content of CTC cells a contained in the blood of the patient based on the number of CTC cells a captured by the cell filter 200, the number of CTC cells a in the region of the cell filter 200 near the right end may be determined by the detection module 01, and the determined number may be compared with a predetermined theoretical number of CTC cells a at the corresponding position to determine the level of the content of CTC cells a in the blood of the patient, so that the severity of the patient's illness can be diagnosed. Since the number of CTC cells a distributed in the region of the cell filter 200 near the right end is small, the efficiency of determining the number of CTC cells a therein can be effectively improved, and thus the efficiency of determining the severity of the patient's illness can be improved.
Alternatively, referring to fig. 7 and 8, fig. 7 is a top view of a cell filter provided in an embodiment of the present application, and fig. 8 is a cross-sectional view of the cell filter at A-A' shown in fig. 7. The cell filter 200 has a plurality of filter holes 200a.
The cell filter 200 includes: a laminated flexible layer 201, a functional layer 202, and a mask layer 203. The functions and actions of the flexible layer 201 and the mask layer 203 are described in the following embodiments of the method for manufacturing a cell filter membrane, and are not described herein.
The functional layer 202 may include: at least one of a conductive layer 202a, a light shielding layer 202b, and a biochemical layer 202c that may be modified by a modification solution.
The conductive layer 202a can provide the cell filter 200 with a certain conductivity, and can detect the resistivity of CTC cells after the CTC cells are captured by the cell filter 200.
The light shielding layer 202b can shield light, and since CTC cells captured by the cell filter 200 are located in the filter hole 200a of the cell filter 200, when the cell filter 200 includes the light shielding layer 202b, the contrast of CTC cells located in the filter hole 200a can be improved, thereby facilitating subsequent observation of the CTC cells by a microscope.
The biochemical layer 202c can be modified by a modifying solution, so that when the CTC cells are captured by the cell filter 200, the biochemical layer 202c modified by the modifying solution can react with the surfaces of different CTC cells, thereby forming different colors. The types of CTC cells captured by the cell filter 200 can be distinguished by the biochemical layer 202 c.
Note that the conductive layer 202a and the light shielding layer 202b in the functional layer 202 may be a metal layer having light shielding property and conductivity, and the metal layer may be, for example, metal molybdenum or metal iron. When the functional layer 202 includes the metal layer, the mechanical strength of the metal layer is high, so that the cell filter membrane 200 has a certain anti-curling capability, and the mechanical strength of the cell filter membrane 200 is effectively improved.
In summary, the treatment apparatus provided in the embodiment of the present application includes: the cell filter comprises a sealing cavity, a cell filter membrane positioned in the sealing cavity, and a first pipeline and a second pipeline which are communicated with the sealing cavity. When the treatment equipment is used for treating a patient, one end of the first pipeline and one end of the second pipeline are communicated with blood vessels of the patient, so that blood of the patient enters the sealed cavity through the first pipeline, CTC cells in the blood of the patient are filtered through the cell filter membrane in the sealed cavity, and the blood with the CTC cells filtered can flow back into the patient through the second pipeline. CTC cells in the blood of a patient can be removed by the treatment apparatus, so that the treatment apparatus can exert a therapeutic effect on the patient. In addition, the cell filter membrane in the treatment equipment can be used for capturing a large amount of CTC cells, so that the accuracy of detecting the CTC cells captured by the cell filter membrane can be ensured.
Referring to fig. 9, fig. 9 is a flowchart of a method for preparing a cell filter according to an embodiment of the application. The preparation method of the cell filter membrane is used for preparing the cell filter membrane 200 in the treatment apparatus 00 shown in fig. 1. The preparation method of the cell filter membrane can comprise the following steps:
step 901, forming a thin film on a light-transmitting substrate.
The light-transmitting substrate may be a transparent substrate of glass, quartz, sapphire, or resin, for example.
Step 902, patterning the thin film to form a cell filter film on the transparent substrate.
And 903, stripping the transparent substrate to obtain the cell filter membrane.
