Detection method of microfluidic chip and plasma separation and diversion integrated microfluidic chip
By designing the microarray structure and diversion assembly in the microfluidic chip, and using capillary action and microfluidic valve adjustment, the problem of difficult plasma release to the detection area is solved, efficient plasma separation and rapid diversion are achieved, and detection efficiency and accuracy are improved.
Patent Information
- Application Number
- CN202411569209.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2024-11-05
- Publication Date
- 2025-08-26
- Estimated Expiration
- 2044-11-05
AI Technical Summary
During the plasma separation process of existing microfluidic chips, the plasma is easily locked in the separation area and is difficult to be effectively released into the detection area, affecting the detection efficiency and accuracy.
The microarray structure and diversion assembly design are adopted to allow plasma to flow along the orifice through capillary action, and the plasma is directed to the chip body through the diversion channel. Combined with the microfluidic valve to adjust the flow speed and direction, the precise amount of plasma is detected.
It realizes efficient separation and rapid release of plasma, improves detection speed and sensitivity, simplifies the operation process, and ensures accurate diversion and enrichment extraction of plasma.
Smart Images

Figure CN119608256B_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the technical field of microfluidic chips, and in particular to a detection method for a microfluidic chip and a plasma separation and diversion integrated microfluidic chip. Background Art
[0002] Plasma separation is a key pre-treatment step in many medical diagnostic and bioanalysis processes, and its efficiency and quality directly affect the accuracy and reliability of subsequent testing. Traditional plasma separation methods usually rely on large equipment such as centrifuges, which are not only complicated to operate but also difficult to meet the needs of point-of-care testing and portable devices. In recent years, the rapid development of microfluidics technology has greatly promoted progress in the field of point-of-care testing. However, since clinical samples are usually whole blood, if the whole blood is separated by equipment such as centrifuges and then directed to a microfluidic chip for testing, it is not only cumbersome to operate but may also cause cross-contamination.
[0003] To address these issues, existing microfluidic chip designs typically integrate various types of filters or microstructures within the blood sample input area for plasma separation. While these structures enable initial plasma separation, they also result in the separated plasma being easily "locked" within the separation zone, making it difficult to effectively release it into the detection area. This inconsistency severely impacts the efficient transfer of plasma to the chip's detection zone, prolonging the entire detection process and reducing both sensitivity and accuracy. Summary of the Invention
[0004] The present invention aims to solve at least one of the technical problems existing in the prior art. To this end, the present invention provides a microfluidic chip detection method and a plasma separation and diversion integrated microfluidic chip, which can effectively separate plasma and divert the plasma to the detection area of the chip body.
[0005] In one aspect, a detection method for a microfluidic chip according to an embodiment of the present invention is applied to a plasma separation and flow guidance integrated microfluidic chip, wherein the plasma separation and flow guidance integrated microfluidic chip includes a sample inlet, a separation component, a flow guidance component, and a chip body; the detection method includes the following steps:
[0006] placing a blood sample into the sample inlet;
[0007] The separation component separates plasma from the blood sample and transports the plasma to the flow guide component;
[0008] The flow guiding component guides the plasma to the chip body;
[0009] The chip body detects the plasma to obtain a detection result.
[0010] According to some embodiments of the present invention, the flow guiding component includes a microarray structure and a plurality of flow guiding channels, wherein the microarray structure has a plurality of channels; the step of guiding the plasma to the chip body by the flow guiding component includes:
[0011] The microarray structure causes the plasma to flow along the pores through capillary action and to be enriched in the guide channel;
[0012] The guide channel guides the plasma in the pore to the chip body.
[0013] According to some embodiments of the present invention, the chip body includes: a first collecting channel and a plurality of first branch flow channels, one end of the first collecting channel is connected to the guide component, the other end of the first collecting channel is provided with a first water absorbent pad, each of the first branch flow channels is connected to the first collecting channel, the first branch flow channel is located between the first water absorbent pad and the guide component, and the first branch flow channel is vertically arranged below the first collecting channel, a test paper is provided in each first branch flow channel, a first measuring positioning hole is provided on the side of each first branch flow channel, and the first measuring positioning hole is located above the test paper, and the bottom of the plurality of first branch flow channels is connected to a first air pressure balance port; a first light-responsive film is provided on the outside of the first branch flow channel;
[0014] The chip body performs detection on the plasma to obtain the detection result, comprising:
[0015] The plasma enters the first collecting channel through the flow guiding component;
[0016] When the plasma reaches the junction of the first collecting channel and the first branch channel, the plasma flows into the first branch channel until it reaches the first measuring positioning hole;
[0017] The plasma in the first collection channel continues to flow forward to the first absorbent pad and no longer flows into the first branch flow channel, so that an independent and quantitative amount of plasma exists in the first branch flow channel;
[0018] The first light-responsive film is irradiated with a preset light, so that the plasma in the first branch flow channel reacts with the test paper to obtain the test result.
[0019] According to some embodiments of the present invention, the chip body includes a second collection channel and a second branch flow channel, one end of the second collection channel is connected to the guide component, the other end of the second collection channel is provided with a second water absorbent pad, the second branch flow channel is connected to the second collection channel, the second branch flow channel is located between the second water absorbent pad and the guide component, and the second branch flow channel is vertically arranged below the second collection channel, the reaction chamber is arranged at the bottom of the second branch flow channel and is connected to the second branch flow channel, the reaction flow channel is connected to the reaction chamber, and the reaction flow channel is arranged parallel to the second collection channel, the bottom of the reaction flow channel is provided with a second measuring positioning hole, and the outside of the reaction flow channel is provided with a second light-responsive film;
[0020] The chip body performs detection on the plasma to obtain the detection result, comprising:
[0021] Printing the detection reagent in the reaction chamber by inkjet printing and making the detection reagent into powder by freeze drying; or modifying the inner surface of the reaction chamber with antibodies to form the detection reagent;
[0022] The plasma enters the second collecting channel through the flow guiding component;
[0023] When the plasma reaches the junction of the second collecting channel and the second branch channel, the plasma flows into the second branch channel, fills the reaction chamber, and reaches the second measuring positioning hole;
[0024] The plasma in the second collection channel continues to flow forward to the second absorbent pad and no longer flows into the second branch flow channel, so that an independent and quantitative amount of plasma exists in the reaction chamber;
[0025] The second light-responsive film is irradiated with a preset light, so that the plasma in the reaction chamber reacts with the detection reagent to obtain the detection result.
[0026] According to some embodiments of the present invention, the flow guide component is a primary flow channel, and the chip body further includes a plurality of secondary flow channels and a plurality of tertiary flow channels, wherein the secondary flow channels correspond one-to-one with the tertiary flow channels, one end of the secondary flow channel is connected to the flow guide component, and the other end of the secondary flow channel is connected to the corresponding tertiary flow channel; a sample separation port is provided on the side of the secondary flow channel;
[0027] The chip body performs detection on the plasma to obtain the detection result, comprising:
[0028] The plasma flows into the secondary flow channel through the primary flow channel and then enters the sample separation port;
[0029] After the plasma passes through the secondary flow channel and enters the tertiary flow channel, the tertiary flow channel absorbs all the plasma in the secondary flow channel;
[0030] The plasma reacts with the detection reagent in the tertiary flow channel to obtain the detection result.
[0031] On the other hand, a plasma separation and flow guidance integrated microfluidic chip according to an embodiment of the present invention includes:
[0032] a sample inlet, the sample inlet being used to receive a blood sample;
[0033] a separation component, communicated with the sample inlet, and configured to separate plasma from the blood sample;
[0034] a flow guide component, connected to the separation component;
[0035] The chip body is in communication with the flow guiding component, and the flow guiding component is used to guide the separated plasma to the chip body.
[0036] According to some embodiments of the present invention, the flow guide assembly includes:
[0037] a microarray structure, connected to the separation component, the microarray structure having a plurality of pores, and the microarray structure is used to make the plasma flow along the pores by capillary action;
[0038] A plurality of diversion channels, each of which is connected to the microarray structure and the chip body respectively, and the diversion channel is used to divert the plasma in the pores to the chip body.
[0039] According to some embodiments of the present invention, each of the diversion channels is connected to the microarray structure through a corresponding collection hole, and by adjusting the gaps between different areas of the microarray structure, the plasma enrichment area of the microarray structure is positioned at the collection hole.
[0040] According to some embodiments of the present invention, the microarray structure is a tree-like structure, and the channel width of the tree-like structure gradually decreases from the trunk to the branch end close to the collection hole, so as to divert the separated plasma to multiple parallel channels with smaller widths before reaching the collection hole.
[0041] According to some embodiments of the present invention, the microarray structure is a concentric ring structure, and the channel width of the concentric ring structure gradually decreases from the outer ring to the inner ring, so that the separated plasma gradually flows from the outer ring to the inner ring toward the collection hole.
[0042] According to some embodiments of the present invention, a plurality of inlets are evenly distributed on the circumference of the outer ring, so that the separated plasma flows evenly into the outer ring through the plurality of inlets.
[0043] According to some embodiments of the present invention, the hydrophilicity of the material of the outer ring is greater than the hydrophilicity of the material of the inner ring, and the inner wall of the concentric annular structure is provided with a flow-guiding texture.
[0044] According to some embodiments of the present invention, the channel width of the microarray structure in the Z-axis direction gradually narrows from top to bottom.
[0045] According to some embodiments of the present invention, the chip body has multiple microchannels, each of which is provided with a microfluidic valve, and the microfluidic valve is used to adjust the flow speed and direction of the plasma so that the plasma flows along the microchannel to the detection area.
[0046] According to some embodiments of the present invention, the chip body includes:
[0047] a first collecting channel, one end of the first collecting channel being in communication with the flow guide assembly, and the other end of the first collecting channel being provided with a first water absorbent pad;
[0048] a plurality of first branch flow channels, each of which is connected to the first collecting channel, the first branch flow channels being located between the first absorbent pad and the flow guide assembly, and the first branch flow channels being vertically disposed below the first collecting channel;
[0049] Among them, a test paper is provided in each of the first branch flow channels, a first measuring positioning hole is provided on the side of each of the first branch flow channels, and the first measuring positioning hole is located above the test paper, and the bottoms of several of the first branch flow channels are connected to a first air pressure balance port; a first light-responsive film is provided on the outside of the first branch flow channel.
