A saliva collection microfluidic device and a preparation method thereof

Abstract

The application provides a saliva collection microfluidic device, which comprises a sampling module, a bubble capturing module, a vacuum module and a detection module. A capillary channel in the sampling module is connected with a collection chamber and a detection chamber, and the detection module is arranged in the detection chamber. Meanwhile, the vacuum module is arranged at least around the detection chamber, so that the flow of the liquid to be detected between the collection chamber and the detection chamber is smooth under the dual action of capillary force and negative pressure of the vacuum chamber. In addition, the bubble capturing module is arranged above the capillary channel to capture bubbles in the saliva sample, so as to eliminate the influence of the bubbles on the detection system. A semi-permeable membrane is arranged above the collection chamber to realize filtration pretreatment of the saliva sample, so as to reduce the viscosity of the saliva and realize filtration of interfering substances. The collection process of the saliva collection microfluidic device is efficient, easy to integrate and widely applicable, so as to improve the accuracy and sensitivity of detection. The application further provides a preparation method of the saliva collection microfluidic device.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of saliva collection, and particularly relates to a saliva collection microfluidic device and a preparation method thereof. BACKGROUND

[0002] Saliva is a complex body fluid secreted by salivary glands, mainly composed of water, inorganic salts, small organic molecules, proteins and hormones. Due to the existence of the blood-saliva barrier, many components in the blood enter saliva through active transport or passive diffusion. Therefore, the presence or change of saliva components can reflect the change of the corresponding substance level in the body, and saliva component detection and analysis are of great significance to disease diagnosis and health condition analysis.

[0003] To successfully achieve the detection of target analytes in saliva, saliva collection needs to be realized first. Saliva collection is generally divided into whole saliva collection and single gland saliva collection. Whole saliva samples can be directly collected by using a container to collect mixed saliva flowing out or spit out in the mouth, or by using a chewing cotton ball. Single gland saliva samples are usually collected by placing a cotton ball near the gland, such as the sublingual gland or the parotid gland.

[0004] The development of microfluidic technology provides a new method for saliva collection, but due to the high viscosity of saliva and the easy generation of bubbles, it is currently difficult to effectively collect saliva samples through microfluidic technology.

[0005] Therefore, how to overcome the above technical defects is a problem to be solved by those skilled in the art. SUMMARY

[0006] The purpose of the present application is to provide a saliva collection microfluidic device and a preparation method thereof, which realizes effective collection of saliva samples through microfluidic technology.

[0007] To solve the above technical problems, the present application provides a saliva collection microfluidic device, comprising: a sampling module, a bubble capturing module, a vacuum module and a detection module.

[0008] The sampling module comprises a collection chamber, a capillary tube and a detection chamber, the collection chamber is used for collecting saliva samples, the detection chamber is used for detecting the collected saliva samples, the sampling port of the collection chamber is provided with a semi-permeable membrane, and the two ends of the capillary tube are respectively communicated with the collection chamber and the detection chamber;

[0009] The bubble capturing module is used for capturing bubbles released by the saliva sample, and the bubble capturing module is located above the capillary tube and communicated with the capillary tube;

[0010] The vacuum module is a vacuum chamber with a vacuum environment,

[0011] The vacuum chamber is arranged outside the detection chamber, and at least the contact surface between the vacuum chamber and the detection chamber is made of a material with gas permeability.

[0012] The vacuum chamber is arranged outside the detection chamber, and at least the contact surface between the vacuum chamber and the detection chamber is made of a material with gas permeability.

[0013] The detection module is arranged in the detection chamber and is used for detecting the saliva sample.

[0014] Optionally, in the saliva collection microfluidic device, the collection chamber is a cylindrical semi-open chamber, one end of the cylindrical semi-open chamber is the sampling port, and the detection chamber is a cylindrical sealed chamber.

[0015] Optionally, in the saliva collection microfluidic device, the number of the collection chambers and the number of the capillary channels are multiple and one-to-one corresponding.