In the related art, the preparation method of the cell filter membrane is as follows: and forming a patterned silicon substrate on the silicon substrate through a patterning etching process, then filling a liquid organic material on the patterned silicon substrate, and forming a cell filter membrane on the patterned silicon substrate after the liquid organic material is solidified. Because the silicon base is a non-light-transmitting material, the cell filter membrane is extremely easy to damage in the process of stripping the silicon base. Therefore, in the related art, a silicon substrate having a cell filtration membrane formed thereon is generally put into a solution (e.g., hydrofluoric acid) for dissolving the silicon substrate, and after the silicon substrate is completely dissolved, the cell filtration membrane is obtained. However, the use of a solution to dissolve the silicon matrix is costly, resulting in a costly preparation of the cell filter. Moreover, the size of the silicon group is generally small, so that the related art cannot prepare a cell filter membrane with a large area.
In the embodiment of the application, the cell filter membrane is formed on the light-transmitting substrate, and the light-transmitting substrate has higher light transmission, so that the light-transmitting substrate can be stripped by adopting a laser stripping technology on the premise of not damaging the cell filter membrane, thereby obtaining the cell filter membrane and effectively reducing the preparation cost of the cell filter membrane. The size of the transparent substrate is far larger than that of the silicon substrate, so that the preparation method of the cell filter membrane shown in the embodiment of the application can prepare the cell filter membrane with larger area, and the cell filter membrane with larger area can be assembled in the treatment equipment shown in fig. 1 to filter CTC cells in blood.
In summary, in the preparation method of the cell filter membrane provided by the embodiment of the application, since the cell filter membrane is formed on the light-transmitting substrate, the light-transmitting substrate has higher light transmission, so that the light-transmitting substrate can be peeled off by adopting the laser peeling technology on the premise of not damaging the cell filter membrane, the cell filter membrane is obtained, and the transparent substrate is not required to be dissolved by adopting a solution, thereby effectively reducing the preparation cost of the cell filter membrane. The size of the transparent substrate is far larger than that of the silicon substrate, so that the cell filter membrane with larger area can be prepared by the preparation method of the cell filter membrane, and the cell filter membrane with larger area can be assembled in the treatment equipment to filter CTC cells in blood.
Optionally, referring to fig. 10, fig. 10 is a flowchart of another preparation method of a cell filter according to an embodiment of the present application. The preparation method of the cell filter is used to prepare the cell filter 200 in the therapeutic apparatus shown in fig. 1, 3 or 4, for example, it is possible to prepare the cell filter shown in fig. 7. The preparation method of the cell filter membrane can comprise the following steps:
step 1001, providing a transparent substrate.
Alternatively, the transparent substrate may be a transparent substrate such as glass, quartz, sapphire, or resin. For example, the transparent substrate can be cleaned by adopting a cleaning process, so that a film can be formed on the transparent substrate normally in the following process.
Step 1002, a thin film is formed on the light-transmitting substrate.
In an embodiment of the present application, the film may include: the flexible film, the functional film and the mask film are laminated in this order in a direction away from the light-transmitting substrate. By way of example, the functional film may include: at least one of a conductive film, a light shielding film, and a biochemical film that can be modified by a modifying solution.
Alternatively, the flexible film may be a Polyimide (english: polyimide; abbreviated as PI) layer. The material of the mask film may be an inorganic material such as silicon nitride or silicon dioxide.
For the conductive film and the light shielding film in the functional film, the conductive film and the light shielding film may be the same layer of film, and the material may be a material having light shielding performance and conductive performance, for example, a metal material such as metallic molybdenum or metallic iron. Of course, the conductive film and the light shielding film may be two different films, in which case the material of the conductive film may be a transparent conductive material such as ITO, and the material of the light shielding film may be metallic chromium or black resin, or the like.
For the biochemical thin film among the functional thin films, the material of the biochemical thin film may be a material that can be modified by a modifying solution, for example, the material of the biochemical thin film may be silicon oxide.
For example, referring to fig. 11, fig. 11 is a schematic diagram of sequentially forming a flexible film, a functional film and a mask film on a transparent substrate according to an embodiment of the present application. The flexible film 02a, the functional film 02b, and the mask film 02c may be sequentially formed on the light-transmitting substrate 02 by any one of a variety of means such as deposition, coating, sputtering, and the like.
Step 1003, performing a patterning process on the mask film to form a mask layer.
In the embodiment of the present application, the manner of performing a patterning process on the mask film to form the mask layer may include the following sub-steps:
and S1, forming a photoresist film on the mask film.
For example, referring to fig. 12, fig. 12 is a schematic diagram illustrating formation of a photoresist film on a mask film according to an embodiment of the present application. A coating apparatus may be used to coat a photoresist film 02d on the mask film 02c.
