CN115166224B - Microfluidic chip, platelet function detection device and method - Google Patents
Microfluidic chip, platelet function detection device and method Download PDFInfo
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- G—PHYSICS
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/483—Physical analysis of biological material
- G01N33/487—Physical analysis of biological material of liquid biological material
- G01N33/49—Blood
- G01N33/4905—Determining clotting time of blood
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- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/483—Physical analysis of biological material
- G01N33/487—Physical analysis of biological material of liquid biological material
- G01N33/49—Blood
- G01N33/4915—Blood using flow cells
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Abstract
The invention relates to the field of medical instruments, in particular to a microfluidic chip, a platelet function detection device and a platelet function detection method. The microfluidic chip comprises a sample inlet, a sample outlet and a runner positioned in the microfluidic chip, wherein the runner comprises a first straight runner, a second straight runner and a bent runner positioned between the first straight runner and the second straight runner and bent for a plurality of times. The first straight flow channel is connected with the sample inlet, the second straight flow channel is connected with the sample outlet, and the first straight flow channel and the second straight flow channel are gradually changed in width, and the farther the first straight flow channel and the second straight flow channel are from the bent flow channel, the wider the second straight flow channel is. The sample outlet is provided with means for detecting the impedance of the sample. The microfluidic chip has the advantages that the detection process is simple and convenient, the detection data can be acquired in real time, and the activation and aggregation of the platelets without a coagulation activator are realized through the flow channel design. The invention also provides a platelet function detection device and a platelet function detection method comprising the microfluidic chip.
Description
Technical Field
The invention relates to the field of medical instruments, in particular to a microfluidic chip, a platelet function detection device and a platelet function detection method.
Background
Platelet activation status is key information for judging the coagulation status of patients and guiding anti-platelet drug therapy and the like. The platelet activation function detection methods which are widely used at present mainly comprise an optical turbidimetry method, a thromboelastography method and the like, however, the methods generally need to be carried out in a central laboratory, are long in time consumption and low in timeliness, namely, can not be analyzed in time after blood is collected. This results in inaccurate analysis results, which can hardly reflect the actual condition of platelet activation in patients. Meanwhile, the methods have high dependency on instruments and equipment, usually require professional operation, and cannot be applied to daily life simply and portably.
Currently, researchers have also used electrical methods in combination with microfluidic techniques to determine platelet activation status. However, in these tests, a blood sample is often activated by a coagulation activator such as heparin, and the content and performance of the coagulation activator will change with the test process, and each test needs to be replaced with a new device or the coagulation activator is added again, so that repeated tests are difficult.
Disclosure of Invention
Based on the above, the invention provides a microfluidic chip, a platelet function detection device and a platelet function detection method. The device detection process is simple and convenient, can acquire detection data in real time, and enables the platelets to realize activation and aggregation on the basis of no need of a coagulation activator through the flow channel design.
In one aspect of the invention, a microfluidic chip is provided, which comprises a sample inlet, a sample outlet and a flow channel positioned in the microfluidic chip, wherein the flow channel comprises a first straight flow channel, a second straight flow channel and a bent flow channel which is positioned between the first straight flow channel and the second straight flow channel and is bent for a plurality of times;
the first straight flow channel is connected with the sample inlet, the second straight flow channel is connected with the sample outlet, and the first straight flow channel and the second straight flow channel are provided with gradual widths, and the farther the first straight flow channel and the second straight flow channel are from the curved flow channel, the wider the width is;
the sample outlet is provided with a device for detecting the impedance of the sample.
In some embodiments, the bending mode of the bending channel is U-shaped bending, V-shaped bending or a combination thereof.
In some embodiments, the bending mode of the bending channel is U-shaped bending, and the bending times are 5-40 times.
In some embodiments, the first straight flow channel and the curved flow channel and the second straight flow channel and the curved flow channel form an L-shaped structure, and the corner is arc-shaped.
In some embodiments, the narrowest region of the first straight flow channel and the curved flow channel are capable of independently providing 0.5×10 4 s -1 ～2.8×10 4 s -1 Is used to control the shear rate of the polymer.
In some embodiments, the wall height of the flow channel is 0.05mm to 2mm.
In some embodiments, the length of the first sprue and the second sprue are independently selected from 1mm to 10mm.
In some embodiments, the material of the microfluidic chip is glass, polydimethylsiloxane, polymethyl methacrylate, polystyrene, epoxy resin or polypropylene.
