CN108627636B

CN108627636B - Device and method for detecting liquid solidification

Info

Publication number: CN108627636B
Application number: CN201710177746.3A
Authority: CN
Inventors: 苏楠; 和建伟
Original assignee: Beijing Bicheng Biotechnology Co ltd
Current assignee: Wuxi Juheyuanqi Biotechnology Co.,Ltd.
Priority date: 2017-03-23
Filing date: 2017-03-23
Publication date: 2022-03-01
Anticipated expiration: 2037-03-23
Also published as: CN108627636A

Abstract

The present invention relates to a device and a method for detecting solidification of a liquid, wherein the device for detecting solidification of a liquid comprises: the sample introduction module is used for wrapping a liquid sample to be detected through a medium and introducing the sample into the detection pipeline in a form of wrapping the liquid sample with the medium when the liquid sample to be detected is introduced, the pressure module is used for providing pressure for the introduced liquid sample wrapped with the medium to push the sample to move in the detection pipeline, the detection pipeline is provided with an inlet and an outlet for enabling the sample to enter and exit, and the pressure sensor is used for detecting the pressure at the inlet of the detection pipeline and outputting a pressure signal.

Description

Device and method for detecting liquid solidification

Technical Field

The present invention relates to an apparatus for detecting solidification of a liquid and a method for detecting solidification of a liquid using the same.

Background

It is known that blood coagulation in a living heart or blood vessel causes thrombosis and thrombotic diseases, for example, Acute Myocardial Infarction (AMI), cerebral thrombosis, Deep Vein Thrombosis (DVT), Disseminated Intravascular Coagulation (DIC), and the like; extravascular bleeding of blood can lead to bleeding and can cause bleeding disorders such as allergic purpura, thrombocytopenic purpura, hemophilia, and liver disease bleeding. In order to effectively inhibit these diseases, it is necessary to periodically detect the thrombosis in the blood of a patient.

Currently, in the whole blood system, a Thrombus Elastogram (TEG) is a common method for measuring blood coagulation and thrombus formation by using a thromboelastometer, and is an index reflecting dynamic changes in blood coagulation (including a rate of fibrin formation, firmness of a dissolved state and a coagulated state, and elasticity). Thrombelastogram is a graph drawn by a thrombelastometer. The main components of a conventional thromboelastometer include: a stainless steel blood cup capable of automatically adjusting the constant temperature (37 ℃), a small stainless steel cylinder inserted into the cup and a sensor capable of being connected with the cylinder. The blood cup is arranged on a reaction tank which can rotate back and forth at an angle of 4 degrees and 45 degrees, and blood is contained between the cup wall and the cylinder. When the blood sample is in a liquid state, the round-trip rotation of the cup can not drive the cylinder, the signal reflected to the tracing paper by the sensor is a straight line, when the blood begins to coagulate, resistance is generated between the cup and the cylinder due to the adhesion of fibrin, the cylinder is driven to move simultaneously by the rotation of the cup, the resistance is increased along with the increase of the fibrin, the movement of the cylinder driven by the cup is changed, and the signal traces the thrombelastogram formed on the tracing paper by the sensor.

In addition, many other liquid coagulation processes are also examined or attended to, for example, some polymer solution coagulation processes, such as protein solution, protein curd, gelatin, and polymer polymerization processes.

Disclosure of Invention

As described above, thromboelastometers are commonly used in the art to measure the coagulation of blood and the formation of thrombi. However, when the thromboelastometer is used for detection, a large amount of blood is often needed, and a large amount of blood needs to be extracted from a patient for detection, which causes great burden to the patient and higher requirements on operation for a clinician.

Therefore, if the detection of blood coagulation can be realized by a small amount of sample, for example, micro-liter, in the field, the burden of the patient and the risk during blood collection can be greatly reduced. In addition, because the detection of blood coagulation needs to avoid the interference of external environment as much as possible in the detection process, a detection device which can realize very small influence on the collected blood in the whole detection process is also needed.

JP2007-271323a discloses a measurement method capable of simultaneously detecting the blood viscosity and the amount of thrombus formation in a short time at low cost. This patent document relates to a blood holding container having an opening to which a capillary tube is connected, a pressurizing device for discharging blood in the blood holding container from the capillary tube at a constant flow rate, and a detecting device for detecting the viscosity of blood and the amount of thrombus formation.

CN102762991A discloses a microchip for platelet measurement and a platelet measurement device using the same. The microchip disclosed in this patent document is a microchip for measuring platelet function by inducing platelet aggregation by flowing blood in a channel, and has a channel provided inside, wherein collagen is at least partially coated in the channel in order to adhere to platelets, a plurality of walls extend in the direction in which blood flows in the channel, and partition the width of the channel to form channel partitions, and the walls are subjected to a treatment for making the surface roughness (Ra) 10 to 200 nm. By using this device, a platelet function of detecting blood using a trace amount of blood can be realized.

CN101292161A discloses a device for monitoring thrombus formation and a method for detecting thrombus formation. Providing a thrombus-inducing agent in at least a portion of the device comprising a thrombus formation chamber; an inlet tube connected to the thrombus formation chamber and through which blood flows into the thrombus formation chamber; and a drug tube connected to the inlet tube and through which a drug for releasing anticoagulation treatment to go or promote blood coagulation is supplied. The method comprises flowing anticoagulated blood into a thrombosis chamber, providing a thrombosis inducing agent that induces thrombosis in at least a portion of the thrombosis chamber while releasing anticoagulation treatment or promoting blood coagulation, thereby monitoring thrombosis.

CN101874208A discloses a microchip and a blood monitoring device. The interior of the microchip comprises: a first channel into which a first liquid selected from whole blood, platelet-rich plasma, and a drug-treated liquid thereof flows; a second flow path connected to the first flow path, into which a second liquid containing a chemical that reacts with the first liquid flows; and a merged channel extending from a connection portion between the first channel and the second channel; the microchip is characterized in that a stirring section having a stirring bar for mixing the first liquid and the second liquid is provided in the merged channel. By using the device, the reaction performance of blood can be detected by effectively mixing trace blood and the medicament.

A cup-based device for blood coagulation measurement and testing is disclosed in CN 102099676A. The device includes a blood clot detection instrument and a cup for the blood clot detection instrument. The cup includes a blood sample receiver inlet and a channel structure, the channel structure including: at least one test channel for making a measurement of blood clotting time; a sampling channel having at least one surface portion that is hydrophilic in communication with the blood sample receiver inlet and the at least one test channel; and a waste channel having at least one surface portion that is hydrophilic in communication with the sampling channel; and a vent opening in communication with the sampling channel. The exposure of the optical sensor activates a pump module of the blood clot detection instrument that draws a desired volume of a blood sample into the at least one test channel.

