CN115672425A - Micro-fluidic chip and detection device that multichannel thrombelastogram detected - Google Patents

Micro-fluidic chip and detection device that multichannel thrombelastogram detected Download PDF

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Publication number
CN115672425A
CN115672425A CN202211384283.5A CN202211384283A CN115672425A CN 115672425 A CN115672425 A CN 115672425A CN 202211384283 A CN202211384283 A CN 202211384283A CN 115672425 A CN115672425 A CN 115672425A
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channel
chamber
micro
air
cavity
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张雷
李文泰
唐国庆
蔡显达
陆寅峰
张世龙
张萌
余占江
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Suzhou Simeide Biotechnology Co ltd
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Suzhou Simeide Biotechnology Co ltd
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Abstract

The invention relates to the technical field of medical instruments, in particular to a micro-fluidic chip for multi-channel thromboelastography detection, which comprises: the device comprises a base body, wherein a sample injection needle and an air inlet needle are arranged on one side of the base body, a first channel and a second channel are arranged at the bottom of the base body, and the first channel and the second channel are communicated or cut off through a sample injection micro valve; a waste liquid cavity is arranged on one side of the substrate, which is close to the sample injection needle and the air inlet needle, a gas path interface is arranged on the surface of the waste liquid cavity, and the quantitative chambers of the plurality of cavity units are sequentially communicated and communicated to the waste liquid cavity; at least one reagent chamber is arranged on the measuring channel corresponding to each mixing chamber, and freeze-drying reagents are preset in the reagent chambers. The invention adopts the microfluidic technology, only needs to insert the blood collection tube into the blood collection cavity of the microfluidic chip, can be matched with equipment to realize the detection of the thrombelastogram, and has less manual steps and high automation degree.

Description

Micro-fluidic chip and detection device that multichannel thrombelastogram detected
Technical Field
The invention relates to the technical field of medical instruments, in particular to a micro-fluidic chip for multi-channel thromboelastography detection and a detection device.
Background
The human body has complex and perfect blood coagulation, anticoagulation and fibrinolysis systems and fine regulation mechanisms thereof, and blood in blood vessels can not bleed or coagulate to form thrombus under normal physiological conditions. However, once the system and its regulatory mechanisms are disrupted, bleeding or thrombosis may result.
The Thromboelastogram (TEG) instrument is an analyzer capable of dynamically monitoring the whole blood coagulation process, can comprehensively reflect the interaction among platelets, blood coagulation factors, fibrinogen, a fibrinolysis system and other cell components in the whole process from blood coagulation to fibrinolysis of a patient by detecting a small amount of whole blood, has accurate data and simple and convenient operation, and is mainly used for comprehensively detecting the whole process of blood coagulation and fibrinolysis and the functions of the platelets. In particular, it can simplify the diagnosis of blood coagulation dysfunction and guide blood component transfusion during operation, and is an international universal device for liver transplantation operation. Blood coagulation and platelet function analyzers are increasingly applied to cardiovascular surgery, liver transplantation operation and other operations with large bleeding amount, and the fields of pediatrics, intensive care, hemostasis research and the like, and become important, accurate and rapid clinical hemostasis tests gradually.
Currently, three thrombus elasticity measurement techniques are developed around the measurement of blood viscoelasticity, which are described as follows:
(1) Haemonetics thrombelastogram apparatus (TEG) of America
The TEG measurement principle is as follows: a sample cup containing blood is prepared, and is oscillated at a certain amplitude and frequency under a temperature environment of 37 deg.C (see fig. 1). The elastic force change of the blood clot is monitored by a probe which is suspended by a metal wire and soaked in a sample, and in the blood coagulation process, after the blood clot couples a sample cup and the probe, the shearing force generated by the rotation of the sample cup can be transmitted to the probe in the sample, so that the motion amplitude of the probe has a direct relation with the strength of the formed blood clot. When the clot is retracted or dissolved, the coupling of the probe to the clot is released and the movement of the sample cup is no longer transmitted to the probe. The rotation of the probe is converted into an electronic signal by the electromagnetic sensor, and a thromboelastogram is generated by the data processing system after data acquisition.
(2) German Tem's rotary thromboelastometer (ROTEM)
The principle of the ROTEM measurement is as follows: the probe is immersed in a sample in the cup, the probe and cup are coupled by blood, and the probe is driven by the spring to oscillate at an initial amplitude of 4.75 degrees for a period of 12 seconds. The probe is free to move when the blood is in a liquid state without coagulation, and the greater the force of the clot to resist rotation of the probe as the clot of blood increases in strength. The rotation amplitude of the probe is in inverse relation to the strength of blood clots, the dynamic change of the probe motion is detected and recorded by an optical displacement sensor, and finally a computer generates a thrombelastogram and a series of detection indexes.
(3) Platelet function analyzer from Sienco USA (Sonoclot)
The Sonoclot working principle is as follows: the disposable hollow probe connected with the ultrasonic sensor is immersed in a sample (0.4 ml of blood or plasma) to be detected in the measuring cup to a certain depth, vertically oscillates at the amplitude of 1 mu m and the frequency of 200Hz, generates certain resistance to the free vibration of the probe due to the viscoelasticity of the sample, gradually increases the resistance of blood clots to the probe along with the blood coagulation, and resistance signals of the probe are obtained by a data acquisition system and displayed in a hemagglutination curve (Sonoclotigniture) mode to reflect the viscoelasticity change in the whole process of blood coagulation.
At present, the most widely used principle of thromboelastography is the principle of suspension wires, and the structure is shown in figure 1. The principle is as follows:
(1) The sample cup is connected with the motor through a transmission mechanism; the sample cover is fixedly connected with the probe, the probe is fixedly connected with the fan-shaped magnetic conduction sheet, and the probe is fixedly connected with the lower end of the thin steel wire; the upper end of the thin steel wire is fixedly connected with the frame; the coil circuit board is fixedly connected with the frame.
