KR102114446B1 - Lap on a chip, method for manufacturing the same and method for testing using the same - Google Patents

Abstract

A platform on which a channel through which a fluid is transferred is formed, a supply unit for supplying a sample to the channel of the platform, at least one analysis unit arranged along the channel to detect biomarkers included in the sample, and connected to the channel to the analysis unit Provided is a lab-on-a-chip that includes a reagent receiving unit for receiving reagents to be supplied, and a driving unit for transferring reagents and samples along the channel to the analysis unit.

Description

Lab-on-a-chip, manufacturing method on lab-on-a-chip and diagnostic method using lab-on-a-chip {LAP ON A CHIP, METHOD FOR MANUFACTURING THE SAME AND METHOD FOR TESTING USING THE SAME}

Disclosed is a lab-on-a-chip for detecting various biomarkers included in a biological sample, a manufacturing method thereof, and a diagnostic method using the lab-on-a-chip.

For example, in the case of disease diagnosis using enzyme immunoassay (ELISA), a lot of time and expensive equipment are used, and skilled technicians are required. Thus, the above-described disease diagnosis could be made only in the laboratory.

Recently, as a concept of point of care testing (POCT), diagnostic devices for simply diagnosing a patient's condition in a short time in the field are required. Accordingly, research on the development of a lab-on-a-chip based disease diagnosis chip capable of microfluidic control has been conducted. These diagnostic chips use blood, urine, etc. as representative samples to detect and quantify biomarkers for specific diseases.

However, conventional diagnostic chips have difficulty in quantitatively analyzing the biomarker when using a small amount of sample, so that only qualitative results can be obtained.

In addition, in order to detect two or more biomarkers, antibody particles for each biomarker must be immobilized in a chip. However, conventional chips have difficulty in obtaining a desired diagnostic effect because a plurality of antibody particles are not properly fixed in the chip.

Provided is a lab-on-a-chip capable of more quickly and accurately detecting a plurality of biomarkers through a small amount of samples, a manufacturing method, and a diagnostic method using the lab-on-a-chip.

Provided is a lab-on-a-chip capable of easily fixing and manufacturing a plurality of antibody particles in each analysis unit, a manufacturing method, and a diagnostic method using the lab-on-a-chip.

Provides a lab-on-a-chip, a manufacturing method and a diagnostic method using the lab-on-a-chip, which can increase the reaction rate of the antibody particles to enable accurate diagnosis even with a small amount of sample and increase the reliability of the analysis results.

The lab-on-a-chip of the present embodiment includes a platform on which a channel through which a fluid is transferred is formed, a supply unit for supplying a sample to the channel of the platform, and at least one analysis unit arranged along the channel to detect biomarkers included in the sample, It may be connected to the channel may include a reagent receiving unit for receiving a reagent to be supplied to the analysis unit, a driving unit for transporting reagents and samples along the channel to the analysis unit.

It may be formed on the platform and connected to the outlet of the analysis unit may include a waste unit for receiving a sample that has passed through the analysis unit.

The supply unit may further include a filter for filtering and supplying the sample.

The supply part may further include a micro-channel formed on the filter outlet side of the platform and connected to the channel to transport the sample through the filter.

The supply part may be a structure provided separately from the platform and detachably coupled to a groove formed in the platform.

The supply part is formed with a space between the micro-channels at the intervals, and a substrate having an outlet through which the sample is discharged by communicating with the micro-channels at the tip, a filter installed in contact with the substrate surface to filter the sample, and a substrate with the filter interposed therebetween It is attached to the surface and may include a cover plate formed with a hole for supplying a sample at a position corresponding to the filter.

The microchannel may be formed of a capillary tube through which a sample is transferred due to a capillary phenomenon.

The microchannel may be formed with a hydrophilic coating film on the surface.

The microchannel may be a structure in which a buffer solution for reducing the surface tension between the filter exit surface and the microchannel is accommodated as a wetting agent.

The filter may further include a wax layer installed on the outlet surface or the micro-channel to selectively block between the buffer solution and the filter outlet surface.

The substrate or / and the cover plate may be formed of an elastic material or plastic material including an elastomer.

The analysis unit may have a structure in which a plurality of units are serially arranged and sequentially connected along a channel.

The analysis unit may include an analysis line through which a fluid flows, a plurality of micro grooves arranged on the bottom surface of the analysis line, and antibody particles that are accommodated in each of the micro grooves to detect a biomarker of a sample.

The microgroove is formed to a size corresponding to the size of the antibody particle, and may be a structure in which one antibody particle is inserted into each microgroove and fixed.

The depth of the microgroove may be d <h <2d. Here, h = depth of the microcavity, d = diameter of the antibody particle.

The micro-groove may be a structure formed in a direction perpendicular to the fluid transfer direction from the bottom surface of the analysis line.

Each of the analysis units may have a structure in which different antibody particles are accommodated.

The antibody particle may be a structure in which a capture antibody is attached to the surface of a bead having magnetic properties.

The reagent accommodating part may include an accommodating line connected to a channel and containing reagents, a plurality of reagents sequentially accommodated in the accommodating line, and an intermediate layer formed between each reagent to prevent interference between reagents.

The driving unit may include a driving chamber connected to a receiving line of the reagent receiving unit, and a thermal expansion material accommodated in the driving chamber and expanded by heat.

The thermal expansion material may be a gas or liquid containing air.

The driving unit may further include a heating unit installed on the platform to apply heat to the driving chamber.

The drive chamber may be formed to extend in one line, and may be formed in a zigzag form or wound toward the center at intervals within a set area.