[0050] According to some embodiments of the present invention, the chip body includes:
[0051] a second collecting channel, one end of the second collecting channel being in communication with the flow guide assembly, and the other end of the second collecting channel being provided with a second water absorbent pad;
[0052] a second branch flow channel, the second branch flow channel being in communication with the second collecting channel, the second branch flow channel being located between the second absorbent pad and the flow guide assembly, and the second branch flow channel being vertically disposed below the second collecting channel;
[0053] a reaction chamber, disposed at the bottom of the second branch flow channel and communicated with the second branch flow channel;
[0054] The reaction channel is connected to the reaction chamber and is arranged in parallel with the second collecting channel. A second measuring positioning hole is provided at the bottom of the reaction channel, and a second light-responsive film is provided outside the reaction channel.
[0055] According to some embodiments of the present invention, the flow guide component is a primary flow channel, and the chip body further includes a plurality of secondary flow channels and a plurality of tertiary flow channels, the secondary flow channels corresponding one to one with the tertiary flow channels, one end of the secondary flow channel is connected to the flow guide component, and the other end of the secondary flow channel is connected to the corresponding tertiary flow channel; a sample separation port is provided on the side of the secondary flow channel, and a quantitative measuring port is provided on the side of the tertiary flow channel.
[0056] According to some embodiments of the present invention, the separation component comprises a filter membrane having a pore size ranging from 0.2 μm to 5 μm.
[0057] According to some embodiments of the present invention, the hydrophilicity of the microfluidic chip is improved by the following method:
[0058] Using benzophenone as a photosensitizer, and evenly coating the photosensitizer on the inner wall of the microfluidic chip;
[0059] filling the microfluidic chip with a methacryloyloxyethyl phosphorylcholine solution;
[0060] Ultraviolet light is used to irradiate the interior of the microfluidic chip, so that the benzophenone and the polymerized monomers of the methacryloyloxyethyl phosphorylcholine solution undergo a bonding reaction, and a hydration layer is formed on the inner wall of the microfluidic chip.
[0061] The detection method and integrated plasma separation and diversion microfluidic chip according to embodiments of the present invention have at least the following beneficial effects: plasma is separated from a blood sample by a separation component, and then the plasma is diverted to the chip body by a diversion component for reaction, thereby obtaining a reaction result. This solution ensures efficient plasma separation while achieving rapid and complete release of the separated plasma, and can effectively divert the plasma to the microfluidic chip for precise quantitative detection. This solution can achieve efficient plasma separation and rapid diversion to the detection area on a microfluidic platform, and support plasma enrichment and extraction, thereby improving detection speed and sensitivity while simplifying the operational process.
[0062] Additional aspects and advantages of the present invention will be set forth in part in the description which follows and, in part, will be obvious from the description which follows, or may be learned by practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS
[0063] The above and / or additional aspects and advantages of the present invention will become apparent and readily understood from the following description of the embodiments with reference to the accompanying drawings, in which:
[0064] Figure 1 A top view of the internal structure of the plasma separation and flow guidance integrated microfluidic chip according to an embodiment of the present invention;
[0065] Figure 2 This is a schematic structural diagram of the sample inlet, separation component, and flow guiding component of the plasma separation and flow guiding integrated microfluidic chip according to an embodiment of the present invention;
[0066] Figure 3 for Figure 2 An enlarged schematic diagram of the guide assembly is shown;
[0067] Figure 4 A top view of the internal structure of the plasma separation and flow guidance integrated microfluidic chip according to an embodiment of the present invention;
[0068] Figure 5 Schematic diagram of the flow of plasma in the microarray structure;
[0069] Figure 6 Schematic diagram of the microarray structure when it is tree-like;
[0070] Figure 7 A flow chart of the steps for improving the hydrophilicity of a microfluidic chip according to an embodiment of the present invention;
[0071] Figure 8 A schematic diagram of a process for improving the hydrophilicity of a microfluidic chip according to an embodiment of the present invention;
[0072] Figure 9 This is a schematic structural diagram of a chip body according to a first embodiment of the present invention;
[0073] Figure 10 This is a schematic structural diagram of a chip body according to a second embodiment of the present invention;
[0074] Figure 11 This is a schematic structural diagram of a chip body according to a third embodiment of the present invention;
[0075] Figure 12 Flow chart of the steps of the detection method of the microfluidic chip according to an embodiment of the present invention;
[0076] Sample inlet 100, separation component 200, flow guide component 300, microarray structure 310, flow guide channel 320, chip body 400, first collection channel 410, first absorbent pad 420, first branch flow channel 430, test paper 440, first measuring positioning hole 450, first air pressure balance port 460, first light response film 470, second collection channel 510, second absorbent pad 520, second branch flow channel 530, reaction chamber 540, reaction flow channel 550, second measuring positioning hole 560, second light response film 570, primary flow channel 610, secondary flow channel 620, tertiary flow channel 630, sample separation port 640, quantitative measuring port 650. DETAILED DESCRIPTION
[0077] The embodiments of the present invention are described in detail below. Examples of the embodiments are shown in the accompanying drawings, wherein the same or similar reference numerals throughout represent the same or similar elements or elements having the same or similar functions. The embodiments described below with reference to the accompanying drawings are exemplary and are only used to explain the present application and are not to be construed as limiting the present application. The step numbers in the following embodiments are provided only for the convenience of explanation and do not limit the order of the steps. The order of execution of the steps in the embodiments can be adaptively adjusted according to the understanding of those skilled in the art.
[0078] In the description of the present invention, it should be understood that descriptions involving orientations, such as up, down, front, back, left, right, etc., indicating orientations or positional relationships, are based on the orientations or positional relationships shown in the accompanying drawings. They are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation. Therefore, they cannot be understood as limitations on the present invention.
[0079] The terms "first," "second," "third," and "fourth," etc., in the specification, claims, and accompanying drawings of the present invention are used to distinguish between different items, not to describe a specific order. Furthermore, the terms "including," "having," and any variations thereof, are intended to cover non-exclusive inclusions. For example, a process, method, system, product, or apparatus comprising a series of steps or elements is not limited to the listed steps or elements, but may optionally include steps or elements not listed, or may optionally include other steps or elements inherent to the process, method, product, or apparatus.
[0080] References to "embodiments" in this disclosure mean that a particular feature, structure, or characteristic described in connection with the embodiment may be included in at least one embodiment of the disclosure. The appearance of this phrase in various places in the specification does not necessarily refer to the same embodiment, nor does it constitute an independent or alternative embodiment that is mutually exclusive of other embodiments. It is understood, both explicitly and implicitly, by those skilled in the art that the embodiments described herein may be combined with other embodiments.
[0081] Currently, two main approaches are used for plasma separation in microfluidic chips: multilayer composite structures and microstructured filtration. Multilayer composite structures typically utilize a filter membrane and a paper-based microfluidic chip to form a multilayer composite structure. The filter membrane is used for initial plasma separation, and the separated plasma is absorbed by the underlying test strip. This structure typically yields semi-quantitative results, making it difficult to achieve precise quantification. Furthermore, this structure cannot concentrate and extract the filtered plasma, which is retained between the filter membrane and the test strip, limiting subsequent in-depth analysis. Because the plasma is trapped within the porous structure, it is difficult to effectively release it, compromising the sensitivity and accuracy of the test. Another common approach involves incorporating microbeads into the chip or fabricating microstructures using photolithography to achieve plasma separation. This approach theoretically offers more precise blood cell isolation and plasma separation. However, the microstructures are prone to clogging during filtration, resulting in slow filtration and reduced detection efficiency. Similar to multilayer composite structures, the separated plasma is difficult to effectively release and collect. Therefore, whether it is a multi-layer composite structure or microstructure filtration, existing plasma separation devices face the challenge of how to quickly and effectively guide the separated plasma into the microfluidic chip for subsequent testing.
[0082] The solution provided by the embodiments of the present invention not only ensures efficient plasma separation, but also achieves rapid and complete release of separated plasma, and can effectively guide the plasma into the microfluidic chip for precise quantitative detection. It can achieve efficient plasma separation and rapid guidance to the detection area on the microfluidic platform, and support plasma enrichment and extraction, which can not only improve the speed and sensitivity of detection, but also simplify the operation process.
[0083] On the one hand, if Figure 1 and Figure 2 As shown, an embodiment of the present invention proposes a plasma separation and diversion integrated microfluidic chip, including a sample inlet 100, a separation component 200, a diversion component 300 and a chip body 400, wherein the sample inlet 100 is used to receive a blood sample; the separation component 200 is connected to the sample inlet 100, and is used to separate plasma from the blood sample; the diversion component 300 is connected to the separation component 200, and the chip body 400 is connected to the diversion component 300, and the diversion component 300 is used to divert the separated plasma to the chip body 400.
[0084] Specifically, if Figure 2As shown, after a blood sample is added to the sample inlet 100, it flows through the sample inlet 100 to the separation assembly 200. In this example, the separation assembly 200 includes a filter membrane located below the sample inlet 100. The filter membrane filters the blood sample, removing plasma and solid components from the blood. The pore size of the filter membrane is designed to be permeable to plasma but not to solid components in the blood sample. For example, the pore size of the filter membrane can range from 0.2 to 5 μm. The principle of extracting plasma from a whole blood sample through the filter membrane relies primarily on the physical separation of cellular and liquid components. In a whole blood sample, the liquid component is primarily plasma, while the solid components include red blood cells, white blood cells, and platelets. When the whole blood sample passes through the filter membrane, plasma passes through the filter membrane due to pressure differential or gravity, while solid components are retained above the filter membrane. This removes cellular components and other large particulate impurities, resulting in a clean plasma sample. The filtered liquid component is plasma, which contains various biochemical components and is convenient for further testing and analysis. After the plasma is filtered out using the filter membrane, the bottom of the filter membrane directly contacts the guide component 300, which guides the separated plasma to the chip body 400, so that the plasma reaches the predetermined detection area for subsequent biochemical analysis.