(2) Step motor with + -rotational speed (omega) 1 ) The sample cup is driven to rotate left and right through a transmission mechanism at a small angle.
(3) The sample cup drives the sample to rotate at a positive or negative rotation speed (omega) 2 ) Small angle left and right rotation, the more blood coagulates, omega 1 And omega 2 The closer together.
(4) The sample drives the sample cover to rotate at +/-speed (omega) 3 ) Small angle left and right rotation, the more blood coagulates, omega 2 And omega 3 The closer together;
(5) The sample cover, the fan-shaped magnetic conductive sheet and the probe rotate at +/-rotation speed (omega) 3 ) The thin steel wire is twisted by rotating left and right at a small angle. When the torsional elasticity of the thin steel wire is equal to the viscous force of the sample, the sample cover reaches the maximum rotation angle. Therefore, the rotation angle of the sample cover is positively correlated with the solidification degree of the sample;
(6) The coil circuit board is provided with a coil which comprises an excitation coil and a feedback coil. A sine excitation signal is input into the excitation coil, and a sine feedback signal is induced in the feedback coil through the magnetic conduction of the fan-shaped magnetic conduction sheet. When the relative positions of the fan-shaped magnetic conductive sheet and the coil circuit board are different, the amplitudes of the induced feedback signals are different. Therefore, the rotating angle of the fan-shaped magnetic conducting sheet can be judged according to the amplitude of the feedback signal. This angle is directly related to the degree of coagulation of the sample.
During testing, the sample cup is placed in the sample cup bracket, the blood sample to be tested and the corresponding reagent are added manually through the liquid transfer gun, the sample cup bracket is moved to the upper part to be contacted with the probe, and the test is started. After the test is completed, the sample cup holder is manually moved to the bottom and the sample cup is removed.
The classical thrombelastogram instrument has complex operation process, and the manual sample adding in the test process easily causes inaccurate liquid adding amount and easily introduces various factors which interfere with the experimental precision. A single test channel can only test one index at a time, and the flux is low.
Disclosure of Invention
In order to solve the technical problems of complex operation process, inaccurate liquid adding amount and the existence of factors interfering with experiment precision of the thromboelastogram detection in the prior art, one embodiment of the invention provides a micro-fluidic chip for multi-channel thromboelastogram detection, which comprises: the substrate is bonded with the front side sealing film and the rear side sealing film on two sides of the substrate;
the matrix comprises a plurality of cavity units and a plurality of corresponding measuring chambers, each cavity unit comprises a quantifying chamber, a mixing chamber and an exhaust chamber, the quantifying chamber is positioned above the mixing chamber, and the exhaust chamber is positioned on one side of the quantifying chamber and the mixing chamber;
the mixing chambers of the chamber units are communicated to the corresponding measuring chambers through measuring channels, wherein the mixing chambers and the measuring channels are communicated or cut off through measuring micro valves; the exhaust chambers are provided with vent holes, and the vent holes are communicated or cut off with the external atmosphere through exhaust micro valves;
the device comprises a substrate, a sample injection needle, an air inlet needle, a first channel, a second channel and a micro-valve, wherein the sample injection needle and the air inlet needle are arranged on one side of the substrate, the bottom of the substrate is provided with the first channel and the second channel, and the first channel and the second channel are communicated or cut off through the sample injection micro-valve;
a waste liquid cavity is arranged on one side of the substrate, which is close to the sample injection needle and the gas inlet needle, a gas path interface is arranged on the surface of the waste liquid cavity, and the quantitative chambers of the plurality of chamber units are sequentially communicated and communicated to the waste liquid cavity;
at least one reagent chamber is arranged on the measuring channel corresponding to each mixing chamber, and freeze-drying reagents are preset in the reagent chambers.
In a preferred embodiment, the inner surface of the waste liquid cavity is provided with an air channel, and the air channel extends to the top of the waste liquid cavity and forms a gap with the top of the waste liquid cavity;
the air channel interface is communicated with the bottom of the air channel.
In a preferred embodiment, the plurality of chamber units includes a first chamber unit, a second chamber unit, and a third chamber unit;
the first chamber unit comprises a first dosing chamber, a first mixing chamber and a first venting chamber; the second chamber unit comprises a second quantitative chamber, a second mixing chamber and a second exhaust chamber; the third chamber unit comprises a third quantitative chamber, a third mixing chamber and a third exhaust chamber;
the first dosing chamber is connected to the waste chamber.
In a preferred embodiment, a sample feeding infrared detection point is arranged on the first channel;
and the surface of the waste liquid cavity is provided with a waste liquid infrared detection point, and the quantitative chambers of the plurality of chamber units are sequentially communicated with each other, communicated to the waste liquid infrared detection point and further communicated to the waste liquid cavity.
In a preferred embodiment, the measurement micro valve and the injection micro valve have the same structure, and comprise:
the first valve core is positioned on the inner side of the front side sealing film, a first cavity is formed between the front side sealing film and the first valve core, and the first cavity is communicated with the first flow passage and the second flow passage.
In a preferred embodiment, the exhaust microvalve includes:
and the second valve core is positioned on the inner side of the front side sealing film, a second cavity is formed between the front side sealing film and the second valve core, and the second cavity is communicated with a fourth flow channel of the third flow channel.
In a preferred embodiment, the microfluidic chip further comprises a top cover plate, a plurality of spin caps and a protective shell,
a plurality of the rotating caps are respectively arranged in the corresponding measuring chambers, the top cover plate covers the top of the base body, and the sample injection needle and the air inlet needle are arranged in the protective shell.