The method of manufacturing the lab-on-a-chip of this embodiment includes a step of immobilizing the antibody particles with the capture antibody attached to the bead surface having magnetic properties on the analysis unit, and the immobilization process is performed on the bottom surface of the analysis line through which the fluid flows. The method may include preparing a lab-on-a-chip having an analysis unit in which a plurality of micro grooves are arrayed, and inserting and fixing the antibody particles into each micro groove.

In the process of inserting and fixing the antibody particles into each micro groove, the antibody particles are accommodated in the assay line, magnetic force is applied to the antibody particles outside the bottom surface of the assay line, and the magnetic particles are moved along the assay line to move the antibody particles. It may include the step of inserting the antibody particles in the micro groove of the bottom of the analysis line while moving.

In addition to the antibody particles immobilized in the micro grooves by transferring fluid to the assay line, a washing process of removing the remaining antibody particles from the assay line may be further included.

The diagnostic method of this embodiment includes a sample supply process of preparing a lab-on-a-chip and supplying a sample to a channel formed on the platform of the lab-on-a-chip, a moving process of moving a sample to an analysis unit provided on the platform, and a reagent for supplying a reagent to the analysis unit It may include a supplying process, detecting a biomarker of a sample with an antibody particle accommodated in a micro groove arranged along the analysis part, and labeling it with a reagent.

The sample supplying process may include a process of filtering the sample with a filter.

The sample supplying process may further include wetting the filter outlet with a buffer solution before filtering the filter.

The moving process may include pushing the sample by applying pressure to the channel for moving the sample.

The moving process may include applying heat to the drive chamber of the platform containing the reagent.

According to this embodiment, it is possible to more quickly and accurately detect a plurality of biomarkers using a small amount of a sample.

Since a plurality of antibody particles are uniformly and stably fixed to each analysis part, quantitative diagnosis is possible while using fewer samples, and reliability of the analysis result can be increased.

By making it easier and easier to fix the antibody particles, it is easy to manufacture and can increase productivity to lower production cost.

By separating plasma from whole blood and immediately diagnosing it, the disease diagnosis procedure can be simplified and the time and cost required for diagnosis can be minimized.

1 is a schematic diagram showing the configuration of a wrap-on-a-chip according to this embodiment.
2 to 4 are views showing the structure of the supply unit of the lab-on-a-chip according to the present embodiment.
5 and 6 are diagrams showing the structure of the driving unit of the lab-on-a-chip according to the present embodiment.
7 is a view showing the structure of the analysis unit of the lab-on-a-chip according to the present embodiment.
8 is a diagram showing a schematic diagram of a lab-on-a-chip integrated with a supply unit and an analysis unit according to the present embodiment.
9 is a schematic diagram showing a process of arranging antibody particles in an analysis part of a lab-on-a-chip according to this embodiment.
10 is a photograph showing a state in which the antibody particles are arrayed and fixed in the analysis part according to the present embodiment.
11 is a view illustrating a manufacturing process of a lab-on-a-chip integrated with a supply unit and an analysis unit according to this embodiment, (a) shows a substrate, a cover plate and a filter used in the lab-on-a-chip manufacturing process, and (b) Denotes a state in which the substrate, the cover plate, and the filter are adhered, and (c) shows a picture when a dye is spilled on the wrap-on-a-chip.
12 is a photograph showing the experimental results of the lab-on-a-chip according to the present embodiment.
13 is a human total PSA ELISA standard curve that quantitatively analyzes the amount of human total PSA in a conventional well plate method as reference data.

Hereinafter, embodiments of the present invention will be described with reference to the accompanying drawings so that those skilled in the art to which the present invention pertains can easily practice. As those of ordinary skill in the art to which the present invention pertains can readily understand, the embodiments described below may be modified in various forms without departing from the concept and scope of the present invention. Where possible, the same or similar parts are indicated by the same reference numerals in the drawings.

The terminology used hereinafter is for reference only to specific embodiments and is not intended to limit the invention. The singular forms used herein also include plural forms unless the phrases clearly indicate the opposite. As used herein, the meaning of “comprising” embodies certain properties, regions, integers, steps, actions, elements and / or components, and other specific properties, regions, integers, steps, actions, elements, components and / or groups It does not exclude the existence or addition of.

All terms including technical terms and scientific terms used hereinafter have the same meaning as those generally understood by those of ordinary skill in the art. The terms defined in the dictionary are further interpreted as having meanings consistent with the related technical literature and the presently disclosed contents, and are not interpreted in an ideal or very formal meaning unless defined.

In the following description, the lab-on-a-chip of the present embodiment will be described as an example in which plasma separated from whole blood is used as a sample for diagnosing vaginal lesions. In addition to plasma separated from whole blood, various samples such as biological fluid including lymph fluid, tissue fluid, and urine or fluid including cells such as somatic cells, bacteria, and viruses may be applied as the sample.

1 schematically shows a configuration of a wrap-on-a-chip according to this embodiment.

As shown in FIG. 1, the lab-on-a-chip 100 of the present embodiment includes a supply unit 20, an analysis unit 50 for detecting biomarkers, and a reagent for a platform 10 on which a channel 12 through which fluid is transferred is formed. It has a structure in which the receiving portion 30 and the driving portion 40 are arranged. In addition, the platform 10 may be further provided with a waste portion 70 connected to the outlet of the analysis portion 50 to receive a sample that is discarded through the analysis portion 50.

The platform 10 may be made of a plate structure. The shape of the platform 10 can be variously modified and is not particularly limited. The platform 10 is formed with a channel 12 through which fluid is transferred. For example, the platform 10 may be formed of a first substrate and a second substrate that is attached to cover the first substrate. The space formed between the first substrate and the second substrate forms a channel 12 for fluid transport. The channel 12 is formed as a cross-section of a predetermined size, and can be understood as a passage through which fluid is transferred. The internal cross-sectional size of the channel 12 can be variously modified. Each component is arranged along the channel 12 formed in the platform 10. Thus, the liquid sample containing the plasma component may be transferred from the supply unit 20 through each analysis unit 50 to the waste unit 70 through the channel 12 which is a space between the first substrate and the second substrate. .

