Blood coagulation detection chip and blood coagulation detection method

Abstract

The invention provides a blood coagulation detection chip and a blood coagulation detection method. The invention relates to the technical field of microfluidics. A blood coagulation detection chip comprises a vibration base; the first sliding layer comprises a first detection area which is configured to contain first liquid, the second sliding layer comprises a second detection area which is configured to contain second liquid, the first sliding layer is fixedly arranged on the vibration base, and the first sliding layer is in sliding connection with the second sliding layer; the first liquid is one of blood and a detection solution, and the second liquid is one of the detection solution and the blood corresponding to the first liquid; wherein the second sliding layer is configured to slide to a preset position relative to the first sliding layer, and the preset position represents a position where the first detection area is aligned with the second detection area; the vibration base is configured to drive the first sliding layer to vibrate by releasing vibration, so that the first liquid in the second detection area is mixed with the second liquid in the first detection area, and blood coagulation detection is carried out.

Description

Technical Field

[0001] This disclosure relates to the field of microfluidics, and more specifically, to a coagulation detection chip and a coagulation detection method. Background Technology

[0002] In related technologies, coagulation function testing is a core and fundamental link in the clinical diagnosis and treatment chain. Surgical screening, differentiation of bleeding disorders, and early warning of disseminated intravascular coagulation all require rapid and accurate coagulation parameters as a basis.

[0003] In realizing the present invention, the inventors discovered that traditional coagulation testing methods have several limitations in terms of timeliness, testing volume, and testing location. Summary of the Invention

[0004] In view of this, the present disclosure provides a coagulation detection chip and a coagulation detection method.

[0005] One aspect of this disclosure provides a coagulation detection chip, comprising: a vibrating base; a first sliding layer including a first detection area configured to contain a first liquid; and a second sliding layer including a second detection area configured to contain a second liquid. The first sliding layer is fixedly disposed on the vibrating base, and the first sliding layer and the second sliding layer are slidably connected. The first liquid is one of blood and a detection solution, and the second liquid is one of a detection solution corresponding to the first liquid and blood. The second sliding layer is configured to slide to a preset position relative to the first sliding layer, the preset position indicating a position that aligns the first detection area and the second detection area. The vibrating base is configured to vibrate the first sliding layer by releasing vibration, causing the first liquid in the second detection area to mix with the second liquid in the first detection area for coagulation detection.

[0006] According to embodiments of this disclosure, the first sliding layer further includes a first microchannel; the second sliding layer further includes a second microchannel; when the second sliding layer is located at an initial position relative to the first sliding layer, the second microchannel is configured to introduce a first liquid into a first detection area; the first microchannel is configured to introduce a second liquid into a second detection area; the initial position indicates a position in which the first microchannel communicates with the second detection area, and the second microchannel communicates with the first detection area.

[0007] According to embodiments of this disclosure, alignment of the first detection area with the second detection area means that the projection of the first detection area into the second detection area coincides with the second detection area.

[0008] According to embodiments of the present disclosure, a first detection area includes a plurality of first grooves; a second detection area includes a plurality of second grooves; alignment of the first detection area and the second detection area means that the projection of at least one first target groove among the plurality of first grooves in the second detection area coincides with at least one second target groove among the plurality of second grooves.

[0009] According to embodiments of this disclosure, when the first liquid and the second liquid are mixed and a coagulation reaction occurs, a blood clot required for coagulation detection is generated; adjacent first grooves are connected by a first channel; adjacent second grooves are connected by a second channel; the first channel and the second channel are configured to prevent the blood clot from moving between adjacent first grooves or adjacent second grooves.

[0010] According to an embodiment of this disclosure, the vibration base includes a glass base and a vibration source; the glass base is provided with an air hole below the first detection area, and when the vibration base vibrates, the air in the air hole resonates, so that the mixed first liquid and the second liquid generate eddies.

[0011] According to embodiments of this disclosure, both ends of the second microchannel and the first microchannel are provided with an inlet and an outlet; the outlet is configured to discharge air from the microchannel when liquid flows into the inlet.

[0012] According to an embodiment of the present disclosure, the first sliding layer further includes a first sliding identifier; the second sliding layer further includes a second sliding identifier; the first sliding identifier and the second sliding identifier are configured to determine whether the second sliding layer is at a preset position relative to the first sliding layer.

[0013] According to an embodiment of this disclosure, a lubricating layer is further provided between the first sliding layer and the second sliding layer, and the lubricating layer includes silicone oil.

[0014] Another aspect of this disclosure provides a coagulation detection method, comprising: introducing a first liquid into a first detection area; introducing a second liquid into a second detection area; sliding a second sliding layer to a preset position relative to the first sliding layer so that the first detection area and the second detection area are aligned; mixing the first liquid and the second liquid and generating an eddy current by vibrating a base; and detecting the coagulation reaction between the first liquid and the second liquid.