Another embodiment of the present invention provides a multi-channel thromboelastogram detecting device, including: the multi-channel thrombus elastogram detection device comprises a bottom plate, a rear vertical plate, a front pressing plate and a rear pressing plate, wherein a micro-fluidic chip for detecting a multi-channel thrombus elastogram is arranged between the front pressing plate and the rear pressing plate;
the rear vertical plate is provided with a plurality of probe modules for detecting a thrombus elastogram of a sample in the microfluidic chip for multi-channel thrombus elastogram detection;
the front pressure plate is provided with a plurality of micro valve driving modules for driving the conduction or the cut-off of a measurement micro valve, an exhaust micro valve and a sample injection micro valve of a micro-fluidic chip for multi-channel thrombus elastogram detection;
the air faucet swing mechanism is characterized in that an air channel interface module is arranged on the front pressing plate and comprises an air faucet swing rod, one end of the air faucet swing rod is hinged to the front pressing plate, the other end of the air faucet swing rod is provided with a driving assembly, and the driving assembly drives the air faucet swing rod to swing in a reciprocating mode;
and the air nozzle swing rod is provided with an air nozzle which corresponds to an air path interface of the micro-fluidic chip for multi-channel thrombus elastogram detection.
In a preferred embodiment, the driving assembly comprises a driving motor, a cam and a return spring, wherein the driving motor and the cam are arranged on the front side of the air nozzle swing rod;
and the reset spring is arranged at the rear side of the air faucet swing rod and is positioned between the air faucet swing rod and the front pressing plate.
In a preferred embodiment, the air tap is connected with a right-angled elbow, and the right-angled elbow is used for connecting an external air source.
The technical scheme provided by the embodiment of the invention has the beneficial effects that at least:
the invention provides a micro-fluidic chip and a detection device for multi-channel thromboelastogram detection.
The invention provides a micro-fluidic chip for multi-channel thromboelastogram detection and a detection device. The multiple measuring chambers can ensure that the volumes of the blood samples participating in the test in each measuring chamber are completely consistent through the quantification in the microfluidic chip. The reagent is preset in the chip in the production process of the microfluidic chip, and a user does not need to add the reagent manually in the test process, so that the influence of nonstandard operation on the test precision is avoided.
The invention provides a micro-fluidic chip for multi-channel thromboelastogram detection and a detection device, wherein only one air path interface is provided, a hole can be pressurized and vacuumized, complex fluid control is realized through two gas driving modes of vacuum and pressure, the sealing difficulty of the micro-fluidic chip and the detection device is reduced, and the air leakage risk in the matching process of the micro-fluidic chip and the detection device is reduced.
The invention provides a micro-fluidic chip for multi-channel thromboelastogram detection and a detection device. For the micro-fluidic chips with different numbers of measuring chambers, only the probe module and the micro-valve driving module need to be increased or reduced according to the number of the measuring chambers of the micro-fluidic chip. The micro-fluidic chip module can be compatible with micro-fluidic chips with different numbers of measuring chambers, and the probe module and the micro-valve driving module can be configured into corresponding working states or non-working states through software during measurement.
Drawings
In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the drawings needed to be used in the description of the embodiments will be briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is obvious for those skilled in the art to obtain other drawings based on these drawings without creative efforts.
FIG. 1 is a schematic diagram of a prior art suspension wire for thromboelastogram detection;
fig. 2 is a front side view exploded view of a microfluidic chip for multi-channel thromboelastography detection in accordance with an embodiment of the present invention.
Figure 3 is a rear side view exploded view of a microfluidic chip for multi-channel thromboelastography detection in accordance with an embodiment of the present invention.
FIG. 4 is a schematic rear side view of a microfluidic chip for multi-channel thromboelastography detection according to an embodiment of the present invention.
FIG. 5 is a schematic front side view cross-sectional view of a microfluidic chip for multi-channel thromboelastography detection in an embodiment of the invention.
FIG. 6 is a schematic diagram of a sample injection microvalve according to one embodiment of the present invention.
FIG. 7 is a schematic representation of the structure of a first exhaust microvalve in accordance with one embodiment of the present invention.
FIG. 8 is a schematic structural diagram of a multi-channel thromboelastography detection device in an embodiment of the invention.
FIG. 9 is a schematic diagram of a probe module according to an embodiment of the present invention.
Fig. 10 is a schematic structural diagram of a microvalve driving module according to an embodiment of the present invention.
Fig. 11 is a schematic diagram of different operating states of a microvalve driver module in accordance with an embodiment of the present invention.
FIG. 12 is a schematic diagram of the disconnection of the air path interface module according to an embodiment of the invention.
FIG. 13 is a schematic view of the closing of the air path interface module in accordance with an embodiment of the present invention.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The terms "first," "second," "third," "fourth," and the like in the description and in the claims, as well as in the drawings, if any, are used for distinguishing between similar elements and not necessarily for describing a particular sequential or chronological order. It is to be understood that the data so used is interchangeable under appropriate circumstances such that the embodiments of the invention described herein are, for example, capable of operation in sequences other than those illustrated or otherwise described herein. Furthermore, the terms "comprises," "comprising," and "having," and any variations thereof, are intended to cover a non-exclusive inclusion, such that a process, method, system, article, or apparatus that comprises a list of steps or elements is not necessarily limited to those steps or elements expressly listed, but may include other steps or elements not expressly listed or inherent to such process, method, article, or apparatus.
Fig. 2 is a front side view angle explosion diagram of a multi-channel thrombelastogram detection microfluidic chip according to an embodiment of the present invention, fig. 3 is a rear side view angle explosion diagram of a multi-channel thrombelastogram detection microfluidic chip according to an embodiment of the present invention, fig. 4 is a rear side view angle cross-sectional diagram of a multi-channel thrombelastogram detection microfluidic chip according to an embodiment of the present invention, and fig. 5 is a front side view angle cross-sectional diagram of a multi-channel thrombelastogram detection microfluidic chip according to an embodiment of the present invention.
