CN111398615A - Detection system and method - Google Patents

Detection system and method Download PDF

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CN111398615A
CN111398615A CN202010379518.6A CN202010379518A CN111398615A CN 111398615 A CN111398615 A CN 111398615A CN 202010379518 A CN202010379518 A CN 202010379518A CN 111398615 A CN111398615 A CN 111398615A
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measured
reaction site
sample
measurement substance
substance
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廖常宇
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Sichuan danuodi Technology Co., Ltd
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Chengdu Liangyi Technology Co ltd
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/5302—Apparatus specially adapted for immunological test procedures
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
    • G01N33/582—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with fluorescent label
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00029—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with flat sample substrates, e.g. slides
    • G01N2035/00099—Characterised by type of test elements
    • G01N2035/00158—Elements containing microarrays, i.e. "biochip"

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Abstract

The application provides a detection system and a method, which are applied to immunoassay, wherein the detection system comprises: the device comprises a micro-fluidic device, a controller, an ultrasonic generator and a measuring device; the controller is respectively connected with the ultrasonic generator and the measuring device; the micro-fluidic device is provided with a micro-channel, at least one reaction site is arranged in the micro-channel, and the reaction site is used for placing a known test object; the controller is used for controlling the ultrasonic generator to generate ultrasonic waves, the coverage area of the ultrasonic waves comprises at least one reaction site in the microchannel, and the ultrasonic waves are used for improving the reaction efficiency of the known test object and the object to be measured; the measuring device is used for measuring the tracer state of the reaction site after reaction and returning the tracer state to the controller, and the tracer state of the reaction site is used for representing the amount of the object to be measured in the sample to be measured; the controller is also used for outputting a detection result corresponding to the object to be measured in the sample to be detected according to the tracer state of the reaction site, so that the efficiency of the immunodetection is improved.

Description

Detection system and method
Technical Field
The present application relates to the field of detection, and in particular, to a detection system and method.
Background
The immune system consists of immune organs, immune cells, immune molecules and a lymphatic circulation network, and diseases such as tumor stages, allergy degree and the like are closely related to the immune system. Thus, the state of the immune system can be judged by measuring the amount of antigen and antibody in the immune system by an immunoassay. In an immunoassay, the amount of antigen or antibody to be measured can be determined by incubating the antigen and the sample so that specific antibodies bind to the antigen during the incubation.
In the prior art, a micro-fluidic chip is often adopted for carrying out immunity measurement, and a micro-channel with smaller size is arranged in the micro-fluidic chip so as to utilize the capillary phenomenon to enable liquid to flow in the channel. At this time, the flow of the sample to be measured in the channel is mainly laminar flow, the reaction efficiency between the antibody and the antigen is low, and the result of the immunoassay can be obtained only by long-time incubation.
Disclosure of Invention
An object of the embodiments of the present application is to provide a detection system and method for improving the efficiency of immunoassay.
In a first aspect, an embodiment of the present invention provides a detection system, which is applied to an immunoassay, where the detection system includes: the device comprises a micro-fluidic device, a controller, an ultrasonic generator and a measuring device; the controller is respectively connected with the ultrasonic generator and the measuring device; the micro-fluidic device is provided with a micro-channel, at least one reaction site is arranged in the micro-channel, the reaction site is used for placing a known test object, and the known test object is used for reacting and combining with an object to be measured in a sample to be measured when the sample to be measured flows into the micro-channel; the controller is used for controlling the ultrasonic generator to generate ultrasonic waves, the coverage range of the ultrasonic waves comprises at least one reaction site in a micro-channel, and the ultrasonic waves are used for improving the reaction efficiency of the known test object and the object to be measured; the measuring device is used for measuring the tracer state of the reaction site after reaction and returning the tracer state to the controller, and the tracer state of the reaction site is used for representing the amount of the object to be measured in the sample to be measured; and the controller is also used for outputting a detection result corresponding to the object to be measured in the sample to be measured according to the tracer state of the reaction site.
According to the embodiment of the application, the ultrasonic generator is arranged, and the ultrasonic wave generated by the ultrasonic generator is utilized to increase the reaction efficiency of the object to be tested and the known test object in the microfluidic device, so that the combination of the object to be tested and the known test object is accelerated, the incubation time of the immunoassay is shortened, and the immunoassay efficiency is improved.
In an optional embodiment, a sample input port is disposed at one end of the microchannel, and the sample input port is used for injecting the sample to be detected, so as to input the sample into the microchannel, and store the sample to be detected after reaction in the microchannel, so as to avoid environmental pollution caused by waste liquid after reaction.
In an optional embodiment, one end of the microchannel is provided with a sample input port, the other end of the microchannel is provided with a waste liquid output port, the sample input port is used for injecting the sample to be detected, the waste liquid output port is connected with a waste liquid vessel, and the waste liquid output port is used for transmitting the sample to be detected after reaction to the waste liquid vessel.