[0016] Optionally, in the saliva collection microfluidic device, the semi-permeable membrane is a polyvinylidene fluoride membrane, a cellulose acetate membrane, a polyamide membrane, or glass paper.

[0017] The sampling module, the bubble capturing module, and the vacuum module are made of one or more of polydimethylsiloxane, polystyrene, cellulose, polyacrylamide, polyethylene polypropylene, cross-linked dextran, silica gel, silicon wafer, agarose gel, polyethylene terephthalate, polyurethane, and polyimide.

[0018] Optionally, in the saliva collection microfluidic device, a sealing bag is further arranged on the sampling module, the bubble capturing module, and the vacuum module, and the sealing bag is sealed after packaging.

[0019] The vacuum chamber is arranged outside the detection chamber, and at least the contact surface between the vacuum chamber and the detection chamber is made of a material with gas permeability.

[0020] Optionally, in the saliva collection microfluidic device, the detection module comprises an electrochemical sensing electrode capable of electrochemical reaction with the saliva sample and transmitting the generated electrical signal to the peripheral circuit.

[0021] Optionally, in the saliva collection microfluidic device, the saliva collection microfluidic device is processed by a reverse mold process or a laser engraving process.

[0022] The present application also provides a preparation method of a saliva collection microfluidic device, which uses the saliva collection microfluidic device described above, and comprises the following steps:

[0023] Cleaning the mold: cleaning the mold used for preparing the saliva collection microfluidic device to ensure that the surface of the mold is clean and free of impurities;

[0024] Reverse molding: mixing the material and curing agent for preparing the saliva collection microfluidic device at a predetermined ratio, fully stirring and uniformly and then vacuuming to remove air bubbles, and then uniformly pouring on the surface of the mold, and again vacuuming to remove air bubbles;

[0025] Curing: placing the reverse molded mold in an oven for curing, and cooling at room temperature after curing;

[0026] Peeling: peeling the cured mold to obtain a microfluidic structure having the sampling module, the bubble trapping module, and the vacuum module, the microfluidic structure being provided with a semi-permeable membrane at the sampling port of the collection chamber, and the semi-permeable membrane being quickly attached with a sealing tape, curing in an oven for a predetermined time, and then overnight processing to obtain the saliva collection microfluidic device.

[0027] Optionally, in the preparation method, after obtaining the microfluidic structure in the peeling step and before providing the semi-permeable membrane at the sampling port of the collection chamber, the microfluidic structure is subjected to oxygen plasma cleaning treatment.

[0028] Optionally, in the preparation method, in the cleaning mold step, isopropyl alcohol and ultrapure water are used to clean the mold of the collection device.

[0029] And / or, in the peeling step, before providing the semi-permeable membrane at the sampling port of the collection chamber, the microfluidic structure peeled off is cleaned with isopropyl alcohol and ultrapure water, respectively.

[0030] The present application provides a saliva collection microfluidic device, which has the following beneficial effects:

[0031] The sampling module is connected with the collecting chamber and the detection chamber through a capillary channel, and the detection module is arranged in the detection chamber and used for detecting the saliva sample. Meanwhile, a vacuum module is arranged at least around the detection chamber in the sampling module, and the flow smoothness of the liquid to be detected between the collecting chamber and the detection chamber is ensured by the double effects of the capillary force and the negative pressure of the vacuum chamber.

[0032] In addition, a bubble capturing module is arranged above the capillary channel and used for capturing bubbles in the saliva sample, so as to exclude the influence of the bubbles on the detection system. A semi-permeable membrane is arranged above the collecting chamber, so as to realize the filtration pretreatment of the collected saliva sample, reduce the viscosity of the saliva, filter the interference, and realize the effective collection of the saliva sample through the micro flow channel technology. The saliva collecting micro fluidic device has the advantages of high efficiency, easy integration and wide application, and can be used for saliva sensor system integration, so as to improve the accuracy and sensitivity of detection. BRIEF DESCRIPTION OF DRAWINGS

[0033] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the drawings needed to be used in the embodiments or the prior art description will be briefly introduced. Obviously, the drawings in the following description are only embodiments of the present application, and other drawings can be obtained by those skilled in the art without creative labor on the basis of the provided drawings.