[0015] According to embodiments of this disclosure, based on the structure of the coagulation detection chip described above, the two detection areas are completely isolated before the first and second sliding layers slide relative to each other, minimizing the possibility of premature liquid mixing. This structure ensures precise controllability at the start of the reaction. Once the second sliding layer slides to a preset position, the two detection areas align and form a reaction chamber of fixed volume. Blood and the test solution can be mixed in a constant ratio without external pumping, eliminating the need for metering pumps and external valves, thus reducing the complexity and cost of the detection chip. Furthermore, the vibrating base uses high-frequency micro-vibration to promote rapid and uniform mixing of the high-viscosity blood and the test solution, shortening the coagulation time interpretation window. The aforementioned coagulation detection chip can meet the requirements of point-of-care testing while also enabling timed and quantitative coagulation analysis, thereby improving coagulation detection efficiency. Attached Figure Description

[0016] The above and other objects, features and advantages of this disclosure will become clearer from the following description of embodiments with reference to the accompanying drawings, in which:

[0017] Figure 1 A schematic diagram of the structure of a coagulation detection chip according to an embodiment of the present disclosure is shown.

[0018] Figure 2(a) schematically shows a top view of the structure when the second sliding layer slides to a preset position relative to the first sliding layer according to an embodiment of the present disclosure.

[0019] Figure 2(b) schematically shows a top view of the structure of the second sliding layer relative to the initial position of the first sliding layer according to an embodiment of the present disclosure.

[0020] Figure 3 A schematic top view of the structure of the reaction chamber according to an embodiment of the present disclosure is shown.

[0021] Figure 4 The schematic diagram illustrates a top view of the structure of the first sliding layer and the second sliding layer according to an embodiment of the present disclosure.

[0022] Figure 5(a) schematically illustrates a process of generating a coagulation reaction by eddy current according to an embodiment of the present disclosure.

[0023] Figure 5(b) schematically illustrates a second process for generating a coagulation reaction via eddy currents according to an embodiment of the present disclosure.

[0024] Figure 5(c) schematically illustrates a process three of generating a coagulation reaction by eddy current according to an embodiment of the present disclosure.

[0025] Explanation of reference numerals in the attached figures:

[0026] 100: First sliding layer; 110: First detection area; 111: First groove; 120: First microchannel; 200: Second sliding layer; 210: Second detection area; 211: Second groove; 220: Second microchannel; 300: Vibration base; 310: Glass base; 320: Vibration source; 400: Reaction chamber; 410: First reaction chamber; 420: Second reaction chamber; 430: Third reaction chamber; 500: Sample inlet; 600: Sample outlet. Detailed Implementation

[0027] The embodiments of the present disclosure will now be described with reference to the accompanying drawings. However, it should be understood that these descriptions are exemplary only and are not intended to limit the scope of the disclosure. In the following detailed description, numerous specific details are set forth to provide a thorough understanding of the embodiments of the present disclosure for ease of explanation. However, it will be apparent that one or more embodiments may be practiced without these specific details. Furthermore, descriptions of well-known structures and techniques are omitted in the following description to avoid unnecessarily obscuring the concepts of the present disclosure.

[0028] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit this disclosure. The terms “comprising,” “including,” etc., as used herein indicate the presence of the stated features, steps, operations, and / or components, but do not exclude the presence or addition of one or more other features, steps, operations, or components.

[0029] All terms used herein (including technical and scientific terms) have the meanings commonly understood by those skilled in the art, unless otherwise defined. It should be noted that the terms used herein are to be interpreted in a manner consistent with the context of this specification, and not in an idealized or overly rigid way.

[0030] Currently, coagulation function testing is a crucial component of clinical diagnosis, preoperative assessment, and anticoagulation therapy monitoring. Traditional coagulation testing methods typically rely on large centrifuges and biochemical analyzers, which suffer from drawbacks such as large sample requirements, long testing times, complex operations, and difficulty in identifying abnormal samples, making it difficult to meet the needs of rapid point-of-care testing.

[0031] Traditional central laboratory models have inherent drawbacks such as large sample volumes, long turnaround times, high dependence on location, and complex quality control processes. This often results in test results lagging behind changes in the patient's condition, increasing the potential risk of bleeding or thrombotic events. Therefore, achieving coagulation testing methods that provide micro-sample, immediate, bedside, and simultaneous acquisition of multiple indicators has become a common technical requirement for improving emergency care efficiency, optimizing anticoagulation management, and reducing medical costs.