This application embodiment can ensure the safe recovery of the sample after the reaction through setting up waste liquid ware and waste liquid delivery outlet to this avoids the pollution that causes the environment.
In an alternative embodiment, two reaction sites are disposed in the microchannel, the known test substance includes a first labeled measurement substance and a first fixed measurement substance, the first labeled measurement substance is disposed in the reaction site at an end of the microchannel near the sample input port, the first fixed measurement substance is disposed in the reaction site at an end of the microchannel near the waste liquid output port, the first labeled measurement substance is used for labeling the measurement substance, and the first fixed measurement substance is used for fixing the labeled measurement substance.
The embodiment marks the object to be measured by placing the first marking measuring object in one mounting position and places the first fixing measuring object in the other mounting position, so that the amount of the object to be measured in the sample can be accurately measured by using a sandwich method.
In an alternative embodiment, two reaction sites are disposed in the microchannel, the known test substance comprises a second labeled measurement substance and a second immobilized measurement substance, the second labeled measurement substance is disposed in the reaction site at an end of the microchannel near the sample input port, the second immobilized measurement substance is disposed in the reaction site at an end of the microchannel near the waste liquid output port, both the second immobilized measurement substance and the measurement substance compete for binding with the second labeled measurement substance, and the second immobilized measurement substance is further used for immobilizing the second labeled measurement substance.
The embodiment of the application places the first fixed measuring object at one reaction position and places the second mark measuring object at the other reaction position, so that the first fixed measuring object and the object to be measured are combined with the second mark measuring object, and the first fixed measuring object and the object to be measured are in a competitive relationship, thereby accurately measuring the amount of the object to be measured in the sample by using a competition method.
In an alternative embodiment, a reaction site is disposed in the microchannel, the known test substance includes a third fixed measurement substance, the third fixed measurement substance is disposed in the reaction site, the sample to be tested further includes a third labeled measurement substance, the third labeled measurement substance is used for labeling the object to be measured, and the third fixed measurement substance is used for fixing the labeled object to be measured.
In the embodiment of the application, the third marked measuring object and the object to be measured in the sample to be measured are combined in advance through reaction, and then the marked object to be measured and the third fixed measuring object placed on the reaction site are combined and reacted to fix the marked object to be measured, so that the amount of the object to be measured in the sample is accurately measured by using a sandwich method.
In an alternative embodiment, a reaction site is disposed in the microchannel, the known test substance comprises a fourth immobilized measurement substance, the fourth immobilized measurement substance is disposed in the reaction site, the sample to be tested further comprises a fourth labeled measurement substance, both the fourth immobilized measurement substance and the measurement substance compete for binding with the fourth labeled measurement substance, and the fourth immobilized measurement substance is further used for immobilizing the fourth labeled measurement substance.
In the embodiment of the application, the fourth labeled measuring object is arranged to be reacted and combined with the object to be measured in the sample to be measured in advance, and then the fourth labeled measuring object which is not reacted and combined is subjected to a combination reaction with the third fixed measuring object placed on the reaction site to fix the fourth labeled measuring object which is not reacted with the object to be measured, so that the amount of the object to be measured in the sample is accurately measured by using a competition method.
In an alternative embodiment, the diameter of the side of the sample input port remote from the waste output port is greater than the diameter of the side close to the waste output port.
The sample input port is arranged in a funnel shape, so that a sample to be tested can be injected into a micro-channel of the micro-fluidic device.
In an alternative embodiment, the microchannel is provided with a filter element on a side thereof close to the sample input port, the filter element being used for filtering impurities in the sample to be tested.
The embodiment of the application filters the impurities in the sample to be detected by setting the filter piece, so that the accuracy of the immunodetection is improved.
In a second aspect, an embodiment of the present invention provides a detection method applied to a detection system, where the detection method includes a microfluidic device, a controller, an ultrasonic generator, and a measurement device; the controller is respectively connected with the ultrasonic generator and the measuring device; the micro-fluidic device is provided with a micro-channel, at least one reaction site is arranged in the micro-channel, the reaction site is used for placing a known test object, and the known test object is used for reacting and combining with an object to be measured in a sample to be measured when the sample to be measured flows into the micro-channel; the detection method comprises the following steps: acquiring a detection start signal; according to the detection starting signal, starting timing and controlling an ultrasonic generator in the detection system to generate ultrasonic waves, wherein the coverage range of the ultrasonic waves comprises at least one reaction site in a micro-channel, and the ultrasonic waves are used for improving the reaction efficiency of the known test object and the object to be measured; when the timing duration reaches a preset duration, sending a detection signal to a measuring device in a detection system so as to enable the measuring device to measure the tracer state of a reaction site after reaction, wherein the tracer state of the reaction site is used for representing the amount of an object to be measured in the sample to be measured; and receiving the tracer state of the reaction site returned by the measuring device, and outputting a detection result corresponding to the object to be measured in the sample to be measured according to the tracer state of the reaction site.