The above information is only for enhancement of understanding of the background of the invention and therefore it may contain information that does not form the prior art that is well known to those of ordinary skill in the art. The above patent applications and the prior art use various devices of relatively complex construction to perform the detection of minute amounts of blood. In addition, in the above-mentioned apparatus, it is often necessary to perform coagulation inhibition treatment on the surface of the member which comes into contact with blood, for example, surface treatment with heparin, polyacetyl lactone, poly-2-methoxyethyl adenine or the like.

In addition, with respect to other liquid samples other than blood samples, there is a similar problem in that it is desired to realize detection with a minute volume and to avoid interference and influence of the liquid sample to the outside during the entire process of detecting coagulation of the liquid.

Further, it is desirable to achieve continuous, rapid, and efficient detection of different liquid samples without mutual interference and contamination between different samples.

In view of the above circumstances, the present invention is intended to provide a liquid coagulation detecting apparatus which has a simple structure, can rapidly detect a coagulation process of a liquid to rapidly obtain information on coagulation of the liquid, such as thrombus formation, and can realize detection only for a trace amount of a liquid sample, and a method for detecting coagulation of the liquid using the apparatus.

The purpose of the invention is realized by the following technical scheme.

1. An apparatus for detecting solidification of a liquid, comprising:

the sample introduction module wraps the sample through the medium when introducing the liquid sample to be detected and introduces the sample into the detection pipeline in the form of wrapping the liquid sample by the medium,

a pressure module which provides pressure to the injected liquid sample wrapped by the medium to push the sample to move in the detection pipeline,

a detection conduit having an inlet and an outlet for the ingress and egress of a sample, an

And the pressure sensor is used for detecting the pressure at the inlet of the detection pipeline and outputting a pressure signal.

2. The apparatus according to item 1, wherein the shape of the detection conduit is one or more selected from a group consisting of a corrugated shape, a broken line shape, a square wave shape, a straight line shape, a spiral shape, and a variable diameter shape.

3. The device according to item 1 or 2, wherein the detection channel is a microchannel, and has an inner diameter of 10 μm to 5 mm, preferably 50 μm to 2 mm, more preferably 100 μm to 1 mm, and further preferably 200 μm to 0.6 mm.

4. The apparatus according to any one of items 1 to 3, wherein the pressure feeding module pushes the sample to move in the detection pipe at a constant pressure or the pressure feeding module pushes the sample to move in the detection pipe at a constant speed.

5. The device of any one of claims 1-4, wherein the pressure feeding module, the sample feeding module, and the detection conduit are in fluid communication.

6. The apparatus of any one of items 1 to 5, wherein the sample introduction module comprises:

a sample channel for sucking and delivering a liquid sample, the sample channel being connected to a module for providing a negative pressure;

the medium channel is used for pushing the medium and is connected with the module for providing positive pressure;

the sample channel and the media channel are in fluid communication.

7. The device according to item 6, wherein the sample channel has an inner diameter of 10 μm to 5 mm, preferably 50 μm to 2 mm, further preferably 100 μm to 1 mm, further preferably 200 μm to 0.6mm, and the medium channel has an inner diameter of 5 μm to 10 mm, preferably 25 μm to 4 mm, further preferably 50 μm to 2 mm, further preferably 100 μm to 1.2 mm.

8. The device according to item 6 or 7, wherein the ratio of the inner diameters of the sample channel and the medium channel (sample channel inner diameter/medium channel inner diameter) is in the range of 1:10 to 10:1, preferably 1:5 to 5:1, and more preferably 1:2 to 2: 1.

9. The device of any one of claims 1 to 8, wherein the sample introduction module and the detection conduit are formed of a hydrophobic material or coated with a hydrophobic material inside.

10. The device according to any one of claims 6 to 9, wherein the sample channel of the sample introduction module is in direct communication with the medium channel.

11. The device of any one of claims 6 to 9, wherein the sample channel and the media channel of the sample introduction module are in fluid communication through a common vessel.

12. The device according to any one of items 1 to 11, wherein the entire device is filled with the medium before the device for detecting solidification of the liquid is put into use.

13. The device according to any one of items 1 to 12, wherein the liquid sample is a blood sample, or a protein liquid sample, or other liquid sample that deforms due to polymerization of macromolecules.

14. A method for detecting liquid coagulation using a device comprising a sample introduction module, a pressure feed module, a detection conduit, and a pressure sensor, comprising the steps of:

the liquid sample to be detected is injected into the detection pipeline through the injection module in a mode that the liquid sample is wrapped by the medium,

pushing the sample to move in the detection conduit by applying pressure to the injected media-encased liquid sample by the pressure module, an

And detecting the pressure at the inlet of the detection pipeline by using a pressure sensor and outputting a pressure signal.

15. The method of item 14, further comprising the steps of:

before detection, the whole detection system is filled with a medium,

when the liquid sample to be detected is fed into the detection pipeline in a mode of wrapping the liquid sample by the medium through the feeding module, the pressure feeding module is closed so that the medium wrapped sample enters the detection pipeline from the inlet of the detection pipeline,

and after the sample introduction is finished, closing the sample introduction module, and opening the pressure supply module to push the sample to move in the detection pipeline.

16. The method of item 14 or 15, wherein a sample module is used comprising:

the sample channel and the media channel are in fluid communication,

the sample introduction step of the sample introduction module comprises the following steps:

the first step is as follows: under the premise that the module for providing negative pressure and the module for providing positive pressure are closed and the sample channel and the medium channel are filled with the medium, the sample introduction module is inserted into the liquid sample to be taken,

the second step is that: the module providing the negative pressure is opened to draw the liquid sample into the sample channel,

the third step: closing the module for providing negative pressure and opening the module for providing positive pressure, thereby pushing the medium out of the medium channel to make the medium contact with the liquid sample sucked in the second step, so that a certain amount of the liquid sample is retained in the sample channel, and thereby a certain amount of the liquid sample retained in the sample channel is coated by the medium,

the fourth step: closing the module for providing positive pressure and keeping closing the module for providing negative pressure, stopping pushing the medium, thereby completing the sample introduction of one time,

and repeating the steps from the first step to the fourth step, thereby completing the new sample introduction of the liquid sample.