[0085] Further, if Figures 2 to 4 As shown, in some embodiments of the present invention, the flow guide component 300 includes a microarray structure 310 and a plurality of flow guide channels 320. The microarray structure 310 is connected to the separation component 200. The microarray structure 310 has multiple channels. The microarray structure 310 is used to make the plasma flow along the channels through capillary action. Each flow guide channel 320 is respectively connected to the microarray structure 310 and the chip body 400. The flow guide channel 320 is used to guide the plasma in the channel to the chip body 400. Specifically, as Figure 3 As shown, the microarray structure 310 includes a plurality of microstructures 311. Through the arrangement of the plurality of microstructures 311, pores are formed in the gaps between the microstructures 311. The microarray structure 310 is in direct contact with the filter membrane of the separation component 200. After the filter membrane filters out the plasma, the microarray structure 310 introduces the filtered plasma into the pores of the microarray structure 310 through capillary action. In this way, the extracted plasma flows spontaneously in the tiny pores of the microarray structure 310. This is because the design of the microarray structure 310 usually includes many tiny pores, and the size and shape of these pores can significantly affect the flow of the fluid. First, the pores inside the microarray structure 310 can enhance the contact area of the liquid and generate capillary action when the liquid enters. The capillary force will cause the liquid to flow rapidly along the pores and fill these tiny spaces. Secondly, the gaps between the microarray structures 310 can also play an important role. These gaps provide additional channels for the flow of liquid, further promoting the extraction of the fluid. As shown in FIG. Figure 3 As shown, in the microarray structure 310, there are also multiple collection holes 312, and each guide channel 320 is connected to the microarray structure 310 through the corresponding collection hole 310. By adjusting the gaps between the microstructures 311 in different areas of the microarray structure 310, the plasma enrichment area of the microarray structure 310 is positioned at the collection hole 312, thereby further promoting the plasma to flow along the microarray structure 310 into each collection hole 312, and then into the chip body 400 along the guide channel 320. In this example, the number of collection holes 312 and guide channels 320 is set to four. It should be noted that the number of collection holes 312 and guide channels 320 can be adjusted according to actual needs, and is not limited to this. Figure 5 As shown in FIG. 3 , the arrow indicates the direction of plasma flow in the microarray structure 310, and the circle indicates the location of the collection hole 312. The closer to the collection hole 312, the denser the distribution of the microstructure 311. The farther away from the collection hole 312, the sparser the distribution of the microstructure 311, thereby enriching the plasma in the collection hole 312. Finally, the plasma guided through the microarray structure 310 enters the chip body 400 through the flow channel 320. Figure 1 As shown, the chip body 400 has multiple microchannels. Microfluidic valves can be set on the microchannels of the chip body 400. The operator can adjust the flow speed and direction of the plasma by controlling the microfluidic valves, so that the plasma can accurately reach the predetermined detection area for subsequent biochemical analysis.
[0086] In this embodiment, the combination of microarray structure 310 and filter membrane ensures efficient plasma separation while preventing rapid clogging of the filter membrane. The microarray structure 310 effectively overcomes the adsorption force of the filter membrane, enabling rapid release of plasma. The design of the diversion channel 320 and microfluidic valve enables precise and quantitative diversion of separated plasma to the detection area. By adjusting the microfluidic valve, plasma can be enriched in specific areas, facilitating subsequent in-depth analysis. The entire process, from sample loading to plasma separation and diversion to the detection area, is automated, significantly simplifying the operational workflow. Because plasma can be quickly and completely released and diverted to the detection area, plasma retention in the filter membrane is avoided, thereby improving detection sensitivity and accuracy. Therefore, the plasma separation and diversion channel 320 provided in this embodiment, through its innovative structural design, successfully addresses the existing issues of difficult plasma release and diversion. This device not only achieves efficient plasma separation but also ensures rapid release and precise diversion of separated plasma, providing a reliable sample pretreatment solution for biochemical analysis on microfluidic chips.
[0087] Furthermore, in some embodiments of the present invention, in order to further improve the flow efficiency and stability of plasma, this embodiment also proposes an arrangement design of a microarray structure 310 that combines a two-dimensional parallel microchannel tree structure and a three-dimensional conical structure to achieve directional capillary action and gradient capillary action, thereby optimizing the flow path and extraction efficiency of the liquid.
[0088] It should be noted here that the capillary action here is not a pump that relies on external force in the traditional sense, but a figurative description of the movement of plasma under the action of capillary force. The scheme mentioned in the context of the present invention does not involve a physical capillary pump, does not rely on external force, and relies entirely on ingenious design to achieve the spontaneous flow of plasma.
[0089] like Figure 6 As shown, on the XY plane, the arrangement of the microstructure 311 of the microarray structure 310 is designed to be a tree-like structure (which can also be understood as a "tree line structure" in some scenarios), and the extracted plasma is diverted to multiple smaller parallel microchannels. In this way, since the contact area of the entire system is increased, it means that more plasma is in contact with the surface of the channel, thereby enhancing the capillary force and evenly distributing the liquid. According to the basic principle of capillary flow, the capillary force is inversely proportional to the diameter of the pipe. Therefore, smaller microchannels can more effectively guide the liquid to flow along the channel. By branching into microchannels of small diameter, the capillary pressure and the driving force of the flow are enhanced. In the specific design, the channel width of the tree-like structure can be gradually reduced from 100μm at the trunk to 10μm at the end of the branch to ensure the generation of directional capillary force.
[0090] It is understood that the width and length of the tree structure are not limited and can be adaptively adjusted based on actual capillary force and flow rate requirements. It is also understood that in this embodiment, the angle and channel width can be adjusted at the branch points of the tree structure, and secondary branches can be designed within each branch to further refine and enhance the capillary action.
[0091] It should be noted that the spontaneous movement of plasma is controlled by capillary phenomena generated by the interaction of liquid surface tension with the chemical and geometric shape of the solid interface, which leads to the overall minimization of the free energy between the solid, liquid and vapor interfaces. These capillary phenomena can be used to spontaneously fill microstructures. The capillary pressure Pc is related to the liquid-gas meniscus in the microchannel and conforms to the following formula:
[0092] Circular microchannel:
[0093]
[0094] where γ is the surface tension of the liquid, θ is the contact angle, and r is the radius of the capillary.
[0095] The above formula I shows that the smaller the radius of the capillary, the greater the capillary pressure
[0096] Rectangular microchannel:
[0097]
[0098] In the above formula II, γ is the surface tension of the liquid, α b , α t , α l , α τ are the contact angles of the liquid on the bottom, top, left and right walls, respectively, and d and w are the depth and width of the channel, respectively. Each wettable wall of the cross section helps the liquid generate negative pressure and draw the liquid into the channel. Therefore, if the cross section changes, a smaller cross section will produce a correspondingly higher capillary pressure difference. The tree-like structure achieves a smooth transition of the fluid by gradually changing the size. The gradual change of the channel reduces the pressure mutation, making the capillary pressure difference of each part smaller. The tree-like structure can evenly distribute the fluid and reduce the pressure fluctuations in the local area. It can also be understood that the flow resistance in the channel is basically constant, resulting in the liquid flowing at a constant rate.
[0099] Regardless of whether the microstructures 311 of the microarray structure 310 are cubes, cylinders, or circular hexagons, the direction of plasma flow during the enrichment process is random. By editing the gaps between the microstructures 311 in different regions of the microarray structure 310 in the XY plane, the direction of plasma enrichment during lateral flow can be controlled. The required area and gaps of the microstructures 311 can be calculated based on the required plasma volume. Specifically, channels with larger collection volumes have larger enrichment areas, thus achieving directional distribution of the extracted plasma within the XY plane. This allows filtered plasma to be concentrated at the collection holes 312 of the diversion channels 320, facilitating plasma enrichment.
[0100] Therefore, this embodiment can increase the capillary pressure P by designing smaller parallel microchannels, thereby increasing the extraction and diversion speed, thereby further improving the mass flow rate. Currently in this embodiment, the spacing between the microarrays is 100 μm, and the entire filtration, extraction and diversion sampling process can be achieved within 3 minutes.
[0101] In some embodiments of the present invention, the tree structure in the above embodiment may be replaced by a concentric ring structure.
[0102] In this embodiment, the concentric ring structure is designed to guide the liquid flow from the outside inward and concentrate it at a central location through the clever arrangement of annular channels. First, the channels are designed in a multi-layered concentric ring configuration, with the annular channels in each layer gradually decreasing in size from the outer ring to the inner ring. This gradual reduction in size ensures that the liquid is gradually guided toward the central area during flow, effectively preventing fluid diffusion and achieving gradual concentration. To ensure uniform fluid entry, multiple inlets, for example, four to six, are evenly distributed around the outer ring. This uniform distribution of inlets ensures uniform fluid entry into the outer ring, achieving uniform flow distribution from the initial stage and preventing biased flow during entry. Furthermore, to optimize the liquid flow path, the channel surfaces can be specially treated. Using a hydrophilic material for the outer ring facilitates smoother liquid entry into the system, while using a relatively hydrophobic material for the inner ring accelerates liquid flow. Furthermore, introducing microstructures or flow-guiding textures on the channel surfaces can further standardize the liquid flow direction and reduce fluid stagnation and eddy currents within the channel.
[0103] In the central area of the design, collection hole 312 is positioned as the final collection point for the liquid. This hole not only ensures efficient liquid collection but also, combined with the separation function of the filter membrane, effectively enriches and separates the target components in the liquid. This design, through the optimized combination of structure and materials, achieves an efficient flow path where liquid enters from multiple inlet points and gradually converges to the central collection hole 312.
