CN114904131B - Microfluidic microneedle device, method of using the same, and method of manufacturing the same - Google Patents
Microfluidic microneedle device, method of using the same, and method of manufacturing the same Download PDFInfo
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- CN114904131B CN114904131B CN202210460129.5A CN202210460129A CN114904131B CN 114904131 B CN114904131 B CN 114904131B CN 202210460129 A CN202210460129 A CN 202210460129A CN 114904131 B CN114904131 B CN 114904131B
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Classifications
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- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
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- A61B5/1468—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means
- A61B5/1473—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using chemical or electrochemical methods, e.g. by polarographic means invasive, e.g. introduced into the body by a catheter
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- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
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Abstract
The invention provides a microfluidic microneedle device, a using method thereof and a manufacturing method thereof. The micro-fluidic microneedle device comprises a micro-fluidic chip, a microneedle and a connecting pipe; the microfluidic chip is provided with a first cavity, a second cavity and a third cavity, wherein the first cavity is communicated with the second cavity, and the second cavity is communicated with the third cavity; the micro needle is connected with the micro-fluidic chip and comprises at least one needle body, a needle channel is arranged in the needle body, one end of the needle channel is communicated with the third cavity, and the other end of the needle channel is arranged at one end, far away from the micro-fluidic chip, of the needle body; the lumen of the connecting tube is communicated with the first cavity. The microfluidic microneedle device combines the microfluidic chip and the microneedles, has the functions of synthesizing the drugs and injecting the drugs, and is beneficial to ensuring that the drugs are mixed and used at once; in addition, the device can also have the functions of extracting the liquid to be analyzed and detecting the liquid to be analyzed.
Description
Technical Field
The invention relates to the technical field of microneedles, in particular to a microfluidic microneedle device, a using method thereof and a manufacturing method thereof.
Background
Currently, clinical microneedle applications include drug release and body fluid extraction. In the case of a microneedle for releasing a drug, the tip of the microneedle is embedded with the drug, and after the microneedle is inserted into a human body or an animal body, the drug at the tip of the microneedle is released into the human body or the animal body. With respect to the microneedle for extracting body fluid, after the microneedle is inserted into a human body or an animal body, the body fluid is drawn out by flowing the body fluid into the microneedle by suction of an external device, and the drawn body fluid can be used for subsequent detection and analysis.
However, the function of the current microneedles is similar to that of conventional syringes, and the main advantage of the microneedles is that the pain caused by the microneedles is low. The existing microneedle has single function, can only be used for simple drug injection, and has no great help to improve the curative effect of the drug; alternatively, current microneedles can only be used for simple fluid extraction, with little assistance in improving the efficiency of analysis or detection.
Disclosure of Invention
The present invention aims to solve at least one of the technical problems existing in the prior art. Therefore, the invention provides a microfluidic microneedle device which has the functions of synthesizing drugs and injecting the drugs, and is beneficial to ensuring the drugs to be used immediately after being combined, thereby ensuring the curative effect of the drugs.
The invention also provides a microfluidic microneedle device which has the functions of extracting the liquid to be analyzed and detecting the liquid to be analyzed, and is beneficial to rapidly acquiring analysis or detection results in or near a human body.
The invention also provides a use method of the microfluidic microneedle device.
The invention also provides a manufacturing method of the microfluidic microneedle device.
According to an embodiment of the first aspect of the present invention, a microfluidic microneedle device comprises: the micro-fluidic chip is provided with a first cavity, a second cavity and a third cavity, wherein a plurality of first cavities are arranged, at least one second cavity is arranged, the first cavity is communicated with the second cavity, and the second cavity is communicated with the third cavity; the micro needle is connected with the micro-fluidic chip and comprises at least one needle body, a needle channel is arranged in the needle body, one end of the needle channel is communicated with the third cavity, and the other end of the needle channel is arranged at one end, far away from the micro-fluidic chip, of the needle body; the connecting pipes are arranged and are connected with the microfluidic chip, and the pipe cavity of each connecting pipe is respectively communicated with one first cavity.
The microfluidic microneedle device provided by the embodiment of the invention has at least the following beneficial effects: raw materials for synthesizing the medicines are sent into the first cavity through the connecting pipe; raw materials can enter the second cavity from the first cavity, and multiple raw materials can form a target medicament after being combined in the second cavity; after the raw materials are combined into the target medicine, the target medicine can enter the third cavity from the second cavity and finally flow out of the needle body through the needle channel. The microfluidic microneedle device can be used for raw materials or medicines to flow in a microfluidic chip of the microfluidic microneedle device, medicines can be injected into a human or animal, and the microfluidic microneedle device can be used for directly synthesizing the medicines in the microfluidic chip, so that the medicines can be used immediately after being mixed, and the curative effect of the medicines is ensured.