In one aspect of the present invention, a platelet function detection device is provided, which includes the microfluidic chip described above.
In another aspect of the present invention, there is further provided a platelet function detecting method, which comprises flowing a blood sample through a flow channel of the microfluidic chip or the device, activating platelets in the blood sample through the first straight flow channel and the curved flow channel, aggregating platelets in the blood sample through the second straight flow channel, and performing an impedance test at a sample outlet to obtain a clotting time signal.
The beneficial effects are that:
based on the micro-fluidic technology, the activation and aggregation of the platelets in the blood sample are realized in a mechanical way through the design of the curved flow channel and the direct flow channel with gradual change width, and the problem that the existing platelet function test equipment depends on a coagulation activator is avoided. The device has simple structure, the detection process is very convenient, and the dependence of platelet function detection on large instruments and professional operators is eliminated. Meanwhile, the device can collect data of platelet function detection in real time, so that dynamic change trend of platelet activation function can be monitored.
In addition, the parallel electrodes arranged on the sample outlet are used for collecting blood coagulation information, so that the impedance change of a blood sample can be effectively measured, and a more accurate test result can be obtained.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are needed in the description of the embodiments or the prior art will be briefly described, and it is obvious that the drawings in the description below are some embodiments of the present invention, and other drawings can be obtained according to the drawings without inventive effort for a person skilled in the art.
Fig. 1 is a schematic perspective view of a microfluidic chip according to an embodiment of the present invention;
fig. 2 is a schematic diagram of a partial enlarged structure of the microfluidic chip a in fig. 1;
FIG. 3 is a graph showing a shear rate profile in a microfluidic chip flow channel according to one embodiment of the present invention;
FIG. 4 is a graph showing impedance change during platelet function testing in accordance with one embodiment of the present invention;
symbol description: 1-a sample inlet; 2-a sample outlet; 21-a first electrode; 22-a second electrode; 3-flow channels; 31-a first straight flow path; 32-a curved runner; 33-second straight flow channel.
Detailed Description
Reference now will be made in detail to embodiments of the invention, one or more examples of which are described below. Each example is provided by way of explanation, not limitation, of the invention. Indeed, it will be apparent to those skilled in the art that various modifications and variations can be made to the present invention without departing from the scope or spirit of the invention. For example, features illustrated or described as part of one embodiment can be used on another embodiment to yield still a further embodiment.
Accordingly, it is intended that the present invention cover such modifications and variations as fall within the scope of the appended claims and their equivalents. Other objects, features and aspects of the present invention will be disclosed in or be apparent from the following detailed description. It is to be understood by one of ordinary skill in the art that the present discussion is a description of exemplary embodiments only, and is not intended as limiting the broader aspects of the present invention.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and/or" as used herein includes any and all combinations of one or more of the associated listed items.
Except where shown or otherwise indicated in the operating examples, all numbers expressing quantities of ingredients, physical and chemical properties, and so forth, used in the specification and claims are to be understood as being modified in all instances by the term "about". For example, therefore, unless indicated to the contrary, the numerical parameters set forth in the foregoing specification and attached claims are approximations that can be varied appropriately by those skilled in the art utilizing the teachings disclosed herein seeking to obtain the desired properties. The use of numerical ranges by endpoints includes all numbers subsumed within that range and any range within that range, e.g., 1 to 5 includes 1, 1.1, 1.3, 1.5, 2, 2.75, 3, 3.80, 4, 5, and the like.
The terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. Without further limitation, an element defined by the phrase "comprising one … …" does not exclude the presence of other like elements in a process, method, article, or apparatus that comprises the element. The terms "first," "second," and the like are used for descriptive purposes only and are not to be construed as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defining "a first" or "a second" may explicitly or implicitly include at least one such feature. In the description of the invention, the meaning of "plurality" means at least two, for example, two, three, etc., unless specifically defined otherwise. In the description of the present invention, the meaning of "several" means at least one, such as one, two, etc., unless specifically defined otherwise.
The terms "center," "upper," "lower," "left," "right," "vertical," "horizontal," "inner," "outer," "top," and the like, as used herein, refer to a direction or positional relationship based on the directions or positional relationships shown in the drawings, which are merely for convenience of description, and do not indicate or imply that the devices or elements must have a particular orientation, be constructed and operated in a particular orientation, and thus are not to be construed as limiting the invention.