And S2, performing exposure treatment and development treatment on the photoresist film to form a mask film with a photoresist pattern.
For example, referring to fig. 13, fig. 13 is a schematic diagram illustrating a mask film with a photoresist pattern according to an embodiment of the present application. The photoresist film may be exposed by an exposure apparatus using a reticle, and then the exposed photoresist film may be developed by a developing apparatus, thereby obtaining a mask film 02c having a photoresist pattern 02d 1.
And S3, performing third etching treatment on the mask film with the photoresist pattern to form a mask layer with the photoresist pattern.
For example, referring to fig. 14, fig. 14 is a schematic diagram illustrating formation of a mask layer with a photoresist pattern according to an embodiment of the present application. The mask film with the photoresist pattern 02d1 may be subjected to a third etching process using an etching apparatus to form the mask layer 203 with the photoresist pattern 02d 1.
And S4, removing the photoresist pattern to form a mask layer.
For example, referring to fig. 15, fig. 15 is a schematic diagram illustrating formation of a mask layer according to an embodiment of the present application. The photoresist pattern in the mask layer 203 with the photoresist pattern is stripped to obtain the mask layer 203.
It should be noted that, the mask layer can be obtained through the above-mentioned sub-steps S1 to S4.
Step 1004, performing a first etching process on the functional film to form a functional layer with a mask layer.
For example, referring to fig. 16, fig. 16 is a schematic diagram illustrating formation of a functional layer with a mask layer according to an embodiment of the present application. An etching apparatus may be used to perform a first etching process on the functional film to form the functional layer 202 with the mask layer 203.
It should be noted that, since the functional film may include: at least one of a conductive film, a light shielding film, and a biochemical film that can be modified by a modifying solution. Accordingly, the functional layer 202 formed through step 1004 may include at least one of a stacked conductive layer, a light shielding layer, and a biochemical layer that may be modified by a modification solution.
It should be further noted that the conductive layer, the light shielding layer and the biochemical layer in the functional layer 202 may refer to the corresponding contents in the foregoing embodiment of the structure of the therapeutic apparatus, which are not described herein.
Step 1005, performing a second etching process on the flexible film to form a flexible layer with a mask layer and a functional layer.
For example, referring to fig. 17, fig. 17 is a schematic diagram of forming a flexible layer with a mask layer and a functional layer according to an embodiment of the present application. The flexible film may be subjected to a second etching process using an etching apparatus to form the flexible layer 201 with the mask layer 203 and the functional layer 202. The laminated flexible layer 201, functional layer 202 and mask layer 203 can constitute the cell filter membrane 200. That is, the cell filter 200 is formed on the light-transmitting substrate 000.
It should be noted that, since the material of the flexible layer 201 in the cell filter 200 is substantially the same as that of the photoresist pattern, if the flexible film is directly etched by the photoresist pattern, the photoresist pattern is also etched, and it is very easy for the photoresist pattern to be completely etched, but the flexible film is not etched yet. For this purpose, the flexible film is etched through the mask layer 203 having a material different from that of the flexible layer 202 to form the flexible layer 201 in the present application.
Step 1006, stripping the transparent substrate to obtain the cell filter membrane.
For example, please refer to fig. 18, fig. 18 is a schematic diagram of a glass-peeled transparent substrate to obtain a cell filter membrane according to an embodiment of the present application. The light-transmitting substrate 000 may be laser peeled using a laser peeling apparatus to obtain the cell filter 200.
It should be noted that, the flexible layer 201 in the cell filter 200 can prevent the functional layer 202 in the cell filter 200 from being damaged during the laser peeling process of the transparent substrate 000, so as to ensure the yield of the product when the cell filter 200 is prepared.
In summary, in the preparation method of the cell filter membrane provided by the embodiment of the application, since the cell filter membrane is formed on the light-transmitting substrate, the light-transmitting substrate has higher light transmission, so that the light-transmitting substrate can be peeled off by adopting the laser peeling technology on the premise of not damaging the cell filter membrane, the cell filter membrane is obtained, and the transparent substrate is not required to be dissolved by adopting a solution, thereby effectively reducing the preparation cost of the cell filter membrane. The size of the transparent substrate is far larger than that of the silicon substrate, so that the cell filter membrane with larger area can be prepared by the preparation method of the cell filter membrane, and the cell filter membrane with larger area can be assembled in the treatment equipment to filter CTC cells in blood.