[0032] In recent years, microfluidic chip technology has provided new solutions for achieving rapid, miniaturized, and automated coagulation detection. Existing microfluidic coagulation detection chips typically achieve sample and reagent mixing through laminar diffusion or passive structures (such as serpentine channels). However, blood is a high-viscosity non-Newtonian fluid. In micrometer-scale channels, the fluid is in a low Reynolds number state, and mixing mainly relies on molecular diffusion, which is extremely inefficient, resulting in long reaction times and insufficient detection sensitivity. Furthermore, some microfluidic devices have failed to achieve the initiation point of coagulation detection reactions, the identification of abnormal samples, and the precise control of the reaction sample volume.

[0033] In view of this, embodiments of the present disclosure provide a coagulation detection chip, comprising: a vibrating base; a first sliding layer including a first detection area configured to contain a first liquid; and a second sliding layer including a second detection area configured to contain a second liquid. The first sliding layer is fixedly disposed on the vibrating base, and the first sliding layer and the second sliding layer are slidably connected. The first liquid is one of blood and a detection solution, and the second liquid is one of a detection solution corresponding to the first liquid and blood. The second sliding layer is configured to slide to a preset position relative to the first sliding layer, the preset position indicating a position that aligns the first detection area and the second detection area. The vibrating base is configured to vibrate the first sliding layer by releasing vibration, causing the first liquid in the second detection area to mix with the second liquid in the first detection area for coagulation detection.

[0034] Figure 1 A schematic diagram of the structure of a coagulation detection chip according to an embodiment of the present disclosure is shown.

[0035] According to embodiments of this disclosure, reference is made to Figure 1 The vibration base 300 supports a first sliding layer 100 and a second sliding layer 200. The vibration base 300 is fixedly connected to the first sliding layer 100, which can be achieved by adhesive bonding. The vibration base 300 can be made of glass. A first detection area 110 is formed in the first sliding layer 100, and a second detection area 210 is formed in the second sliding layer 200.

[0036] The first detection area 110 can be used to contain a first liquid, and the second detection area 210 can be used to contain a second liquid. The first and second liquids are corresponding; a coagulation reaction occurs when the first and second liquids are mixed. Specifically, when the first liquid is blood, the second liquid can be a detection solution; conversely, when the first liquid is a detection solution, the second liquid can be blood. The detection solutions can include various types, such as buffer solutions containing recombinant tissue factor and calcium ions, or high-concentration thrombin solutions, etc.

[0037] Figure 2(a) schematically shows a top view of the structure when the second sliding layer slides to a preset position relative to the first sliding layer according to an embodiment of the present disclosure.

[0038] According to embodiments of this disclosure, reference is made to Figure 1As shown in Figure 2(a), the first sliding layer 100 and the second sliding layer 200 can slide relative to each other. When the first sliding layer 100 and the second sliding layer 200 slide to a preset position, the first detection area 110 and the second detection area 210 will align, so that the first detection area 110 and the second detection area 210 can form a closed reaction chamber 400. In this reaction space, the first liquid and the second liquid can mix. At this time, the vibrating base 300 can release vibration, causing the first sliding layer 100 supported on it to vibrate, thereby further and fully mixing the first liquid and the second liquid in the mixed state, completing the coagulation reaction required for coagulation detection.

[0039] According to embodiments of this disclosure, vibration can be generated in the vibration base 300 in various ways. For example, the vibration base may include a rigid base and a vibration unit, which may be a magnetic element capable of generating high-frequency vibration, such as an electromagnetic oscillator, an eccentric rotary motor, or a piezoelectric oscillator. The high-frequency vibration of the vibration base 300 can promote thorough and rapid mixing of blood and the test solution, thereby improving the efficiency of the coagulation reaction.

[0040] According to embodiments of this disclosure, based on the structure of the coagulation detection chip described above, the two detection areas are completely isolated before the first and second sliding layers slide relative to each other, minimizing the possibility of premature liquid mixing. This structure ensures precise controllability at the start of the reaction. Once the second sliding layer slides to a preset position, the two detection areas align and form a reaction chamber of fixed volume. Blood and the test solution can be mixed in a constant ratio without external pumping, eliminating the need for metering pumps and external valves, thus reducing the complexity and cost of the detection chip. Furthermore, the vibrating base uses high-frequency micro-vibration to promote rapid and uniform mixing of the high-viscosity blood and the test solution, shortening the coagulation time interpretation window. The aforementioned coagulation detection chip can meet the requirements of point-of-care testing while also enabling timed and quantitative coagulation analysis, thereby improving coagulation detection efficiency.