According to the embodiment of the application, the ultrasonic wave generated by the ultrasonic generator is utilized to increase the reaction efficiency of the object to be tested and the known test object in the microfluidic device, so that the combination of the object to be tested and the known test object is accelerated, the incubation time of the immunoassay is shortened, and the immunoassay efficiency is improved.
In an optional embodiment, the outputting a detection result corresponding to the object to be measured in the sample to be measured according to the tracer state of the reaction site includes: and processing the tracer state of the reaction site by utilizing a pre-established relation corresponding graph to determine the detection result of the object to be measured in the sample to be measured, wherein the relation corresponding graph is used for representing the corresponding relation between the tracer state of the reaction site and the amount of the object to be measured.
The embodiment of the application can rapidly determine the amount of the object to be measured in the sample according to the tracer state of the reaction site by using the relation mapping chart, and the efficiency of outputting the detection result corresponding to the object to be measured in the sample to be measured is improved.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings that are required to be used in the embodiments of the present application will be briefly described below, it should be understood that the following drawings only illustrate some embodiments of the present application and therefore should not be considered as limiting the scope, and that those skilled in the art can also obtain other related drawings based on the drawings without inventive efforts.
Fig. 1 is a schematic structural diagram of a detection system according to an embodiment of the present disclosure;
fig. 2 is a schematic structural diagram of a microfluidic device according to an embodiment of the present disclosure;
FIG. 3 is a schematic structural diagram of a microchannel according to an embodiment of the present disclosure;
FIG. 4 is a schematic structural diagram of another microchannel provided in the embodiments of the present application;
fig. 5 is a schematic flowchart of a detection method according to an embodiment of the present application.
Icon: 100-a detection system; 110-a controller; 120-a microfluidic device; 121-a microchannel; 1211 — a sample input port; 1212-a waste outlet; 1213-filter element; 1214-a reaction site; 130-an ultrasonic generator; 140-measuring means.
Detailed Description
The technical solutions in the embodiments of the present application will be described below with reference to the drawings in the embodiments of the present application.
In the immunoassay, an antigen-antibody incubation reaction is performed, and the incubation process is a kinetic process of competitive binding. The efficiency of specific binding due to antigen and antibody is millions to billions times that of non-specific binding. For example, when a specific antibody competes with a non-specific antibody, i.e., for the antigen to be measured, both the specific and non-specific antibodies are intended to bind to the antigen, while the specific antibody competes with the non-specific antibody.
Thus, the amount of the antigen corresponding to the specific antibody in the sample can be determined by sufficiently specifically binding the antigen to the specific antibody over time under the same reaction efficiency. And finally, determining the individual vaccination result and the like corresponding to the sample to be detected according to the result obtained by the immunoassay. Therefore, how to obtain the result of the immunoassay rapidly is an urgent problem to be solved in the medical field, and the present application provides a detection system and a detection method to improve the efficiency of the immunoassay.
Fig. 1 is a schematic structural diagram of a detection system 100 provided in an embodiment of the present application, which is applied to an immunoassay, where the detection system 100 includes: a controller 110, a microfluidic device 120, an ultrasonic generator 130, and a measurement apparatus 140; the controller 110 is respectively connected with the ultrasonic generator 130 and the measuring device 140; the micro-fluidic device 120 is provided with a micro-channel 121, at least one reaction site 1214 is arranged in the micro-channel 121, the reaction site 1214 is used for placing a known test object, and the known test object is used for reacting and combining with an object to be measured in a sample to be measured when the sample to be measured flows into the micro-channel 121; the controller 110 is configured to control the ultrasonic generator 130 to generate ultrasonic waves, the coverage of the ultrasonic waves includes at least one reaction site 1214 in the micro-channel 121, and the ultrasonic waves are used to improve the efficiency of the reaction between the known test substance and the object to be measured; the measuring device 140 is configured to measure a tracer state of the reaction site 1214 after the reaction and return the tracer state to the controller 110, where the tracer state of the reaction site 1214 is used to characterize an amount of the substance to be measured in the sample to be measured; the controller 110 is further configured to output a detection result corresponding to the object to be measured in the sample to be measured according to the tracer status of the reaction site 1214.
The microfluidic device 120 may be a microfluidic chip, and the effective structure for receiving the fluid through the microfluidic chip has a micron scale at least in one dimension. Due to the micro-scale structure, the fluid exhibits and develops specific properties therein that differ from those of the macro-scale. Thus developing unique assay-generated properties. In the embodiment of the present application, the microfluidic device 120 is configured with the micro-channel 121 having a smaller diameter, so as to utilize the capillary phenomenon to circulate the sample to be measured in the micro-channel 121, and perform an incubation reaction with the known test substance disposed in the micro-channel 121, so that the reaction site 1214 can present different tracer states after the known test substance is combined with the sample to be measured by the reaction. The measuring device 140 can measure the tracer state of the reaction site 1214 after the reaction, and convert the tracer state into an electrical signal to be transmitted to the controller 110, so that the controller 110 receives the electrical signal corresponding to the tracer state and determines the detection result of the sample to be measured according to the tracer state.