[0104] The above description primarily addresses the special design of microarray structure 310 in the XY plane. After filtration, plasma reaches collection well 312 and flows downward under capillary forces and gravity. However, to optimize the speed and efficiency of this flow diversion, in this embodiment, the design of microstructure 311 of microarray structure 310 is primarily optimized in the Z-axis direction, leveraging gravity to enhance capillary flow.
[0105] In the Z-axis direction, the microchannel is designed to be narrower from top to bottom. In some cases, it can also be understood as a tapered channel, for example, it can be designed as a conical channel with an inclination angle or a truncated cone channel. In some other embodiments, it can also be a spiral microchannel. The spiral path increases the flow distance and enhances the capillary force. Gradient control is achieved by changing the pitch. By gradually expanding the lateral dimension of the channel, the capillary effect and the stability of the vertical flow of the liquid are further enhanced. Gravity and capillary force are used to promote the flow of liquid in the Z-axis direction to achieve the effect of diversion.
[0106] In the Z-axis direction perpendicular to the XY plane, the microstructure 311 is designed to be a circular hexagon or a cone with a certain inclination angle in the Z direction. The principle is to achieve a more efficient and stable top-down extraction process in the Z direction by gradually expanding the lateral dimensions of the capillary pump. By expanding the lateral dimensions of the capillary pump (such as designing it into a circular hexagon or cone), the channel cross-section of the liquid flow can be increased, thereby reducing the flow resistance of the fluid. This design makes the flow of the fluid in the Z direction smoother, avoiding local excessive flow velocity and pressure drop caused by narrow channels. When the lateral dimensions of the channel increase, the capillary effect can play a role on a larger surface area, enhancing the driving ability of the liquid when flowing in the Z axis. Especially for smaller channels, the stronger the capillary force, the more significant the propulsion effect of the liquid in the channel. The conical design with an inclination angle can make the flow of liquid in the Z-axis direction more efficient. The inclined channel can use the combined effect of gravity or capillary force to better guide the liquid to flow downward and reduce possible stagnation areas. In the tapered structure, the changes in the direction and velocity of liquid flow facilitate the expulsion of bubbles, reducing their interference with flow and ensuring liquid continuity. As the transverse dimensions of the capillary pump gradually expand, liquid is better extracted during flow. This structure effectively draws liquid above the membrane into the channel below through capillary action, improving extraction efficiency.
[0107] For example, in the Z-axis, perpendicular to the XY plane, the channels in the microfluidic chip gradually expand into a circular hexagonal tapered structure. The tapered channel gradually widens from a smaller diameter at the end of the microchannel to the location of the collection hole, ensuring more efficient vertical liquid extraction. The principle of the tapered design is to reduce the resistance to liquid flow by increasing the lateral dimension of the channel. The expanded channel cross-section allows the capillary effect to operate over a larger surface area, enhancing the liquid propulsion effect in the Z direction.
[0108] During operation, the liquid to be processed (such as blood, sample solution) is introduced into the sample inlet 100 of the microfluidic chip. Due to the design of the tree-like structure, the liquid is first evenly distributed to multiple parallel microchannels in the XY plane. The diameter of each microchannel is small and the capillary action is strong, so the liquid can flow smoothly without an external driving force. When the liquid flows along the microchannel to the conical structure in the Z direction, the capillary action and gravity work together to push the liquid from top to bottom to be extracted to the collection hole. The gradually expanding design of the conical structure helps to reduce the resistance during liquid flow, avoid local pressure drops caused by excessive flow rate, and ensure the continuity and stability of the liquid. The combined design of the tree-like structure and the conical structure significantly improves the fluid driving efficiency of the capillary pump, allowing the liquid to be evenly distributed and stably flow to the collection hole. By optimizing and adjusting the channel width of the tree-like structure and the inclination angle of the conical structure, the required channel size and gap can be calculated according to actual needs to ensure that liquids of different volumes can be accurately distributed and extracted.
[0109] In summary, this embodiment significantly enhances capillary forces and the driving force of liquid flow by combining the tree-like structure of two-dimensional parallel microchannels with the three-dimensional tapered capillary pump design, enabling efficient and stable liquid extraction. By rationally designing the microchannel size and structure, it ensures smooth and continuous liquid flow in both the XY plane and the Z direction, thereby improving the extraction efficiency and precision of the microfluidic chip.
[0110] The above embodiments all improve the microfluidic chip from the perspective of structural design. In this embodiment, the channel structure of the microarray structure 310 and the channel structure of the chip body 400 are improved from the material direction to enhance their filtration and diversion efficiency. Since the liquid components in plasma are generally water (accounting for about 90%, which is the main component of plasma), protein, electrolytes, nutrients, etc. The channel material of the microfluidic chip in the prior art is mainly polymethyl methacrylate (PMMA). From a chemical structure point of view, the main chain of PMMA is composed of a carbon-carbon chain, and the side chain contains an ester group. Although the ester group has a certain polarity, the polarity of the entire molecular structure is relatively low, resulting in poor hydrophilicity. In addition, the surface energy of PMMA is relatively low, which makes it difficult for liquid to spread on its surface, which is not conducive to interaction with water. Therefore, when using microfluidic chips for biochemical analysis and testing of plasma samples in the prior art, the poor hydrophilicity of the microfluidic chips results in poor liquid flow within the channels. However, the microfluidic chips of the present invention primarily rely on the interaction between the liquid and the channel walls. Poor hydrophilicity means that capillary forces are affected, resulting in increased flow resistance, which in turn weakens the capillary action to a certain extent. Therefore, in order to achieve efficient separation of plasma on the same chip and quickly and effectively direct it to the detection area for subsequent analysis, this embodiment uses zwitterionic polymers for grafting to improve the hydrophilicity of the channels.
[0111] Specifically, if Figure 7 and Figure 8 As shown in this example, the hydrophilicity of the microfluidic chip was improved by the following methods:
[0112] Step S100: using benzophenone as a photosensitizer and evenly coating the photosensitizer on the inner wall of the microfluidic chip;
[0113] Step S200: filling the microfluidic chip with a methacryloyloxyethyl phosphorylcholine solution;
[0114] Step S300: using ultraviolet light to irradiate the interior of the microfluidic chip to cause a bonding reaction between benzophenone and the polymerized monomers in the methacryloyloxyethyl phosphorylcholine solution, thereby forming a hydration layer on the inner wall of the microfluidic chip.
[0115] See also Figure 8 First, benzophenone is used as a photosensitizer, which is evenly coated and pre-adsorbed on the inner wall surface of the PMMA chip channel. Subsequently, a methacryloyloxyethyl phosphorylcholine (pMPC) solution is introduced to fill the entire microfluidic channel. In this step, pMPC, as a zwitterionic polymer, is electrically neutral and can bind to benzophenone. Next, ultraviolet light is used to irradiate the inside of the PMMA chip channel. Ultraviolet light irradiation triggers the activation of benzophenone, and a bonding reaction occurs with the polymerized monomers of pMPC. In this process, the pMPC monomer forms a layer of stable grafted polymer on the inner wall of the microfluidic chip. Due to the zwitterionic structure of pMPC, the polymer chains carry positive and negative charges at the same time, and eventually form a thick hydration layer on the PMMA surface. This hydration layer not only enhances the hydrophilicity of the inner surface of the PMMA chip channel, but also effectively prevents the nonspecific adsorption of biomolecules (such as proteins and peptides) on the inner wall.
[0116] It should be noted that if Figure 8 The PMMA in the formula is polymethyl methacrylate, PMMA-BP refers to polymethyl methacrylate mixed with some additives or modifiers, and PMMA-pMPC refers to the modified product after polymethyl methacrylate and polymethacryloyloxyethyl phosphorylcholine are grafted.
[0117] It can be understood that this embodiment only uses polymethacryloyloxyethyl phosphorylcholine as an example of a zwitterionic polymer, and in other scenarios, other zwitterionic polymers may also be used.
[0118] The hydrophilicity of the modified microfluidic chip's inner surface has been significantly enhanced due to the introduction of phosphorylcholine groups (pMPC). After actual testing, the contact angle of a simple PMMA microfluidic chip was 67°, while the contact angle after grafting modification became 15°. Even after standing for 7 days, the contact angle was only 21°. This is because the long-range electrostatic interaction between pMPC and water molecules forms a high-density hydration layer. This hydration layer not only effectively repels the adsorption of proteins and other biomolecules, significantly reducing sample loss, but also reduces the capillary resistance within the channel, thereby improving the detection sensitivity of the microfluidic system in biological sample analysis. In addition, the anti-fouling properties of pMPC further enhance the biocompatibility of the chip, reduce the adhesion of substances such as platelets to the surface, and reduce the risk of coagulation. This modification improves the overall performance of the microfluidic chip, making it more reliable and sensitive in the analysis of complex biological samples.
[0119] Figure 1 The figure shows a design of a chip body 400. Figure 9 As shown, the embodiment of the present invention further proposes another design concept of the chip body 400, so that the microfluidic chip can optimize the traditional semi-quantitative detection method into quantitative antigen-antibody detection.
[0120] like Figure 9 As shown, in this example, the chip body 400 includes a first collecting channel 410 and several first branch flow channels 430, one end of the first collecting channel 410 is connected to the guide component 300, and the other end of the first collecting channel 410 is provided with a first water absorbent pad 420; each first branch flow channel 430 is connected to the first collecting channel 410, the first branch flow channel 430 is located between the first water absorbent pad 420 and the guide component 300, and the first branch flow channel 430 is vertically arranged below the first collecting channel 410; wherein, a detection test paper 440 is provided in each first branch flow channel 430, a first measuring positioning hole 450 is provided on the side of each first branch flow channel 430, and the first measuring positioning hole 450 is located above the detection test paper 440, and the bottom of several first branch flow channels 430 is connected to the first air pressure balance port 460; a first light response film 470 is provided on the outside of the first branch flow channel 430.