17. The method of item 16, wherein the primary sample and the new primary sample are different liquid samples.

18. The method of any one of claims 14 to 17, wherein the liquid sample is a blood sample, or a protein liquid sample, or other liquid sample that deforms due to polymerization of macromolecules.

19. The method of any one of claims 14 to 18, which is detected using the device of any one of claims 1 to 13.

As described above, the apparatus for detecting coagulation of a liquid of the present invention has a simple structure, and can detect the coagulation time and the coagulation state of a liquid (e.g., blood) in a minute amount of a liquid sample (e.g., a blood sample amount). In addition, when the detection device of the present invention is used, the liquid sample (e.g., blood sample) is wrapped by the medium, so that the liquid sample (e.g., blood sample) is ensured not to be interfered by outside unnecessarily during the detection process, and the whole process of the coagulation of the liquid sample, such as the time when the blood starts to coagulate after the procoagulant drug and factor are added and the strength during the coagulation (the strength of thrombus), can be accurately detected.

In addition, since the apparatus of the present invention employs a given sample introduction module as described below, different liquid samples can be continuously introduced to achieve continuous, one-time processing of a large number of different liquid samples. The liquid samples fed each time can be properly isolated from each other and are not mutually polluted and influenced, so that continuous feeding of various liquid samples and effective detection can be realized.

The above description is only an overview of the technical solutions of the present invention, and in order to make the technical means of the present invention more clearly apparent, and to make the implementation of the content of the description possible for those skilled in the art, and to make the above and other objects, features and advantages of the present invention more obvious, the following description is given by way of example of the specific embodiments of the present invention.

Drawings

Various other advantages and benefits of the present invention will become apparent to those of ordinary skill in the art upon reading the following detailed description of the preferred embodiments. The drawings are only for purposes of illustrating the preferred embodiments and are not to be construed as limiting the invention. It is obvious that the drawings described below are only some embodiments of the invention, and that for a person skilled in the art, other drawings can be derived from them without inventive effort. Also, like parts are designated by like reference numerals throughout the drawings.

FIG. 1 is a schematic view of the detection apparatus of the present invention.

FIG. 2 is a schematic diagram of a sample injection module used in the detection apparatus of the present invention.

Fig. 3(a) is a schematic flow chart of a sample injection module of the present invention for wrapping droplets with a medium, cutting and pushing the droplets, and fig. 3(b) is an operation flow chart of a sample injection module of the present invention for injecting a liquid sample.

FIGS. 4(a) and (b) are schematic views of two other sample introduction modules used in the detection apparatus of the present invention.

FIG. 5 is a schematic view of another sample injection module used in the detection apparatus of the present invention.

FIG. 6 is a schematic view of a test tube used in the test device of the present invention.

FIG. 7 is a schematic view of another inspection duct used in the inspection apparatus of the present invention.

FIG. 8 is another schematic view of the detection device of the present invention.

Fig. 9 shows the result of detection by the detection device in the embodiment.

Detailed Description

Specific embodiments of the present invention will be described in more detail below with reference to the accompanying drawings. While specific embodiments of the invention are shown in the drawings, it should be understood that the invention may be embodied in various forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art.

1. Device for detecting liquid solidification

The device for detecting solidification of a liquid of the present invention comprises: the sample introduction module wraps the liquid sample to be detected through a medium when the liquid sample to be detected is introduced, and introduces the sample into the detection pipeline in a form that the liquid sample is wrapped by the medium; a pressure module which provides pressure to the injected liquid sample wrapped by the medium to push the sample to move in the detection pipeline; a detection pipe having an inlet and an outlet for the sample to enter and exit, and a pressure sensor for detecting the pressure at the inlet of the detection pipe and outputting a pressure signal.

The sample injection module used in the apparatus for detecting liquid coagulation of the present invention is not particularly limited as long as it is a module capable of realizing sample injection in the form of a medium including a liquid sample, and will be described in detail hereinafter.

Fig. 1 shows a schematic view of a detection device of the present invention. It can be seen that in the apparatus for detecting liquid coagulation of the present invention, the feeding pressure module, the sample introduction module, and the detection conduit are in fluid communication. The detection device of the present invention should have its entire device filled with a medium before use. When the detection device is used, when the liquid sample to be detected is injected into the detection pipeline in a mode of wrapping the liquid sample by the medium through the injection module, the pressure feeding module is closed, so that the medium wrapped sample enters the detection pipeline from the inlet of the detection pipeline, such as the sample to be detected shown in fig. 1. And after the sample introduction is finished, closing the sample introduction module, and opening the pressure supply module to push the sample to move in the detection pipeline. As the liquid sample gradually solidifies from a liquid state to a solid state in the detection conduit, a pressure sensor in the device may be used to detect a change in pressure at the inlet of the detection conduit and, based on the output pressure signal, record the change in pressure to reflect the entire state from liquid to solidification.

It can be understood by those skilled in the art that if the pressure module pushes the liquid sample to move in the detection pipeline at a constant pressure, the pressure detected by the pressure sensor at the inlet of the detection pipeline will gradually increase because the liquid sample will gradually change from liquid to solid, and at this time, the process of gradually increasing the pressure detected by the pressure sensor can be recorded, and a curve of gradually increasing the pressure can be output as the detection result.

It will be understood by those skilled in the art that if the sample is pushed to the pressure module to move at a constant speed in the detection pipe, since the liquid sample gradually changes from liquid to solid, the pressure detected by the pressure sensor at the inlet of the detection pipe gradually increases, and then the process of the pressure detected by the pressure sensor gradually increasing may be recorded, and a curve of the pressure gradually increasing may be output as the detection result.

The sample, which is completely solidified in the detection pipe and has completed the detection, is discharged from the outlet of the detection pipe in a medium-packed form.

2. Sample introduction module

As described above, the sample injection module used in the device of the present invention is not particularly limited, and in the present invention, sample injection is performed in the manner shown in fig. 2 to 5, for example, and any other sample injection module capable of achieving the sample injection requirement of the present invention may be used.

Fig. 2 shows a schematic diagram of a sample injection module according to the present invention. Fig. 2 schematically shows the correlation of the sample channel and the medium channel. As can be seen from fig. 2, the sample introduction module comprises: a sample channel for sucking and delivering a liquid sample, the sample channel being connected to a module for providing a negative pressure; a media channel for pushing media, the media channel connected to the means for providing positive pressure, the sample channel and the media channel in fluid communication.