[0041] According to embodiments of this disclosure, the first sliding layer further includes a first microchannel; the second sliding layer further includes a second microchannel; when the second sliding layer is located at an initial position relative to the first sliding layer, the second microchannel is configured to introduce a first liquid into a first detection area; the first microchannel is configured to introduce a second liquid into a second detection area; the initial position indicates a position in which the first microchannel communicates with the second detection area, and the second microchannel communicates with the first detection area.

[0042] Figure 2(b) schematically shows a top view of the structure of the second sliding layer relative to the initial position of the first sliding layer according to an embodiment of the present disclosure.

[0043] According to embodiments of this disclosure, reference is made to Figure 1As shown in Figures 2(a) and 2(b), the first sliding layer 100 may further include a first microchannel 120, and the second sliding layer 200 may further include a second microchannel 220. The aforementioned initial position can be the relative position of the first sliding layer 100 and the second sliding layer 200 as shown in Figure 2(b). When the second sliding layer 200 is in the initial position relative to the first sliding layer 100, the first microchannel 120 is connected to the second detection area 210, and the second microchannel 210 is connected to the first detection area 110. In this case, the first liquid can be introduced into the first detection area 110 through the second microchannel 210; the second liquid can also be introduced into the second detection area 210 through the first microchannel 120, thereby completing the liquid position presetting work of the detection solution and blood before coagulation detection.

[0044] According to embodiments of this disclosure, in the initial position, the first microchannel is connected to the second detection area, and the second microchannel is connected to the first detection area, forming a microchannel path that can be used for liquid position preset. This allows the two liquids to be independently and quantitatively filled before sliding, without the need for an external pump valve. Subsequently, only one relative sliding is required to switch to the preset position. This structure compresses the three independent modules of sample injection, metering, and mixing required by traditional chips into a single sliding action within the same plane, simplifying the operation process, further shortening the detection preparation time, and avoiding sample loss and cross-contamination, thereby achieving rapid and efficient coagulation detection.

[0045] According to embodiments of this disclosure, alignment of the first detection area with the second detection area means that the projection of the first detection area into the second detection area coincides with the second detection area.

[0046] According to an embodiment of this disclosure, referring to FIG2(b), the projection of the first detection area onto the second detection area coincides with the second detection area, indicating that, when aligned, the first and second detection areas can enclose a sealed reaction chamber 400. Taking FIG2(b) as an example, the sealed reaction chamber 400 is composed of multiple interconnected cylindrical and cuboid spaces, within which the coagulation reaction occurs. The reaction chamber creates a space for the coagulation reaction to occur, isolates external interference, and prevents leakage. Furthermore, the shape of the sealed reaction chamber 400 is not limited herein.

[0047] According to embodiments of this disclosure, a sliding operation can completely overlap the vertical projections of the first and second detection areas, forming a stable reaction chamber for the reaction to occur. Furthermore, the overlap of the two detection areas creates a closed reaction chamber, preventing liquid stagnation and bubble entrainment caused by steps or dead angles, ensuring a constant mixing volume each time, improving detection repeatability and reliability, and reducing manufacturing and assembly tolerance requirements.

[0048] Figure 3A schematic top view of the structure of the reaction chamber according to an embodiment of the present disclosure is shown.

[0049] According to embodiments of the present disclosure, a first detection area includes a plurality of first grooves; a second detection area includes a plurality of second grooves; alignment of the first detection area and the second detection area means that the projection of at least one first target groove among the plurality of first grooves in the second detection area coincides with at least one second target groove among the plurality of second grooves.

[0050] Figure 4 The schematic diagram illustrates a top view of the structure of the first sliding layer and the second sliding layer according to an embodiment of the present disclosure.

[0051] According to embodiments of this disclosure, the above-described reaction chamber 400 structure can also take various forms, such as multiple non-connected cylindrical spaces, see reference. Figure 4 The reaction chamber 400 may include a first reaction chamber 410, a second reaction chamber 420, and a third reaction chamber 430. To enable the formation of the first reaction chamber 410, the second reaction chamber 420, and the third reaction chamber 430 through sliding, a plurality of first grooves may be included in the first detection area, and a plurality of second grooves may be included in the second detection area. After the sliding operation, at least one reaction chamber can be formed by the projection of the first target groove and the second target groove coinciding, thereby allowing the blood and reaction solution to mix, facilitating a coagulation reaction.

[0052] According to embodiments of this disclosure, the above-described structure employs an array-like alignment structure of multiple first grooves with multiple second grooves. As long as any set of first target grooves and second target grooves project to coincide, a reaction chamber can be established, thereby reducing the dependence of the coagulation detection chip on sliding accuracy. Furthermore, even if individual grooves fail due to processing errors or contamination, the remaining grooves can still normally form a reaction chamber and initiate a coagulation reaction, ensuring mixing efficiency and normal detection, while also achieving redundancy and fault tolerance. This structural design maintains micron-level positioning accuracy while improving manufacturing tolerance, which is beneficial for low-cost mass production and long-term storage stability of the detection chip.