[0121] It should be noted that Figure 9 The left side of the figure is a combination of the sample inlet 100, the separation component 200 and the flow guide component 300. In this embodiment, the working process of the microfluidic chip is as follows:
[0122] A 5-15 μl blood sample is added to the sample inlet 100 using a pipette. The blood will spontaneously separate into plasma through the filter membrane. When plasma seeps out from the lower surface of the filter membrane, the microarray structure 310 will be activated. Due to the additive effect of capillary action, the microarray structure 310 will generate a large capillary action, rapidly drawing the plasma from the filter membrane into the diversion channel 320, and then flowing through the diversion channel 320 into the first collection channel 410. When the plasma flows through the junction of the first collection channel 410 and the first branch channel 430, due to the different flow channel dimensions, it will spontaneously flow into the first branch channel 430 until it stops at the position of the first measuring positioning hole 450. At this time, the plasma in the first collection channel 410 continues to flow forward to the first absorbent pad 420. Due to the strong capillary force of the first absorbent pad 420, the plasma in the first collection channel 410 will be quickly absorbed to the first absorbent pad 420 and disconnected from the first branch channel 430. At this time, independent and quantitative plasma exists in the first branch channel 430. At this time, the first light-responsive film 470 is irradiated with 470nm blue light, and the plasma will move toward the test paper 440 under the action of the light-induced Laplace pressure difference. The antigens in the plasma will react and bind with the test paper 440, such as the antigen-antibody binding of the new coronavirus. Since the sample is quantitative and the light-controlled sample can be transported back and forth, the antigen in the sample can fully react with the detection reagent fixed on the test strip. Therefore, a more accurate quantitative detection process can be achieved based on the degree of color change (grayscale) of the test strip than using only a filter membrane + test strip.
[0123] like Figure 10 As shown, in some embodiments of the present invention, another design concept of the chip body 400 is proposed. In this example, the chip body 400 includes a second collection channel 510, a second branch flow channel 530, a reaction chamber 540 and a reaction flow channel 550. One end of the second collection channel 510 is connected to the guide component 300, and the other end of the second collection channel 510 is provided with a second water absorbent pad 520. The second branch flow channel 530 is connected to the second collection channel 510, and the second branch flow channel 530 is located between the second water absorbent pad 520 and the guide component 300, and the second branch flow channel 530 is vertically arranged below the second collection channel 510; the reaction chamber 540 is arranged at the bottom of the second branch flow channel 530 and is connected to the second branch flow channel 530; the reaction flow channel 550 is connected to the reaction chamber 540, and the reaction flow channel 550 is arranged parallel to the second collection channel 510. The bottom of the reaction flow channel 550 is provided with a second measuring positioning hole 560, and the outside of the reaction flow channel 550 is provided with a second light response film 570. In this embodiment, the working process of the microfluidic chip is as follows:
[0124] Reagent pre-packaging: First, use inkjet printing to print the detection reagent in the reaction chamber 540. The reagent volume is 0.5-1.5 μL. The microfluidic chip with the quantitative reagent in the reaction chamber 540 is placed in a freeze dryer for processing. The detection reagent becomes powder after freeze drying. At this time, the second light-responsive film 570 is attached to the microfluidic chip loaded with the detection reagent powder. The flow channel structure in the chip is as follows: Figure 10 Alternatively, antibody modification is performed: antibodies are modified on the channel surface of the reaction chamber 540 . The antibody modification method may be to introduce amine groups on the substrate surface and then bind and fix the antibodies to the amine groups. Other methods may also be used.
[0125] Blood pretreatment: 5-15 μl of blood is added to the sample inlet 100 using a pipette. The blood will spontaneously separate from the plasma through the filter membrane. When plasma seeps out from the lower surface of the filter membrane, the microarray structure 310 in the reaction chamber 540 will be activated. Due to the additive effect of capillary action, the array will generate a large capillary action, rapidly drawing the plasma from the filter membrane into the second collection channel 510. When the plasma flows through the junction of the second collection channel 510 and the second branch channel 510, due to the different channel dimensions, it will spontaneously flow into the second branch channel 510 and further fill the reaction chamber 540 until it stops at the second measuring positioning hole 560. At this time, the plasma in the second collection channel 510 continues to flow forward to the second absorbent pad 520. Due to the strong capillary force of the second absorbent pad 520, the plasma in the second collection channel 510 is quickly drawn to the second absorbent pad 520 and disconnected from the second branch channel 530. At this point, an independent, quantitative amount of plasma exists in the reaction chamber 540. At this point, 470nm blue light is used to illuminate the second photoresponsive film 570, causing the plasma to oscillate back and forth under the action of the light-induced Laplace pressure differential, thoroughly mixing and reacting with the lyophilized reagent powder pre-embedded in the reaction chamber 540. During the reaction, target proteins in the plasma, such as NTpro-BNP (brain natriuretic peptide), bind to the antibodies modified on the microspheres in the antibody reagent, causing the entire reaction system to emit fluorescence. Due to the excess antibody reagent, the intensity of the fluorescence signal is positively correlated with the concentration of the protein marker in the plasma, thereby enabling quantitative immunoassays on trace blood samples.
[0126] like Figure 11As shown, in some embodiments of the present invention, another design concept for the chip body 400 is also proposed. In this example, the flow guide component 300 is a primary flow channel 610, and the chip body 400 also includes a plurality of secondary flow channels 620 and a plurality of tertiary flow channels 630. The secondary flow channels 620 correspond to the tertiary flow channels 630 one by one, and one end of the secondary flow channel 620 is connected to the flow guide component 300, and the other end of the secondary flow channel 620 is connected to the corresponding tertiary flow channel 630; a sample separation port 640 is provided on the side of the secondary flow channel 620, and a quantitative measurement port 650 is provided on the side of the tertiary flow channel 630.
[0127] This embodiment uses a microfluidic chip for sample distribution and quantitative measurement. A complex flow channel system, including branch channels and a trap valve (i.e., sample separation port 640), is designed within the microfluidic chip. Capillary force and air pressure are used to control liquid flow, thereby achieving efficient sample processing. The microfluidic chip operates as follows:
[0128] First, a blood sample is loaded into the sample inlet 100 of the microfluidic chip. After preliminary filtration, the blood flows into the primary channel 610. As the filtration process progresses, the capillary force in the primary channel 610 gradually increases. When the capillary force reaches a certain level, it exceeds that of the tertiary channel 630, trapping the unfiltered blood and plasma from the filter membrane in the primary channel 610 and preventing it from entering the secondary channel 620. Next, a pneumatically controlled intercept valve disconnects the separated plasma from the primary channel 610 at the secondary channel 620. This process ensures that only the pre-filtered plasma is stored in the secondary channel 620. The plasma is then directed into the tertiary channel 630, enabling quantitative measurement. The tertiary channel 630 is specifically designed with a precise volume to ensure consistent sample volume with every operation. After the plasma enters the tertiary channel 630, a capillary pump (a non-physical pump) begins to aspirate the excess plasma from the secondary channel 620. At this stage, due to the weak capillary force of the secondary flow channel 620, the liquid will be drawn from this area first, ensuring that the secondary flow channel 620 is completely emptied. The completion of this step not only achieves the separation of the samples, but also ensures the independence of each sample.
[0129] It should be noted that in the primary flow channel 610, a filtration process from blood to plasma occurs. If the radii of the primary flow channel 610, the secondary flow channel 620, and the tertiary flow channel 630 are r1>r2>r3, then the capillary force is P1<P2<P3, so the fluid can flow from the primary flow channel 610→secondary flow channel 620→tertiary flow channel 630. When the capillary force in the primary flow channel 610 gradually increases and exceeds the tertiary flow channel 630, it is equivalent to the fluid no longer actively flowing to the tertiary flow channel 630, because the capillary force of the tertiary flow channel 630 is smaller than that of the primary flow channel 610, then the liquid will not flow from the secondary flow channel 620 into the tertiary flow channel 630, then the fluid in the secondary flow channel 620 cannot flow and reversely blocks the liquid flowing from the primary flow channel 610, so the plasma will be blocked in the primary flow channel 610. When the air pressure control interception valve (i.e., the sample separation port 640, which is actually an air hole) is opened, the cross-sectional area of the air hole is smaller than the cross-sectional area of the secondary flow channel 620. Therefore, part of the liquid in the secondary flow channel 620 flows to the tertiary flow channel 630, and part flows to the sample separation port 640 of the secondary flow channel 620. The atmosphere will block the intersection of the secondary flow channel 620 and the sample separation port 640, so that the fluid in the primary flow channel 610 cannot flow to the secondary flow channel 620, but the secondary flow channel 620 The fluid in the secondary flow channel 620 continues to flow to the tertiary flow channel 630. When the pores in the tertiary flow channel 630 are opened, the fluid in the secondary flow channel 620 is divided into two paths at the intersection with the tertiary flow channel 630, one part flows clockwise and the other part flows counterclockwise. When the pores in the tertiary flow channel 630 are opened, the clockwise and counterclockwise flowing parts of the fluid will squeeze the air inside the tertiary flow channel 630 and discharge it. When the tertiary flow channel 630 is completely filled, a liquid column will be formed and automatically closed, completing the measuring process.
[0130] Through the above steps, the microfluidic chip effectively achieves precise sample distribution and quantitative measurement. Each processing step leverages a combination of physical properties and chip structure to ensure efficient and accurate sample processing. Subsequently, the distributed and quantified samples can be further analyzed and tested in independent channels. This design eliminates the problems of sample cross-contamination and quantitative inaccuracies associated with traditional methods.
[0131] In summary, the microfluidic chip of the embodiment of the present invention can be applied to a one-step immune reaction, can be applied to a complex multi-step reaction, and can also be used as a pre-processing structure.