According to an embodiment of the present invention, there is provided a microfluidic chip for multichannel thromboelastography detection, including: the rotary cap comprises a top cover plate 1, a plurality of rotary caps 2, a base body 3, a protective shell 7, a front side sealing film 5 and a rear side sealing film 6 which are bonded on two sides of the base body 3.
The substrate 3 comprises a plurality of chamber units of an array and a corresponding plurality of measurement chambers. The plurality of rotating caps 2 are respectively arranged in the corresponding measuring chambers, and the top cover plate 1 covers the top of the base body 3.
According to an embodiment of the present invention, each chamber unit includes a quantitative chamber located above the mixing chamber, a mixing chamber located at one side of the quantitative chamber and the mixing chamber, and an exhaust chamber communicating with the mixing chamber.
In a specific embodiment, taking three chamber units and three measuring chambers as an example, the plurality of chamber units include a first chamber unit, a second chamber unit and a third chamber unit. The first chamber unit comprises a first dosing chamber 305, a first mixing chamber 306 and a first exhaust chamber 304; the second chamber unit comprises a second quantitative chamber 308, a second mixing chamber 309 and a second exhaust chamber 307; the third chamber unit includes a third quantitative chamber 311, a third mixing chamber 312, and a third exhaust chamber 310.
The first dosing chamber 305 communicates with a first mixing chamber 306, the second dosing chamber 308 communicates with a second mixing chamber 309, and the third dosing chamber 311 communicates with a third mixing chamber 312. Different lyophilized reagents are preset in the first mixing chamber 306, the second mixing chamber 309 and the third mixing chamber 312, and magnetic beads are preset in the first mixing chamber 306, the second mixing chamber 309 and the third mixing chamber 312.
The mixing chambers of the plurality of chamber units are connected to the corresponding measuring chambers through measuring channels, and in a specific embodiment, the plurality of measuring chambers includes a first measuring chamber 313, a second measuring chamber 316, and a third measuring chamber 319. The first mixing chamber 306 is connected to the corresponding first measuring chamber 313 via a first measuring channel 336, the second mixing chamber 309 is connected to the corresponding second measuring chamber 316 via a second measuring channel 337, and the third mixing chamber 312 is connected to the corresponding third measuring chamber 319 via a third measuring channel 338.
According to the embodiment of the invention, the plurality of measuring chambers are provided with a vertical surface above, and the measuring channel is communicated to the measuring chambers through the vertical surface above the measuring chambers. As shown in fig. 2, taking the first measurement chamber 313 as an example, a vertical surface 3131 is disposed above the first measurement chamber 313, and the first measurement channel 336 is connected to the vertical surface 3131 and further connected to the first measurement chamber 313. By forming a vertical plane above the plurality of measurement chambers, the thickness of the microfluidic chip is greatly reduced.
According to an embodiment of the invention, the mixing chamber and the measurement channel are opened or closed by a measurement microvalve. In a particular embodiment, the metering microvalves include a first metering microvalve 324, a second metering microvalve 326, and a third metering microvalve 328. The first mixing chamber 306 and the first measuring channel 336 are switched on or off by means of a first measuring microvalve 324, the second mixing chamber 309 and the second measuring channel 337 are switched on or off by means of a second measuring microvalve 326, and the third mixing chamber 312 and the third measuring channel 338 are switched on or off by means of a third measuring microvalve 328.
According to the embodiment of the invention, at least one reagent chamber is arranged on the measuring channel corresponding to each mixing chamber, and freeze-drying reagents are preset in the reagent chambers. In a specific embodiment, a first reagent chamber 314 and a second reagent chamber 315 are arranged on the first measurement channel 336, a third reagent chamber 317 and a fourth reagent chamber 318 are arranged on the second measurement channel 337, and a fifth reagent chamber 320 and a sixth reagent chamber 321 are arranged on the third measurement channel 338. Different lyophilized reagents are preset in the first and second reagent chambers 314 and 315, the third and fourth reagent chambers 317 and 318, and the fifth and sixth reagent chambers 320 and 321, respectively.
According to the embodiment of the invention, the vent holes are formed in the exhaust chambers, and the vent holes are communicated with the external atmosphere or cut off through the exhaust micro valves. In a specific embodiment, the first exhaust chamber 304 is provided with a first ventilation hole 339, the second exhaust chamber 307 is provided with a second ventilation hole 340, and the third exhaust chamber 310 is provided with a third ventilation hole 341. The first venting hole 339 is controlled to be communicated or cut off with the external atmosphere through the first venting micro valve 323, the second venting hole 340 is controlled to be communicated or cut off with the external atmosphere through the second venting micro valve 325, and the third venting hole 341 is controlled to be communicated or cut off with the external atmosphere through the third venting micro valve 327.
According to the embodiment of the invention, one side of the base body 3 is provided with the sample injection needle 8 and the air inlet needle 9, and the sample injection needle 8 and the air inlet needle 9 are arranged in the protective shell 7. The bottom of the substrate 3 has a first channel 334 and a second channel 335, and the first channel 334 and the second channel 335 are connected or disconnected by the sample inlet micro valve 322.
When a test is required, the blood collection tube 10 is inserted into the protective case 7, and the sample injection needle 8 and the air inlet needle 9 are inserted into the blood collection tube 10 through the sealing film of the blood collection tube 10 to sample. The sample injection needle 8 is communicated with the first channel 334 and is responsible for extracting a blood sample from the blood sampling tube 10, and the air inlet needle 9 is communicated with the external atmosphere, so that the vacuum degree generated in the blood sampling tube when the blood sample is extracted is avoided.