[0053] According to embodiments of this disclosure, when the first liquid and the second liquid are mixed and a coagulation reaction occurs, a blood clot required for coagulation detection is generated; adjacent first grooves are connected by a first channel; adjacent second grooves are connected by a second channel; the first channel and the second channel are configured to prevent the blood clot from moving between adjacent first grooves or adjacent second grooves.

[0054] According to embodiments of this disclosure, when the first liquid and the second liquid mix in the reaction chamber created after alignment, the coagulation cascade is triggered: phospholipid-tissue factor (or activator) provides a catalytic surface, calcium ions restart the conversion of prothrombin to thrombin, thrombin rapidly cleaves fibrinogen, releases fibrin peptides and polymerizes into a three-dimensional network structure, which encapsulates red blood cells and platelets, ultimately forming a blood clot that can be identified by the naked eye or an optical system; the amount, hardness and formation time of this blood clot are the direct signal sources for coagulation detection.

[0055] According to embodiments of this disclosure, reference is made to Figure 4 A first channel 112 may be included between multiple first grooves 111 within the first detection area 110; a second channel 212 may be included between multiple second grooves 211 within the second detection area 210; the number of first grooves 111, second grooves 211, first channels 112, and second channels 212 is... Figure 4 The example shown is for illustrative purposes only and is not intended to be limiting.

[0056] According to embodiments of this disclosure, reference is made to Figure 4 Since the multiple grooves are interconnected, the detection area after hydrophilic treatment can be more convenient and faster when setting the liquid position. Furthermore, after the reaction chamber is formed by sliding the second sliding layer in the first detection area 110 and the second detection area 210, although the first channel 112 and the second channel 212 will form a channel space, the blood clot generated by the above reaction will not flow into other grooves through the channel space because its volume increases.

[0057] According to the embodiments of this disclosure, the diameter of the first groove 111 and the second groove 211 can be set to 600 μm, the width of the first channel 112 and the second channel 212 can be set to 300 μm, and the spacing between adjacent grooves can be set to 100 μm; the depth of the first groove 111, the second groove 211, the first channel 112 and the second channel 212 can be set to 47 μm.

[0058] According to embodiments of this disclosure, the passage of blood clots can be restricted by adjusting the width and depth of the first and second channels. This allows liquids, such as blood or test solutions, to flow between adjacent grooves, maintaining a concentration balance between the first and second liquids. Simultaneously, it creates steric hindrance to the formed three-dimensional fibrin-erythrocyte network, i.e., the blood clot, preventing it from breaking or migrating to other grooves due to subsequent vibrations or capillary flow. This structure ensures the complete retention of the blood clot within each groove, avoiding inaccurate quantitative analysis caused by reaction crosstalk. Furthermore, it improves the stability of test results and facilitates independent image capture of each groove after testing.

[0059] According to an embodiment of this disclosure, the vibration base includes a glass base and a vibration source; the glass base is provided with an air hole below the first detection area, and when the vibration base vibrates, the air in the air hole resonates, so that the mixed first liquid and the second liquid generate eddies.

[0060] According to embodiments of this disclosure, reference is made to Figure 1 The vibration base 300 may include a glass base 310 and a vibration source 320. An air hole may be provided in the glass base below the first detection area. When the vibration source 320 vibrates, the air in the air hole will resonate. Furthermore, the first sliding layer 100 and the second sliding layer 200 may be made of flexible material. The resonance can generate a vortex in the first liquid and the second liquid mixed above the air hole.

[0061] According to embodiments of this disclosure, the aforementioned flexible material can be made of polydimethylsiloxane (PDMS). Furthermore, the volume of the first sliding layer can be... The volume of the second sliding layer can be

[0062] According to embodiments of this disclosure, the vibration source 320 can be a piezoelectric ceramic, and its diameter can be [missing information]. ,thickness The glass base 310 can be [sized in size]. The glass base 310 can be used to fix and place the vibration source 320 by opening a circular through hole of the corresponding size.

[0063] According to embodiments of this disclosure, an air hole is formed below the first detection area in the glass base. When excited by the vibration source, the air inside the hole forms a resonant cavity, which can generate high-frequency pulsating pressure. The vibration induced by air resonance can break the laminar boundary and induce microscale eddies. Compared with simple solid conduction, air resonance amplifies the amplitude by one time or more, enabling high-viscosity blood and the detection solution to be uniformly mixed within milliseconds, shortening the time to reach the coagulation initiation point. In addition, for tiny cell fragments, lipid particles, and other interfering particles mixed in the blood, due to their extremely small size, they are less affected by air resonance and only move randomly or chaotically with the background flow field, so they will not affect the judgment and recognition of imaging detection. At the same time, the air hole isolates the vibration source from the surrounding structure, reduces power consumption and noise, and prevents heat from being transferred to the blood, ensuring detection accuracy.