[0034] Figure 1 A structure schematic diagram of a saliva collecting micro fluidic device provided by the embodiment of the present application is shown in the figure.

[0035] Figure 2 A front view of a saliva collecting micro fluidic device provided by the embodiment of the present application is shown in the figure.

[0036] In the above figure:

[0037] 1-collecting chamber;

[0038] 2-capillary channel;

[0039] 3-detection chamber;

[0040] 4-vacuum chamber. DETAILED DESCRIPTION

[0041] The embodiments of the present application will be described in detail below, and examples of the embodiments are shown in the drawings, wherein the same or similar reference signs represent the same or similar elements or elements with the same or similar functions throughout. The embodiments described below by referring to the drawings are exemplary and are only used to explain the present application, and cannot be understood as a limitation of the present application.

[0042] The core of the present application is to provide a saliva collecting micro fluidic device and a preparation method thereof, and the effective collection of the saliva sample is realized through the micro flow channel technology.

[0043] In order for those skilled in the art to better understand the technical solutions provided by the present application, the present application will be further described in detail below with reference to the drawings and specific embodiments.

[0044] The present application is a saliva collection microfluidic device designed based on microfluidic technology. The analysis capability of microfluidic technology in the field of life science and medical diagnosis significantly exceeds that of macroscopic system, with the advantages of small volume, low consumption of analysis reagent, low cost, high analysis efficiency, fast analysis speed, high degree of integration and automation, etc.

[0045] Please refer to Figures 1-2 The present application provides a saliva collection microfluidic device, which comprises a sampling module, a bubble capture module, a vacuum module and a detection module.

[0046] The sampling module comprises a collection chamber 1, a capillary channel 2 and a detection chamber 3. The collection chamber 1 is used for collecting saliva samples, and the detection chamber 3 is used for detecting the collected saliva samples. The sampling port of the collection chamber 1 is provided with a semi-permeable membrane, and a sealing tape is pasted above the semi-permeable membrane. The two ends of the capillary channel 2 are respectively communicated with the collection chamber 1 and the detection chamber 3.

[0047] The bubble capture module is used for capturing the bubbles released by the saliva sample. The bubble capture module is located above the capillary channel 2 and is communicated with the capillary channel 2. The capillary channel 2 and the bubble capture module are the same chamber. The bubble capture chamber formed by the bubble capture module has a protruding structure compared with the collection chamber 1 and the detection chamber 3, and is located above the capillary channel 2 due to the influence of gas density. The bubble capture chamber can capture bubbles.

[0048] The vacuum module is a vacuum chamber 4 with a vacuum environment. The shape and size of the vacuum chamber 4 can be adaptively selected according to actual needs.

[0049] Among them, the vacuum chamber 4 is arranged outside the detection chamber 3, and at least the contact surface of the vacuum chamber 4 and the detection chamber 3 is made of a material with gas permeability; or, the vacuum chamber 4 is arranged outside the capillary channel 2 and the detection chamber 3, and at least the contact surface of the vacuum chamber 4 and the capillary channel 2 and the detection chamber 3 is made of a material with gas permeability.

[0050] The detection module is arranged in the detection chamber 3 and is used for detecting the saliva sample.

[0051] It should be noted that the sampling port of the collection chamber 1 is sealed by the semi-permeable membrane, which is used for the aggregation and purification of the saliva sample. The semi-permeable membrane can realize the pretreatment and purification of the liquid sample, reduce the viscosity of the saliva and remove the potential interferents, thereby improving the accuracy and sensitivity of the detection.

[0052] The saliva collection microfluidic device provided by the scheme, the sampling module is connected with the collection chamber 1 and the detection chamber 3 through the capillary channel 2, the detection module is arranged in the detection chamber 3, and the saliva sample is detected. At the same time, at least the vacuum module is arranged around the detection chamber 3 in the sampling module, and the flow smoothness of the to-be-detected liquid between the collection chamber 1 and the detection chamber 3 is ensured by the double effects of the capillary force and the negative pressure of the vacuum chamber 4.