According to the embodiment of the present invention, a waste liquid chamber 333 is provided at a side of the base body 3 near the injection needle 8 and the gas inlet needle 9 (the shield case 7). The surface of the waste liquid cavity 333 is provided with a gas path interface 301, and the quantitative chambers of the plurality of chamber units are communicated in sequence and communicated to the waste liquid cavity 333. In a specific embodiment, the first dosing chamber 305 communicates with the second dosing chamber 308 via a third channel 342, the second dosing chamber 308 communicates with the third dosing chamber 311 via a fourth channel 343, the third dosing chamber 311 communicates with the second channel 335 via a sixth channel 344, and the first dosing chamber 305 communicates with the waste reservoir 333.
According to an embodiment of the present invention, the waste liquid chamber 333 has a gas path channel on an inner surface thereof, which extends to the top of the waste liquid chamber 333 and forms a gap with the top of the waste liquid chamber 333. The air channel interface 301 is communicated with the bottom of the air channel. When the sample enters the waste liquid cavity 333 from the first quantitative chamber 305, the gas path interface 301 is ensured not to be blocked by the sample entering the waste liquid cavity 333 because the path channel extends to the top of the waste liquid cavity 333.
According to the embodiment of the invention, the first channel 334 is provided with the sample feeding infrared detection point 302, and the surface of the waste liquid cavity 333 is provided with the waste liquid infrared detection point 303.
The quantitative chambers of the plurality of chamber units are communicated in sequence, communicated to the waste liquid infrared detection point 303 and further communicated to the waste liquid cavity 333. In one embodiment, the first dosing chamber 305 is connected to the waste infrared detection point 303 and further to the waste chamber 333.
According to the embodiment of the present invention, the measurement micro valves (the first measurement micro valve 324, the second measurement micro valve 326, and the third measurement micro valve 328) are the same as the injection micro valve 322, and the injection micro valve 322 is exemplified in the embodiment. As shown in fig. 6, a schematic structural diagram of a sample injection micro valve in an embodiment of the present invention, the sample injection micro valve 322 includes: the first valve core 4 is positioned inside the front side sealing film 5, a first cavity 11 is formed between the front side sealing film 5 and the first valve core 4, and the first cavity 11 is communicated with the first flow passage 329 and the second flow passage 330. The first flow passage 329 communicates with the first passage 334, and the second flow passage 330 communicates with the second passage 335.
When it is desired to communicate the first channel 334 and the second channel 335, the microvalve plunger 1604 outside the front sealing film 5 is not actuated, and the first flow channel 329 and the second flow channel 330 are communicated through the first cavity 11, thereby communicating the first channel 334 and the second channel 335 (shown in fig. 6 (a)).
When it is necessary to block the first channel 334 and the second channel 335, the front side sealing film 5 is driven by the outside of the front side sealing film 5 through the micro valve push rod 1604 to press the front side sealing film 5 into the first cavity 11, and the first flow channel 329 and the second flow channel 330 are blocked by the front side sealing film 5, thereby blocking the first channel 334 and the second channel 335 (shown in fig. 6 (b)).
The first measurement micro valve 324, the second measurement micro valve 326, and the third measurement micro valve 328 have the same structure as the sample injection micro valve 322, and the principle of controlling the connection and disconnection is the same as the sample injection micro valve 322, which is not described herein again.
According to the embodiment of the present invention, the plurality of exhaust chambers are controlled to be opened or closed to the external atmosphere by the exhaust micro valves, and the first exhaust micro valve 323, the second exhaust micro valve 325 and the third exhaust micro valve 327 have the same structure, and the first exhaust micro valve 323 is exemplified in the embodiment for explanation. Fig. 7 is a schematic diagram showing the structure of a first exhaust micro valve in an embodiment of the present invention, and a first exhaust micro valve 323 includes: and a second cavity 11' is formed between the front side sealing film 5 and the second valve core 4' and is communicated with the third flow passage 331 and the fourth flow passage 332 by the second valve core 4' positioned inside the front side sealing film 5. The third flow passage 331 communicates with the outside atmosphere, and the fourth flow passage 332 communicates with the first venting hole 339 of the first venting chamber 304.
When it is necessary to communicate the first exhaust chamber 304 with the external atmosphere, the microvalve plunger 1604 outside the front sealing film 5 does not operate, and the third flow channel 331 and the fourth flow channel 332 communicate with each other through the second cavity 11', so that the first exhaust chamber 304 and the external atmosphere communicate with each other (fig. 7 (c)).
When it is necessary to block the first exhaust chamber 304 from the external atmosphere, the outside of the front sealing film 5 drives the front sealing film 5 to press into the second cavity 11' through the micro valve lift rod 1604, and the third flow channel 331 and the fourth flow channel 332 are blocked by the front sealing film 5, so as to block the first exhaust chamber 304 from the external atmosphere (shown in fig. 6 (d)).
The second exhaust micro valve 325 and the third exhaust micro valve 327 have the same structure as the first exhaust micro valve 323, and the principle of controlling the opening and closing is the same as the first exhaust micro valve 323, which is not described herein again.
In a preferred embodiment, the matrix 3 material includes but is not limited to PC, ABS, PMMA, PP.
In a preferred embodiment, the front and back side seal film 5, 6 materials include but are not limited to PC, ABS, PMMA, PP, PET. The front side sealing film 5 and the rear side sealing film 6 have certain toughness and can be slightly deformed.
In a preferred embodiment, the material of the first valve spool 4 and the second valve spool 4' includes, but is not limited to, silicone.
In a preferred embodiment, the front and back side sealing films 5 and 6 are bonded to the substrate 3 by a bonding process including, but not limited to, heat pressing, adhesive bonding, ultrasonic welding, laser welding.