[0132] When a microfluidic chip is used for a one-step immune response, all processes are performed directly within the chip. For example, lyophilized reagents can be pre-embedded in channels, allowing for in-situ fluorescence reaction and detection with the sample after measurement. This embodiment utilizes a microfluidic chip to implement a one-step immune response, integrating sample distribution, reagent dissolution, immune response, and fluorescence detection into a single system. Lyophilized reagents are pre-embedded in specific channels of the microfluidic chip. These reagents are optimized during production based on the target analyte, ensuring that they react with the specific antigens or antibodies in the sample after dissolution. A blood sample is loaded into the chip's inlet. Using capillary force and air pressure control, the sample undergoes a preliminary filtration in the primary flow channel to remove cellular components. The filtered plasma is then directed to the tertiary flow channel for precise quantitative measurement, ensuring a consistent sample volume for the reaction, thereby improving the reproducibility and accuracy of the results. When the sample flows into the channel containing the lyophilized reagent, the liquid properties of the sample dissolve the lyophilized reagent, forming a uniform reaction mixture. This process occurs automatically within the chip, requiring no additional operation. The target analyte in the sample then undergoes a specific immune reaction with the reagent. After the immune reaction is complete, the sample in the channel enters the detection area directly. Optical components embedded in the chip excite and detect the fluorescent signal. The intensity of the fluorescent signal is proportional to the concentration of the target analyte. The signal intensity is read by the detection instrument to quantitatively analyze the target analyte content in the sample. The resulting data is transmitted to a computer system for analysis. Combined with a standard curve, the concentration of the target analyte in the sample can be accurately calculated. The entire process is completed within the microfluidic chip, eliminating external handling steps and reducing the risk of contamination.
[0133] When microfluidic chips are used for complex multi-step reactions, such as molecular testing, they can be integrated into other functional modules after the sampling structure to enable multiplexed sample testing. For example, a specific number of sample-splitting and sampling reaction units can be set based on several markers corresponding to a disease category, such as six hormone test items, liver function, and kidney function, allowing the measurement and testing functions to be implemented on the same chip based on the required sample volume. This embodiment aims to integrate multi-step reactions into a microfluidic chip to achieve multiplexed sample testing. For multiple markers corresponding to a disease category, such as six hormone test items, liver function, and kidney function, the chip is designed to enable sample splitting, sampling, and multiplexed testing. The chip is equipped with multiple sample-splitting and sampling units, each optimized for a different marker. Each unit is connected to a central sample inlet to ensure equal distribution of sample upon inflow. Each sampling unit is pre-loaded with lyophilized reagents required for the corresponding marker test. The module is internally designed with specific reaction and detection areas to meet different testing requirements. A blood sample is placed at the chip's central inlet, where it is automatically distributed to each sampling unit through capillary force or air pressure. During the flow process, precise control of sample volume is achieved through microfluidic channel design, ensuring that each unit receives the exact sample volume. After the sample flows to each measuring unit, it dissolves the pre-embedded freeze-dried reagent and undergoes a specific chemical or immunological reaction. The reagents and reaction conditions of each unit are pre-set to match its detection target. After the reaction is complete, the sample enters the detection area directly. The signal of each marker is read using the chip's integrated optical or electrochemical detection elements. This microfluidic chip achieves one-step integration of multiple sample detection, improving detection efficiency and reducing the number of operational steps and errors in traditional methods.
[0134] When the microfluidic chip is used as a pre-processing structure, the micro-sample solution after measurement can be combined with other microfluidic chips to achieve immune, biochemical, and molecular detection. In this embodiment, the microfluidic chip is used as a pre-processing structure, so that the micro-sample solution that has been accurately measured can be combined with other subsequent microfluidic chips to achieve immune, biochemical, and molecular detection. The chip contains a sample distribution and measurement unit that can extract a precise volume of micro-sample solution from the original sample. Through microfluidic technology, capillary force-driven or pressure-controlled channels are designed to achieve automatic separation and precise measurement of samples. The sample is placed in the chip inlet, and the channels and filters designed inside the chip are used to automatically remove unnecessary components, such as cells. The sample is accurately measured in the chip and distributed to multiple outlet channels, ready for transmission to subsequent detection chips. The pre-processing chip is designed with a standardized fluid interface so that it can be easily connected to subsequent immune, biochemical, or molecular detection chips to achieve seamless sample transfer. The processed micro-sample solution is transmitted to the target detection chip using the Laplace pressure difference. The sample is transferred to a microfluidic chip integrated with antibodies or antigens for specific binding and fluorescence detection. The sample then enters a biochemical reaction chip for analysis through enzymatic reactions, such as those used for molecular biology assays like PCR amplification or nucleic acid hybridization. This integrated design enables a systematic process from sample pretreatment to multiplexed detection, providing an efficient and accurate solution for complex sample analysis.
[0135] On the other hand, based on the plasma separation and flow guidance integrated microfluidic chip of the above-mentioned embodiment, the embodiment of the present invention also proposes a detection method of the microfluidic chip, such as Figure 12 As shown, the detection method includes the following steps:
[0136] Step S1000: placing a blood sample at the sample inlet 100;
[0137] Step S2000: the separation component 200 separates plasma from the blood sample and transfers the plasma to the flow guide component 300;
[0138] Step S3000: the flow guiding component 300 guides the plasma to the chip body 400;
[0139] Step S4000: The chip body 400 detects the plasma and obtains the test results.
[0140] Specifically, if Figure 2As shown, after a blood sample is added to the sample inlet 100, it flows through the sample inlet 100 to the separation assembly 200. In this example, the separation assembly 200 includes a filter membrane located below the sample inlet 100. The filter membrane filters the blood sample, removing plasma and solid components from the blood. The pore size of the filter membrane is designed to be permeable to plasma but not to solid components in the blood sample. For example, the pore size of the filter membrane can range from 0.2 to 5 μm. The principle of extracting plasma from a whole blood sample through the filter membrane relies primarily on the physical separation of cellular and liquid components. In a whole blood sample, the liquid component is primarily plasma, while the solid components include red blood cells, white blood cells, and platelets. When the whole blood sample passes through the filter membrane, plasma passes through the filter membrane due to pressure differential or gravity, while solid components are retained above the filter membrane. This removes cellular components and other large particulate impurities, resulting in a clean plasma sample. The filtered liquid component is plasma, which contains various biochemical components and is convenient for further testing and analysis. After the plasma is filtered out using the filter membrane, the bottom of the filter membrane directly contacts the guide component 300, which guides the separated plasma to the chip body 400, so that the plasma reaches the predetermined detection area for subsequent biochemical analysis.
[0141] Furthermore, in this example, the flow guide component 300 includes a microarray structure 310 and a plurality of flow guide channels 320. The microarray structure 310 has multiple channels. The above step S3000 specifically includes the following two steps:
[0142] (1) The microarray structure 310 allows plasma to flow along the pores through capillary action and accumulate in the flow channel 320;
[0143] (2) The diversion channel 320 diverts the plasma in the channel to the chip body 400.
[0144] Specifically, if Figure 3As shown, the microarray structure 310 includes a plurality of microstructures 311. Through the arrangement of the plurality of microstructures 311, pores are formed in the gaps between the microstructures 311. The microarray structure 310 is in direct contact with the filter membrane of the separation component 200. After the filter membrane filters out the plasma, the microarray structure 310 introduces the filtered plasma into the pores of the microarray structure 310 through capillary action. In this way, the extracted plasma flows spontaneously in the tiny pores of the microarray structure 310. This is because the design of the microarray structure 310 usually includes many tiny pores, and the size and shape of these pores can significantly affect the flow of the fluid. First, the pores inside the microarray structure 310 can enhance the contact area of the liquid and generate capillary action when the liquid enters. The capillary force will cause the liquid to flow rapidly along the pores and fill these tiny spaces. Secondly, the gaps between the microarray structures 310 can also play an important role. These gaps provide additional channels for the flow of liquid, further promoting the extraction of the fluid. As shown in FIG. Figure 3 As shown, in the microarray structure 310, there are also multiple collection holes 312, and each guide channel 320 is connected to the microarray structure 310 through the corresponding collection hole 310. By adjusting the gaps between the microstructures 311 in different areas of the microarray structure 310, the plasma enrichment area of the microarray structure 310 is positioned at the collection hole 312, thereby further promoting the plasma to flow along the microarray structure 310 into each collection hole 312, and then into the chip body 400 along the guide channel 320. In this example, the number of collection holes 312 and guide channels 320 is set to four. It should be noted that the number of collection holes 312 and guide channels 320 can be adjusted according to actual needs, and is not limited to this. Figure 5 As shown in FIG. 3 , the arrow indicates the direction of plasma flow in the microarray structure 310, and the circle indicates the location of the collection hole 312. The closer to the collection hole 312, the denser the distribution of the microstructure 311. The farther away from the collection hole 312, the sparser the distribution of the microstructure 311, thereby enriching the plasma in the collection hole 312. Finally, the plasma guided through the microarray structure 310 enters the chip body 400 through the flow channel 320. Figure 1 As shown, the chip body 400 has multiple microchannels. Microfluidic valves can be set on the microchannels of the chip body 400. The operator can adjust the flow speed and direction of the plasma by controlling the microfluidic valves, so that the plasma can accurately reach the predetermined detection area for subsequent biochemical analysis.
[0145] like Figure 9As shown, in some embodiments of the present invention, the chip body 400 includes a first collecting channel 410 and several first branch flow channels 430, one end of the first collecting channel 410 is connected to the guide component 300, and the other end of the first collecting channel 410 is provided with a first water absorbent pad 420; each first branch flow channel 430 is connected to the first collecting channel 410, the first branch flow channel 430 is located between the first water absorbent pad 420 and the guide component 300, and the first branch flow channel 430 is vertically arranged below the first collecting channel 410; wherein, a detection test paper 440 is provided in each first branch flow channel 430, a first measuring positioning hole 450 is provided on the side of each first branch flow channel 430, and the first measuring positioning hole 450 is located above the detection test paper 440, and the bottom of several first branch flow channels 430 is connected to the first air pressure balance port 460; a first light response film 470 is provided on the outside of the first branch flow channel 430. In this embodiment, the above step S4000 includes the following four steps:
[0146] (1) Plasma enters the first collection channel 410 through the flow guide component 300;
[0147] (2) When the plasma reaches the junction of the first collecting channel 410 and the first branch channel 430, the plasma flows into the first branch channel 430 until it reaches the first measuring positioning hole 450;
[0148] (3) The plasma in the first collecting channel 410 continues to flow forward to the first absorbent pad 420 and no longer flows into the first branch flow channel 430, so that independent and quantitative plasma exists in the first branch flow channel 430;
[0149] (4) Using a preset light to illuminate the first light-responsive film 470, the plasma in the first branch flow channel 430 reacts with the test paper 440 to obtain a test result.