[0053] In addition, the bubble capture module is arranged above the capillary channel 2 to capture bubbles in the saliva sample, so as to exclude the influence of the bubbles on the detection system. The semi-permeable membrane is arranged above the collection chamber 1, so as to realize the filtration pretreatment of the collected saliva sample, reduce the viscosity of the saliva, realize the filtration of the interference, and realize the effective collection of the saliva sample through the microfluid channel technology. The collection process of the saliva collection microfluidic device is efficient, easy to integrate, and widely used, and can be used for saliva sensor system integration, so as to improve the accuracy and sensitivity of detection.

[0054] It is proved by experiments that the to-be-detected dye or sample is added dropwise above the sampling chamber of the collection module, so that the fluid is introduced into the detection chamber 3 through the semi-permeable membrane and the capillary channel 2 under the negative pressure of the vacuum module and the capillary effect. Among them, the bubbles are gathered and captured in the bubble capture chamber above the capillary channel 2 and will not enter the detection chamber 3. The whole process is an active drainage process, without the need of external action.

[0055] In specific embodiments, the collection chamber 1 is a cylindrical semi-open chamber, one end of the cylindrical semi-open chamber is a sampling port, the saliva of the collector is placed into the sampling port, and the cylindrical structure is convenient for collection.

[0056] The detection chamber 3 is a cylindrical sealed chamber. The capillary channel 2 and the bubble capture chamber can be a strip-shaped structure.

[0057] Of course, the collection chamber 1, the capillary channel 2, the bubble capture chamber and the detection chamber 3 can be designed into any shape according to actual conditions, as long as the respective functions can be met.

[0058] In a specific embodiment, the collection chamber 1 is arranged as a cylindrical semi-open chamber and is sealed by a semi-permeable membrane, for aggregation and purification of the saliva sample. The detection chamber 3 is arranged as a cylindrical closed chamber and is sealed by a sealing tape wrapped outside the detection chamber 3, for collecting the saliva sample and realizing detection. The capillary channel 2 is used for connecting the collection chamber 1 and the detection chamber 3, to realize the flow of the saliva sample from the collection chamber 1 to the detection chamber 3.

[0059] The radius of the collection chamber 1 is set to 0.25-0.75 mm and is uniformly distributed in the sampling module. The width and height of the capillary flow channel are set to 0.25-0.5 mm. The length of the capillary channel 2 matches the distance between the collection chamber 1 and the detection chamber 3. The radius of the detection chamber 3 and the volume of the chamber are set to match the volume of the sample to be detected. Here, the radius is set to 0.8 mm and the volume is set to 50 μL.

[0060] The vacuum module is composed of a vacuum chamber 4 surrounding the sampling module. The vacuum module is a fully enclosed chamber, sealed on the outside. The vacuum module and the sampling module are independent of each other and do not communicate with each other, and are used to form a negative pressure around the sampling module.

[0061] In use, the gas in the sampling module is affected by the negative pressure and diffuses to the vacuum module, promoting the flow of liquid in the collection chamber 1 of the sampling module to the detection chamber 3.

[0062] The spacing between the vacuum module and the sampling module can be selected between 0.25-0.5 mm, and the volume of the vacuum module is set to 1.5-3 times the volume of the sampling module. The bubble capture module is set between the sampling chamber and the detection chamber 3 of the sampling module and is located above the capillary channel 2, which is in communication with the capillary channel 2, and is used to capture bubbles in the sampling module. The height is set to 0.125-0.25 mm, and the length matches the capillary channel 2.

[0063] In order to improve the collection efficiency, the number of collection chambers 1 and capillary channels 2 is multiple and one-to-one correspondence. As shown in Figure 1 The number of collection chambers 1 and capillary channels 2 is three, one collection chamber 1 corresponds to one capillary channel 2, and three capillary channels 2 are in communication with the detection chamber 3.

[0064] It should be noted that the semi-permeable membrane is a kind of membrane that only allows certain molecules or ions to diffuse in and out, and has selectivity for different particles.