According to some embodiments of the invention, the microneedle further comprises a porous substrate and a non-porous substrate, the non-porous substrate being connected to a periphery of the porous substrate, the non-porous substrate being connected to the microfluidic chip to cover the microfluidic chip; the needle body is connected to one side of the porous substrate far away from the microfluidic chip and protrudes towards the direction far away from the microfluidic chip relative to the porous substrate, the porous substrate is provided with a connecting pore canal, and two ends of the connecting pore canal are respectively communicated with the third cavity and the needle canal.
According to an embodiment of the first aspect of the present invention, a microfluidic microneedle device comprises: the micro-fluidic chip is provided with a first cavity, a second cavity and a third cavity, wherein a plurality of first cavities are arranged, at least one second cavity is arranged, the first cavity is communicated with the second cavity, and the second cavity is communicated with the third cavity; the micro needle is connected with the micro-fluidic chip and comprises at least one needle body, a needle channel is arranged in the needle body, one end of the needle channel is communicated with the third cavity, and the other end of the needle channel is arranged at one end, far away from the micro-fluidic chip, of the needle body; the connecting pipes are connected with the microfluidic chip, and the pipe cavity of each connecting pipe is respectively communicated with one first cavity; and the reagent is arranged in the first cavity.
The microfluidic microneedle device provided by the embodiment of the invention has at least the following beneficial effects: the needle body of the micro needle can be pricked into human tissue or animal body tissue, the liquid to be analyzed can enter the micro-fluidic chip through the needle channel, and the liquid to be analyzed entering the first cavity is combined with the reagent in the first cavity and reacts. The microfluidic microneedle device of the embodiment has the functions of extracting the liquid to be analyzed and performing in-situ detection on the liquid to be analyzed, and is beneficial to rapidly acquiring analysis or detection results in or near a human body.
According to some embodiments of the invention, the microfluidic chip is transparent; alternatively, the microfluidic chip further comprises a microelectrode; one end of the microelectrode is arranged on the wall surface of the first cavity, and the microelectrode is used for transmitting an electric signal generated by chemical reaction in the first cavity.
A method of using a microfluidic microneedle device according to an embodiment of the second aspect of the present invention comprises: injecting a feedstock into the first cavity; delivering the raw materials in the plurality of first cavities to the second cavity, and combining the plurality of raw materials to form a medicament; and delivering the medicine to the third cavity, and enabling the medicine in the third cavity to flow out from one end of the needle body, which is far away from the microfluidic chip.
The use method of the microfluidic microneedle device provided by the embodiment of the invention has at least the following beneficial effects: can directly synthesize the medicine in the microfluidic chip, and ensure the medicine to be used immediately, thereby ensuring the curative effect of the medicine.
A method of using a microfluidic microneedle device according to an embodiment of the second aspect of the present invention comprises: drawing liquid to be analyzed into the microfluidic chip through the needle channel; delivering the liquid to be analyzed into at least one of the first cavities, and combining the liquid to be analyzed with the reagent in the first cavity.
The use method of the microfluidic microneedle device provided by the embodiment of the invention has at least the following beneficial effects: the liquid to be analyzed can be extracted and in-situ detection can be carried out on the liquid to be analyzed, and the method is beneficial to rapidly acquiring analysis or detection results in or near a human body.
According to a third aspect of the present invention, a method for manufacturing a microfluidic microneedle device includes: manufacturing a microfluidic chip, wherein the microfluidic chip is provided with a first cavity, a second cavity and a third cavity, the first cavity is provided with a plurality of cavities, the second cavity is provided with at least one cavity, the first cavity is communicated with the second cavity, and the second cavity is communicated with the third cavity; manufacturing a microneedle, wherein the microneedle comprises at least one needle body, and the interior of the needle body is provided with a through needle channel; connecting the micro needle with the micro-fluidic chip so as to enable the needle track to be communicated with the third cavity; and connecting the microfluidic chip with a connecting pipe so that the first cavity is communicated with the cavity of the connecting pipe.
The use method of the microfluidic microneedle device provided by the embodiment of the invention has at least the following beneficial effects: can manufacture the micro-fluidic microneedle device with the functions of drug synthesis and drug injection.