The sample channel and the media channel are shown in direct communication in the schematic diagram of fig. 2, and those skilled in the art will appreciate that fig. 2 is merely illustrative and that the manner in which the sample channel and the media channel communicate is not limited to that shown in fig. 2. The sample channel and the media channel are in fluid communication, i.e. fluid may enter the media channel from the sample channel and enter the sample channel from the media channel. In the following, the invention also provides several variants for achieving fluid communication between the sample channel and the medium channel. Those skilled in the art will appreciate that any means of enabling fluid communication is within the scope of the present invention.

The sample channel and the media channel are connected to a module for providing negative pressure and a module for providing positive pressure, respectively, as shown in fig. 2. In the present invention, the module for providing negative pressure and providing positive pressure is not particularly limited, and any means known to those skilled in the art can be used, for example, pushing and sucking by means of, for example, a syringe to provide positive pressure and negative pressure, respectively, or a pump capable of providing positive pressure and negative pressure can be cited, and the sample injection module of the present invention preferably uses a plunger pump, a syringe pump, or the like, since it is used in the field of microfluidics; the medium may also be provided by a positive or negative pressure gas source; or any other manner in which the same functionality may be achieved.

In addition, the working time of the positive pressure and the negative pressure can be controlled by the switch of the electromagnetic valve, so that automatic continuous sample introduction at the appointed time can be realized.

As shown in fig. 3(a) and (b), a schematic flow chart of injecting a liquid sample by using a sample injection module is shown. As shown in fig. 3(a), the medium channel and the sample channel of the sample introduction module are filled with a medium before the 1-suction step, and in the 1-suction step, the module for providing a negative pressure is opened, an excess liquid sample is sucked into the sample channel by the negative pressure, and the liquid sample is brought into fluid communication with the medium channel, as shown by an arrow in the upper left diagram of fig. 3(a), and in the case shown in the schematic diagram of fig. 3(a), the liquid sample is directly in contact with the medium channel, which covers the outlet of the medium channel in contact with the sample channel. In the 2-cut (separation) step, the block providing negative pressure is first closed and the block providing positive pressure is opened, at which time the medium in the medium channel is lifted out and brought into contact with an excess amount of the liquid sample, which is cut (the sample is divided into two parts), and the excess sample is pushed out of the sample channel, as indicated by the arrow in the upper right drawing of fig. 3 (a). In the 3-push-out step, the positive pressure is continuously supplied to push the excess sample out of the sample channel completely, so that the liquid sample retained in the sample channel is coated with the medium (or can be coated), and then the module for supplying the positive pressure is closed and the module for supplying the negative pressure is kept closed, so that the sample injection is completed once, as shown by the arrow in the lower right diagram of fig. 3 (a). In the 4-re-suction step, the module providing the negative pressure is opened again, a new sample is sucked in, and the sample which has been coated or wrapped with the medium in the previous step is pushed forward. As described above, the steps in the sample injection method of the present invention are repeated again, thereby implementing the sample injection process of a new sample.

The entire process is further illustrated in fig. 3(b), and a sample container, in which a liquid sample to be taken is placed, is also schematically illustrated in fig. 3 (b).

The method for sampling the trace liquid sample comprises the following steps:

the first step is as follows: under the premise that the module for providing negative pressure and the module for providing positive pressure are closed and the sample channel and the medium channel are filled with the medium, the sample introduction module is inserted into the liquid sample to be taken (as shown in the leftmost diagram in figure 3 (b)),

the second step is that: the module providing the negative pressure is opened to draw the liquid sample into the sample channel (as shown in the second drawing from the left in figure 3 (b)),

the third step: closing the module for providing negative pressure and opening the module for providing positive pressure, thereby pushing the medium out of the medium channel to contact the medium with the liquid sample sucked in the second step, so that a certain amount of the liquid sample is retained in the sample channel, and thereby a certain amount of the liquid sample retained in the sample channel is coated with the medium (as shown in the middle graph of FIG. 3 (b)),

the fourth step: closing the module for supplying positive pressure and keeping closing the module for supplying negative pressure, stopping pushing in the medium, thereby completing the sample injection once (as shown in the second figure at the right side of figure 3 (b)),

repeating the steps from the first step to the fourth step, thereby completing a new sample injection (as shown in the rightmost diagram of fig. 3 (b)).

In the above method, a certain amount of the liquid sample refers to the amount of the liquid sample to be detected in the present invention, and the certain amount is not particularly limited, and a person skilled in the art knows how to select an appropriate amount for determining the coagulation process of the liquid sample according to the subsequent processing or detection of the sample, and for example, there can be mentioned: 1 nanoliter to 20 microliters, 2 nanoliters to 15 microliters, 5 nanoliters to 10 microliters, 10 nanoliters to 9 microliters, 50 nanoliters to 5 microliters and the like, and specifically, for example, 20 microliters, 15 microliters, 10 microliters, 9 microliters, 8 microliters, 7 microliters, 6 microliters, 5 microliters, 4 microliters, 3 microliters, 2 microliters, 1.5 microliters, 1 microliters, 900 nanoliters, 800 nanoliters, 700 nanoliters, 600 nanoliters, 500 nanoliters, 400 nanoliters, 300 nanoliters, 200 nanoliters, 100 nanoliters, 50 nanoliters, 30 nanoliters, 10 nanoliters, 5 nanoliters, 1 nanoliter and the like can be mentioned.

As can be seen from the above description, with the sample injection module as described above, sample injection of a liquid sample can be effectively achieved, and the liquid sample is cut and pushed out by the medium (i.e., the sample is divided into two parts and a certain amount of the sample used subsequently is retained, or the sample near the sample channel is separated from a certain amount of the sample used subsequently), and then the remaining liquid sample to be processed is wrapped by the medium, thereby completing sample injection once. By the device and the method, different liquid samples can be continuously fed, and each liquid sample can be isolated from each other and does not interfere with each other.

In addition, the inlet end of the sample channel of the sample injection module can be closed when no sample injection is performed, and the closing manner can be, but is not limited to, manner one: the sleeve type is that a cap which can be sleeved on the inlet end is adopted, and the cap is buckled on the inlet end to be closed; the second method comprises the following steps: press-type, making a soft, e.g. rubber, pad and pressing on the inlet end to effect closure.