[0065] The semi-permeable membrane used in the present case can use but is not limited to polyvinylidene fluoride membrane (PVDF), cellulose acetate membrane, polyamide membrane, glass paper, etc. The above materials can realize the pretreatment and purification of liquid samples, reduce the viscosity of saliva and remove potential interferents, and improve the accuracy and sensitivity of detection.

[0066] The sampling module, bubble capture module and vacuum module can use one or more of polydimethylsiloxane, polystyrene, cellulose, polyacrylamide, polyethylene polypropylene, cross-linked dextran, silica gel, silicon wafer, agarose gel, polyethylene terephthalate, polyurethane and polyimide. The combination mode can be adaptively selected according to actual needs.

[0067] Since the saliva collection microfluidic device is made of gas-permeable material, the cavity made of gas-permeable material needs to be in a certain negative pressure environment and treated overnight to achieve a vacuum state. If it is in the atmospheric environment for a long time, the vacuum effect will gradually be lost.

[0068] In order to make the vacuum chamber 4 maintain the vacuum state for a longer time, the sampling module (the detection module is arranged in the detection chamber 3), the bubble capture module and the vacuum module after being integrally formed can be processed as follows:

[0069] In one form, the scheme further includes a sealing bag covering the sampling module, the bubble capture module and the vacuum module, and the sealed bag after packaging is sealed for sealing.

[0070] The sealing bag can be a plastic bag, an aluminum bag or the like.

[0071] After the vacuum chamber 4 reaches the vacuum state, it needs to be used immediately or stored in the sealed bag, and the sealed bag is subjected to vacuum treatment to prevent gas penetration. In actual use, the device as a whole is subjected to vacuum treatment and stored in the packaging bag in a vacuum state. When used, the vacuum sealing bag is removed and the saliva collection microfluidic device is used for detection as soon as possible.

[0072] In another form, a non-air-permeable material layer is attached to the top of the semi-permeable membrane.

[0073] The vacuum chamber 4 is arranged outside the detection chamber 3, the collection chamber 1, the capillary channel 2 and the vacuum chamber 4 are provided with a non-air-permeable material layer, and the contact surface of the vacuum chamber 4 and the detection chamber 3 is made of a material with gas permeability;

[0074] Or, the vacuum chamber 4 is arranged outside the capillary channel 2 and the detection chamber 3, the collection chamber 1 and the vacuum chamber 4 are provided with a non-air-permeable material layer, and the contact surface of the vacuum chamber 4 and the capillary channel 2 and the detection chamber 3 is made of a material with gas permeability.

[0075] The above-mentioned non-air-permeable material layer can be made of sealing tape or other materials.

[0076] On the basis of the above specific embodiments, the detection module includes an electrochemical sensing electrode, which can react with the saliva sample and transmit the generated electrical signal to the peripheral circuit. The electrochemical sensing electrode is integrated in the detection chamber 3, which can generate an electrical signal through an electrochemical reaction and transmit it to the peripheral circuit to realize detection of the saliva sample.

[0077] In the integration process, the surface of the detection chamber 3 and the electrochemical sensing electrode is treated by plasma, the sensing part of the electrochemical sensing electrode is placed directly below the detection chamber 3, and the circuit part extends out, and the integration of the electrochemical sensing electrode and the detection chamber 3 can be achieved by overnight at room temperature. The circuit part of the electrochemical sensing electrode is connected to the peripheral circuit through a wire. The negative pressure provided by the vacuum module makes the saliva sample to be tested flow quickly to the detection chamber 3 of the sampling module, and then to the detection area where the electrochemical sensing electrode is located, and then the electrochemical reaction is carried out. By combining with the instrument matched with the saliva collection microfluidic device of the present application, accurate detection results can be obtained.

[0078] In the above embodiment, the size, shape, and specific structure of the electrochemical sensing electrode can be changed according to actual conditions, and all similar non-essential changes should be within the protection scope of the present application.