According to some embodiments of the invention, connecting the microneedles to the microfluidic chip comprises the steps of: and connecting the micro needle and the micro-fluidic chip together in a bonding mode.
According to some embodiments of the invention, the manufacturing of the microneedle comprises the steps of: manufacturing a main body, wherein the main body comprises a needle body and a porous substrate, the needle body is connected to the porous substrate, and the porous substrate is provided with a connecting pore canal capable of communicating with the needle canal; adding a substrate raw material liquid into a container, putting the main body into the container, and enabling the outer edge of the porous substrate to be in contact with the substrate raw material liquid; solidifying the base stock solution in the container; separating the solidified substrate raw material liquid from the container to obtain the micro needle.
According to some embodiments of the invention, the method further comprises the steps of: and embedding the reagent in the first cavity.
The use method of the microfluidic microneedle device provided by the embodiment of the invention has at least the following beneficial effects: the microfluidic microneedle device with the functions of liquid extraction and in-situ analysis and detection can be manufactured.
Additional aspects and advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention.
Drawings
The invention is further described with reference to the accompanying drawings and examples, in which:
FIG. 1 is an exploded schematic view of a microfluidic microneedle device of the present invention;
fig. 2 is a schematic diagram of a microfluidic chip of a microfluidic microneedle device of the present invention;
FIG. 3 is a cross-sectional view of a microfluidic microneedle device of the present invention;
FIG. 4 is a schematic illustration of one method of using a microfluidic microneedle device according to a first embodiment of the present invention;
FIG. 5 is a schematic illustration of one method of using a microfluidic microneedle device according to a second embodiment of the present invention;
FIG. 6 is a schematic diagram of a method of manufacturing a microfluidic microneedle device of the present invention;
FIG. 7 is a schematic illustration of a method of manufacturing microneedles in some embodiments of the present invention;
fig. 8 is a schematic view of a body immersed in a substrate feed solution.
Reference numerals: 100-microfluidic microneedle device, 101-needle body, 102-porous substrate, 103-non-porous substrate, 104-microfluidic chip, 105-connecting tube, 106-microneedle, 107-holding tank, 108-main body, 201-first cavity, 202-first linking channel, 203-second cavity, 204-second linking channel, 205-third cavity, 301-needle channel, 302-linking channel, 401-container, 402-substrate raw material liquid.
Detailed Description
Embodiments of the present invention are described in detail below, examples of which are illustrated in the accompanying drawings, wherein like or similar reference numerals refer to like or similar elements or elements having like or similar functions throughout. The embodiments described below by referring to the drawings are illustrative only and are not to be construed as limiting the invention.
In the description of the present invention, it should be understood that references to orientation descriptions such as upper, lower, front, rear, left, right, etc. are based on the orientation or positional relationship shown in the drawings, are merely for convenience of description of the present invention and to simplify the description, and do not indicate or imply that the apparatus or elements referred to must have a particular orientation, be constructed and operated in a particular orientation, and thus should not be construed as limiting the present invention.
In the description of the present invention, the meaning of a number is one or more, the meaning of a number is two or more, and greater than, less than, exceeding, etc. are understood to exclude the present number, and the meaning of a number is understood to include the present number. The description of the first and second is for the purpose of distinguishing between technical features only and should not be construed as indicating or implying relative importance or implicitly indicating the number of technical features indicated or implicitly indicating the precedence of the technical features indicated.
In the description of the present invention, unless explicitly defined otherwise, terms such as arrangement, installation, connection, etc. should be construed broadly and the specific meaning of the terms in the present invention can be reasonably determined by a person skilled in the art in combination with the specific contents of the technical scheme.
In the description of the present invention, the descriptions of the terms "one embodiment," "some embodiments," "illustrative embodiments," "examples," "specific examples," or "some examples," etc., mean that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the present invention. In this specification, schematic representations of the above terms do not necessarily refer to the same embodiments or examples. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.
First embodiment:
the present embodiment provides a microfluidic microneedle device 100, and the microfluidic microneedle device 100 is used for drug administration, referring to fig. 1, the microfluidic microneedle device 100 includes a microfluidic chip 104, a microneedle 106, and a connection tube 105.