For example, a known test substance on the reaction site 1214 reacts with a large amount of a substance to be measured with a fluorescent tracer, the reaction site 1214 shows specific fluorescence after the reaction, and the fluorescence intensity of the corresponding reaction site 1214 after the reaction is different due to the different content of the substance to be measured in the sample to be measured. Thus, the tracer state of the reaction site 1214 may be the fluorescence intensity of the reaction site 1214, the measurement device 140 may measure the fluorescence intensity of the reaction site 1214, and the controller 110 may calculate the amount of the object to be measured from the fluorescence intensities of the reaction site 1214. The measuring device 140 may be a fluorescence detection photodiode, and the fluorescence detection photodiode converts an optical signal into an electrical signal, i.e., converts the fluorescence intensity of the reaction site 1214 into a corresponding current signal. The type of the measuring device 140 is not limited, and can be adjusted according to the actual detection requirement.
For another example, a known test substance on the reaction site 1214 reacts with a large amount of an enzyme-labeled substance to be measured, so that the reaction site 1214 after the reaction can develop a color reaction with a substrate to thereby develop a color. Meanwhile, due to the different contents of the substances to be measured in the samples to be measured, the colors of the corresponding reaction sites 1214 after reaction are also different. Thus, the tracer state of the reaction site 1214 can be the color displayed by the reaction site 1214, the measuring device 140 can measure the color of the reaction site 1214, and the controller 110 can calculate the amount of the object to be measured according to the different colors of the reaction site 1214. The measuring device 140 may be an image capturing device, and the image capturing device captures an image of the reaction site 1214, so that the controller 110 determines the color of the reaction site 1214 according to the image of the reaction site 1214. The specific type of the measuring device 140 is not limited, and can be adjusted according to the actual detection requirement.
For another example, a known test substance on the reaction site 1214 is reacted with an isotope-labeled object to be measured, and the reaction site 121 after the reaction can detect different isotope contents by radiation detection. Thus, the tracer state of the reaction site 1214 can be the radiation intensity of the reaction site 1214, the measuring device 140 can measure the radiation intensity of the reaction site 1214, and the controller 110 can calculate the amount of the object to be measured according to the different radiation intensities of the reaction site 1214. The measuring device 140 may be a radiation detecting device, and the radiation detecting device is used to collect the radiation intensity of the reaction site 1214 so that the controller 110 can determine the amount of the object to be measured according to the radiation intensity of the reaction site 1214. The specific type of the measuring device 140 is not limited, and can be adjusted according to the actual detection requirement.
It can be stated that there are many types of immunoassays, for example, five immunoassays for hepatitis b that detect whether there is hepatitis b surface antibody in a sample to be tested, and further, for example, whether there is allergic antigen in a sample to be tested. Therefore, for different immunoassays, the types of known test substances disposed in the micro channel 121 may be different, and may be antigens or antibodies, and the specific types of known test substances may be adjusted according to the specific types of immunoassays. In addition, the sample to be detected can be individual body fluid or liquid in a culture dish, the specific type of the sample to be detected is not limited, and the sample to be detected can be adjusted according to actual detection requirements.
Furthermore, the ultrasonic generator 130 may be disposed near the microfluidic device 120, and generates ultrasonic waves with the ultrasonic generator 130 as an origin, and the ultrasonic waves may cause micro bubble nuclei in the liquid to vibrate under the action of the ultrasonic waves, so that the liquid in the microchannel 121 forms a turbulent flow, which is equivalent to "stirring" the known measurement object and the object to be measured in the microchannel, thereby improving the reaction efficiency of the known measurement object and the object to be measured, so that the known measurement object and the object to be measured may be combined more quickly, shortening the incubation time in the immunoassay process, and improving the immunoassay efficiency.
Furthermore, the ultrasonic wave generated by the ultrasonic generator 130 can cover one reaction site 1214 or a plurality of reaction sites 1214 in the micro-channel 121, thereby ensuring that the reaction efficiency of the known test substance and the object to be measured is improved. The specific coverage of the ultrasonic wave can be adjusted according to the actual detection requirement.
Fig. 2 is a schematic structural diagram of a microfluidic device 120 provided in an embodiment of the present application, one end of the microchannel 121 is provided with a sample input port 1211, and the other end is provided with a waste liquid output port 1212, the sample input port 1211 is used for injecting the sample to be detected, the waste liquid output port 1212 is connected with a waste liquid dish, and the waste liquid output port 1212 is used for transmitting the sample to be detected after the reaction to the waste liquid dish.
Thus, a sample to be measured can be injected into the microchannel 121 from the sample input port 1211, so that an object to be measured in the sample can be reacted and combined with a known test object placed in the microfluidic device 120, and a waste liquid after the reaction is completed, which includes a liquid of the sample to be measured and a substance that is not reacted and combined, is output through the waste liquid output port 1212. The unreacted bound substances may include substances in the sample that do not specifically bind to known test substances, such as: when the test substance is known as an antigen, the substance that is not subjected to reactive binding may be a nonspecific antibody corresponding to the antigen or an antigen. The unreacted bound species may also include impurities in the sample to be tested, such as hemoglobin.