[0079] The electrochemical sensing electrode is widely used in the prior art and can be applied to key components and carriers in the fields of medical treatment, heavy metal detection, poultry flu, waste water and waste treatment, seawater desalination, and chlor-alkali electrolysis. The electrochemical sensing electrode is used in combination with a detection reagent and an instrument to form an electrochemical system, which is convenient to use, light in weight, and cost-effective. Therefore, the specific structure of the electrochemical sensing electrode is not limited further.

[0080] The collection method using the electrochemical sensing electrode can save auxiliary consumables, simplify the detection process, and integrate the collection and detection processes, which is conducive to the integration of a saliva analyte sensor-based system.

[0081] The saliva collection microfluidic device is made of flexible materials, and the processing methods include but are not limited to reverse molding and laser engraving.

[0082] When the reverse molding process is used, the main material of the saliva collection microfluidic device can be any one or more of polydimethylsiloxane (PDMS), polystyrene (PS), cellulose, polyacrylamide (PAM), polyethylene polypropylene (PP), cross-linked dextran, silica gel, silicon wafer, and agarose gel. The mold corresponding to the saliva collection microfluidic device can be directly processed by mechanical processing, 3D printing, or laser engraving, or prepared by mechanical processing, 3D printing, and photolithography.

[0083] When the laser engraving process is used to process the saliva collection microfluidic device, the main material of the saliva collection microfluidic device can be a flexible material such as polyethylene terephthalate (PET), polyurethane (TPU), and polyimide (PI). Different power lasers are used to engrave the surface of the flexible film to obtain a saliva collection microfluidic device with a corresponding depth.

[0084] Further, the application also provides a preparation method of the saliva collection microfluidic device, which applies the saliva collection microfluidic device described above, and comprises the following steps:

[0085] Cleaning the mold: clean the mold for preparing the saliva collection microfluidic device to ensure that the surface of the mold is clean and free of impurities. Specifically, isopropyl alcohol and ultrapure water can be used to clean the mold of the collection device.

[0086] Molding: mix the material for preparing the saliva collection microfluidic device and the curing agent in a predetermined ratio, fully stir them to be uniform, and then vacuum to remove air bubbles. Pour the mixture uniformly onto the surface of the mold, and then vacuum again to remove air bubbles.

[0087] Curing: place the molded mold in an oven for curing. After curing, cool it at room temperature.

[0088] Peeling: peel the cured mold to obtain a microfluidic structure with a sampling module, a bubble trapping module, and a vacuum module. The microfluidic structure is provided with a semi-permeable membrane at the sampling port of the collection chamber 1. The semi-permeable membrane is quickly attached with a sealing tape. After curing in the oven for a predetermined time, it is treated overnight to obtain the saliva collection microfluidic device.

[0089] Further, in the peeling step, after obtaining the microfluidic structure and before providing the semi-permeable membrane at the sampling port of the collection chamber 1, the microfluidic structure is subjected to oxygen plasma cleaning treatment. The electrochemical sensing electrode and the detection chamber 3 are integrated after the microfluidic structure is treated by plasma.

[0090] The above method can modify the surface of the microfluidic structure. The saliva collection microfluidic device can be subjected to surface modification by methods such as oxygen plasma cleaning, ultraviolet light grafting, and block polymer modification, to improve its hydrophilicity and further optimize the sample collection efficiency.

[0091] Further, in the mold cleaning step, isopropyl alcohol and ultrapure water are used to clean the mold of the collection device.

[0092] In the peeling step, before the semi-permeable membrane is provided at the sampling port of the collection chamber 1, the peeled microfluidic structure is cleaned with isopropyl alcohol and ultrapure water, respectively.

[0093] Among them, isopropyl alcohol and ultrapure water are relatively inexpensive solvents in industry, have wide applications, can be freely mixed with water, have stronger solubility for lipophilic substances than ethanol, and can be used as a cleaning oil removal agent.

[0094] In a specific embodiment, the application provides a preparation method of a saliva collection microfluidic device, which comprises the following steps:

[0095] First, the mold of the collection device is cleaned with isopropyl alcohol and ultrapure water to ensure that the surface of the mold is clean and free of impurities.