In the description of the present invention, unless explicitly stated and limited otherwise, the terms "mounted," "connected," and "connected" are to be construed broadly, and may be, for example, fixedly connected, detachably connected, or integrally connected; can be mechanically or electrically connected; can be directly connected or indirectly connected through an intermediate medium, and can be communication between two elements. The specific meaning of the above terms in the present invention can be understood by those skilled in the art according to the specific circumstances.
In one aspect of the invention, a microfluidic chip is provided, which comprises a sample inlet, a sample outlet and a runner positioned in the microfluidic chip, wherein the runner comprises a first straight runner, a second straight runner and a bent runner positioned between the first straight runner and the second straight runner and bent for a plurality of times;
the first straight flow channel is connected with the sample inlet, the second straight flow channel is connected with the sample outlet, and the first straight flow channel and the second straight flow channel are gradually changed in width, and the farther the first straight flow channel and the second straight flow channel are away from the bent flow channel, the wider the width is;
the sample outlet is provided with means for detecting the impedance of the sample.
By providing the first straight flow channel with a gradual width, the blood sample has a larger shear rate when flowing through the narrow flow channel region, so that the blood sample can smoothly flow into the curved flow channel, and platelets in the blood sample can be activated at the shear rate. The same tortuous path turns may also provide shear to the blood sample, thereby imparting a shear rate to the blood sample that may be sufficient to further activate the platelets. While widening the second straight flow channel near the sample outlet is beneficial to reducing the shear rate and the aggregation of the platelets in the blood sample.
In some embodiments, the narrowest region of the first straight flow passage and the tortuous flow passage can independently provide 0.5X10 4 s -1 ～2.8×10 4 s -1 To activate platelets in the blood sample. Preferably, the narrowest region of the first straight flow passage and the curved flow passage are independently capable of providing 1.6X10 4 s -1 ～2.8×10 4 s -1 Is used to control the shear rate of the polymer. The widest region of the second sprue can provide 300s -1 ～600s -1 Is used to control the shear rate of the polymer. Other areas of the flow channel can provide 100s -1 ～800s -1 So that the blood sample can smoothly flow through the flow channel.
In some embodiments, the bending mode of the bending channel is U-shaped bending, V-shaped bending or a combination thereof. Preferably, the bending mode of the bending channel is U-shaped bending. More preferably, the number of times of U-shaped bending is 5 to 40 times, for example, 10 times, 15 times, 20 times, 30 times. Still more preferably, the number of times of U-shaped bending is 5 to 20. Most preferably, the number of times of U-shaped bending is 10, and the corner is a semicircular arc. Further, the radius of the semicircle is 5mm to 15mm, for example, 7mm, 9mm, 12mm may be used.
The number of the U-shaped structures in the curved flow channel is controlled to enable the curved flow channel to have a certain length and a certain number of curved parts, so that on one hand, the flowing time of blood samples can be regulated and controlled, further, the activation and aggregation effects of blood platelets can be observed, and on the other hand, the curved parts can fully activate the blood platelets in the blood samples.
In some embodiments, an L-shaped structure is formed between the first straight flow channel and the curved flow channel and between the second straight flow channel and the curved flow channel, and the corner is arc-shaped. Preferably, the corner is a circular arc of 1/4 circle, and the radius of the circular arc is 0.8-2 mm. More preferably, the radius of the arc is 1mm.
In some embodiments, the overall structure of the microfluidic chip may be a cylinder, a cube, a cuboid, or the like. Preferably, the whole structure of the microfluidic chip is cuboid, wherein the length of the microfluidic chip is 15-30 mm, the width of the microfluidic chip is 10-20 mm, and the height of the microfluidic chip is 0.1-5 mm. Preferably, the microfluidic chip is 20mm long, 10mm wide and 5mm high.
In some embodiments, the first straight flow channel has a maximum width of 0.5mm to 1.5mm, the second straight flow channel has a maximum width of 0.5mm to 5mm, and the curved flow channel has a width of 0.1mm to 0.3mm. Preferably, the maximum width of the first straight flow channel is 1mm, the maximum width of the second straight flow channel is 1.5mm, and the width of the curved flow channel is 0.2mm.
In some embodiments, the lengths of the first and second straight flow channels are independently selected from 1mm to 10mm. Preferably, the first straight flow path has a length of 4mm and the second straight flow path has a length of 1.5mm.
In some embodiments, the sample inlet and the sample outlet are openings formed in the height direction of the microfluidic chip.