The supply unit 20 supplies a sample to the analysis unit 50 along the channel 12. 2 to 4 show a supply unit 20 according to the present embodiment. Hereinafter, the structure of the supply unit 20 will be described with reference to FIGS. 2 to 4.

The supply unit 20 may include a filter 21 to separate and supply plasma from whole blood. The filter 21 filters blood cells in whole blood and passes a fluid sample containing plasma components. The filter 21 may be formed of pores of various sizes or various materials to filter biological cells, inorganic particles, or organic particles. The filter 21 of this embodiment may be formed with pores capable of filtering blood cells of approximately 5 to 10 μm in size. In addition, the filter 21 may be formed of a biologically inert material to be applied to a biological sample.

On the outlet side of the filter 21 of the supply unit 20 is located a micro-channel 22 through which the filtered plasma is transferred through the filter 21. The microchannel 22 contacts the filter 21 exit side and extends toward the channel 12 and is connected to the channel 12. A plurality of fine flow paths 22 are formed at intervals to contact the filter 21 exit side. Thus, the plasma filtered through the filter 21 flows through the microchannel 22 contacting the filter 21 exit side and is transferred to the channel 12.

In this embodiment, the supply unit 20 may be a structure provided separately from the platform 10 and detachably coupled to the groove 14 formed in the platform 10. Accordingly, since the supply unit 20 is separately separated from the platform 10, it is possible to more conveniently perform necessary operations such as supply of samples.

In addition to the above-described structure, the supply unit may be integrally formed on the platform. In the case of such a structure, a micro-channel and an outlet are formed in the first substrate constituting the platform, and holes are formed in the second substrate, the first substrate and the second substrate are attached, and a filter is mounted through the holes in the second substrate to supply the supply. Can be achieved.

Hereinafter, a structure in which the supply unit 20 is detachable from the platform 10 will be described as an example.

To this end, the supply unit 20 is formed on the surface of the micro-channel 22 is spaced apart, the substrate 23, the substrate 23 having an outlet 26 to communicate with the micro-channel 22 is discharged from the tip, the substrate ( 23) a filter 21 installed in contact with the surface and the sample is filtered, attached to the surface of the substrate 23 with the filter 21 interposed therebetween, and a cover plate formed with holes 25 at positions corresponding to the filters 21 ( 24).

The substrate 23 and the cover plate 24 attached to the substrate 23 are formed in a size and shape corresponding to the groove 14 of the platform 10. The cover plate 24 may be attached to the substrate 23 to form a body. The space formed between the substrate 23 and the cover plate 24 forms a micro-channel 22. The substrate 23 is exposed through the hole 25 formed in the cover plate 24, and the filter 21 is inserted into the substrate 23 through the hole 25. The filter 21 may be formed in a shape and size corresponding to the hole 25.

Both the cover plate 24 or the substrate 23 and the cover plate 24 may be formed of an elastic material or a plastic material including an elastomer. Accordingly, when pressure is applied to the cover plate 24, the micro-channel 22 is pressed and the cross-sectional area is narrowed, so that the fluid transferred to the micro-channel 22 can be more easily transferred to the tip outlet 26. Specifically, the plastic material may be made of a polyester material.

A groove 14 is formed in the platform 10 in a size corresponding to the supply unit 20. The channel 12 is formed on the inner side surface of the groove 14 in a position corresponding to the outlet 26 formed on the substrate 23. Accordingly, when the supply unit 20 is coupled to the groove 14 of the platform 10, the outlet 26 of the supply unit 20 is connected to the channel 12 of the platform 10. Therefore, the fluid flowing out through the outlet portion 26 of the supply unit 20 may be transferred to the channel 12.

A plurality of microchannels 22 are formed on the surface of the substrate 23 at intervals. The plurality of micro-channels 22 are formed to extend in a straight line on the substrate 23 and communicate with the outlet 26 at the front end of the substrate 23.

In this embodiment, the microchannel 22 may be formed of a capillary tube through which a sample is transferred due to a capillary phenomenon.

Accordingly, a flow of fluid flow due to capillary action occurs on the filter 21 exit side. Therefore, when the whole blood is supplied to the input side of the filter 21, plasma is sucked into the microchannel 22 contacting the filter 21 exit side due to the capillary phenomenon. Thus, plasma can be more quickly filtered through the filter 21 in whole blood. Plasma that has passed through the filter 21 flows rapidly by the capillary phenomenon along the micro channel 22 that is in contact with the filter 21 exit side.

A hydrophilic coating film may be further formed on the surface of the microchannel 22 so that the fluid that has passed through the filter 21 can be transported smoothly along the microchannel 22. For example, the substrate 23 and the cover plate 24 may be attached by oxygen plasma treatment, and the oxygen plasma may be treated again or a hydrophilic polymer may be coated. By treating the microchannel 22 with a hydrophilic coating, the surface tension of the fluid and air is reduced to allow plasma to flow along the microchannel 22 at a faster rate.

In addition, a blood-friendly buffer solution such as a PBS solution may be previously accommodated in the microchannel 22 so as to further lower the fluid surface resistance of the microchannel 22. That is, the supply unit 20 may have a structure in which a buffer solution is accommodated as a wetting agent between the filter 21 exit side and the micro-channel 22. The buffer liquid comes into contact with the filter outlet side to make the filter outlet side wet.