[0096] Then, the main material of the saliva collection microfluidic device is mixed with the curing agent at a ratio of 10:1, fully stirred and uniformly mixed, and vacuumed to remove bubbles. The main material of the saliva collection microfluidic device can be any one or more of polydimethylsiloxane (PDMS), polystyrene (PS), cellulose, polyacrylamide (PAM), polyethylene polypropylene (PP), cross-linked dextran, silica gel, silicon wafer, agarose gel.

[0097] Next, the mold of the saliva collection microfluidic device covered with the PDMS mixture is placed in an 80℃ oven for 40min for curing, and then cooled at room temperature and peeled off using tweezers.

[0098] Then, the peeled-off microfluidic channel is cleaned with isopropyl alcohol and ultrapure water, respectively, and dried with nitrogen, and the dust and impurities are removed with a dust removal tape to obtain a microfluidic channel structure.

[0099] Finally, the microfluidic channel structure is subjected to oxygen plasma cleaning treatment, activated for 45s, and quickly attached with a sealing tape and a semi-permeable membrane, and the bubbles generated during the attachment process are removed using tweezers. After being fixed in a 37℃ oven for 1h, it is treated overnight at -95kPa to obtain a saliva collection microfluidic device for use.

[0100] The saliva collection microfluidic device based on microfluidic technology is based on the principle of capillary channel 2, and a vacuum module is used to form negative pressure around the collection module. With the dual action of negative pressure and capillary force, the sample to be tested can be quickly transferred to the detection chamber 3, thereby providing a saliva collection device that is efficient, easy to integrate, and widely applicable.

[0101] The saliva collection microfluidic device can be integrated with sensing electrodes and other devices, and is widely used in the collection and detection of saliva metabolites, salt ions, biomolecules and other substances, and has broad prospects in the field of saliva-based medical sensing instruments.

[0102] As shown in the present application and claims, unless the context clearly indicates otherwise, "one", "a", "an", and / or "the" do not refer to the singular, but can also include the plural. Generally speaking, the terms "comprise" and "include" only indicate the inclusion of the steps and elements explicitly identified, and these steps and elements do not constitute an exclusive list, and the method or device can also include other steps or elements. The element defined by the phrase "comprising a" does not exclude the presence of another identical element in the process, method, product or device.

[0103] In the description of the embodiments of the present application, unless otherwise specified, " / " represents the meaning of or, for example, A / B can represent A or B; "and / or" herein is only a description of the relationship between the associated objects, which means that there can be three relationships, for example, A and / or B, which can represent: A exists alone, A and B exist together, and B exists alone. In addition, in the description of the embodiments of the present application, "multiple" means two or more than two.

[0104] In the description of the present application, unless otherwise expressly limited, the words such as setting, installing, connecting, etc. should be broadly understood, and those skilled in the art can reasonably determine the specific meaning of the above words in the present application according to the specific content of the technical solution.

[0105] The embodiments in the specification are described in a progressive manner, and each embodiment focuses on the difference from other embodiments. The same and similar parts between the embodiments can be mutually referred to.

[0106] The principles and implementation modes of the present application are described by applying specific examples herein. The above description of the embodiments is only used to help understand the method of the present application and its core idea. It should be pointed out that for those skilled in the art, without departing from the principles of the present application, some improvements and modifications can be made to the present application, and these improvements and modifications also fall within the protection scope of the claims of the present application.

Claims

1. A microfluidic device for saliva collection, characterized in that, include: Sampling module, bubble capture module, vacuum module, and detection module; The sampling module includes a collection chamber, a capillary tube, and a detection chamber. The collection chamber is used to collect saliva samples, and the detection chamber is used to detect the collected saliva samples. The sampling port of the collection chamber is provided with a semi-permeable membrane, and the two ends of the capillary tube are respectively connected to the collection chamber and the detection chamber. The bubble capturing module is used to capture bubbles released from the saliva sample. The bubble capturing module is located above the capillary and is connected to the capillary. The vacuum module is a vacuum chamber with a vacuum environment. Wherein, the vacuum chamber is disposed outside the detection chamber, and at least the contact surface between the vacuum chamber and the detection chamber is made of a gas-permeable material; or, the vacuum chamber is disposed outside the capillary tube and the detection chamber, and at least the contact surface between the vacuum chamber and the capillary tube and the detection chamber is made of a gas-permeable material; The detection module is located in the detection chamber and is used to detect saliva samples.