The shape of the sample inlet can be any shape, such as a cylinder or a prism. When the shape of the sample inlet is prismatic, it is preferably prismatic, and may be, for example, regular triangular prism, square, regular pentagonal prism, regular hexagonal prism, or the like. More preferably, the shape of the sample inlet is cylindrical, the diameter of the bottom surface of the sample inlet is 1 mm-2 mm, and the height is 0.1 mm-5 mm. Preferably, the diameter of the bottom surface of the sample inlet is 1mm, and the height is 5mm.
The shape of the sample outlet can be any shape, such as a cylinder or a regular prism, and is preferably a cuboid. More preferably, the width of the sample outlet is the same as the maximum width of the second direct current channel, the length is 2 mm-5 mm, and the height is 0.1 mm-5 mm. Preferably, the width of the sample outlet is 1.5mm, the length is 3mm, and the height is 5mm.
In some embodiments, the length of the two side portions of each circular arc in the curved flow channel is 2 mm-3.5 mm. Preferably, the length of the two side portions of each circular arc is 2.6mm.
In some embodiments, the channel wall height is 0.05mm to 2mm.
In some embodiments, the microfluidic chip may be a bulk solid material, the interior of which can form a flow channel by embedding or molding. Preferably, the flow channels are formed by molding within the bulk solid material. More preferably, the flow channels are formed by photolithography.
In some embodiments, the material of the microfluidic chip is selected from materials commonly used for preparing microfluidic chips, for example, metal, glass, or high molecular polymer. From the viewpoint of forming the flow channel, the material of the microfluidic chip is preferably a high molecular polymer, and the high molecular polymer may be a thermoplastic polymer, a curable polymer, or a solvent-volatile polymer. The thermoplastic polymer may be polyamide, polymethyl methacrylate, polycarbonate, polystyrene, or polypropylene, among others. The curable polymer may be selected from Polydimethylsiloxane (PDMS), epoxy, polyurethane, or the like. The solvent-volatile polymer may be an acrylic resin, a fluoroplastic, or the like. More preferably, the material of the microfluidic chip is PDMS.
In some embodiments, the device for detecting the impedance of the sample comprises a first electrode and a second electrode which are positioned on two inner side walls of the sample outlet, wherein the two inner side walls are oppositely arranged, the first electrode and the second electrode form parallel electrodes, and a frequency of 1 kHz-20 kHz and a voltage of 0.05V-1V can be generated between the first electrode and the second electrode, and the frequency can be 5kHz, 10kHz, 12kHz and 15 kHz.
In some embodiments, the first electrode and the second electrode have a thickness of 0.05mm to 0.5mm.
In some embodiments, the material of the electrode may be selected from materials commonly used to prepare electrodes, including but not limited to Pt, au, cu, ni, ag, or combinations thereof. Preferably, the electrode material is Au.
In order to avoid the adhesion of the blood sample to the wall of the flow channel, the flow channel may be surface modified, and the modifying material may be salicylic acid derivative.
In some embodiments, the microfluidic chip further comprises a horizontal substrate below the chip, the substrate comprising any plane having a substantially horizontal surface. Preferably, the material of the horizontal substrate may be glass, polycarbonate, polyurethane, polydimethylsiloxane, or the like. More preferably, the material of the horizontal substrate is glass, and the thickness of the horizontal substrate is 1mm.
In one aspect of the present invention, a platelet function detection device is provided, which includes the microfluidic chip described above.
In another aspect of the present invention, there is further provided a platelet function detecting method, which comprises flowing a blood sample through a flow channel of the microfluidic chip or the device, activating platelets in the blood sample through the first straight flow channel and the curved flow channel, aggregating platelets in the blood sample through the second straight flow channel, and performing an impedance test at a sample outlet to obtain a clotting time signal.
Specifically, one end of the sample inlet is connected with the sample retaining needle to sample, the blood sample enters the first straight flow passage through the sample inlet, and when flowing through the narrowed region of the first straight flow passage, the blood sample is subjected to 0.5×10 4 s -1 ～2.8×10 4 s -1 So that platelets in the blood sample are activated; the blood sample can also be subjected to 0.5X10 when flowing through the bent portion of the curved flow channel 4 s -1 ～2.8×10 4 s -1 To further sufficiently activate platelets; finally, the blood sample was subjected to 300s when flowing through the widened region of the second flow path -1 ～600s -1 To cause platelets in the blood sample to aggregate at the outlet and to measure the impedance of the blood sample via electrodes connected to the outlet to obtain a clotting time signal.