The embodiment of the application considers that the reflected sample may still have infectivity, so that the safe recovery of the reacted sample can be ensured by arranging the waste liquid vessel and the waste liquid output port 1212, thereby avoiding pollution to the environment.
It should be noted that the sample to be tested may be manually injected into the sample input 1211 through a device such as a dropper by a user, or may be automatically injected into the sample input 1211 through a device such as a mechanical arm, and the specific injection manner of the sample to be tested is not limited, and may be selected according to actual requirements.
As another embodiment of the present application, one end of the microchannel is provided with a sample input port, and the sample input port is used for injecting the sample to be measured. Wherein, the micro-channel can be only provided with a sample input port and not provided with a waste liquid discharge port, so that the waste liquid after reaction is left in the micro-channel, and the environmental pollution caused by the waste liquid after random discharge is avoided.
As an embodiment of the present application, a diameter of a side of the sample input port 1211 distant from the waste liquid output port 1212 is larger than a diameter of a side close to the waste liquid output port 1212. Thus, by setting the sample input port 1211 to be "funnel-shaped", the sample to be measured can be more conveniently injected from the sample input port 1211.
On the basis of the above embodiment, a filter 1213 is disposed on a side of the micro channel 121 close to the sample input 1211, and the filter 1213 is used for filtering impurities in the sample to be tested. The impurities in the sample to be detected can be macromolecular substances such as hemoglobin and glucose, and the influence of the impurities in the sample to be detected on the accuracy of the immunoassay can be reduced through the filtering element 1213.
Fig. 3 is a schematic structural diagram of a micro channel 121 according to an embodiment of the present disclosure, and as an implementation manner of the present disclosure, two reaction sites 1214 are disposed in the micro channel 121, the known test substance includes a first labeled measurement substance and a first fixed measurement substance, the first labeled measurement substance is disposed in the reaction site 1214 at an end of the micro channel 121 close to the sample input port 1211, the first fixed measurement substance is disposed in the reaction site 1214 at an end of the micro channel 121 close to the waste liquid output port 1212, the first labeled measurement substance is used to label the object to be measured, and the first fixed measurement substance is used to fix the labeled object to be measured.
Wherein, the first label measuring object carries a label which can be an enzyme label or a fluorescent agent. The first labelled measurement species may be reactively bound to a specific measurement species such that the carried label labels the measurement species. The first fixed measurement object can be fixed on the corresponding reaction site 1214, and is combined with the object to be measured through incubation reaction, and the object to be measured is fixed on the reaction site 1214, so that the labeled object to be measured can change the state of the tracer in the reaction site 1214.
Taking the object to be measured as an antigen for illustration, the first labeled measuring object may be an antibody a carrying a tracer fluorescent substance, the first fixed measuring object may be an antibody B fixed on the reaction site 1214, and both the antibody a and the antibody B may specifically bind to an antigen C to be measured in the sample to be measured. Therefore, when a sample to be measured is injected into the micro channel 121, the antigen C to be measured reacts and combines with the antibody a, the antibody a also marks the antigen C to be measured, and the marked antigen C to be measured reacts and combines with the antibody B and is fixed on the reaction site 1214 where the antibody B is located, so that the reaction site 1214 emits fluorescence. At this time, the higher the fluorescence intensity, the more the content of the antigen C to be measured in the sample.
Taking the object to be measured as an antibody for illustration, the first labeled measuring object may be an antigen D carrying a tracer fluorescent substance, the first fixed measuring object may be an antibody E fixed on the reaction site 1214, and both the antibody E and the antibody F to be measured in the sample to be measured can be specifically bound to the antigen D. Therefore, when the sample to be measured is injected into the micro channel 121, the antibody F to be measured reacts and binds with the antigen D, the antigen D also labels the antibody F to be measured, and the product of the reaction and binding of the antigen D and the antibody F reacts and binds with the antibody E and is fixed on the reaction site 1214 where the antibody E is located, so that the reaction site 1214 emits fluorescence. At this time, the higher the fluorescence intensity, the more the content of the antibody F to be measured in the sample.
Thus, with the sandwich method, the amount of the substance to be measured in the sample can be determined quickly from the fluorescence intensity of the reaction site 1214. The specific types of the first marked measuring object and the first fixed measuring object can be adjusted according to the type of the object to be measured.
As another embodiment of the present application, two reaction sites 1214 are disposed in the microchannel 121, the known test substance includes a second labeled test substance and a second fixed test substance, the second labeled test substance is disposed in the reaction site 1214 at an end of the microchannel 121 close to the sample input port 1211, the second fixed test substance is disposed in the reaction site 1214 at an end of the microchannel 121 close to the waste liquid output port 1212, and both the second fixed test substance and the test substance compete with the second labeled test substance for binding, and the second fixed test substance is further used for fixing the second labeled test substance.