Referring to fig. 2, the microfluidic chip 104 has a microfluidic channel including a first cavity 201, a second cavity 203, and a third cavity 205. The first cavity 201 is provided in plurality, the second cavity 203 is provided with at least one, the first cavity 201 communicates with the second cavity 203, and the second cavity 203 communicates with the third cavity 205. More specifically, the microfluidic channel further includes a first linking channel 202 and a second linking channel 204, wherein two ends of the first linking channel 202 are respectively communicated with the first cavity 201 and the second cavity 203, and two ends of the second linking channel 204 are respectively communicated with the second cavity 203 and the third cavity 205. Namely, the first cavity 201 and the second cavity 203 are communicated through a first connecting channel 202; i.e. the second cavity 203 and the third cavity 205 are in communication via the second engagement channel 204.
The micro needle 106 is connected to the micro fluidic chip 104, and referring to fig. 1, the micro needle 106 includes a needle body 101, and an end of the needle body 101 remote from the micro fluidic chip 104 is used to be pricked into human tissue or animal body tissue, for example, an end of the needle body 101 remote from the micro fluidic chip 104 is provided as a tip so that the needle body 101 is pricked into human tissue or animal body tissue. Referring to fig. 3, the needle 101 is hollow, the needle 101 has a through needle channel 301 therein, and if one end of the needle 101 away from the microfluidic chip 104 is referred to as the end of the needle 101, one end of the needle channel 301 communicates with the third cavity 205 (e.g., the needle channel 301 communicates with the third cavity 205 through the engagement channel 302), and the other end of the needle channel 301 is disposed at the end of the needle 101, so that the drug can be released into the human or animal body through the end of the needle 101.
Referring to fig. 1 or 2, one end of the connection pipe 105 is connected to the microfluidic chip 104, and a lumen of the connection pipe 105 communicates with the first cavity 201. The connecting tubes 105 are also provided with a plurality of connecting tubes 105, and the lumen of each connecting tube 105 is respectively communicated with one first cavity 201.
If a drug required by a human or animal is a target drug, referring to fig. 4, one of the methods of using the microfluidic microneedle device 100 of the present embodiment is as follows: raw materials for synthesizing the medicine are fed into the first chamber 201 through the connection tube 105; then, the raw materials enter the second cavity 203 from the first cavity 201, and a plurality of raw materials are combined in the second cavity 203 to form a target medicament; after the raw materials are combined into the target medicine, the target medicine enters the third cavity 205 from the second cavity 203, and finally the target medicine flows out of the needle body 101 through the needle track 301. The microfluidic microneedle device 100 of the present embodiment can be used for directly synthesizing drugs in the microfluidic chip 104, and ensure that the drugs are used immediately after being combined, thereby ensuring the curative effect of the drugs.
The above raw materials are combined to form the target drug or synthesized to form the target drug, specifically, the raw materials can be mixed together to form the target drug, or a chemical reaction occurs between certain raw materials to form the target drug; the drug with higher concentration can be used as one of the raw materials, the diluted liquid is used as the other raw material, and the high-concentration drug and the diluted liquid are mixed, so that the drug with lower concentration is formed, and the drug with lower concentration is used as the target drug.
During use of the microfluidic microneedle device 100 of the present embodiment, a first conveying device (not shown) that cooperates with the microfluidic microneedle device 100 may be provided, and the first conveying device is used to convey the raw material into the microfluidic chip 104. The first delivery device may be provided as a peristaltic pump, syringe pump or the like, the outlet end of which is connected to the connection tube 105. If the first conveying device is set to be a pump which cannot store raw materials, such as a peristaltic pump, the first conveying device can be further provided with a hopper matched with the first conveying device, the hopper is used for storing raw materials, the hopper can be set to be a container such as a pot or a bottle, the hopper can be provided with a plurality of containers, each container stores different raw materials, and the inlet end of the first conveying device can be connected with the hopper through a pipe.
After the first conveying device is started, under the driving action of the first conveying device, raw materials can be conveyed into the microfluidic chip 104 along the connecting pipe 105 and sequentially flow through the first cavity 201 and the second cavity 203, after medicines are formed in the second cavity 203, the medicines can be conveyed into the third cavity 205 through the continuous pumping action of the first conveying device, and finally the medicines flow out from the tail end of the needle body 101.
In addition, by controlling the first delivery device delivery power, the dosage of the raw material delivered into the microfluidic chip 104 may be adjusted, thereby adjusting the dose, the dose concentration, or the dose rate of the microfluidic microneedle device 100.