The buffer solution may be the same solution as the fluid that has passed through the filter 21. Alternatively, the buffer solution may be a solution having no particles to be separated and not affecting a biological sample. The buffer solution may be any solution that can reduce the capillary pressure of the pores of the filter 21 at the exit side of the filter 21 and reduce the surface resistance of the microchannel 22.

The buffer solution may be preliminarily accommodated in the microchannel 22 of the substrate 23 when the supply unit 20 is manufactured by attaching the substrate 23 and the cover plate 24, for example. Alternatively, when using the supply unit 20, before dropping the whole blood into the filter 21, the buffer solution may be first dropped into the filter 21 to be supplied to the filter 21 exit side and the microchannel 22.

The buffer liquid is brought into contact with the filter liquid in advance by the buffer liquid between the outlet side and the microchannel 22. In this state, when whole blood is supplied to the input side of the filter 21, the plasma of the whole blood passes directly through the pores of the filter 21 without surface resistance by the cohesive force of the buffer liquid contacting the filter 21 exit side, and the micro-channel 22 Flows smoothly.

Therefore, the resistance of the fluid flow is reduced, so that it is possible to sufficiently filter the whole blood through the filter 21 without capillary action alone without applying a force from the outside.

In this embodiment, the buffer solution acting as a wetting agent can be brought into contact with the filter outlet side only when the sample is supplied to the filter while being accommodated in the micro-channel.

To this end, a wax layer for selectively blocking the contact between the filter outlet side and the buffer liquid may be provided between the outlet side of the filter and the buffer liquid accommodated in the microchannel 22. The wax layer may be formed on the outgoing side of the filter 21 or the microchannel 22. The wax layer blocks between the filter outlet side and the buffer liquid, and is removed as necessary to contact the buffer liquid to the filter outlet side. The wax layer may be a thin film structure of a wax material that melts by heat. The wax layer may be melted and removed by, for example, a user's body temperature or a light source or heat source irradiated from the outside.

Thus, when the device is not used, the filter exit side is blocked by the wax layer and does not contact the buffer solution. In addition, when the user applies a body temperature or a heat source to the filter when using the device, the wax layer is melted and removed. When the wax layer is removed, the buffer solution contained in the micro-channel is brought into contact with the filter outlet surface, so that the filter outlet surface can be made wet.

The plasma filtered through the filter 21 flows toward the outlet 26 along the micro-channel 22 by the capillary phenomenon, is moved to the outlet 26 by the pressure pressing the cover plate 24, and the outlet 26 and It is transferred to the channel 12 of the connected platform 10. As mentioned, the supply unit 20 is made of an elastic material, and by applying an external force, the inner cross-sectional area of the micro-channel 22 is narrowly deformed to transfer fluid.

The platform 10 is provided with a reagent supply unit 20 and a driving unit 40 at the inlet side of the channel 12 connected to the supply unit 20.

The reagent receiving unit 30 is connected to the channel 12 to accommodate the reagent 32 to be supplied to the analysis unit 50. The reagent receiving unit 30 is connected to the channel 12, the receiving line 31 containing the reagent 32 required for analysis, a plurality of reagents 32 sequentially received in the receiving line 31, each reagent ( 32) may be formed between the intermediate layer 33 to prevent interference between the reagents (32). The receiving line 31 is formed as a cross section of a predetermined size, such as the channel 12, and can be understood as a passage through which fluid is transferred. The inner cross-sectional size of the receiving line 31 can be variously modified. The receiving line 31 may be formed on the first substrate of the platform 10.

In this embodiment, the receiving line 31 is a single elongated passage, a plurality of reagents 32 are sequentially received therein. The plurality of reagents 32 may be sequentially arranged in accordance with the order of use for disease analysis. The reagent 32 may be reagents for biomarker measurement provided in accordance with each analysis unit 50. The reagent 32 may be a primary detection antibody according to a biomarker, a secondary detection antibody with fluorescence bound to the primary detection antibody. The reagent 32 may be applied to any material capable of analyzing and quantifying the biomarker by changing the optical signal such as fluorescence and luminescence in response to the biomarker. Among the reagents 32 sequentially arranged along the receiving line 31, the reagent disposed last may be a buffer solution 34 for washing the analysis unit 50. The buffer solution 34 is moved along the channel 12 and finally passes through the analysis part 50 to wash the analysis part 50.

In this embodiment, the reagent is a washing buffer solution, a primary detection antibody according to a biomarker, a washing buffer solution, a secondary detection antibody with fluorescence that can be attached to the primary detection antibody, and a washing buffer solution are sequentially placed in the receiving line. Can be. The wash buffer solution can be, for example, PBST or TBST. A polyclonal antibody can be used as the primary detection antibody used for detection. The primary detection antibody may be, for example, polyclonal anti PSA antibody in the case of prostate cancer. The secondary detection antibody is a detection antibody with fluorescence bound to the primary detection antibody. The secondary detection antibody may be, for example, a fluorophore-labeled anti rabbit antibody when the primary detection antibody is an antibody made from rabbits. Thus, the reagent is washed buffer solution, the primary detection antibody, the washing buffer solution, the secondary detection antibody, the washing buffer solution is sequentially moved to the analysis unit along the channel.

An intermediate layer 33 is formed between the plurality of reagents 32 and the reagents 32 in the receiving line 31 to prevent mixing between the reagents 32. The intermediate layer 33 may be formed of a gas such as air or a liquid that is not mixed with a reagent. For example, the intermediate layer 33 may be an organic solvent that does not mix with water.

The receiving line 31 is connected to the channel 12 through the inlet side of the channel 12 formed in the platform 10. Accordingly, when the reagent 32 accommodated in the receiving line 31 moves to the channel 12, the sample and reagent 32 are sequentially pushed along the channel 12 by pushing the sample introduced into the channel 12. It is moved to the analysis unit 50.