In the sample introduction module of the present invention, the size of the sample introduction module is not particularly limited, and is preferably a size that helps to achieve the medium-wrapped liquid sample. For example, the inner diameter of the sample channel is 10 μm to 5 mm, preferably 50 μm to 2 mm, more preferably 100 μm to 1 mm, and still more preferably 200 μm to 0.6 mm. For example, the sample channel can have an inner diameter of 10 microns, 20 microns, 30 microns, 40 microns, 50 microns, 60 microns, 70 microns, 80 microns, 90 microns, 100 microns, 200 microns, 300 microns, 400 microns, 500 microns, 600 microns, 700 microns, 800 microns, 900 microns, 1 mm, 1.5 mm, 2 mm, 3 mm, 4 mm, 5 mm. The above specific values are merely illustrative and may be any specific value from 10 μm to 5 mm.

For example, the inner diameter of the medium channel is 5 μm to 10 mm, preferably 25 μm to 4 mm, more preferably 50 μm to 2 mm, and still more preferably 100 μm to 1.2 mm. For example, the media channel can have an inner diameter of 5 microns, 6 microns, 7 microns, 8 microns, 9 microns, 10 microns, 20 microns, 30 microns, 40 microns, 50 microns, 60 microns, 70 microns, 80 microns, 90 microns, 100 microns, 200 microns, 300 microns, 400 microns, 500 microns, 600 microns, 700 microns, 800 microns, 900 microns, 1 mm, 1.5 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6mm, 7 mm, 8 mm, 9 mm, 10 mm. The above specific values are merely illustrative and may be any specific value from 5 μm to 10 mm.

Further, the relation of the inner diameters between the sample channel and the medium channel is not particularly limited as long as it is a ratio that contributes to the realization of the medium-wrapped liquid sample, and for example, the ratio of the inner diameters of the sample channel and the medium channel (sample channel inner diameter/medium channel inner diameter) is in the range of 1:10 to 10:1, preferably 1:5 to 5:1, more preferably 1:2 to 2:1, and may be, for example, 1: 1.

In the above, the inner diameter referred to in the present invention is the diameter of the inner channel of the medium channel or the sample channel.

In the present invention, as described above, the liquid sample is a blood sample or a polymer solution such as a protein solution, a gelatin solution, a protein curd, a polymer material solution, or the like.

The medium used in the present invention is generally a lipophilic medium, and various kinds of oils generally used in the art can be used. Such as mineral oil, low temperature paraffin, vegetable oil.

In the present invention, the material of the sample injection module is not limited, and any material may be used as long as the medium can wrap the liquid sample by the operation of the present invention. Preferably, the sample channel and the medium channel are formed of a hydrophobic material or coated with a hydrophobic material therein. Examples of the hydrophobic material include organic polymer materials having hydrophobicity such as Polytetrafluoroethylene (PTFE), polymethyl methacrylate (PMMA), Polyethylene (PE), polypropylene (PP), and Polystyrene (PS), and metal materials such as stainless steel, titanium alloy, copper, platinum, and gold may be used.

In one specific embodiment of the sample introduction module employed in the present invention, the sample channel thereof is in direct communication with the medium channel. Reference may be made in particular to the direct communication by means of a three-way valve as shown in fig. 3(a), so that when the liquid sample is cut by the medium, the medium pushed out by the positive pressure can directly contact and cut the sucked excess liquid sample and further push out the excess liquid sample, wrapping the sample desired for the subsequent operation or detection.

In the method of sampling a minute amount of liquid sample using this embodiment, in the second step, the module for supplying negative pressure is opened to draw an excess amount of liquid sample into the sample channel and cover a portion where the medium channel directly communicates with the sample channel (the liquid sample directly contacts with the medium channel, which covers the outlet where the medium channel contacts with the sample channel), and in the third step: closing the module for providing negative pressure and opening the module for providing positive pressure, thereby pushing out the medium from the medium channel to make the medium contact with the liquid sample sucked in the second step, and pushing out the redundant liquid sample in the sample channel from the sample channel to make a certain amount of the liquid sample remained in the sample channel, and thus making a certain amount of the liquid sample remained in the sample channel coated by the medium.

In another specific embodiment of the sample introduction module employed in the present invention, the sample channel and the medium channel are in fluid communication via a common vessel. Reference may be made in particular to the two exemplary embodiments given in fig. 4(a) and (b).

In the method of sampling a minute amount of liquid sample using this embodiment, in the second step, the module for providing negative pressure is opened to suck the liquid sample into the sample channel, and in the third step: closing the module providing negative pressure and opening the module providing positive pressure, thereby pushing the medium out of the medium channel to bring the medium into contact with the liquid sample aspirated in the second step (e.g., into contact at the sample channel port, as shown in fig. 4(a) and 3 (b)), and separating the liquid sample inside the sample channel from the liquid sample outside the sample channel (e.g., in the vicinity of or attached to the sample channel port), so that a certain amount of the liquid sample remains in the sample channel, and thereby the certain amount of the liquid sample remaining in the sample channel is coated with the medium.

Specifically, in fig. 4(a), the inner diameter of the sample channel is smaller than the inner diameter of the medium channel, and the medium channel is in the form of a sleeve with the sample channel, i.e. the medium channel is located outside the sample channel, and the medium channel and the sample channel can be in fluid communication by a medium-filled container located below. As shown in fig. 4(a), the media channel and the sample channel can be brought into fluid communication by filling the lower receptacle with a medium and inserting the inlets of the media channel and the sample channel into the medium-filled receptacle.

Thus, when sampling is performed by the liquid sampler, first, in a first step, the sampling module shown in fig. 4(a) is inserted into the liquid sample to be sampled under the condition that the module for providing negative pressure and the module for providing positive pressure are closed and the sample channel and the medium channel are filled with the medium, and at this time, the container filled with the medium is inserted into the liquid sample to be sampled together with the medium channel and the sample channel. In a second step, the module providing the negative pressure is opened to draw the liquid sample through the medium-filled container into the sample channel, with the end of the liquid sample at the inlet of the sample channel, which can be in fluid contact with the medium. In a third step: closing the module for providing negative pressure and opening the module for providing positive pressure, thereby pushing the medium out of the medium channel to make the medium contact with the liquid sample sucked in the second step (mainly the sample is positioned at the end of the sample channel inlet), and separating the liquid sample in the sample channel from the liquid sample outside the sample channel, so that a certain amount of the liquid sample is retained in the sample channel, and thus the certain amount of the liquid sample retained in the sample channel is coated by the medium. In this embodiment, the liquid sample outside the sample channel is typically outside and near the inlet of the sample channel, or is a sample outside the sample channel. And finally, closing the module for supplying positive pressure and keeping closing the module for supplying negative pressure, and stopping pushing the medium, thereby completing the sample introduction of the sample once. And repeating the steps from the first step to the fourth step, thereby completing the sample introduction of a new time.