Fig. 8 is a schematic structural diagram of a multi-channel thromboelastogram detection apparatus according to an embodiment of the present invention, fig. 9 is a schematic structural diagram of a probe module according to an embodiment of the present invention, fig. 10 is a schematic structural diagram of a micro-valve driving module according to an embodiment of the present invention, fig. 11 is a schematic structural diagram of different operating states of a micro-valve driving module according to an embodiment of the present invention, fig. 12 is a schematic structural diagram of an open air circuit interface module according to an embodiment of the present invention, fig. 13 is a schematic structural diagram of a closed air circuit interface module according to an embodiment of the present invention, and with reference to fig. 8 to 13, according to an embodiment of the present invention, a multi-channel thromboelastogram detection apparatus is provided, which includes: bottom plate 12, back riser 13, preceding clamp plate 18 and back clamp plate 19.
The microfluidic chip for multi-channel thromboelastogram detection provided by the invention is arranged between the front pressing plate 18 and the rear pressing plate 19 to perform thromboelastogram detection.
And a plurality of probe modules 15 are arranged on the rear vertical plate 13 and used for carrying out thrombus elastogram detection on a sample in the microfluidic chip for multi-channel thrombus elastogram detection. When the micro-fluidic chip for multi-channel thromboelastogram detection is inserted between the front pressing plate 18 and the rear pressing plate 19, the plurality of probe modules 15 correspond to the plurality of rotating caps 2, in this embodiment, the plurality of probe modules 15 and the plurality of rotating caps 2, and probes of the plurality of probe modules 15 are respectively inserted into the corresponding rotating caps 2 to perform thromboelastogram detection. In the embodiment, the plurality of probe modules 15 are controlled to move vertically up and down by the probe moving module 14, so that the probes of the plurality of probe modules 15 are respectively inserted into the corresponding rotating caps 2.
As shown in fig. 9, the probe module 15 includes a slider 1501, a wire spring 1502, a probe 1503, a laser emitter 1504, a plane mirror 1505, and a photometric circuit board 1506.
The slider 1501 in the probe module 15 drives the wire spring 1502 to make the probe 1503 swing, the laser transmitter 1504 transmits a laser beam to the plane mirror 1505, and the reflected laser beam is reflected to the photometric circuit board 1506. By detecting the spot position at 1506, the swing angle of the probe 1503 can be determined.
The probe module 15 inserts the probe 1503 into the rotating cap 2 of the microfluidic chip for multi-channel thromboelastogram detection through vertical movement, and enables the rotating cap 2 to swing with the probe 1503 at a fixed amplitude and frequency through interference fit between the two (the rotating cap 2 and the probe 1503 do not move relatively).
When measuring the viscoelasticity of blood, the base body 3 is kept fixed, and the rotary cap 2 is swung with the probe 1503. When the blood viscoelasticity is small, the probe 1503 swings large, the wire spring 1502 deforms small, and the light spot swings large. When the blood viscoelasticity is large, the swing of the probe 1503 is small, the wire spring 1502 becomes large, and the swing of the light spot is small. Therefore, the blood viscoelasticity is judged according to the light spot amplitude, and a thromboelastogram curve is drawn.
According to the embodiment of the invention, a plurality of micro valve driving modules 16 are arranged on the front pressure plate 18, and are used for conducting or cutting off a measurement micro valve, an exhaust micro valve and a sample injection micro valve of a micro-fluidic chip for multi-channel thromboelastogram detection. When the micro-fluidic chip for multi-channel thromboelastogram detection is inserted between the front platen 18 and the rear platen 19, the plurality of micro-valve driving modules 16 correspond to the measurement micro-valves, the exhaust micro-valves and the sample injection micro-valves, in this embodiment, 7 micro-valve driving modules 16 correspond to the first measurement micro-valve 324, the second measurement micro-valve 326, the third measurement micro-valve 328, the first exhaust micro-valve 323, the second exhaust micro-valve 325, the third exhaust micro-valve 327 and the sample injection micro-valve 322, respectively.
As shown in fig. 10 and 11, the micro valve driving module 16 includes a stepping motor 1601, a cam member 1602, a spring 1603, a micro valve post 1604, a return spring 1605, and a cam rocker 1606.
When the stepping motor 1601 is rotated to rotate the cam member 1602, and the cam rocker 1606 is located above, the return spring 1605 presses the microvalve plunger 1604 and the elastic sheet 1603, and the microvalve plunger 1604 retracts into the front platen 18 (see (e) in fig. 11).
When the stepping motor 1601 is rotated to drive the cam member 1602 to rotate and the cam rocker 1606 is located below, the cam rocker 1606 presses the elastic piece 1603, the elastic piece 1603 presses the micro valve post 1604, and the micro valve post 1604 pushes out of the front pressure plate 18, thereby driving the micro valve (fig. 11 (f)).
According to the embodiment of the invention, the air path interface module 17 is arranged on the front pressing plate 18, and the air path interface module 17 is positioned on one side of the micro-fluidic chip for detecting the multi-channel thrombus elastogram, which is close to the sample injection needle 8 and the air inlet needle 9 (the protective shell 7). When the micro-fluidic chip for multi-channel thromboelastogram detection is inserted between the front pressing plate 18 and the rear pressing plate 19, the air path interface module 17 corresponds to the air path interface 301.
As shown in fig. 12 and 13, the air channel interface module 17 includes an air faucet swing link 1703, one end of the air faucet swing link 1703 is hinged to the front pressing plate 18, and the other end of the air faucet swing link 1703 is provided with a driving assembly. The driving assembly drives the air tap swing rod 1703 to swing back and forth.