[0150] Specifically, in this embodiment, the working process of the microfluidic chip is as follows:
[0151] A 5-15 μl blood sample is added to the sample inlet 100 using a pipette. The blood will spontaneously separate into plasma through the filter membrane. When plasma seeps out from the lower surface of the filter membrane, the microarray structure 310 will be activated. Due to the additive effect of capillary action, the microarray structure 310 will generate a large capillary action, rapidly drawing the plasma from the filter membrane into the diversion channel 320, and then flowing through the diversion channel 320 into the first collection channel 410. When the plasma flows through the junction of the first collection channel 410 and the first branch channel 430, due to the different flow channel dimensions, it will spontaneously flow into the first branch channel 430 until it stops at the position of the first measuring positioning hole 450. At this time, the plasma in the first collection channel 410 continues to flow forward to the first absorbent pad 420. Due to the strong capillary force of the first absorbent pad 420, the plasma in the first collection channel 410 will be quickly absorbed to the first absorbent pad 420 and disconnected from the first branch channel 430. At this time, independent and quantitative plasma exists in the first branch channel 430. At this time, the first light-responsive film 470 is irradiated with 470nm blue light, and the plasma will move toward the test paper 440 under the action of the light-induced Laplace pressure difference. The antigens in the plasma will react and bind with the test paper 440, such as the antigen-antibody binding of the new coronavirus. Since the sample is quantitative and the light-controlled sample can be transported back and forth, the antigen in the sample can fully react with the detection reagent fixed on the test strip. Therefore, a more accurate quantitative detection process can be achieved based on the degree of color change (grayscale) of the test strip than using only a filter membrane + test strip.
[0152] like Figure 10 As shown, in some embodiments of the present invention, the chip body 400 includes a second collecting channel 510, a second branch flow channel 530, a reaction chamber 540 and a reaction flow channel 550, one end of the second collecting channel 510 is connected to the guide component 300, and the other end of the second collecting channel 510 is provided with a second water absorbent pad 520, the second branch flow channel 530 is connected to the second collecting channel 510, the second branch flow channel 530 is located between the second water absorbent pad 520 and the guide component 300, and the second branch flow channel 530 is vertically arranged below the second collecting channel 510; the reaction chamber 540 is arranged at the bottom of the second branch flow channel 530 and is connected to the second branch flow channel 530; the reaction flow channel 550 is connected to the reaction chamber 540, and the reaction flow channel 550 is arranged parallel to the second collecting channel 510, the bottom of the reaction flow channel 550 is provided with a second measuring positioning hole 560, and the outside of the reaction flow channel 550 is provided with a second light response film 570. In this embodiment, the above step S4000 includes the following five steps:
[0153] (1) Printing the detection reagent in the reaction chamber 540 by inkjet printing and making the detection reagent into powder by freeze drying; or, modifying the inner surface of the reaction chamber 540 with antibodies to form the detection reagent;
[0154] (2) Plasma enters the second collection channel 510 through the flow guide component 300;
[0155] (3) When the plasma reaches the junction of the second collection channel 510 and the second branch channel 530, the plasma flows into the second branch channel 530, fills the reaction chamber 540, and reaches the second measuring positioning hole 560;
[0156] (4) The plasma in the second collection channel 510 continues to flow forward to the second absorbent pad 520 and no longer flows into the second branch flow channel 530, so that an independent and quantitative amount of plasma exists in the reaction chamber 540;
[0157] (5) Using a preset light to illuminate the second light-responsive film 570, the plasma in the reaction chamber 540 reacts with the detection reagent to obtain a detection result.
[0158] Specifically, in this embodiment, the working process of the microfluidic chip is as follows:
[0159] Reagent pre-packaging: First, use inkjet printing to print the detection reagent in the reaction chamber 540. The reagent volume is 0.5-1.5 μL. The microfluidic chip with the quantitative reagent in the reaction chamber 540 is placed in a freeze dryer for processing. The detection reagent becomes powder after freeze drying. At this time, the second light-responsive film 570 is attached to the microfluidic chip loaded with the detection reagent powder. The flow channel structure in the chip is as follows: Figure 10 Alternatively, antibody modification is performed: antibodies are modified on the channel surface of the reaction chamber 540 . The antibody modification method may be to introduce amine groups on the substrate surface and then bind and fix the antibodies to the amine groups. Other methods may also be used.
[0160] Blood pretreatment: 5-15 μl of blood is added to the sample inlet 100 using a pipette. The blood will spontaneously separate from the plasma through the filter membrane. When plasma seeps out from the lower surface of the filter membrane, the microarray structure 310 in the reaction chamber 540 will be activated. Due to the additive effect of capillary action, the array will generate a large capillary action, rapidly drawing the plasma from the filter membrane into the second collection channel 510. When the plasma flows through the junction of the second collection channel 510 and the second branch channel 510, due to the different channel dimensions, it will spontaneously flow into the second branch channel 510 and further fill the reaction chamber 540 until it stops at the second measuring positioning hole 560. At this time, the plasma in the second collection channel 510 continues to flow forward to the second absorbent pad 520. Due to the strong capillary force of the second absorbent pad 520, the plasma in the second collection channel 510 is quickly drawn to the second absorbent pad 520 and disconnected from the second branch channel 530. At this point, an independent, quantitative amount of plasma exists in the reaction chamber 540. At this point, 470nm blue light is used to illuminate the second photoresponsive film 570, causing the plasma to oscillate back and forth under the action of the light-induced Laplace pressure differential, thoroughly mixing and reacting with the lyophilized reagent powder pre-embedded in the reaction chamber 540. During the reaction, target proteins in the plasma, such as NTpro-BNP (brain natriuretic peptide), bind to the antibodies modified on the microspheres in the antibody reagent, causing the entire reaction system to emit fluorescence. Due to the excess antibody reagent, the intensity of the fluorescence signal is positively correlated with the concentration of the protein marker in the plasma, thereby enabling quantitative immunoassays on trace blood samples.
[0161] like Figure 11 As shown, in some embodiments of the present invention, the flow guide component 300 is a primary flow channel 610, and the chip body 400 further includes a plurality of secondary flow channels 620 and a plurality of tertiary flow channels 630. The secondary flow channels 620 correspond one to one with the tertiary flow channels 630. One end of the secondary flow channel 620 is connected to the flow guide component 300, and the other end of the secondary flow channel 620 is connected to the corresponding tertiary flow channel 630. A sample separation port 640 is provided on the side of the secondary flow channel 620, and a quantitative measurement port 650 is provided on the side of the tertiary flow channel 630. In this embodiment, the above-mentioned step S4000 includes the following three steps:
[0162] (1) Plasma flows through the primary flow channel 610 into the secondary flow channel 620 and then into the sample separation port 640;
[0163] (2) After the plasma passes through the secondary flow channel 620 and enters the tertiary flow channel 630, the tertiary flow channel 630 absorbs all the plasma in the secondary flow channel 620;
[0164] (3) The plasma reacts with the detection reagent in the tertiary flow channel 630 to obtain the detection result.
[0165] This embodiment uses a microfluidic chip for sample distribution and quantitative measurement. A complex flow channel system, including branch channels and a trap valve (i.e., sample separation port 640), is designed within the microfluidic chip. Capillary force and air pressure are used to control liquid flow, thereby achieving efficient sample processing. The microfluidic chip operates as follows:
[0166] First, a blood sample is loaded into the sample inlet 100 of the microfluidic chip. After preliminary filtration, the blood flows into the primary channel 610. As the filtration process progresses, the capillary force in the primary channel 610 gradually increases. When the capillary force reaches a certain level, it exceeds that of the tertiary channel 630, trapping the unfiltered blood and plasma from the filter membrane in the primary channel 610 and preventing it from entering the secondary channel 620. Next, a pneumatically controlled intercept valve disconnects the separated plasma from the primary channel 610 at the secondary channel 620. This process ensures that only the pre-filtered plasma is stored in the secondary channel 620. The plasma is then directed into the tertiary channel 630, enabling quantitative measurement. The tertiary channel 630 is specifically designed with a precise volume to ensure consistent sample volume with every operation. After the plasma enters the tertiary channel 630, a capillary pump (a non-physical pump) begins to aspirate the excess plasma from the secondary channel 620. At this stage, due to the weak capillary force of the secondary flow channel 620, the liquid will be drawn from this area first, ensuring that the secondary flow channel 620 is completely emptied. The completion of this step not only achieves the separation of the samples, but also ensures the independence of each sample.
[0167] Through the above steps, the microfluidic chip effectively achieves precise sample distribution and quantitative measurement. Each processing step leverages a combination of physical properties and chip structure to ensure efficient and accurate sample processing. Subsequently, the distributed and quantified samples can be further analyzed and tested in independent channels. This design eliminates the problems of sample cross-contamination and quantitative inaccuracies associated with traditional methods.
[0168] The embodiments of the present invention are described in detail above with reference to the accompanying drawings. However, the present invention is not limited to the above embodiments. Various changes can be made within the knowledge of ordinary technicians in the relevant technical field without departing from the scope of the present invention.