In the above-described embodiment shown in fig. 4(a), the container filled with the medium may be a tapered container such as a tip of a pipette, or a syringe needle, or any other similar container as long as it can suck the liquid sample into the sample channel through the container when it is inserted into the liquid sample together with the sample channel and the medium channel.

Further, as described above, the container containing the liquid sample may be a 96-well plate, a test tube, a flask, a petri dish, or the like, which is various open systems. Furthermore, in the embodiment shown in fig. 3(a), the inner diameter of the medium channel is larger than that of the sample channel, and those skilled in the art can understand that the opposite way, that is, the inner diameter of the medium channel is smaller than that of the sample channel, and the embodiment in which the medium channel is located inside the sample channel can be realized as long as the method for injecting a micro-amount liquid sample described in the present invention can be realized. In the present invention, it is preferable that the inner diameter of the medium channel is larger than that of the sample channel, so that cutting of an unnecessary sample can be better achieved.

Further, as shown in fig. 4(a), the sample inlet of the sample channel extends out of the medium channel, and those skilled in the art can also understand that the sample inlet of the sample channel and the medium inlet of the medium channel may be parallel, or the sample inlet of the sample channel may be located in the medium channel, as long as the method for injecting a trace amount of liquid sample described in the present invention can be implemented. In the present invention, it is preferable that the length of the sample channel is longer than that of the medium channel, so that cutting of an unnecessary sample can be better achieved.

Fig. 4(b) shows another embodiment in which the sample channel and the medium channel are not formed as a sleeve, but two channels are arranged in parallel, and the embodiment is identical to the embodiment shown in fig. 4 (a). In this case, the invention describes a method for sampling a trace amount of liquid sample. The inner diameters of the channel and the medium channel can be the same or different, so long as the method for injecting the trace liquid sample can be realized. In addition, the sample inlet of the sample channel and the medium inlet of the medium channel may be parallel or non-parallel, as long as the method for sampling a trace amount of liquid sample described in the present invention can be implemented. In the present invention, it is preferable that the length of the sample channel is longer than that of the medium channel, so that cutting of an unnecessary sample can be better achieved.

In addition, the sample introduction module of the present invention can take samples for different samples, after the first sample introduction of the liquid sample is finished, the pipeline near the sample inlet can be cleaned by wiping, flushing, etc., and then the sample introduction module can be inserted into different sample liquids for sampling in the second sample introduction, for example, for a 96-well plate or a multi-sample system, different samples can be simultaneously introduced by using one sample introduction module, so that the detection of the multi-system sample can be simply realized, and the samples entering the sample channel can not be polluted and influenced by each other in the process of being transported to the micro-pipeline system because the samples pass through the medium space between each other.

In addition to the sample introduction modules shown in fig. 2 to 4, the detection apparatus of the present invention may also utilize a sample introduction module as shown in fig. 5. The schematic diagram of the sample introduction module is shown in fig. 5, and the sample introduction module has a three-way form, and the sample introduction module utilizes a positive pressure supply to push a liquid sample into a pipeline, then a medium module utilizing the positive pressure supply pushes a medium into the pipeline to wrap the liquid sample, and then the sample to be transferred in the form of the medium wrapped liquid sample is formed and finally enters a detection pipeline (which can also be a detection chip) of the device of the present invention. In addition, the other descriptions in the sample module related to fig. 5 can refer to the sample module described above with respect to fig. 2 to 4.

As described above, it can be understood by those skilled in the art that, in addition to the sample injection module shown in fig. 2 to 5, the detection device of the present invention can adopt any sample injector which can be used in the field to realize sample injection in the form of medium-wrapped sample.

3. Pressure supply module

The pressure supply module used in the detection device of the present invention can provide positive pressure in the same manner as the module for providing positive pressure mentioned in the sample introduction module above to push the sample to be detected to move in the detection pipeline, and any manner known to those skilled in the art can be implemented, such as providing positive pressure by pushing through a needle tube, or providing positive pressure by a pump, preferably using a plunger pump, a syringe pump, etc. for the pressure supply module; the medium can also be pushed by a positive pressure gas source to provide pressure; or any other manner in which the same functionality may be achieved.

As described above, the pressure feeding module pushes the sample to move in the detection pipe at a constant pressure or the pressure feeding module pushes the sample to move in the detection pipe at a constant speed.

The sample to be tested is preferably pushed at a constant pressure in the test line.

4. Detection pipeline

In the detection device of the present invention, a detection pipe having a certain length and shape is used for moving a liquid sample to be detected therein and completing a solidification process from a liquid to a solid.

The shape of the detection pipeline is selected from one or more than two of a corrugated shape, a broken line shape, a square wave shape, a straight line shape, a spiral shape and a reducing shape.

One specific example of corrugation can be seen in the schematic view of the test tube in the device shown in fig. 1.

One specific example of a square wave shape can be seen in the schematic diagram of the detection conduit shown in fig. 6.

One specific example of a broken line shape can be seen in the schematic view of the inspection duct shown in fig. 7.

Furthermore, the spiral, straight and tapered shapes have shapes that can be understood by those skilled in the art. The variable diameter shape refers to a shape in which the inner diameter of the detection pipeline has a change, and the specific shape is not limited at all. In addition, the above figures are only schematic illustrations, and those skilled in the art can select a suitable shape of the detection conduit according to their needs.

The detection duct may be a combination of the above-mentioned shapes, and for example, a combination duct of a corrugated shape and a square wave shape may be used, and the combination may be arbitrarily selected from the above-mentioned types, or may be a combination of two or more types.

In addition, the detection channel is a microchannel, and has an inner diameter of 10 micrometers to 5 millimeters, preferably 50 micrometers to 2 millimeters, more preferably 100 micrometers to 1 millimeter, and still more preferably 200 micrometers to 0.6 millimeter.

There is no limitation on the length of the detection conduit over which the sample can move, as long as it is ensured that the liquid sample can be solidified from a liquid state to a solid state while moving in the detection conduit. For example, it may be, for example, 1cm to 150cm, preferably 10cm to 120cm, such as 10cm, 20cm, 30cm, 40cm, 50cm, 60cm, 70cm, 80cm, 90cm, 100cm, 110cm, 120cm, etc.

Furthermore, it will be understood by those skilled in the art that the liquid sample may also be caused to reciprocate within the detection conduit, and therefore the length of the detection conduit is merely exemplary, and those skilled in the art can select a suitable length depending on the manner in which the particular liquid sample is to be solidified.