The driving unit 40 transfers the reagent 32 and the sample to the analysis unit 50 by applying a transfer pressure to the transfer line.

5 and 6 show embodiments of the driving unit 40. 5 and 6 differ only in the arrangement form of the driving unit 40, and the structure is the same, so the embodiment illustrated in FIG. 5 will be described below, and the structure illustrated in FIG. 6 is replaced with this.

As shown in FIG. 5, the driving unit 40 is a driving chamber 41 connected to the receiving line 31 of the reagent receiving unit 30, a thermal expansion material accommodated in the driving chamber 41 and expanded by heat It may include.

The drive chamber 41 can be understood as an interior space having an area of a predetermined size. The size of the inner space of the drive chamber 41 can be variously modified. The driving chamber 41 may be formed on the first substrate of the platform 10.

The drive chamber accommodates a thermal expansion material therein, and a space in which the thermal expansion material can expand is sufficient, and its shape can be variously modified. For example, the drive chamber may have an elongated line shape.

The leading end of the driving chamber 41 extends to the receiving line 31 and communicates with the receiving line 31. Accordingly, the thermal expansion material discharged from the leading end of the driving chamber 41 is pushed to the receiving line 31 so that the reagent 32 accommodated in the receiving line 31 can be pushed and moved.

In the present embodiment, the drive chamber 41 may be formed to extend in one line and wound toward the center at intervals within the set area. In addition to the wound structure, the driving chamber 41 may be formed in a zigzag form with a gap as shown in FIG. 6.

Accordingly, even in a limited narrow region, the entire length of the driving chamber 41 can be formed. Accordingly, a sufficient amount of thermal expansion material is accommodated in the driving chamber 41, and the thermal expansion material is expanded along the driving chamber 41 to eject it into the receiving line 31. As the thermal expansion material is ejected through the exit side of the driving chamber 41, the sample and the reagent 32 are pushed and moved to the analysis unit 50 through the channel 12.

The expanded thermally expandable material is moved to the channel 12, thereby pushing the sample and reagent toward the analysis unit. The outlet 26 of the supply portion or the hole 25 of the supply portion may be blocked so that the thermal expansion material moved to the channel does not escape to the supply portion through the outlet portion 26 connected to the channel. For example, after the sample is transferred to the channel, the hole of the supply unit may be blocked and blocked before the driving unit is operated. Accordingly, the expanded thermally expandable material moves to the channel so that samples and reagents can be continuously pushed and moved toward the analysis unit without exiting the supply unit.

The thermal expansion material may be a gas or liquid containing air. The thermal expansion material is a material that expands in volume due to heat, and may be a material that expands in volume by heat at various temperatures, including a user's body temperature. Further, the thermal expansion material may be a material that does not react with the sample or reagent 32.

For example, when the thermally expanding material expands to the user's body temperature, the device can be driven without a separate heat source. In the case of such a structure, the user can expand the thermal expansion material and supply samples and reagents to the analysis unit by holding the one side of the driving chamber or the supply unit of the device by hand and applying body temperature.

In another embodiment, the driving unit 40 of the present apparatus may further include a heating unit (not shown) that is installed on the platform 10 and applies heat to the driving chamber 41.

The heating unit may be an electric heater that dissipates heat by receiving external power. For example, the heat transfer heater is a planar heating element having a relatively thin and large area and may be installed on the first substrate or the second substrate at a position corresponding to the driving chamber 41.

The heating unit may have a structure using chemical exothermic energy in addition to electrical energy. The heating unit may be used by generating heat by mixing a substance that causes an exothermic reaction when mixing liquid, solid, or gas. For example, the heating unit may be a structure using thermal energy generated by a curing reaction.

As heat is applied to the driving unit 40, the thermal expansion material accommodated in the driving unit 40 expands. The reagent 32 accommodated in the receiving line 31 is transferred to the channel 12 by the expansion pressure of the thermally expanding material. Accordingly, the sample introduced into the channel 12 is pushed by the reagent 32 to move to the analysis unit 50.

The analysis unit 50 is disposed along the channel 12 to detect biomarkers included in the sample.

The analysis unit 50 is accommodated in the analysis line 55 through which the fluid flows, the plurality of micro grooves 56 formed on the bottom surface of the analysis line 55, and each of the micro grooves 56 Antibody particles (57) for detecting biomarkers may be included.

In the present embodiment, the analysis unit 50 may have a structure in which a plurality of serially arranged channels are sequentially connected along the channel 12. Although the structure in which four analysis units 50 are sequentially arranged along the channel 12 is illustrated in FIG. 1, the present invention is not limited thereto, and may be formed in various numbers of 3 or less or 5 or more. Hereinafter, the first analysis unit 51, the second analysis unit 52, the third analysis unit 53, and each analysis unit 50 connected to the channel 12 along the fluid transport direction for convenience of explanation. It is referred to as 4 analysis unit 54. The simple analysis unit 50 may refer to all of each analysis unit.

Each of the analysis units 50 may have a structure in which different antibody particles 57 are received and detected for different biomarkers. Accordingly, multiple detection of various disease factors is possible using one lab-on-a-chip 100.

For example, the first analysis unit 51 accepts antibody particles 57 that are associated with PSA (prostate cancer marker), and the second analysis unit 52 binds CEA (gastrointestinal cancer tumor marker) antibody particles. (57) is accommodated, the third analysis unit 53 may be accommodated antibody particles (57) coupled to AFP (liver cancer tumor marker).