[0064] According to embodiments of this disclosure, both ends of the second microchannel and the first microchannel are provided with an inlet and an outlet; the outlet is configured to discharge air from the microchannel when liquid flows into the inlet.

[0065] According to embodiments of this disclosure, reference is made to Figure 1Figures 2(a) and 2(b) show that an inlet 500 and an outlet 600 are provided at both ends of the first microchannel 120 and the second microchannel 220. Both the inlet 500 and the outlet 600 penetrate the second sliding layer, allowing both the first and second microchannels to communicate with the external atmosphere. When the first liquid or the second liquid flows into the microchannel through the inlet 500, the outlet 600 discharges the air inside the microchannel, preventing the formation of air bubbles that could affect coagulation detection within the microchannel and the detection area.

[0066] According to embodiments of this disclosure, the diameters of the inlet and outlet can be set to...

[0067] According to embodiments of this disclosure, the sample outlet allows gas in the microchannel to be discharged immediately without the need for additional puncture or aspiration steps; the above structural design can eliminate reaction dead zones and optical interference caused by residual air bubbles, ensuring that the liquid quickly and uniformly fills the entire detection area of ​​the groove array, shortening preparation time and improving detection repeatability.

[0068] According to an embodiment of the present disclosure, the first sliding layer further includes a first sliding identifier; the second sliding layer further includes a second sliding identifier; the first sliding identifier and the second sliding identifier are configured to determine whether the second sliding layer is at a preset position relative to the first sliding layer.

[0069] According to embodiments of this disclosure, when sliding the second sliding layer, the positions of the first sliding indicator and the second sliding indicator can be referenced to determine whether the second sliding layer has reached a preset position. Specifically, refer to... Figure 1 The cross-shaped alignment structure next to the first detection area, for example, the first sliding marker may include two columns of alignment structures. The column closer to the first detection area can be the first alignment structure, and the column farther from the first detection area can be the second alignment structure. The second sliding marker may include a third alignment structure. When the second sliding layer is in its initial position, the projection of the third alignment structure can coincide with the second alignment structure from a top-down view. After sliding the second sliding layer, when the projection of the third alignment structure coincides with the first alignment structure, the second sliding layer has reached the preset position.

[0070] According to embodiments of this disclosure, the first sliding marker and the second sliding marker constitute an alignment reference that can be recognized by the naked eye or an image; when the two coincide in a preset manner, it can be confirmed at once that the second sliding layer has reached the preset position without the need for additional sensors or electronic control feedback. Using the above structure can simplify the construction of the overall coagulation detection chip, reduce power consumption and cost, and avoid overshoot or springback errors caused by mechanical limits, thereby improving repeatability and ensuring batch consistency of coagulation detection.

[0071] According to an embodiment of this disclosure, a lubricating layer is further provided between the first sliding layer and the second sliding layer, and the lubricating layer includes silicone oil.

[0072] According to embodiments of this disclosure, the aforementioned lubricating layer can be configured as a silicone oil with a viscosity of 12,500 centistokes. The lubricating layer fills the microscopic gap between the first and second sliding layers, forming a reliable liquid seal during sliding, effectively isolating blood from the detection solution and preventing leakage.

[0073] According to embodiments of this disclosure, the above-mentioned coagulation detection chip can be assembled using the following steps.

[0074] Step 1: Prepare the mold.

[0075] After drawing the mold layout, the SU-8 mold for the first sliding layer and the SU-8 mold for the second sliding layer are produced through steps such as baking, exposure, photolithography, development, and hardening.

[0076] Step 2: Prepare the coagulation detection chip.

[0077] The PDMS prepolymer and curing agent are thoroughly mixed at a mass ratio of 10:1, centrifuged, and then poured and spin-coated onto the prepared SU-8 mold. After curing in an oven (80°C for 2 hours), the mixture is peeled off to obtain the first and second sliding layers. Subsequently, a punch can be used to punch inlet and outlet ports at predetermined positions on the second sliding layer as needed.

[0078] Step 3: Assemble the vibration base.

[0079] Use epoxy resin adhesive to fix the vibration source to the glass base.

[0080] Step 4: Bonding and lubrication layer treatment.