Wherein the second fixed measurement object and the object to be measured both compete with the second labeled measurement object for binding, i.e., indicating that both the second fixed measurement object and the object to be measured want to bind with the second labeled measurement object under a constant amount of the second labeled measurement object, and the second fixed measurement object and the object to be measured are in a competitive relationship. Thus, when the amount of the second labeled measurement substance and the amount of the second immobilized measurement substance are constant, the tracer state of the reaction site 1214 can be brought into a competitive binding state, and the amount of the measurement substance can be reflected in a reverse direction.
It should be noted that the second labeled measurement substance and the second immobilized measurement substance in the micro channel 121 are respectively disposed in different reaction sites 1214, and they are not combined with each other without injecting the sample to be measured.
Taking the object to be measured as an antigen for illustration, the first labeled measuring object may be an antibody G carrying a tracer fluorescent substance, the first fixed measuring object may be an antigen H fixed on the reaction site 1214, the antigen H and the antigen I to be measured in the sample to be measured can both specifically bind to the antibody G, and the antigen H and the antigen I to be measured belong to a competition relationship. Therefore, when the sample to be measured is injected into the micro channel 121, the antigen I to be measured reacts and binds with a portion of the antibody G, and another portion of the antibody G reacts and binds with the antigen H, and is fixed on the reaction site 1214 where the antigen H is located, so that the reaction site 1214 emits fluorescence. At this time, the higher the fluorescence intensity, the smaller the content of the antigen I to be measured in the sample.
Taking an object to be measured as an antibody for illustration, the first labeled measurement object may be an antigen J carrying a tracer fluorescent substance, the first fixed measurement object may be an antibody K fixed on the reaction site 1214, both the antibody K and an antibody L to be measured in a sample to be measured may specifically bind to the antigen J, and the antibody K and an antibody L to be measured belong to a competitive relationship.
Thus, by the above competition method, the amount of the substance to be measured in the sample can be determined in reverse quickly from the fluorescence intensity of the reaction site 1214. The specific types of the second marked measuring object and the second fixed measuring object can be adjusted according to the type of the object to be measured.
Fig. 4 is a schematic structural diagram of another micro channel 121 provided in the embodiment of the present application, as an implementation manner of the present application, a reaction site 1214 is disposed in the micro channel 121, the known test substance includes a third fixed measurement substance, the third fixed measurement substance is placed in the reaction site 1214, the sample to be tested further includes a third labeled measurement substance, the third labeled measurement substance is used for labeling the object to be measured, and the third fixed measurement substance is used for fixing the labeled object to be measured.
In the embodiment of the present application, the third labeled measurement object and the object to be measured are combined by reacting outside the micro channel 121, and then the labeled object to be measured is injected into the micro channel 121, combined with the third fixed measurement object, and fixed on the corresponding reaction site 1214. The binding mode of the third labeled measuring substance, the third immobilized measuring substance and the object to be measured is the same as the immunoassay mode of the sandwich method, and the details are not repeated here.
In another embodiment of the present application, a reaction site 1214 is disposed in the microchannel 121, the known test substance includes a fourth fixed measurement substance, the fourth fixed measurement substance is disposed in the reaction site 1214, the sample to be tested further includes a fourth labeled measurement substance, the fourth fixed measurement substance and the object to be measured both compete for binding with the fourth labeled measurement substance, and the fourth fixed measurement substance is further used for fixing the fourth labeled measurement substance.
In the embodiment of the present application, the fourth labeled measurement object and the object to be measured are reacted and combined outside the micro channel 121, and then the reacted sample to be measured is injected into the micro channel 121, so that the fourth labeled measurement object that is not combined with the object to be measured in the sample to be measured and the fourth fixed measurement object are reacted and fixed on the corresponding reaction site 1214. The combination of the fourth labeled measuring substance, the fourth immobilized measuring substance and the object to be measured is the same as the immunoassay method of the competition method, and the details are not repeated here.
Fig. 5 is a schematic flow chart of a detection method provided in an embodiment of the present application, and based on the same inventive concept, a detection method is further provided in an embodiment of the present application, and is applied to the detection system 100, wherein the microfluidic device 120, the controller 110, the ultrasonic generator 130, and the measurement apparatus 140; the controller 110 is respectively connected with the ultrasonic generator 130 and the measuring device 140; the micro-fluidic device 120 is provided with a micro-channel 121, at least one reaction site 1214 is arranged in the micro-channel 121, the reaction site 1214 is used for placing a known test object, and the known test object is used for reacting and combining with an object to be measured in a sample to be measured when the sample to be measured flows into the micro-channel 121; the detection method comprises the following steps:
step 510: a detection start signal is acquired.
The detection start signal may be a signal sent by the power supply to the controller when the user turns on the power supply, or a signal sent by the user to the controller through the terminal device. The specific type of the detection start signal is not limited, and can be adjusted according to actual requirements.