A control may be accommodated in the fourth analysis unit 54. The control group is to check whether the biomarker is non-specifically attached to the antibody particle. Normally, when a positive signal comes out when analyzing an ELISA, a control experiment is performed together to determine whether this is a result of a specific binding or a false positive due to a non-specific binding. In this embodiment, the fourth analysis unit 54 is provided as a control, so that it can be compared with the experimental results of other analysis units. In the fourth analysis unit 54, for example, antibody particles that are surface treated (such as PEG) that do not react with any biomarker other than the antibody that captures PSA on the antibody particle can be accommodated. Thus, in the fourth analysis unit, the primary detection antibody injected sequentially and the secondary detection antibody labeled with fluorescence do not bind to the antibody particles contained in the fourth analysis unit. As a result, no fluorescent signal appears in the fourth analysis unit. Therefore, when signals are output from other first to third analysis units, the result can be compared using the fourth analysis unit as a control for comparing results.

The analysis line 55 is formed as a cross section of a predetermined size, such as the channel 12, and can be understood as a passage through which fluid is transferred. The inner cross-sectional size of the analysis line 55 can be variously modified. The analysis line 55 may be formed on the first substrate of the platform 10.

The analysis line 55 may consist of one line. In this embodiment, the analysis line 55 may be formed to extend in one line and may be formed in a zigzag form within the set area. Accordingly, the analysis line 55 may be densely arranged in a limited narrow area. Therefore, the antibody particles 57 arranged along the analysis line 55 are densely gathered within a limited area of the analysis unit 50, thereby improving the diagnostic effect.

The microgroove 56 fixes each antibody particle 57 to the analysis line 55 in an even distribution. The antibody particles 57 are regularly arranged and fixed to the bottom surface of the analysis line 55 by the micro grooves 56.

7 shows the fixing structure of the analysis line according to the present embodiment.

As shown, the microgrooves 56 are arranged at intervals on the bottom surface along the analysis line 55. The micro grooves 56 are designed to be arranged in a uniform distribution on the bottom surface of the analysis line 55. The arrangement form of the micro grooves 56 can be variously modified as long as a uniform distribution can be achieved.

The micro-groove 56 is formed by digging in the form of a groove on the bottom surface of the analysis line 55 to capture and fix the antibody particles 57. The micro grooves 56 are formed in a size corresponding to the size of the antibody particles 57. In this embodiment, the microgroove 56 may be formed by digging into a hemispherical shape corresponding to the spherical antibody particle 57. One antibody particle 57 is inserted into each microgroove 56 and fixed.

In this embodiment, the depth of the micro-groove 56 may be d <h <2d. Here, h = the depth of the microcavity 56 and d = the diameter of the antibody particle 57. The depth h of the microgroove is the distance from the bottom surface of the analysis line to the inner tip of the microgroove.

If the depth (h) of the micro groove (56) is smaller than the diameter (d) of the antibody particle (57), the antibody particle is unstable and the antibody particle escapes from the micro groove by the flow of fluid flowing along the analysis line. Is generated. If the depth (h) of the micro-groove 56 exceeds twice the diameter (d) of the antibody particle 57, the thickness of the device becomes thicker, and the problem of the diffusion of the cleaning solution for cleaning the antibody particle and the analysis line takes a long time. Occurs.

In addition, in this embodiment, the micro-groove 56 may be formed in a direction perpendicular to the fluid flow direction from the bottom surface of the analysis line 55. Accordingly, the micro grooves and the flow of the fluid are arranged at right angles. Therefore, the antibody particles inserted into the microgrooves cannot easily escape from the microgrooves along the fluid flow.

As described above, the antibody particles 57 are stably inserted and fixed in the microgroove to maintain the uniform arrangement on the analysis line regardless of the fluid flow.

The micro grooves 56 are arranged along the analysis line 55 and the antibody particles 57 are inserted and fixed in each of the micro grooves 56, so that the antibody particles 57 are uniformly distributed along the analysis line 55. Array can be fixed. As described above, the antibody particles 57 are uniformly arranged in the analysis line 55, thereby improving the quantitative measurement effect.

The antibody particle 57 may have a structure in which a capture antibody is attached to the surface of a bead having magnetism. The capture antibody is an antibody that binds to and fixes the biomarker.

For example, streptavidin, avidin, or anti-biotin protein is immobilized by covalent bonding to a magnetic micro-sized bead surface using an EDC / NHS coupling method. In addition, the antibody particles can be prepared by reacting the biotin-attached capture antibody so that the capture antibody is immobilized on the surface of the magnetic bead. Streptavidin is coated on the surface of the bead, and biotin capable of binding streptavidin is attached to the capture antibody. When the bead and the capture antibody are left at room temperature for 30 minutes, the capture antibody is bound to the bead.

8 shows a schematic diagram of a lab-on-a-chip in which the supply unit 20 and the analysis unit 50 according to the present embodiment are integrated. As shown in FIG. 8, plasma is filtered through the filter 21 of the supply unit 20 and then supplied to the analysis unit 50 through the microchannel 22.

Figure 9 illustrates the process of immobilizing the antibody particles in the analytical unit for the manufacture of a lab-on-a-chip according to this embodiment.

The lab-on-a-chip of this embodiment undergoes a process of arranging and fixing the antibody particles 57 to the analysis unit 50 in the manufacturing process.

To this end, as shown in FIG. 9, a lab-on-a-chip equipped with an analysis unit 50 in which a plurality of micro grooves 56 are arranged on the bottom surface of the analysis line 55 through which a fluid flows is prepared, The antibody particles 57 are injected into the inner space of the analysis line 55 of the analysis unit 50. At this time, a magnet 80 for applying magnetic force to the antibody particles 57 having magnetism is disposed outside the analysis line 55 of the lab-on-a-chip 100. The magnet 80 is disposed outside the bottom surface of the analysis line 55. The magnet can be a permanent magnet or an electromagnet. The magnet 80 may be located at one end of the analysis line 55.