It should be noted that, in some use cases, the microfluidic chip 104 and the micro needle 106 of the present embodiment may be disposed in a human body or an animal body (as shown in fig. 2), for example, the microfluidic chip 104 and the micro needle 106 are buried in the human body by a surgical method, and the microfluidic chip 104 and the micro needle 106 are introduced into the human body by a patient swallowing method; the connection tube 105 needs to have a portion outside the human body and a portion inside the human body. In other usage scenarios, the microfluidic chip 104 and the micro-needles 106 may be disposed outside the human body, for example, the microfluidic chip 104 is attached to the skin surface of the human body, and the micro-needles 106 are inserted into the skin.
Second embodiment:
the present embodiment provides a microfluidic microneedle device 100, and the microfluidic microneedle device 100 of the present embodiment is used for extraction and detection analysis of body fluid. The microfluidic microneedle device 100 of the present embodiment is similar to the microfluidic microneedle device 100 of the first embodiment, with the main difference that the microfluidic microneedle device 100 of the present embodiment further includes a reagent, wherein the reagent is disposed in the first cavity 201.
Reagents are used to bind to and react with body fluids for detection and analysis of the body fluids; the reagent may be pre-buried in the first cavity 201 during the manufacturing process of the microfluidic chip 104. The pre-buried reagent can be in powder, granular or gel form, or can be in liquid state; in some embodiments, during the fabrication of the microfluidic chip 104, after the microfluidic channels are formed, reagents are placed into the first cavity 201 (e.g., smeared onto the walls of the first cavity 201).
The microfluidic microneedle device 100 of the present embodiment is beneficial for improving the efficiency of detection and analysis of body fluids. Specifically, referring to fig. 5, one of the methods of use of the present embodiment is generally as follows: after the micro needle 106 is inserted into the human tissue or animal body tissue, a liquid to be analyzed (e.g., a body fluid of a human or animal) is drawn into the microfluidic chip 104 from the through-needle path 301, and the liquid to be analyzed is caused to flow through the third chamber 205, the second chamber 203, and the first chamber 201 in this order, so that the liquid to be analyzed and the reagent in the first chamber 201 are combined and reacted. The microfluidic microneedle device 100 of the present embodiment has both the functions of extracting a liquid to be analyzed and detecting the liquid to be analyzed, and is beneficial to rapidly acquiring an analysis or detection result in or near a human body.
It should be noted that, referring to fig. 2, in other embodiments, the microfluidic chip 104 may not be provided with the second cavity 203 for connection, and the first cavity 201 may be directly connected to the third cavity 205 through the first connection channel 202.
The microfluidic microneedle device 100 of the second embodiment may be used with a second delivery device connected to the connection tube 105, which may also be configured as a peristaltic pump, a syringe pump, or the like, and the second delivery device is used to pump out the gas or the liquid in the microfluidic chip 104 to create a pressure differential and allow the body fluid to enter the microfluidic chip 104 through the needle channel 301 of the needle body 101.
Different types of reagents may be pre-buried in different first cavities 201, for example, in fig. 2, assuming that the detection of one parameter of the liquid to be analyzed requires the reagent in the uppermost first cavity 201, a second conveying device corresponding to the first cavity 201 may be started to pump the liquid to be analyzed into the first cavity 201. Still referring to fig. 2, assuming that detection of all parameters needs to be performed simultaneously, four second delivery devices (each of the connection pipes 105 is connected to one second delivery device) may be activated simultaneously, drawing a portion of the liquid to be analyzed into four first cavities 201, respectively.
Similar to the first embodiment, the microfluidic microneedle device 100 of the present embodiment may have the microfluidic chip 104 and the microneedles 106 disposed in a human body or an animal body in some use scenarios; in other applications, the microfluidic chip 104 may be attached to the skin of a human or animal, and the microneedles 106 may be inserted into the skin.
Based on the second embodiment, the reaction result of the liquid to be analyzed and the reagent can be obtained by visual observation, and also can be obtained by the output of the electric signal of the microfluidic microneedle device 100.
In some embodiments, the microfluidic chip 104 is integrally disposed outside the human body, and the microfluidic chip 104 is made of a transparent material so that a user can observe the reaction result of the liquid to be analyzed and the reagent in the first cavity 201. For example, in some cases, if the pH value of the liquid to be analyzed needs to be detected, the reagent may be set as a pH reagent, and after the pH reagent is combined with the liquid to be analyzed, the color of the mixed liquid may be changed, and the user may observe the color of the mixed liquid and compare the color of the mixed liquid with the color chart, so as to determine the pH value of the liquid to be analyzed. In order to obtain a detection result by observation, a reagent capable of undergoing a color change after reacting with a target component in a liquid to be analyzed should be selected, which is not exemplified herein.