Step 520: and according to the detection starting signal, starting timing and controlling an ultrasonic generator in the detection system to generate ultrasonic waves, wherein the coverage range of the ultrasonic waves comprises at least one reaction site in a micro-channel, and the ultrasonic waves are used for improving the reaction efficiency of the known test object and the object to be measured.
Step 530: and when the timing duration reaches a preset duration, sending a detection signal to a measuring device in the detection system so as to enable the measuring device to measure the tracer state of the reaction site after reaction, wherein the tracer state of the reaction site is used for representing the amount of the object to be measured in the sample to be measured.
Step 540: and receiving the tracer state of the reaction site returned by the measuring device, and outputting a detection result corresponding to the object to be measured in the sample to be measured according to the tracer state of the reaction site.
In the embodiment of the present application, when the controller 110 receives the detection start signal, that is, the immunoassay is started, the controller 110 may control the ultrasonic generator to generate the ultrasonic wave, so as to accelerate the immunoassay efficiency. Meanwhile, the controller may start timing, when the timing duration reaches a preset duration, which is equivalent to that the reaction between the known test object and the object to be measured is completed, the controller 110 may control the measuring device 140 to measure the tracer state of the reaction site 1214, and the controller 110 outputs the detection result corresponding to the object to be measured in the sample to be measured according to the tracer state, so as to implement the rapid detection of immunity.
As an embodiment of the present application, step 540 may specifically include: and processing the tracer state of the reaction site by utilizing a pre-established relation corresponding graph to determine the detection result of the object to be measured in the sample to be measured, wherein the relation corresponding graph is used for representing the corresponding relation between the tracer state of the reaction site and the amount of the object to be measured.
Taking the label as the fluorescent agent as an example, when the sandwich method is used for immunoassay, the relationship map may include a positive correlation curve, the lower the fluorescence intensity of the reaction site 1214, the less the amount of the substance to be measured in the sample to be measured, and conversely, the higher the fluorescence intensity of the reaction site 1214, the more the amount of the substance to be measured in the sample to be measured. When the competitive method is used for the immunoassay, the relational mapping graph may include a curve with a negative correlation, the higher the fluorescence intensity of the reaction site 1214, the less the amount of the substance to be measured in the sample to be measured, and conversely, the lower the fluorescence intensity of the reaction site 1214, the more the amount of the substance to be measured in the sample to be measured.
Therefore, the quantity of the object to be measured in the sample to be measured can be quickly determined according to the relation corresponding diagram, so that the detection result corresponding to the object to be measured is output, and the efficiency of the immunodetection is improved.
Furthermore, the relational map can be plotted according to the historical fluorescence intensity of the reaction site 1214 in the plurality of immunoassays and the historical amount of the substance to be measured.
In summary, the embodiment of the present application provides a detection system 100 and a method, in which an ultrasonic generator 130 is disposed in the detection system 100, and the ultrasonic wave generated by the ultrasonic generator 130 is used to improve the reaction efficiency between an object to be tested and a known test object in a microfluidic device 120, thereby accelerating the combination between the object to be tested and the known test object, and shortening the incubation time of an immunoassay, so as to improve the efficiency of the immunoassay.
In the embodiments provided in the present application, it should be understood that the disclosed apparatus and method may be implemented in other ways. The above-described embodiments of the apparatus are merely illustrative, and for example, the division of the units is only one logical division, and there may be other divisions when actually implemented, and for example, a plurality of units or components may be combined or integrated into another system, or some features may be omitted, or not executed. In addition, the shown or discussed mutual coupling or direct coupling or communication connection may be an indirect coupling or communication connection of devices or units through some communication interfaces, and may be in an electrical, mechanical or other form.
In addition, units described as separate parts may or may not be physically separate, and parts displayed as units may or may not be physical units, may be located in one place, or may be distributed on a plurality of network units. Some or all of the units can be selected according to actual needs to achieve the purpose of the solution of the embodiment.
Furthermore, the functional modules in the embodiments of the present application may be integrated together to form an independent part, or each module may exist separately, or two or more modules may be integrated to form an independent part.
It should be noted that the functions, if implemented in the form of software functional modules and sold or used as independent products, may be stored in a computer readable storage medium. Based on such understanding, the technical solution of the present application or portions thereof that substantially contribute to the prior art may be embodied in the form of a software product stored in a storage medium and including instructions for causing a computer device (which may be a personal computer, a server, or a network device) to execute all or part of the steps of the method according to the embodiments of the present application. And the aforementioned storage medium includes: various media capable of storing program codes, such as a usb disk, a removable hard disk, a Read-Only Memory (ROM), a Random Access Memory (RAM), a magnetic disk, or an optical disk.
In this document, relational terms such as first and second, and the like may be used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions.