The antibody particles 57 injected into the analysis line 55 flow along the analysis line 55 by the magnetic force of the magnet 80 and are collected where the magnet 80 is located. In this state, the magnet 80 disposed at one end of the analysis line 55 is moved along the analysis line 55 toward the other end. The magnet 80 is moved toward the other front end while applying a magnetic force to the analysis line 55. As the magnet 80 moves while applying a magnetic force, the antibody particles 57 injected into the analysis line 55 are attracted to the magnetic force and moved along the magnet 80.

The antibody particles 57 are moved along the analysis line 55 by being in close contact with the bottom of the analysis line 55 where the magnet 80 is located by magnetic force. In this process, the antibody particles 57 are captured and fixed in the micro grooves 56 formed on the bottom surface of the analysis line 55, respectively.

After the magnet is completely moved to the other end of the assay line 55, residual antibody particles are removed from the assay line by washing. When washing, the magnetic force can be removed from the analysis line 55. The washing liquid is transferred to the analysis line 55 to wash the analysis line 55. The washing solution may be a solution such as PBS (phosphate buffered saline) or pluronic solution. In addition to the antibody particles 57 fixedly inserted into the microcavity 56 by the washing solution, the remaining antibody particles 57 are removed from the analysis line 55. In the washing process, the antibody particles are inserted into the micro grooves deeply formed in the direction perpendicular to the flow direction of the washing liquid, so that they can be maintained in a fixed state without escaping from the micro grooves by the flow of the washing liquid. Thus, only the remaining antibody particles that are not inserted and immobilized in the microfluid in the assay line flow out of the assay line along the flow of the washing liquid and are removed.

10 is a photograph showing a state in which the antibody particles 57 are arranged and fixed to the analysis unit 50. As shown in FIG. 9, the antibody particles 57 are evenly arranged and fixed on the analysis line 55 of the analysis unit 50 through the present embodiment.

Meanwhile, the sample or reagent 32 that is discarded through the analysis unit 50 is transferred to the disposal unit 70 connected to the analysis unit 50 for processing. The waste part 70 is connected to the outlet of the analysis part 50 to receive a fluid such as a sample or reagent to be discarded. The waste portion 70 is formed in a predetermined size so that the interior can be understood as an empty space. The shape or size of the waste portion 70 can be variously modified. The waste portion 70 may be formed on the first substrate of the platform 10. The waste portion 70 may further include an air hole communicating with the outside on one side. As the channel 12 and the outside air formed on the platform 10 flow through the air hole, the resistance of the fluid being transported along the channel 12 is minimized to smoothly transport the fluid from the supply unit 20 to the waste unit 70. Can be.

11 illustrates a manufacturing process of the lab-on-a-chip in which the supply unit 20 and the analysis unit 50 according to the present embodiment are integrated.

The lab-on-a-chip of the present embodiment includes a substrate 23 on which a channel 12 including a supply unit 20 and an analysis unit 50 is formed, a cover plate 24, and a hole 25 of the cover plate 24 in the manufacturing process Prepare the filter 21 cut into shape, attach it using double-sided tape, treat trimethoxy silane on the cover plate 24, and then treat the substrate 23 and the cover plate 24 with oxygen plasma to filter 21 ) Together.

Hereinafter, a diagnostic process using a lab-on-a-chip according to this embodiment will be described.

By supplying whole blood to the lab-on-a-chip 100 according to the present embodiment, it is possible to more easily and effectively diagnose a plurality of diseases.

The lab-on-a-chip 100 is divided into three analysis units 50 and one control group. Each analysis unit 50 accommodates antibody particles 57 with fixed capture antibodies that bind to different disease factor biomarkers. The antibody particles 57 in which the capture antibody is immobilized in each of the analytical units 50 are inserted and fixed in the micro grooves 56 uniformly arranged to be uniformly distributed along the analysis line 55. The receiving line 31 is pre-filled with reagents 32 for analysis. In the receiving line 31, each reagent 32 is separated by an organic solvent that does not mix with air or water.

When the above-described lab-on-a-chip is prepared, a sample is supplied to the lab-on-a-chip and filtered through a filter and transferred to an analysis unit.

When whole blood is dropped on the filter 21 mounted on the supply part 20 of the lab-on-a-chip 100, blood cells in the whole blood are filtered by the filter 21 and the plasma is filtered to flow through the micro flow path 22. Will flow out.

Samples including plasma in the microchannel 22 are moved to the outlet side of the supply unit 20 by the capillary phenomenon of the microchannel 22 and the external pressure pressing the cover plate 24 and supplied to the channel 12 of the platform 10 do.

In the process of feeding the sample, the filter outlet side can be wetted in advance with the buffer solution wetted before filtering the filter. When the user applies heat such as body temperature to the micro flow path of the filter or supply unit, the wax layer blocking the filter exit side and the buffer liquid contained in the micro flow path is melted and removed. As a result, the filter exit side is exposed, and is wetted while wetted by contact with the buffer solution previously contained in the microchannel. Therefore, plasma of whole blood supplied to the filter inlet side can be smoothly filtered to the filter outlet side through the filter pores without surface resistance.

When the plasma separation and supply of the sample from the supply unit 20 to the channel 12 are made, the drive unit 40 is operated to transfer the sample and reagent 32 to the analysis unit 50.

The driving unit 40 may be driven through a user's body temperature or a separate heat source provided by the user. Alternatively, the driving unit 40 may be driven by a heat source generated from a heating unit installed on the platform 10.