In other embodiments, if the microfluidic chip 104 is disposed in a human body, an electrochemical signal generated by reacting a reagent with a liquid to be analyzed can be considered, and the electrochemical signal is sent to the data processing device through the microelectrode embedded in the microfluidic chip 104, so that a user can determine a detection result according to the signal received by the data processing device.
The microfluidic chip 104 includes a microelectrode, one end of which is disposed on a wall surface of the first cavity 201, and the other end of which is connected to a data processing device (the data processing device may be a computer) through a cable such as a wire. For example, the microelectrode is configured as a copper wire, one end of the copper wire is disposed on the wall surface of the first cavity 201, and the other end of the copper wire is electrically connected with the conducting wire. If the target component in the liquid to be analyzed reacts with the reagent and generates an electrochemical signal, an electrical signal (electrochemical signal) is transmitted to the data processing device through the microelectrode in contact with the mixed liquid. The user can judge the detection result according to the existence of the electric signal or the strength of the electric signal. It should be noted that if the microfluidic chip 104 is disposed outside the human body, it is also conceivable to determine the detection result by electrochemical means.
Based on the first embodiment or the second embodiment, in the microfluidic microneedle device 100, the microneedles 106 may further include a porous substrate 102 and a non-porous substrate 103. Referring to fig. 1, a non-porous substrate 103 is attached to the periphery of a porous substrate 102, and the non-porous substrate 103 is attached to a microfluidic chip 104 and covers the microfluidic chip 104; the needle 101 is connected to a side of the porous substrate 102 remote from the microfluidic chip 104, and the needle 101 protrudes with respect to the porous substrate 102 in a direction remote from the microfluidic chip 104. Referring to fig. 1, the non-porous substrate 103 has a receiving groove 107 in which the porous substrate 102 is disposed, and the needle 101 penetrates the non-porous substrate and protrudes upward with respect to the upper side surface of the non-porous substrate 103.
Referring to fig. 3, the porous substrate 102 has engagement channels 302, and each of the engagement channels 302 has two ends that are respectively in communication with the second cavity 203 and one of the needle tracks 301. The non-porous substrate 103 is arranged to increase the contact area or the connection area of the micro-needle 106 and the micro-fluidic chip 104, improve the connection firmness of the micro-needle 106 and the micro-fluidic chip 104, and cover the micro-fluidic channel on the micro-fluidic chip 104 to prevent the liquid in the micro-fluidic chip 104 from leaking. In order to ensure that the micro-needles 106 have a sufficient active area, the micro-needles 106 may be provided with a plurality of needle bodies 101, and the plurality of needle bodies 101 are distributed in an array.
Referring to fig. 6, a method of manufacturing the microfluidic microneedle device 100 is described, the method comprising:
s10: manufacturing a microfluidic chip 104;
s20: manufacturing the micro needle 106;
s30: connecting the micro-needle 106 with the micro-fluidic chip 104 and communicating the needle track 301 with the third cavity 205;
s40: the connection pipe 105 is connected to the microfluidic chip 104.
The sequence numbers of "S10", "S20", "S30", "S40", etc. in the above steps are mainly for convenience of the following description, and the sequence numbers do not strictly limit the time sequence of the steps unless specifically described. For example, the micro-fluidic chip 104 may be fabricated followed by fabrication of the micro-needles 106; alternatively, the microneedles 106 may be manufactured after the microfluidic chip 104 is manufactured; alternatively, the micro-needles 106 may be manufactured at the same time as the micro-fluidic chip 104 is manufactured.
In step S10, the microfluidic chip 104 may be specifically manufactured by 3D printing, etching, reverse molding, and the like. The material of the microfluidic chip 104 may be various polymer materials that can be molded, such as PDMS (polydimethylsiloxane), PLGA (polylactic-co-glycolic acid), and PMMA (polymethyl methacrylate), and may also be materials such as silicon, metal, alloy, and hydrogel. If the microfluidic chip 104 needs to be transparent, the microfluidic chip 104 may be made of PDMS, PLGA, PMMA, hydrogel, or other materials. If the microfluidic microneedle device 100 of the second embodiment is to be manufactured, the step S10 further includes a step of embedding the reagent into the first cavity 201.
In some embodiments, step S20 may specifically be directly manufacturing the entire microfluidic chip 104 by 3D printing, etching, reverse molding, and the like. The optional material of the microneedles 106 is the same as that of the microfluidic chip 104 and will not be repeated here.