The driving assembly includes a driving motor 1701, a cam 1702, and a return spring 1704, and the driving motor 1701 and the cam 1702 are disposed at a front side of the air faucet swing lever 1703. Return spring 1704 is disposed on the rear side of air nozzle swing lever 1703 between air nozzle swing lever 1703 and front platen 18. An air nozzle 1706 is arranged on the air nozzle swing rod 1703, and the air nozzle 1706 corresponds to the air path interface 301 of the micro-fluidic chip for multi-channel thrombus elastogram detection.
In a preferred embodiment, air nozzle 1706 is connected to elbow 1705, and elbow 1705 is used to connect to an external air source, which creates a vacuum or pressure.
In a preferred embodiment, the air nozzles 1706 are a soft material, including but not limited to silicone, nitrile rubber, and viton.
The air path interface module 17 controls the driving motor 1701 to drive the air nozzle swing rod 1703 to swing, so that the air nozzle 1706 is disconnected or closed with the air path interface 301 of the micro-fluidic chip for multi-channel thrombus elastogram detection.
Specifically, when the driving motor 1701 is rotated to position the cam 1702 at the front side, the return spring 1704 pushes the nozzle swing link 1703, the nozzle swing link 1703 drives the nozzle 1706 and the quarter bend 1705 to return, so that the nozzle 1706 retracts into the front platen 18, and the nozzle 1706 is disconnected from the air passage interface 301 (shown in fig. 12).
When the driving motor 1701 is rotated to make the cam 1702 located at the rear side, the cam 1702 extrudes the air tap swing rod 1703, the air tap swing rod 1703 drives the air tap 1706 and the quarter bend 1705 to move towards the rear side, so that the air tap 1706 is tightly attached to the front side sealing film 5 of the micro-fluidic chip and generates a certain deformation, the air tap 1706 is closed with the air path interface 301, and the air tap 1706 is communicated with the air path inside the micro-fluidic chip through the air path interface 301 (shown in fig. 13).
The following describes the process of the thromboelastogram test of the invention.
(1) A sample is withdrawn.
The sample injection micro valve 322 is conducted, and the other micro valves are closed. The air channel interface 301 is evacuated to draw the sample from the blood collection tube 10 into the third quantitative chamber 311, the second quantitative chamber 308, and the first quantitative chamber 305 in this order. When the waste liquid infrared detection point 303 detects that the sample has flowed, it indicates that the third quantitative chamber 311, the second quantitative chamber 308, and the first quantitative chamber 305 are filled with the sample, and the evacuation is stopped.
(2) The sample is mixed with the reagent.
The third exhaust microvalve 327 is open and the remaining microvalves are closed. The air interface 301 pressurizes the sample from the third metering chamber 311 into the third mixing chamber 312. Due to the other microvalves being closed, the sample of the first and second dosing chambers 305, 308 does not enter the first and second mixing chambers 306, 309. The freeze-dried reagent and the magnetic beads preset in the third mixing chamber 312 are reciprocated by the permanent magnet outside the chip to achieve uniform mixing of the reagent and the sample.
The second exhaust microvalve 325 is open and the remaining microvalves are closed. The air interface 301 pressurizes the sample from the second metering chamber 308 to the second mixing chamber 309. With the other microvalves closed, the sample in the first dosing chamber 305 does not enter the first mixing chamber 306. The lyophilized reagent and the magnetic beads preset in the second mixing chamber 309 reciprocate through a permanent magnet outside the chip to realize uniform mixing of the reagent and the sample.
The first exhaust microvalve 323 is open and the remaining microvalves are closed. The air interface 301 pressurizes the sample from the first dosing chamber 305 to the first mixing chamber 306. The freeze-dried reagent and the magnetic beads preset in the first mixing chamber 306 reciprocate through the permanent magnet outside the chip to realize the uniform mixing of the reagent and the sample.
(3) The mixed sample enters a measuring chamber for measurement.
The third measurement microvalve 328 is open and the remaining microvalves are closed. The air interface 301 pressurizes the sample from the third mixing chamber 312 to the third measurement chamber 319. In the process, the sample passes through the fifth reagent chamber 320 and the sixth reagent chamber 321 in sequence, and the lyophilized reagents in the fifth reagent chamber 320 and the sixth reagent chamber 321 are dissolved. With the other microvalves closed, the samples of the first mixing chamber 306 and the second mixing chamber 309 do not enter the first measurement chamber 313 and the second measurement chamber 316.
The second measuring microvalve 326 is open and the remaining microvalves are closed. The air interface 301 pressurizes the sample from the second mixing chamber 309 to the second measurement chamber 316. In the process, the sample passes through the third reagent chamber 317 and the fourth reagent chamber 318 in sequence, and the lyophilized reagents in the third reagent chamber 317 and the fourth reagent chamber 318 are dissolved. The sample of the first mixing chamber 306 does not enter the first measurement chamber 313 because the other microvalves are closed.
The first measuring microvalve 324 is open and the remaining microvalves are closed. The gas circuit interface 301 pressurizes the sample from the first mixing chamber 306 to the first measurement chamber 313. In the process, the sample passes through the first reagent chamber 314 and the second reagent chamber 315 in sequence, and the lyophilized reagents in the first reagent chamber 314 and the second reagent chamber 315 are dissolved.
(4) The thromboelastogram was measured.
After all the blood samples enter the measurement chamber, the probe 1503 of the probe module 15 of the multi-channel thromboelastogram detection apparatus is inserted into the spin cap 2, and the thromboelastogram test is started.
Finally, it should be noted that: the above embodiments are only used to illustrate the technical solution of the present invention, and not to limit the same; while the invention has been described in detail and with reference to the foregoing embodiments, it will be understood by those skilled in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some or all of the technical features may be equivalently replaced; and the modifications or the substitutions do not make the essence of the corresponding technical solutions depart from the scope of the technical solutions of the embodiments of the present invention.