In some embodiments, the blood sample is blood, plasma or serum, which may be of peripheral blood origin.
The microfluidic chip, the platelet function detection device and the method of the present invention are described in further detail below with reference to specific examples.
Examples
The microfluidic chip used in this embodiment will be described in detail with reference to fig. 1 to 2. The manufacturing process is as follows: firstly, a pipeline plan drawing is used as a mask film plate, and an epoxy resin SU-8 photoresist silicon wafer mold with the thickness of 100+/-10 mu m is processed on a glass substrate with the thickness of 1mm by using the mask film plate, and is packaged by tin paper. And then mixing Polydimethylsiloxane (PDMS) and a curing agent according to the mass ratio of 10:1, vacuumizing, pouring into a die coated with tinfoil, vacuumizing again to remove bubbles, and curing in an oven at 80 ℃ for 45min. And then taking out the cured PDMS chip, punching to manufacture a sample inlet 1 and a sample outlet 2, and carrying out plasma treatment on the PDMS and a glass phase to adhere the PDMS with the micro-channels to the glass substrate.
The microfluidic chip comprises a sample inlet 1, a sample outlet 2 and a flow channel 3 positioned in the microfluidic chip. The flow channel 3 comprises a first straight flow channel 31, a second straight flow channel 33 and a curved flow channel 32 between said first straight flow channel 31 and said second straight flow channel 33. The first straight flow channel 31 is connected with the sample inlet 1, the second straight flow channel 33 is connected with the sample outlet 2, and the first straight flow channel 31 and the second straight flow channel 33 are gradually changed in width, and the farther the first straight flow channel is from the curved flow channel 32, the wider the second straight flow channel is. The sample outlet 2 is provided with a first electrode 21 and a second electrode 22, which are parallel to each other, on opposite inner side walls.
The sample inlet 1 is an opening arranged on the microfluidic chip, the shape of the sample inlet is cylindrical, and the diameter of the bottom surface of the cylindrical sample inlet is 1mm and the height of the cylindrical sample inlet is 5mm. The length of the first straight flow channel 31 is 4mm, the maximum width is the same as the diameter of the bottom surface of the sample inlet 1, and the narrowed width is the same as the width of the curved flow channel 32, and is 0.2mm. The first straight flow channel 31 and the curved flow channel 32 are connected in an L shape, the corner is a circular arc of 1/4 circle, and the radius of the circular arc is 1mm. The runner 32 is connected to the first runner 31 and has a length perpendicular to the portion of the first runner 31 of 0.5mm. The second straight flow channel 33 and the curved flow channel 32 are also L-shaped, the corner is a circular arc of 1/4 circle, and the radius of the circular arc is 1mm. The length of the portion of the curved flow path 32 connected to the second straight flow path 33 and perpendicular to the second straight flow path 33 is 0.5mm. The length of the remaining portion of the runner 32 perpendicular to the first runner 31 and the second runner 33 is 2.6mm. The curved flow channel 32 has a semicircular arc at each corner, and the radius of the semicircular arc is 10mm. The length of the sample outlet 2 was 3mm, the height was 5mm, and the width was 1.5mm as the maximum width of the second straight flow path 33.
When the detection is performed, the sample inlet 1 is connected to the sampling device, and the blood sample is allowed to reach the sample outlet 2 through the flow channel 3 for detection. The narrowest region of the first straight flow channel 31 is capable of providing a shearing force to give a blood sample of 2.0X10 4 s -1 Which allows for a smoother flow into the flow channel 32 and activation of platelets therein. The curvature in the curved channel 32 still provides the shear rate to the blood sample, further activating the platelets in the blood sample. While the enlarged area of the second flow channel 33 can reduce the shear rate of the blood sample, the widest area of the second flow channel 33 in this embodiment can provide 500s -1 Thereby achieving platelet aggregation. The parallel electrodes arranged on the sample outlet 2 are used for carrying out impedance test to obtain a coagulation time signal, and the effects of platelet activation and coagulation are obtained through impedance change.
FIG. 3 is a graph showing the shear rate distribution of a blood sample flowing through the flow channel 3, wherein the first straight flow channel 31 is narrowed and the second straight flow channel 33 is seenThere is a relatively pronounced change in shear rate in the enlarged region. The shear rate of the blood sample immediately after entering the first straight flow channel 31 from the sample inlet 1 is 600s -1 This is consistent with the shear rate of blood flow in normal human blood vessels. After passing through the reduced area of the first straight flow passage 31, the shear rate increases to 2.0X10 4 s -1 This shear rate may well mimic the pathological shear rate resulting from severe atherosclerotic lesions or thrombosis-induced vascular stenosis. After the blood sample enters the expansion region of the second straight flow channel 33, the shear rate gradually decreases and finally reaches 500s -1 Whereby platelet aggregation is achieved at the sample outlet 2.