Claims
1. A detection method based on a microfluidic chip, characterized in that: The invention relates to a plasma separation and flow diversion integrated microfluidic chip, which comprises a sample inlet, a separation component, a flow diversion component and a chip body, wherein the flow diversion component comprises: a microarray structure and a plurality of flow diversion channels, wherein the microarray structure is connected to the separation component, the microarray structure comprises a plurality of microstructures, and a pore is formed in the gap between each of the microstructures through the arrangement of the plurality of microstructures, and the microarray structure is used to make the plasma flow along the pore by capillary action; each of the flow diversion channels is respectively connected to the microarray structure and the chip body, and the flow diversion channel is used to divert the plasma in the pore to the chip body; each of the flow diversion channels is connected to the corresponding collection hole through the corresponding collection hole. The microarray structure is connected, and the plasma-enriched area of the microarray structure is positioned at the collection hole by adjusting the gaps between the microstructures in different areas of the microarray structure; the microstructures of the microarray structure are arranged in a tree-like structure or a concentric ring structure, and the pore width of the tree-like structure gradually decreases from the trunk to the branch end close to the collection hole, so that the separated plasma is diverted to multiple parallel pores with smaller widths before reaching the collection hole, or the pore width of the concentric ring structure gradually decreases from the outer ring to the inner ring, so that the separated plasma gradually flows from the outer ring to the inner ring toward the collection hole; the channel width of the microarray structure in the Z-axis direction gradually narrows from top to bottom; the detection method comprises the following steps: placing a blood sample into the sample inlet; The separation component separates plasma from the blood sample and transports the plasma to the flow guide component; The flow guiding component guides the plasma to the chip body; The chip body detects the plasma to obtain a detection result; The flow guiding component guides the plasma to the chip body, including: The microarray structure causes the plasma to flow along the pores through capillary action and to be enriched in the guide channel; The guide channel guides the plasma in the pore to the chip body.
2. The detection method of the microfluidic chip according to claim 1, characterized in that: The chip body includes: a first collecting channel and a plurality of first branch flow channels, one end of the first collecting channel is connected to the guide component, the other end of the first collecting channel is provided with a first water absorbent pad, each of the first branch flow channels is connected to the first collecting channel, the first branch flow channel is located between the first water absorbent pad and the guide component, and the first branch flow channel is vertically arranged below the first collecting channel, a test paper is provided in each first branch flow channel, a first measuring positioning hole is provided on the side of each first branch flow channel, and the first measuring positioning hole is located above the test paper, and the bottom of the plurality of first branch flow channels is connected to a first air pressure balance port; a first light-responsive film is provided on the outside of the first branch flow channel; The chip body detects the plasma to obtain the test results, including: The plasma enters the first collecting channel through the flow guiding component; When the plasma reaches the junction of the first collecting channel and the first branch channel, the plasma flows into the first branch channel until it reaches the first measuring positioning hole; The plasma in the first collection channel continues to flow forward to the first absorbent pad and no longer flows into the first branch flow channel, so that an independent and quantitative amount of plasma exists in the first branch flow channel; The first light-responsive film is irradiated with a preset light, so that the plasma in the first branch flow channel reacts with the test paper to obtain the test result.
3. The detection method of the microfluidic chip according to claim 1, characterized in that: The chip body includes a second collecting channel and a second branch flow channel, one end of the second collecting channel is connected to the guide component, the other end of the second collecting channel is provided with a second water absorbent pad, the second branch flow channel is connected to the second collecting channel, the second branch flow channel is located between the second water absorbent pad and the guide component, and the second branch flow channel is vertically arranged below the second collecting channel, the reaction chamber is arranged at the bottom of the second branch flow channel and is connected to the second branch flow channel, the reaction flow channel is connected to the reaction chamber, and the reaction flow channel is arranged parallel to the second collecting channel, the bottom of the reaction flow channel is provided with a second measuring positioning hole, and the outside of the reaction flow channel is provided with a second light-responsive film; The chip body detects the plasma to obtain the test results, including: Printing the detection reagent in the reaction chamber by inkjet printing and making the detection reagent into powder by freeze drying; or modifying the inner surface of the reaction chamber with antibodies to form the detection reagent; The plasma enters the second collecting channel through the flow guiding component; When the plasma reaches the junction of the second collecting channel and the second branch channel, the plasma flows into the second branch channel, fills the reaction chamber, and reaches the second measuring positioning hole; The plasma in the second collection channel continues to flow forward to the second absorbent pad and no longer flows into the second branch flow channel, so that an independent and quantitative amount of plasma exists in the reaction chamber; The second light-responsive film is irradiated with a preset light, so that the plasma in the reaction chamber reacts with the detection reagent to obtain the detection result.
4. The detection method of the microfluidic chip according to claim 1, characterized in that: The flow guide component is a primary flow channel, and the chip body further includes a plurality of secondary flow channels and a plurality of tertiary flow channels. The secondary flow channels correspond one-to-one with the tertiary flow channels. One end of the secondary flow channel is connected to the flow guide component, and the other end of the secondary flow channel is connected to the corresponding tertiary flow channel. A sample separation port is provided on the side of the secondary flow channel. The chip body detects the plasma to obtain the test results, including: The plasma flows into the secondary flow channel through the primary flow channel and then enters the sample separation port; After the plasma enters the tertiary flow channel through the secondary flow channel, the tertiary flow channel absorbs all the plasma in the secondary flow channel; The plasma reacts with the detection reagent in the tertiary flow channel to obtain the detection result.
5. A plasma separation and flow guidance integrated microfluidic chip, characterized in that: include: a sample inlet, the sample inlet being used to receive a blood sample; a separation component, communicated with the sample inlet, and configured to separate plasma from the blood sample; a flow guide component, connected to the separation component; A chip body is connected to the flow guide component, and the flow guide component is used to guide the separated plasma to the chip body; Wherein, the diversion component includes: a microarray structure and a plurality of diversion channels, the microarray structure is connected to the separation component, the microarray structure includes a plurality of microstructures, and through the arrangement of the plurality of microstructures, a channel is formed in the gap between each of the microstructures, and the microarray structure is used to make the plasma flow along the channel by capillary action; each of the diversion channels is respectively connected to the microarray structure and the chip body, and the diversion channel is used to divert the plasma in the channel to the chip body; each of the diversion channels is connected to the microarray structure through the corresponding collection hole, and by adjusting the microarray structure The gaps between the microstructures in different areas make the plasma-enriched area of the microarray structure the location of the collection hole; the arrangement of the microstructures of the microarray structure is a tree structure or a concentric ring structure, and the channel width of the tree structure gradually decreases from the trunk to the branch end close to the collection hole, so that the separated plasma is diverted to multiple parallel channels with smaller widths before reaching the collection hole, or the channel width of the concentric ring structure gradually decreases from the outer ring to the inner ring, so that the separated plasma gradually flows from the outer ring to the inner ring toward the collection hole; the channel width of the microarray structure in the Z-axis direction gradually narrows from top to bottom.
6. The plasma separation and flow guidance integrated microfluidic chip according to claim 5, characterized in that: A plurality of inlets are evenly distributed on the circumference of the outer ring, so that the separated plasma can evenly flow into the outer ring through the plurality of inlets.
7. The plasma separation and flow guidance integrated microfluidic chip according to claim 5, characterized in that: The hydrophilicity of the material of the outer ring is greater than that of the material of the inner ring, and the inner wall of the concentric annular structure is provided with a flow-guiding texture.
8. The plasma separation and flow guidance integrated microfluidic chip according to claim 5, characterized in that: The chip body has a plurality of microchannels, each of which is provided with a microfluidic valve, and the microfluidic valve is used to adjust the flow speed and direction of the plasma so that the plasma flows along the microchannel to the detection area.
9. The plasma separation and flow guidance integrated microfluidic chip according to claim 5, characterized in that: The chip body includes: a first collecting channel, one end of the first collecting channel being in communication with the flow guide assembly, and the other end of the first collecting channel being provided with a first water absorbent pad; a plurality of first branch flow channels, each of which is connected to the first collecting channel, the first branch flow channels being located between the first absorbent pad and the flow guide assembly, and the first branch flow channels being vertically disposed below the first collecting channel; Among them, a test paper is provided in each of the first branch flow channels, a first measuring positioning hole is provided on the side of each of the first branch flow channels, and the first measuring positioning hole is located above the test paper, and the bottoms of several of the first branch flow channels are connected to a first air pressure balance port; a first light-responsive film is provided on the outside of the first branch flow channel.
10. The plasma separation and flow guidance integrated microfluidic chip according to claim 5, characterized in that: The chip body includes: a second collecting channel, one end of the second collecting channel being in communication with the flow guide assembly, and the other end of the second collecting channel being provided with a second water absorbent pad; a second branch flow channel, the second branch flow channel being connected to the second collecting channel, the second branch flow channel being located between the second absorbent pad and the flow guide assembly, and the second branch flow channel being vertically disposed below the second collecting channel; a reaction chamber, disposed at the bottom of the second branch flow channel and communicated with the second branch flow channel; The reaction channel is connected to the reaction chamber and is arranged in parallel with the second collecting channel. A second measuring positioning hole is provided at the bottom of the reaction channel, and a second light-responsive film is provided outside the reaction channel.
11. The plasma separation and flow guidance integrated microfluidic chip according to claim 5, characterized in that: The flow guide component is a primary flow channel, and the chip body also includes several secondary flow channels and several tertiary flow channels. The secondary flow channels correspond one-to-one to the tertiary flow channels. One end of the secondary flow channel is connected to the flow guide component, and the other end of the secondary flow channel is connected to the corresponding tertiary flow channel; a sample separation port is provided on the side of the secondary flow channel, and a quantitative measuring port is provided on the side of the tertiary flow channel.
12. The plasma separation and flow guidance integrated microfluidic chip according to claim 5, characterized in that: The separation component includes a filter membrane, and the pore size of the filter membrane ranges from 0.2 μm to 5 μm.
13. The plasma separation and flow guidance integrated microfluidic chip according to claim 5, characterized in that: The hydrophilicity of the microfluidic chip is improved by the following methods: Using benzophenone as a photosensitizer, and evenly coating the photosensitizer on the inner wall of the microfluidic chip; filling the microfluidic chip with a methacryloyloxyethyl phosphorylcholine solution; Ultraviolet light is used to irradiate the interior of the microfluidic chip, so that the benzophenone and the polymerized monomers of the methacryloyloxyethyl phosphorylcholine solution undergo a bonding reaction, and a hydration layer is formed on the inner wall of the microfluidic chip.
Citation Information
Patent Citations
Whole blood filtration and quantitative transfer micro-fluidic chip
CN105879936A