[0081] The surface of the first sliding layer, the bottom surface of the second sliding layer, and the top surface of the glass base are treated with a plasma cleaner, and the detection area and microchannels are treated with a hydrophilic agent. The bottom surface of the first sliding layer is then bonded to the top surface of the glass base using alignment marks to achieve an irreversible bond.

[0082] Next, the lubricating layer is prepared: First, 12,500 centis is spin-coated onto the glass slide at a speed of 9,000 revolutions per minute for 30 seconds, and a layer of silicone oil is adhered to the upper surface of the first sliding layer with transparent tape to serve as a lubricating layer, so as to achieve the functions of sealing and lubrication.

[0083] Step 5: Overall assembly and alignment.

[0084] The second sliding layer is placed on top of the first sliding layer. Its position can be adjusted under a microscope using the first and second sliding markers.

[0085] According to an embodiment of this disclosure, a coagulation detection method includes: introducing a first liquid into a first detection area; introducing a second liquid into a second detection area; sliding a second sliding layer to a preset position relative to the first sliding layer so that the first detection area and the second detection area are aligned; mixing the first liquid and the second liquid and generating an eddy current by vibrating a base; and detecting the coagulation reaction between the first liquid and the second liquid.

[0086] Figures 5(a) to 5(c) schematically illustrate the process of generating a coagulation reaction by eddy current according to an embodiment of the present disclosure.

[0087] According to the embodiments of this disclosure, referring to Figures 5(a) to 5(c), the above-described coagulation detection method can be performed using the following method.

[0088] Referring to Figure 5(a), under resonance, the air inside the air hole begins to generate high-frequency resonance, inducing acoustic flow in the fluid within the surrounding reaction chamber. At this time, red blood cells and dispersed particles are simultaneously subjected to acoustic flow drag force and acoustic radiation force. Since the magnitude of acoustic radiation force is highly correlated with particle volume, larger red blood cells are dominated by the acoustic field force and begin to move in a regular circular motion along specific streamlines; while tiny cell fragments, lipid particles, and other interfering particles mixed in the sample, due to their extremely small size, are subjected to weak acoustic radiation force and cannot form regular trajectories, only moving randomly or chaotically with the background flow field. This mixing mode allows background noise to be filtered out by image recognition algorithms in the early stages of the reaction, locking the red blood cell population as an effective signal source. At this stage, the blood viscosity is low, and the blood and the detection solution are undergoing intense microscopic mixing.

[0089] Referring to Figure 5(b), as mixing deepens, the eddy current field further induces erythrocyte aggregation, forming clear image features. Furthermore, the eddy current field accelerates the contact between coagulation factors and blood cells, activating the coagulation cascade reaction, causing fibrinogen to begin converting into fibrin monomers. The microscopic viscosity of the liquid gradually increases, and the movement trajectory of erythrocytes begins to be inhibited by viscous resistance, resulting in a narrowing of the movement amplitude. Meanwhile, free lipid particles or fragments cannot be effectively captured and remain free-floating on the periphery of the eddy current or in the background.

[0090] Referring to Figure 5(c), as the coagulation reaction nears its endpoint, a large amount of fibrin intertwines to form a network structure, tightly wrapping and adhering red blood cells together to form a dense blood clot. At this point, the red blood cells no longer rotate with the acoustic flow. By tracking the moment when the fibrin network stops moving, the coagulation endpoint can be accurately determined. This detection method based on specific blood clot dynamics reduces the shortcomings of traditional turbidity methods, which are easily affected by sample background color or impurities, and accurately defines the moment when the coagulation reaction begins based on the starting point determined by the sliding operation.

[0091] According to embodiments of this disclosure, the reaction chamber structure synthesized using sliding operation can limit the reaction time and amount of blood and test solution, achieving simultaneous quantitative mixing of micro-volume liquids. The piezoelectric ceramic oscillator enables efficient mixing of blood and test solution within the reaction chamber, resulting in a stronger detection signal and improved detection sensitivity. The entire coagulation detection chip requires only microliters of blood and test solution, saving costs and reducing patient discomfort during blood collection. Furthermore, by using ultrasonic perturbation and microscopic imaging, the movement patterns of cell populations and clots under ultrasonic microfluidic flow field perturbation are analyzed, effectively avoiding the influence of interfering substances, thereby improving detection accuracy and correcting abnormal samples. The first and second sliding layers can be made of flexible materials and can be mass-produced using mature soft lithography technology. Combined with commercially available piezoelectric ceramics and other components, the overall manufacturing cost is low, making it suitable for manufacturing disposable coagulation detection chips.