In one embodiment of the present invention, the structure of the device when it is assumed to reciprocate a liquid sample in a detection conduit is shown, and a schematic diagram thereof is shown in fig. 8. The device comprises a valve group and a pipeline, wherein a detection pipeline is connected between two ports as shown in figure 8 and is communicated with a sample injector (namely a sample injection module) through an interface, and a sample outlet is in a closed state when not in use; the reciprocating motion of the sample is realized by switching the valve combination, and when the valves 1 and 3 are opened in combination and the valves 2 and 4 are closed in combination, the sample moves from right to left; when the valves 2 and 4 are opened in a combined mode and the valves 1 and 3 are closed in a combined mode, the sample moves from left to right; in the sample reciprocating motion, the medium for pushing the sample to move always enters from the interface of the pressure feeding module end and flows out from the medium outlet.

The material of the detection line of the present invention is not limited, and may be any material that can move a liquid sample wrapped in a medium. Preferably, the sample channel and the medium channel of the sample introduction module are made of the same material, for example, hydrophobic material or coated with hydrophobic material. Examples of the hydrophobic material include organic polymer materials having hydrophobicity such as Polytetrafluoroethylene (PTFE), polymethyl methacrylate (PMMA), Polyethylene (PE), polypropylene (PP), and Polystyrene (PS), and metal materials such as stainless steel, titanium alloy, copper, platinum, and gold may be used.

5. Pressure sensor

The pressure sensor in the detection device of the present invention is not limited in any way as long as it can detect a change in pressure at the inlet of the detection pipe and output a pressure signal. Can be any pressure sensor that can be used in the microfluidic field. Such as micro air pressure sensors, micro hydraulic pressure sensors.

6. Method for detecting liquid coagulation

The invention also provides a method for detecting liquid coagulation, which uses a device comprising a sample feeding module, a pressure feeding module, a detection pipeline and a pressure sensor for detection, and comprises the following steps: injecting a liquid sample to be detected into a detection pipeline in a mode that the liquid sample is wrapped by a medium through an injection module; providing pressure to the injected liquid sample wrapped by the medium by a pressure module to push the sample to move in the detection pipeline; and detecting the pressure at the inlet of the detection pipeline by using the pressure sensor and outputting a pressure signal.

In addition, the method of the present invention further comprises: before detection, the whole detection system is filled with a medium, when a liquid sample to be detected is fed into the detection pipeline in a mode of wrapping the liquid sample by the medium through the feeding module, the pressure feeding module is closed so that the medium wrapped sample enters the detection pipeline from the inlet of the detection pipeline, and after feeding is finished, the feeding module is closed and the pressure feeding module is opened so as to push the sample to move in the detection pipeline.

In a specific embodiment, the detection method of the present invention uses a sample module comprising: a sample channel for sucking and delivering a liquid sample, the sample channel being connected to a module for providing a negative pressure; the medium channel is used for pushing the medium and is connected with the module for providing positive pressure; the sample channel is communicated with the medium channel in a fluid mode, and the sample introduction step of the sample introduction module comprises the following steps: the first step is as follows: under the premise that the module for providing negative pressure and the module for providing positive pressure are closed and the sample channel and the medium channel are filled with the medium, the sample introduction module is inserted into the liquid sample to be taken, and the second step is as follows: opening the module providing negative pressure to draw the liquid sample into the sample channel, and the third step: closing the module for providing negative pressure and opening the module for providing positive pressure, thereby pushing the medium out of the medium channel to make the medium contact with the liquid sample sucked in the second step, so that a certain amount of the liquid sample is retained in the sample channel, and thereby a certain amount of the liquid sample retained in the sample channel is coated by the medium, and the fourth step: and closing the module for supplying positive pressure and keeping closing the module for supplying negative pressure, stopping pushing the medium, thus completing sample introduction of one time of samples, and repeating the steps from the first step to the fourth step, thus completing sample introduction of a new time of liquid samples.

As described above, the sample injection by the sample injection module can realize that the liquid sample injected last time and the liquid sample injected next time are different liquid samples. For example, it may be a blood sample from a different patient, or a blood sample taken before and after administration from the same patient, or the like.

In addition to blood samples, it will be understood by those skilled in the art that the device and method of the present invention can be used to detect coagulation of other polymer solutions, such as protein solutions, protein curd, gelatin solutions, and polymers or monomers thereof.

Examples

The detection device used in this example was constructed substantially in the manner of fig. 1.

The pressure module adopts a mode of pushing a medium by a constant pressure air source, and a set of constant pressure air source is formed by using a Kammer brand KLP01 diaphragm pump purchased from Kanzhen fluid technology (Shanghai) Limited, a Songtao brand DP-101 type air pressure sensor switch module purchased from Shenzhen Shangfeng apparatus instrument Limited and a 1L volume stainless steel air storage tank; pushing the medium in the serum bottle by a constant pressure gas source; the serum bottle is connected with the detection pipeline through a polytetrafluoroethylene tube with the inner diameter of 0.6mm, so that in actual operation, the gas pushes the mineral oil and pushes the liquid sample to move.

Wherein the medium is mineral oil, and the pressure of the gas source is controlled at 8 KPa.

The detection pipeline is in a corrugated shape as shown in figure 1, the cross section of the detection pipeline is square, the pipe diameter is 0.6mm multiplied by 0.6mm, the total length of the detection pipeline is 60cm, and the detection pipeline is made of polymethyl methacrylate (PMMA);

the pressure sensor uses a miniature gas-liquid universal pressure sensor (XGZP 6847 model pressure sensor module purchased from WU lake core sensory sensor technology, Inc.) to output a 0-5V voltage signal with a measuring range of 0-10 KPa.

The sample introduction module is composed of a positive pressure module (connected with positive pressure), a negative pressure module (connected with negative pressure), a sample introduction port, a buffer pipeline (used as a sample channel and a medium channel), a sample transfer port and the like, and the schematic diagram of the sample introduction module is shown in fig. 2. The positive pressure module is shared with the pressure supply module; the negative pressure module comprises a Kamoel brand KLP01 diaphragm pump purchased from Kachuan er fluid technology (Shanghai) Limited company, a Songtao brand DP-101 air pressure sensor switch module purchased from Shenzhen Shangfeng instrument limited company and a 250mL capacity stainless steel air storage tank, so as to form a set of stable and constant negative pressure air source; a stable negative pressure air source is connected with the serum bottle; the serum bottle is connected with the negative pressure interface of the sample injector through a polytetrafluoroethylene tube with the inner diameter of 0.6 mm. (ii) a The sample inlet is a needle-shaped stainless steel short pipe with the inner diameter of 0.6mm, and is provided with a cap type sealing cover, and the sample inlet is sealed by the sealing cover when the sample introduction operation is not needed; the buffer pipeline is a PMMA pipeline with the cross section of 0.6mm multiplied by 0.6mm, and is directly communicated with the corresponding interface of the detection pipeline through the sample transfer outlet.