The above description is only an example of the present application and is not intended to limit the scope of the present application, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, improvement and the like made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims (10)

1. A test system for use in immunoassay testing, the test system comprising:
the device comprises a micro-fluidic device, a controller, an ultrasonic generator and a measuring device; the controller is respectively connected with the ultrasonic generator and the measuring device;
the micro-fluidic device is provided with a micro-channel, at least one reaction site is arranged in the micro-channel, the reaction site is used for placing a known test object, and the known test object is used for reacting and combining with an object to be measured in a sample to be measured when the sample to be measured flows into the micro-channel;
the controller is used for controlling the ultrasonic generator to generate ultrasonic waves, the coverage range of the ultrasonic waves comprises at least one reaction site in a micro-channel, and the ultrasonic waves are used for improving the reaction efficiency of the known test object and the object to be measured; the measuring device is used for measuring the tracer state of the reaction site after reaction and returning the tracer state to the controller, and the tracer state of the reaction site is used for representing the amount of the object to be measured in the sample to be measured; and the controller is also used for outputting a detection result corresponding to the object to be measured in the sample to be measured according to the tracer state of the reaction site.
2. The detection system according to claim 1, wherein one end of the microchannel is provided with a sample input port for injecting the sample to be detected.
3. The detection system according to claim 1, wherein one end of the microchannel is provided with a sample input port, and the other end of the microchannel is provided with a waste liquid output port, the sample input port is used for injecting the sample to be detected, the waste liquid output port is connected with a waste liquid vessel, and the waste liquid output port is used for transmitting the reacted sample to be detected into the waste liquid vessel.
4. The detection system according to claim 3, wherein two reaction sites are provided in the microchannel, the known test substance comprises a first labeled measurement substance and a first fixed measurement substance, the first labeled measurement substance is disposed in the reaction site at an end of the microchannel near the sample input port, the first fixed measurement substance is disposed in the reaction site at an end of the microchannel near the waste liquid output port, the first labeled measurement substance is used for labeling the measurement substance, and the first fixed measurement substance is used for fixing the labeled measurement substance.
5. The detection system according to claim 3, wherein two reaction sites are provided in the microchannel, the known test substance comprises a second labeled measurement substance and a second immobilized measurement substance, the second labeled measurement substance is disposed in the reaction site at an end of the microchannel near the sample input port, the second immobilized measurement substance is disposed in the reaction site at an end of the microchannel near the waste liquid output port, the second immobilized measurement substance and the measurement substance both compete for binding with the second labeled measurement substance, and the second immobilized measurement substance is further used for immobilizing the second labeled measurement substance.
6. The detection system according to claim 3, wherein a reaction site is disposed in the microchannel, the known test substance comprises a third fixed measurement substance, the third fixed measurement substance is disposed in the reaction site, the sample to be tested further comprises a third labeled measurement substance, the third labeled measurement substance is used for labeling the object to be measured, and the third fixed measurement substance is used for fixing the labeled object to be measured.
7. The test system according to claim 3, wherein a reaction site is disposed in the microchannel, the known test substance comprises a fourth immobilized measurement substance, the fourth immobilized measurement substance is disposed in the reaction site, the test sample further comprises a fourth labeled measurement substance, the fourth immobilized measurement substance and the object to be measured both compete for binding with the fourth labeled measurement substance, and the fourth immobilized measurement substance is further used for immobilizing the fourth labeled measurement substance.
8. The detection system according to any one of claims 3 to 7, wherein a diameter of a side of the sample input port remote from the waste liquid output port is larger than a diameter of a side close to the waste liquid output port.
9. The detection method is characterized by being applied to a detection system, wherein the detection system comprises a microfluidic device, a controller, an ultrasonic generator and a measuring device; the controller is respectively connected with the ultrasonic generator and the measuring device; the micro-fluidic device is provided with a micro-channel, at least one reaction site is arranged in the micro-channel, the reaction site is used for placing a known test object, and the known test object is used for reacting and combining with an object to be measured in a sample to be measured when the sample to be measured flows into the micro-channel;
the detection method comprises the following steps:
acquiring a detection start signal;
according to the detection starting signal, starting timing and controlling an ultrasonic generator in the detection system to generate ultrasonic waves, wherein the coverage range of the ultrasonic waves comprises at least one reaction site in a micro-channel, and the ultrasonic waves are used for improving the reaction efficiency of the known test object and the object to be measured;
when the timing duration reaches a preset duration, sending a detection signal to a measuring device in a detection system so as to enable the measuring device to measure the tracer state of a reaction site after reaction, wherein the tracer state of the reaction site is used for representing the amount of an object to be measured in the sample to be measured;
and receiving the tracer state of the reaction site returned by the measuring device, and outputting a detection result corresponding to the object to be measured in the sample to be measured according to the tracer state of the reaction site.
10. The detection method according to claim 9, wherein outputting a detection result corresponding to the object to be measured in the sample to be measured according to the tracer status of the reaction site comprises:
and processing the tracer state of the reaction site by utilizing a pre-established relation corresponding graph to determine the detection result of the object to be measured in the sample to be measured, wherein the relation corresponding graph is used for representing the corresponding relation between the tracer state of the reaction site and the amount of the object to be measured.
CN202010379518.6A 2020-05-07 2020-05-07 Detection system and method Pending CN111398615A (en)

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