2. The saliva collection microfluidic device according to claim 1, characterized in that, The collection chamber is a cylindrical semi-open chamber, with one end of the cylinder serving as the sampling port, and the detection chamber is a cylindrical sealed chamber.

3. The saliva collection microfluidic device according to claim 1, characterized in that, There are multiple collection chambers and capillary channels, and each corresponds to the other one-to-one.

4. The saliva collection microfluidic device according to claim 1, characterized in that, The semi-permeable membrane is a polyvinylidene fluoride membrane, a cellulose acetate membrane, a polyamine membrane, or cellophane; And / or, the sampling module, the bubble capture module, and the vacuum module are made of one or more of the following: polydimethylsiloxane, polystyrene, cellulose, polyacrylamide, polyethylene polypropylene, crosslinked dextran, silica gel, silicon wafer, agarose gel, polyethylene terephthalate, polyurethane, and polyimide.

5. The saliva collection microfluidic device according to claim 1, characterized in that, It also includes a sealing bag covering the sampling module, the bubble trapping module and the vacuum module, and the sealed bag is sealed after packaging; Alternatively, a non-permeable material layer is adhered above the semi-permeable membrane, wherein the vacuum chamber is disposed outside the detection chamber, and the outer surfaces of the collection chamber, the capillary tube, and the vacuum chamber are provided with non-permeable material layers, and the contact surface between the vacuum chamber and the detection chamber is made of a gas-permeable material; or, the vacuum chamber is disposed outside the capillary tube and the detection chamber, and the outer surfaces of the collection chamber and the vacuum chamber are provided with non-permeable material layers, and the contact surface between the vacuum chamber and the capillary tube and the detection chamber is made of a gas-permeable material.

6. The saliva collection microfluidic device according to any one of claims 1-5, characterized in that, The detection module includes an electrochemical sensing electrode, which can undergo an electrochemical reaction with the saliva sample and transmit the generated electrical signal to the peripheral circuit.

7. The saliva collection microfluidic device according to any one of claims 1-5, characterized in that, The saliva collection microfluidic device is manufactured using a molding process or a laser engraving process.

8. A method for preparing a saliva collection microfluidic device, characterized in that, The application of the saliva collection microfluidic device according to any one of claims 1-7 includes the following steps: Cleaning the mold: Clean the mold used to prepare the saliva collection microfluidic device to ensure that the mold surface is clean and free of impurities; Molding: Mix the materials for preparing the saliva collection microfluidic device and the curing agent in a preset ratio, stir thoroughly and remove air bubbles by vacuuming, then pour evenly onto the surface of the mold, and remove air bubbles by vacuuming again. Curing: Place the molded mold in an oven for curing, and then cool it at room temperature after curing; Peeling: The cured mold is peeled to obtain a microfluidic structure with the sampling module, the bubble capturing module and the vacuum module. A semi-permeable membrane is set at the sampling port of the collection chamber of the microfluidic structure. Sealing tape is quickly attached to the semi-permeable membrane. After curing in an oven for a preset time, it is left overnight to obtain the saliva collection microfluidic device.

9. The preparation method according to claim 8, characterized in that, In the stripping step, after obtaining the microchannel structure and before the microchannel structure is placed with a semi-permeable membrane at the sampling port of the acquisition chamber, the microchannel structure is further subjected to oxygen plasma cleaning treatment.

10. The preparation method according to claim 8, characterized in that, In the mold cleaning step, isopropanol and ultrapure water are used to clean the mold of the collection device; And / or, in the stripping step, before the microchannel structure is placed with a semi-permeable membrane at the sampling port of the collection chamber, the stripped microchannel structure is cleaned with isopropanol and ultrapure water, respectively.

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