Materials used in the experiment:

sheep plasma (for heparin sodium titer detection) was purchased from litsea cubeba to Ming Biochemical auxiliary factory, stored at-18 ℃ and thawed at 4 ℃ before the experiment and activated at 37 ℃ for 1 hour.

The calcium chloride solution purchased from the company Hissemcang Biotechnology (Wuxi) Ltd has a calcium ion concentration of 0.02mol/L, is prepared at the above concentration, is stored at a low temperature of 4 ℃ and is preheated to room temperature when used. The calcium ion is used for promoting coagulation reaction of sheep plasma.

After the experimental material is prepared, taking the activated goat plasma, adding calcium chloride, and timing (taking 0 second at this time), wherein the sample is positioned in a centrifugal tube; samples were injected through the injection module and detection was started at the 120 second time point.

Wherein, the sample A is the calcium chloride solution added with 85 mu L into 120 mu L of the sheep plasma, the sample B is the calcium chloride solution added with 80 mu L into 120 mu L of the sheep plasma, and the sample C is the calcium chloride solution added with 75 mu L into 120 mu L of the sheep plasma.

Fig. 9 shows the blood coagulation process of the samples A, B and C detected by the detecting device of the present invention, and it can be seen from fig. 9 that the three samples start to coagulate after about 200 seconds after the calcium chloride is added. And enters the plateau state after about 250 seconds.

It can be seen that the time to start coagulation is not substantially affected after adding different amounts of calcium chloride which promotes the coagulation reaction of the sheep plasma. But the pressure when reaching the plateau state is different due to the different amount of calcium ions added, which reflects the different intensity of blood clots formed due to the different concentration of calcium ions added to promote the coagulation reaction of the sheep plasma.

The results of the above examples show that the time at which the liquid solidifies and the intensity of the solidification of the reaction liquid can be effectively detected using the apparatus of the present invention.

The present application is susceptible to various modifications and alternative forms, specific embodiments have been shown by way of example in the drawings and have been described in detail herein. However, the application is not intended to be limited to the particular forms disclosed. On the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the scope of the application, which is defined by the appended claims and their legal equivalents.

The numerical ranges recited in the present invention each include data for both endpoints of the numerical range, and also include each of the specific values in the numerical range, and the numerical values can be combined with the endpoints at will to form a new subrange.

Claims

1. An apparatus for detecting solidification of a liquid, comprising:

A pressure sensor for detecting a pressure at an inlet of the detection pipe and outputting a pressure signal;

the shape of the detection pipeline is selected from one or more than two of a corrugated shape, a broken line shape and a square wave shape;

the pressure feeding module pushes the sample to move in the detection pipeline at a constant pressure or the pressure feeding module pushes the sample to move in the detection pipeline at a constant speed;

the pressure supply module, the sample introduction module and the detection pipeline are in fluid communication;

the advance kind module includes:

the sample channel and the media channel are in fluid communication via a common receptacle;

the length of the sample channel is longer than that of the medium channel;

the inner diameter of the sample channel is smaller than the inner diameter of the medium channel, and the medium channel and the sample channel are in the form of a sleeve, namely the medium channel is positioned at the outer side of the sample channel.

2. The device of claim 1, wherein the detection conduit is a microchannel having an inner diameter of 10 micrometers to 5 millimeters.

3. The device of claim 1, wherein the detection conduit is a microchannel having an inner diameter of 50 micrometers to 2 millimeters.

4. The device of claim 1, wherein the detection conduit is a microchannel having an inner diameter of 100 micrometers to 1 millimeter.

5. The device of claim 1, wherein the detection conduit is a microchannel having an inner diameter of 200 micrometers to 0.6 millimeters.

6. The device of claim 1, wherein the sample channel has an inner diameter of 10 microns to 5 millimeters and the media channel has an inner diameter of 5 microns to 10 millimeters.

7. The device of claim 1, wherein the sample channel has an inner diameter of 50 micrometers to 2 millimeters.

8. The device of claim 1, wherein the sample channel has an inner diameter of 100 micrometers to 1 millimeter.

9. The device of claim 1, wherein the sample channel has an inner diameter of 200 micrometers to 0.6 millimeters.

10. The device of claim 1, wherein the media channel has an inner diameter of 25 microns to 4 millimeters.

11. The device of claim 1, wherein the media channel has an inner diameter of 50 microns to 2 millimeters.

12. The device of claim 1, wherein the media channel has an inner diameter of 100 microns to 1.2 millimeters.

13. The device of claim 1, wherein the ratio of the inner diameters of the sample channel and the medium channel (sample channel inner diameter/medium channel inner diameter) is in the range of 1:5 to 1: 2.

14. The apparatus of claim 1, wherein the sample introduction module and the detection conduit are formed of or coated with a hydrophobic material.

15. The device of any one of claims 1 to 14, wherein the entire device is filled with the medium before the device for detecting the solidification of the liquid is put into use.

16. The device according to any one of claims 1 to 14, wherein the liquid sample is a blood sample, or a protein liquid sample, or other liquid sample that deforms due to polymerization of macromolecules.

17. A method for detecting liquid coagulation using a device comprising a sample introduction module, a pressure feed module, a detection conduit, and a pressure sensor, comprising the steps of:

Detecting the pressure at the inlet of the detection pipeline by using a pressure sensor and outputting a pressure signal;

the advance kind module includes:

the length of the sample channel is longer than that of the medium channel;

18. The method of claim 17, further comprising the steps of:

before detection, the whole detection system is filled with a medium,

19. The method according to claim 17 or 18, wherein the step of feeding the sample module comprises the steps of:

20. The method of claim 19, wherein the primary sample and the new primary sample are different liquid samples.

21. The method of claim 17 or 18, wherein the liquid sample is a blood sample, or a protein liquid sample, or other liquid sample that deforms due to polymerization of macromolecules.

22. The method of claim 17 or 18, which is detected using the device of any one of claims 1 to 16.