[0092] The flowcharts and block diagrams in the accompanying drawings illustrate the architecture, functionality, and operation of possible implementations of systems, methods, and computer program products according to various embodiments of the present disclosure. In this regard, each block in a flowchart or block diagram may represent a module, segment, or portion of code containing one or more executable instructions for implementing a specified logical function. It should also be noted that in some alternative implementations, the functions indicated in the blocks may occur in a different order than those indicated in the drawings. For example, two consecutively indicated blocks may actually be executed substantially in parallel, and they may sometimes be executed in reverse order, depending on the functions involved. It should also be noted that each block in a block diagram or flowchart, and combinations of blocks in a block diagram or flowchart, may be implemented using a dedicated hardware-based system that performs the specified function or operation, or using a combination of dedicated hardware and computer instructions. Those skilled in the art will understand that the features described in the various embodiments of the present disclosure can be combined and / or combined in various ways, even if such combinations are not explicitly described in the present disclosure. In particular, the features described in the various embodiments of this disclosure may be combined and / or combined in various ways without departing from the spirit and teachings of this disclosure. All such combinations and / or combinations fall within the scope of this disclosure.

[0093] The embodiments of this disclosure have been described above. However, these embodiments are for illustrative purposes only and are not intended to limit the scope of this disclosure. Although various embodiments have been described above, this does not mean that the measures in the various embodiments cannot be used advantageously in combination. Various substitutions and modifications can be made by those skilled in the art without departing from the scope of this disclosure, and all such substitutions and modifications should fall within the scope of this disclosure.

Claims

1. A coagulation detection chip, characterized in that: include: Vibration base; The first sliding layer includes a first detection area configured to contain a first liquid. The second sliding layer includes a second detection area configured to contain a second liquid. The first sliding layer is fixedly disposed on the vibration base and slidably connected to the second sliding layer. The first liquid is one of blood and a detection solution, and the second liquid is one of a detection solution corresponding to the first liquid and blood. The second sliding layer is configured to slide to a preset position relative to the first sliding layer, wherein the preset position indicates a position that aligns the first detection area with the second detection area; The vibration base is configured to vibrate the first sliding layer by releasing vibration, so that the first liquid in the second detection area mixes with the second liquid in the first detection area for coagulation detection.

2. The coagulation detection chip according to claim 1, characterized in that: The first sliding layer further includes a first microchannel; The second sliding layer also includes a second microchannel; When the second sliding layer is in an initial position relative to the first sliding layer, the second microchannel is configured to introduce the first liquid into the first detection area; the first microchannel is configured to introduce the second liquid into the second detection area; the initial position indicates a position in which the first microchannel is connected to the second detection area and the second microchannel is connected to the first detection area.

3. The coagulation detection chip according to claim 1, characterized in that: Alignment of the first detection area with the second detection area means that the projection of the first detection area onto the second detection area coincides with the second detection area.

4. The coagulation detection chip according to claim 1, characterized in that: The first detection area includes multiple first grooves; The second detection area includes multiple second grooves; The alignment of the first detection area with the second detection area means that the projection of at least one first target groove among the plurality of first grooves in the second detection area coincides with at least one second target groove among the plurality of second grooves.

5. The coagulation detection chip according to claim 4, characterized in that: When the first liquid and the second liquid are mixed and a coagulation reaction occurs, a blood clot is generated that is required for coagulation testing. The adjacent first grooves are connected by a first channel; The adjacent second grooves are connected by a second channel; The first channel and the second channel are configured to prevent the blood clot from moving between adjacent first grooves or adjacent second grooves.

6. The coagulation detection chip according to claim 1, characterized in that: The vibration base includes: a glass base and a vibration source; The glass base has an air hole below the first detection area. When the vibrating base vibrates, the air in the air hole resonates, causing the mixed first liquid and second liquid to generate eddies.

7. The coagulation detection chip according to claim 2, characterized in that: Both ends of the second microchannel and the first microchannel are provided with an inlet and an outlet; The outlet is configured to expel air from the microchannel when liquid flows into the inlet.

8. The coagulation detection chip according to claim 2, characterized in that: The first sliding layer also includes a first sliding identifier; The second sliding layer also includes a second sliding indicator; The first sliding indicator and the second sliding indicator are configured to determine whether the second sliding layer is in a preset position relative to the first sliding layer.

9. The coagulation detection chip according to claim 1, characterized in that: A lubricating layer, comprising silicone oil, is further provided between the first sliding layer and the second sliding layer.

10. A method for detecting coagulation using a coagulation detection chip as described in any one of claims 1-9, characterized in that: Includes the following steps: The first liquid is introduced into the first detection area; The second liquid is introduced into the second detection area; The second sliding layer is slid to a preset position relative to the first sliding layer so that the first detection area is aligned with the second detection area; The vibrating base mixes the first liquid with the second liquid and generates a vortex. Detect the coagulation reaction between the first and second fluids.

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