Fig. 4 is a graph showing the measured impedance at the sample outlet 2 over time. As the blood sample is activated, the blood aggregates, and its impedance is measured to increase over time. Therefore, the invention can realize effective activation and aggregation of the blood platelets without a coagulation activator, and more accurate results are measured.
The technical features of the above-described embodiments may be arbitrarily combined, and all possible combinations of the technical features in the above-described embodiments are not described for brevity of description, however, as long as there is no contradiction between the combinations of the technical features, they should be considered as the scope of the description.
The above examples illustrate only a few embodiments of the invention, which are described in detail and are not to be construed as limiting the scope of the invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. Accordingly, the scope of protection of the present invention is to be determined by the appended claims.
Claims (7)
1. The microfluidic chip is characterized by comprising a sample inlet, a sample outlet and a runner positioned in the microfluidic chip, wherein the runner comprises a first straight runner, a second straight runner and a bent runner which is positioned between the first straight runner and the second straight runner and is bent for a plurality of times;
the first straight flow channel is connected with the sample inlet, the second straight flow channel is connected with the sample outlet, and the first straight flow channel and the second straight flow channel are provided with gradual widths, and the farther the first straight flow channel and the second straight flow channel are from the curved flow channel, the wider the width is; the narrowest region of the first straight flow passage and the curved flow passage can independently provide 0.5X10 4 s -1 ~ 2.8×10 4 s -1 The wall height of the flow channel is 0.05 mm-2 mm, and the lengths of the first straight flow channel and the second straight flow channel are independently selected from 1 mm-10 mm;
the sample outlet is provided with a device for detecting the impedance of the sample.
2. The microfluidic chip according to claim 1, wherein the bending mode of the bent channel is U-shaped bending, V-shaped bending or a combination thereof.
3. The microfluidic chip according to claim 2, wherein the bending mode of the bent channel is U-shaped bending, and the bending times are 5-40 times.
4. The microfluidic chip according to any one of claims 1 to 3, wherein an L-shaped structure is formed between the first straight flow channel and the curved flow channel and between the second straight flow channel and the curved flow channel, and the corner is arc-shaped.
5. The microfluidic chip according to claim 1, wherein the microfluidic chip is made of glass, polydimethylsiloxane, polymethyl methacrylate, polystyrene, epoxy resin or polypropylene.
6. A platelet function detection device comprising the microfluidic chip according to any one of claims 1 to 5.
7. A method for detecting platelet function, comprising flowing a blood sample through the microfluidic chip according to any one of claims 1 to 5, activating platelets in the blood sample through the first straight flow channel and the curved flow channel, aggregating platelets in the blood sample through the second straight flow channel, and performing an impedance test at a sample outlet to obtain a clotting time signal.
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| CN102348506A (en) * | 2009-03-10 | 2012-02-08 | 莫纳什大学 | Platelet aggregation using a microfluidics device |
| CN104884954A (en) * | 2012-12-31 | 2015-09-02 | 高丽大学校产学协力团 | Apparatus and method for testing multi-function and drug response of centrifugal microfluidics-based platelets |
| CN204758612U (en) * | 2015-05-13 | 2015-11-11 | 刘军 | Anti -coagulant agent drug effect detector |
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| KR101481240B1 (en) * | 2012-12-27 | 2015-01-19 | 고려대학교 산학협력단 | Apparatus and method for monitoring platelet function and drug response in a microfluidic-chip |
| EP3058367B1 (en) * | 2013-10-16 | 2019-01-09 | President and Fellows of Harvard College | A microfluidic device for real-time clinical monitoring and quantitative assessment of whole blood coagulation |
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| CN102348506A (en) * | 2009-03-10 | 2012-02-08 | 莫纳什大学 | Platelet aggregation using a microfluidics device |
| CN104884954A (en) * | 2012-12-31 | 2015-09-02 | 高丽大学校产学协力团 | Apparatus and method for testing multi-function and drug response of centrifugal microfluidics-based platelets |
| CN204758612U (en) * | 2015-05-13 | 2015-11-11 | 刘军 | Anti -coagulant agent drug effect detector |
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