It is noted that in the drawings, the size of layers and regions may be exaggerated for clarity of illustration. Moreover, it will be understood that when an element or layer is referred to as being "on" another element or layer, it can be directly on the other element or intervening layers may be present. In addition, it will be understood that when an element or layer is referred to as being "under" another element or layer, it can be directly under the other element or intervening layers or elements may be present. In addition, it will be understood that when a layer or element is referred to as being "between" two layers or elements, it can be the only layer between the two layers or elements, or more than one intervening layer or element may also be present. Like reference numerals refer to like elements throughout.
In the present disclosure, the terms "first" and "second" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance. The term "plurality" refers to two or more, unless explicitly defined otherwise.
The foregoing description of the preferred embodiments of the present application is not intended to limit the application, but is intended to cover all modifications, equivalents, alternatives, and improvements falling within the spirit and principles of the application.
Claims (7)
1. A therapeutic apparatus, comprising:
sealing the box body;
the cell filter membrane is positioned in the sealing box body, the sealing box body is separated by the cell filter membrane to obtain two cavities, the two cavities comprise a first cavity and a second cavity, and the cell filter membrane is provided with a plurality of filter holes;
a first pipeline with one end communicated with the first cavity of the sealing box body and a second pipeline with one end communicated with the second cavity of the sealing box body;
the end, far away from the sealing box body, of the first pipeline and the end, far away from the sealing box body, of the second pipeline are ports communicated with blood vessels; the cell filter membrane is used for capturing circulating tumor cells through the filter hole;
the cell filter membrane comprises: a laminated flexible layer, a functional layer, and a mask layer, the functional layer comprising: at least one of a conductive layer, a light shielding layer and a biochemical layer which can be modified by a modifying liquid.
2. The treatment apparatus according to claim 1, wherein,
the sealing box body comprises: a first housing and a second housing detachably connected;
the edge of the cell filter membrane is detachably connected with the opening of the first shell or the opening of the second shell, one end of the first pipeline is communicated with the first shell, and one end of the second pipeline is communicated with the second shell.
3. The treatment apparatus according to claim 1, wherein,
the treatment apparatus further comprises: a sensor located within the first conduit and/or the second conduit, and a processor connected to the sensor;
wherein the processor is configured to determine whether the cell filter membrane is clogged based on information of the fluid parameter detected by the sensor.
4. A treatment apparatus according to claim 3, wherein,
the first pipeline is a liquid inflow pipeline, and the sensor in the first pipeline is a pressure sensor;
the second pipeline is a liquid outflow pipeline, and the sensor in the second pipeline is a flow rate sensor;
wherein the processor is configured to: when the pressure sensor detects that the pressure of the fluid in the first pipeline is greater than a pressure threshold value, determining that the cell filter membrane is blocked;
the processor is further configured to: and when the flow rate of the liquid in the second pipeline detected by the flow rate sensor is smaller than a flow rate threshold value, determining that the cell filter membrane is blocked.
5. A therapeutic apparatus according to any one of claims 1 to 4,
the direction of extension of the cell filter membrane is parallel to the direction of gravity.
6. A method of preparing a cell filter membrane for use in the treatment apparatus of any one of claims 1 to 5, the method comprising:
forming a thin film on a light-transmitting substrate;
patterning the film to form a cell filter film on the light-transmitting substrate;
stripping the light-transmitting substrate to obtain the cell filter membrane;
wherein the film comprises: a flexible film, a functional film and a mask film which are sequentially laminated along a direction away from the light-transmitting substrate; the functional film includes: at least one of a conductive film, a light shielding film, and a biochemical film that can be modified by a modifying liquid;
patterning the thin film to form a cell filter film on the light-transmitting substrate, comprising:
performing a patterning process on the mask film to form a mask layer;
performing first etching treatment on the functional film to form a functional layer with the mask layer;
and carrying out second etching treatment on the flexible film to form a flexible layer with the mask layer and the functional layer.
7. The method of claim 6, wherein performing a patterning process on the mask film to form a mask layer comprises:
forming a photoresist film on the mask film;
performing exposure treatment and development treatment on the photoresist film to form a mask film with a photoresist pattern;
performing third etching treatment on the mask film with the photoresist pattern to form a mask layer with the photoresist pattern;
and removing the photoresist pattern to form the mask layer.
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