In other embodiments, step S20 may specifically be to first manufacture the body 108 of the microneedle 106 (the body 108 includes the needle body 101 and the porous substrate 102), and then form the non-porous substrate 103 around the periphery of the body 108. The body 108 may also be manufactured by 3D printing, etching, reverse molding, etc. Referring to fig. 7, a relatively simple and inexpensive way of manufacturing the non-porous substrate 103 is described. First, a base raw material liquid 402 is poured into a container 401 (e.g., a petri dish, a beaker), then the main body 108 is put into the container 401, and the main body 108 is immersed in the base raw material liquid 402 (as shown in fig. 8); with reference to fig. 8, the outer edge of the porous substrate 102 is in contact with the substrate material liquid 402, and at least a part of the needle 101 of the main body 108 needs to be disposed above the liquid surface of the substrate material liquid 402. The substrate stock solution 402 in the petri dish is then solidified, for example, the container 401 is put into an oven for baking, and the substrate stock solution 402 is solidified. After the substrate raw material liquid 402 is solidified, the substrate raw material liquid 402 and the container 401 are separated from each other, and the solidified substrate raw material liquid 402 forms the nonporous substrate 103; the separation may be performed by peeling the entire solidified substrate material liquid 402 from the container 401, or by cutting a part of the substrate material liquid 402 connected to the porous substrate 102 with a cutter and peeling the part of the cut substrate material liquid 402 from the container 401 (the part of the cut substrate material liquid 402 is the non-porous substrate 103).
During the process of placing the main body 108 into the container 401, the side of the porous substrate 102 facing away from the needle 101 is easily contacted with the substrate raw material liquid 402; if the substrate material liquid 402 is cured, and the cured substrate material liquid 402 covers one end of the connecting channels 302 of the porous substrate 102, polishing the micro-needles 106 after the micro-needles 106 are separated from the container 401 is required, and the substrate material liquid 402 blocking the connecting channels 302 is removed.
In some embodiments, step S30 may specifically be bonding the micro-needles 106 with the microfluidic chip 104. Bonding specifically refers to the fixation of two objects together by van der waals, molecular, and even atomic forces. For example, the manufactured micro-needles 106 and the micro-fluidic chip 104 can be placed into a plasma cleaner to be processed for a period of time, so as to ensure the cleanness and flatness of the joint surfaces of the micro-needles and the micro-fluidic chip; after the treatment, the two are pressed together, so that the micro-needle 106 is bonded with the micro-fluidic chip 104.
In the manufacturing process of the microfluidic chip 104, a preformed hole (not shown, the preformed hole communicates with the first cavity 201) into which the connection pipe 105 is inserted may be provided on the microfluidic chip 104. For step S40, the connection pipe 105 may be inserted into the preformed hole, and the junction between the connection pipe 105 and the microfluidic chip 104 is poured by using the pouring material, and then the connection pipe 105 and the microfluidic chip 104 are integrally placed into the oven for drying, so that the pouring material is cured; the cured casting material connects the connection pipe 105 and the microfluidic chip 104 together, and seals the gap between the connection pipe 105 and the microfluidic chip 104. The connecting pipe 105 can be a silica gel pipe or a Teflon pipe, or an artificial biological pipeline such as an electronic blood vessel; the casting material may be selected according to the material of the microfluidic chip 104, for example, the microfluidic chip 104 is made of PDMS material, and the casting material may be selected from PDMS material.
The embodiments of the present invention have been described in detail with reference to the accompanying drawings, but the present invention is not limited to the above embodiments, and various changes can be made within the knowledge of one of ordinary skill in the art without departing from the spirit of the present invention. Furthermore, embodiments of the invention and features of the embodiments may be combined with each other without conflict.
Claims (7)
1. Microfluidic microneedle device, characterized by comprising:
the microfluidic chip is provided with a first cavity, a second cavity, a third cavity, a first connecting channel and a second connecting channel, wherein a plurality of first cavities are arranged, one second cavity is arranged, two ends of the first connecting channel are respectively communicated with the first cavity and the second cavity, two ends of the second connecting channel are respectively communicated with the second cavity and the third cavity, the first cavity is communicated with the second cavity through the first connecting channel, and the second cavity is communicated with the third cavity through the second connecting channel;
the micro needle is connected with the micro-fluidic chip and comprises at least one needle body, a needle channel is arranged in the needle body, one end of the needle channel is communicated with the third cavity, and the other end of the needle channel is arranged at one end, far away from the micro-fluidic chip, of the needle body;
the connecting pipes are connected with the microfluidic chip, and the pipe cavity of each connecting pipe is respectively communicated with one first cavity;
under the drive of a first conveying device, raw materials can be conveyed into the microfluidic chip along the connecting pipe and sequentially flow through the first cavity and the second cavity, multiple raw materials are combined in the second cavity to form target medicines, and the dosage of the raw materials conveyed into the microfluidic chip can be adjusted by controlling the conveying power of the first conveying device, so that the dosage, the concentration or the speed of administration of the microfluidic microneedle device can be adjusted.