Claims (10)

1. A microfluidic chip for multi-channel thromboelastography detection, the microfluidic chip comprising: the substrate is bonded with the front side sealing film and the rear side sealing film on two sides of the substrate;
the substrate comprises a plurality of cavity units and a plurality of corresponding measuring chambers, each cavity unit comprises a quantifying chamber, a mixing chamber and an exhaust chamber, the quantifying chamber is positioned above the mixing chamber, and the exhaust chamber is positioned on one side of the quantifying chamber and one side of the mixing chamber;
the mixing chambers of the chamber units are communicated to the corresponding measuring chambers through measuring channels, wherein the mixing chambers and the measuring channels are communicated or cut off through measuring micro valves; the exhaust chambers are provided with vent holes, and the vent holes are communicated or cut off with the external atmosphere through exhaust micro valves;
the device comprises a substrate, a sample injection needle, an air inlet needle, a first channel, a second channel and a micro-valve, wherein the sample injection needle and the air inlet needle are arranged on one side of the substrate, the bottom of the substrate is provided with the first channel and the second channel, and the first channel and the second channel are communicated or cut off through the sample injection micro-valve;
the quantitative cavity comprises a substrate, a sample injection needle, an air inlet needle, a plurality of cavity units and a plurality of gas path interfaces, wherein a waste liquid cavity is arranged on one side of the substrate, which is close to the sample injection needle and the air inlet needle, a gas path interface is arranged on the surface of the waste liquid cavity, and the quantitative cavities of the cavity units are sequentially communicated and communicated to the waste liquid cavity;
at least one reagent chamber is arranged on the measuring channel corresponding to each mixing chamber, and freeze-drying reagents are preset in the reagent chambers.
2. The microfluidic chip for multichannel thromboelastography detection according to claim 1, wherein an air channel is formed on the inner surface of the waste liquid cavity, extends to the top of the waste liquid cavity and forms a gap with the top of the waste liquid cavity;
the air channel interface is communicated with the bottom of the air channel.
3. The microfluidic chip for multichannel thromboelastography detection according to claim 1, wherein the plurality of chamber units comprise a first chamber unit, a second chamber unit and a third chamber unit;
the first chamber unit comprises a first dosing chamber, a first mixing chamber and a first venting chamber; the second chamber unit comprises a second quantifying chamber, a second mixing chamber and a second exhaust chamber; the third chamber unit comprises a third quantitative chamber, a third mixing chamber and a third exhaust chamber;
the first dosing chamber is connected to the waste chamber.
4. The microfluidic chip for multi-channel thromboelastography detection according to claim 1, wherein a sample injection infrared detection point is arranged on the first channel;
the surface of the waste liquid cavity is provided with a waste liquid infrared detection point, and the quantitative chambers of the plurality of chamber units are sequentially communicated and communicated to the waste liquid infrared detection point and further communicated to the waste liquid cavity.
5. The microfluidic chip for multi-channel thromboelastogram detection according to claim 1, wherein the measurement micro valve and the sample injection micro valve have the same structure, and comprise:
the first valve core is positioned on the inner side of the front side sealing film, a first cavity is formed between the front side sealing film and the first valve core, and the first cavity is communicated with the first flow passage and the second flow passage.
6. The microfluidic chip for multichannel thromboelastography detection according to claim 1, wherein the exhaust microvalve comprises:
and the second valve core is positioned on the inner side of the front side sealing film, a second cavity is formed between the front side sealing film and the second valve core, and the second cavity is communicated with a fourth flow channel of the third flow channel.
7. The microfluidic chip for multichannel thromboelastography detection according to claim 1, wherein the microfluidic chip further comprises a top cover plate, a plurality of spin caps and a protective shell,
a plurality of the rotating caps are respectively arranged in the corresponding measuring chambers, the top cover plate covers the top of the base body, and the sample injection needle and the air inlet needle are arranged in the protective shell.
8. A multi-channel thromboelastogram test device, the test device comprising: the multi-channel thrombus elastogram detection device comprises a bottom plate, a rear vertical plate, a front pressure plate and a rear pressure plate, wherein a micro-fluidic chip for detecting the multi-channel thrombus elastogram as claimed in any one of claims 1 to 7 is arranged between the front pressure plate and the rear pressure plate;
a plurality of probe modules are arranged on the rear vertical plate and used for carrying out thromboelastogram detection on a sample in the microfluidic chip for multi-channel thromboelastogram detection according to any one of claims 1 to 7;
the front pressure plate is provided with a plurality of micro valve driving modules for driving the conduction or the disconnection of a measurement micro valve, an exhaust micro valve and a sample injection micro valve of the micro-fluidic chip for the multi-channel thromboelastogram detection of any one of claims 1 to 7;
the air faucet swing mechanism is characterized in that an air channel interface module is arranged on the front pressing plate and comprises an air faucet swing rod, one end of the air faucet swing rod is hinged to the front pressing plate, the other end of the air faucet swing rod is provided with a driving assembly, and the driving assembly drives the air faucet swing rod to swing in a reciprocating mode;
the air tap is arranged on the air tap swing rod and corresponds to an air path interface of a micro-fluidic chip for multi-channel thromboelastogram detection in any one of claims 1 to 6.
9. The multi-channel thromboelastogram detection device according to claim 8, wherein the driving assembly comprises a driving motor, a cam and a return spring, and the driving motor and the cam are arranged on the front side of the air nozzle swing link;
and the reset spring is arranged at the rear side of the air faucet swing rod and is positioned between the air faucet swing rod and the front pressing plate.
10. The multi-channel thromboelastogram detection device of claim 8, wherein the air tap is connected with a right-angled elbow, and the right-angled elbow is used for connecting with an external air source.
CN202211384283.5A 2022-11-07 2022-11-07 Micro-fluidic chip and detection device that multichannel thrombelastogram detected Pending CN115672425A (en)

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