2. The microfluidic microneedle device of claim 1, wherein the microneedle further comprises a porous substrate and a non-porous substrate, the non-porous substrate being attached to a periphery of the porous substrate, the non-porous substrate being attached to the microfluidic chip to cover the microfluidic chip;
the needle body is connected to one side of the porous substrate far away from the microfluidic chip and protrudes towards the direction far away from the microfluidic chip relative to the porous substrate, the porous substrate is provided with a connecting pore canal, and two ends of the connecting pore canal are respectively communicated with the third cavity and the needle canal.
3. Microfluidic microneedle device, characterized by comprising:
the microfluidic chip is provided with a first cavity, a second cavity, a third cavity, a first connecting channel and a second connecting channel, wherein a plurality of first cavities are arranged, one second cavity is arranged, two ends of the first connecting channel are respectively communicated with the first cavity and the second cavity, two ends of the second connecting channel are respectively communicated with the second cavity and the third cavity, the first cavity is communicated with the second cavity through the first connecting channel, and the second cavity is communicated with the third cavity through the second connecting channel;
the micro needle is connected with the micro-fluidic chip and comprises at least one needle body, a needle channel is arranged in the needle body, one end of the needle channel is communicated with the third cavity, and the other end of the needle channel is arranged at one end, far away from the micro-fluidic chip, of the needle body;
the connecting pipes are connected with the microfluidic chip, and the pipe cavity of each connecting pipe is respectively communicated with one first cavity;
a reagent disposed in the first cavity;
one end of the microelectrode is arranged on the wall surface of the first cavity and is used for transmitting an electric signal generated by chemical reaction in the first cavity;
each connecting pipe is respectively connected with a second conveying device, the second conveying devices are used for extracting gas or liquid in the microfluidic chip so as to manufacture pressure difference and enable body fluid to enter the microfluidic chip through a needle channel, different first cavities are pre-buried with different types of reagents, and according to detection requirements of different parameters, the body fluid can be extracted into the corresponding first cavities by starting different second conveying devices.
4. A microfluidic microneedle device according to claim 3, wherein the microfluidic chip is transparent.
5. A method of manufacturing a microfluidic microneedle device according to any one of claims 1 to 4, comprising the steps of:
manufacturing a microfluidic chip, wherein the microfluidic chip is provided with a first cavity, a second cavity and a third cavity, a plurality of first cavities are arranged, one second cavity is arranged, the first cavity is communicated with the second cavity, and the second cavity is communicated with the third cavity;
manufacturing a microneedle, wherein the microneedle comprises at least one needle body, and the interior of the needle body is provided with a through needle channel;
connecting the micro needle with the micro-fluidic chip so as to enable the needle track to be communicated with the third cavity;
and connecting the microfluidic chip with a connecting pipe so that the first cavity is communicated with the cavity of the connecting pipe.
6. The method of manufacturing a microfluidic microneedle device according to claim 5, wherein connecting the microneedle with the microfluidic chip comprises the steps of: and connecting the micro needle and the micro-fluidic chip together in a bonding mode.
7. The method of manufacturing a microfluidic microneedle device according to claim 5, wherein manufacturing the microneedle comprises the steps of:
manufacturing a main body, wherein the main body comprises a needle body and a porous substrate, the needle body is connected to the porous substrate, and the porous substrate is provided with a connecting pore canal capable of communicating with the needle canal;
adding a substrate raw material liquid into a container, putting the main body into the container, and enabling the outer edge of the porous substrate to be in contact with the substrate raw material liquid;
solidifying the base stock solution in the container;
separating the solidified substrate raw material liquid from the container to obtain the micro needle.
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| WO2011116388A1 (en) * | 2010-03-19 | 2011-09-22 | Nanostar Health Corporation | Body fluid sampling/fluid delivery device |
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| CN112312898A (en) * | 2018-06-29 | 2021-02-02 | 强生消费者公司 | Three-dimensional microfluidic device for delivery of active substances |
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