As heat is applied to the driving unit 40, the volume of the thermal expansion material filled in the driving chamber 41 expands. The expansion pressure of the thermal expansion material is applied to the receiving line 31 connected to the driving chamber 41, and the reagent 32 accommodated in the receiving line 31 is pushed toward the channel 12 and moved. That is, the volume of the thermal expansion material inside the driving chamber 41 is increased by the heat energy applied to the driving unit 40, and the thermal expansion material is discharged to the driving chamber 41 by the increased volume. Accordingly, the thermal expansion material pushes the reagent 32 in the receiving line 31 so that the fluid is moved. The reagents 32 are moved in the order filled in the receiving line 31.

The reagent 32 pushed out of the receiving line 31 pushes and moves the sample introduced into the channel 12. Accordingly, the sample and reagent 32 are moved to the analysis unit 50 along the channel 12.

When the sample and the reagent are supplied to the analysis unit, the biomarker of the sample is detected by the antibody particles accommodated in the micro groove of the analysis unit and labeled with the reagent, thereby making it possible to diagnose the sample.

In the analysis section 50, the antibody particles 57 are regularly arranged along the analysis line 55 to be fixed in a uniform distribution. The sample passes through each analysis unit 50 arranged in series and passes through the antibody particles 57 fixed to each analysis unit 50. As the sample passes through the analysis unit 50, a specific biomarker contained in the sample reacts to a specific capture antibody attached to the antibody particle 57 of each analysis unit 50, and is caught by the antibody particle 57.

Antibody particles 57 to which different specific capture antibodies are attached are fixed to each analytical section 50, so that different biomarkers are used as antibodies in each analytical section 50 in the course of the sample passing through each of the analytical sections 50. Particle 57 is caught.

The sample flows by the driving unit 40 while passing through the analysis unit 50. In this process, the sample comes into contact with the antibody particles 57 of the analysis unit 50 in a dynamic state. Therefore, an antigen-antibody reaction is performed between the sample and the antibody particle 57 in a fluid flow state by the driving unit 40, so that a faster reaction can be induced compared to a static state.

The biomarker is attached to the antibody particles 57 as the sample passes through the antibody particles 57 uniformly arranged along the analysis line 55. The reagent 32 that is moved along with the sample passes through each analysis unit 50. In this process, the primary detection antibody and the secondary detection antibody with fluorescence are sequentially coupled to the biomarker captured on the surface of the antibody particle 57.

For example, when the biomarker is PSA, the primary detection antibody may be a polyclonal anti PSA antibody. The fluorescently detected secondary detection antibody may be an anti PSA FITC labeled antibody bound to a biomarker. For example, when the host is a rabbit, the secondary detection antibody has an enzyme such as fluorescent or peroxidase (HRP) or alkaline phosphatase (AP) attached to the anti rabbit antibody that can be attached to the primary detection antibody. Antibodies can be used. The reagent 32 is attached to the biomarker caught on the surface of the antibody particle 57, and finally, the biomarker can be detected by a fluorescence signal.

Analysis of biomarkers may be performed by quantitative analysis of disease marker biomarkers included in a sample using fluorescence signal-based enzyme immunoassay (ELISA).

As such, the biomarker is attached to the antibody particles 57 arranged in the analysis unit 50 by moving the sample and the reagent 32 to each analysis unit 50, and fluorescent treatment may be performed with the reagent 32. Each analysis unit 50 provided in the lab-on-a-chip 100 detects biomarkers in response to different biomarkers. Samples and reagents 32 that have passed through the analysis unit 50 are moved to a disposal unit 70 connected to the analysis unit 50 and disposed of.

Finally, the buffer solution 34 located at the rear end of the reagent 32 moved through the channel 12 passes through the analysis part 50 to wash the analysis part 50. Biomarkers and reagents held on the antibody particles 57 by washing the inner surface of the analysis line 55 and the microparticles 56 and the surface of the antibody particles 57 fixed to the microgrooves 56 by the buffer solution 34 In addition, all residue is removed. Accordingly, the concentration of the biomarker caught on the surface of the antibody particle 57 can be more accurately detected.

The concentration of the biomarker is detected in proportion to the intensity of the fluorescent signal. As mentioned, in the analysis section 50, the antibody particles 57 are regularly arranged along the analysis line 55 within a certain space to form a uniform distribution. Accordingly, the fluorescent signal can be more accurately detected and analyzed for each analysis unit 50. Therefore, more reliable biomarker quantitative analysis can be performed.

[Experimental Example]

12 is a photograph showing the experimental results of the lab-on-a-chip according to the present embodiment.

After the antibody particles with the capture antibody were arranged and fixed to the analysis unit 50 of the lab-on-a-chip prepared according to this embodiment, samples and reagents, primary detection antibody and secondary detection antibody, were sequentially transferred and processed. In this experiment, the disease factor biomarker was PSA, and 10ng / mL, 20ng / mL, and 40ng / mL were used, respectively.

In FIG. 12, 10 ng / mL, 20 ng / mL, and 40 ng / mL, respectively, are samples obtained by transporting a biomarker-containing sample through the above-described treatment process, and PSA is bound to the antibody particles and finally a secondary detection antibody is attached. This is a photo taken after processing. The PSA 0 ng / mL of FIG. 12 is a transported sample without a biomarker, and is a photograph of a measurement in which PSA is not bound to antibody particles.

As shown in FIG. 12, when there is PSA in plasma, fluorescence is observed, such as PSA 10 ng / mL, PSA 20 ng / mL, and PSA 40 ng / mL in FIG. 12, and there is no PSA in plasma, FIG. 12 No fluorescence is observed, such as PSA of 0 ng / mL. Accordingly, it can be confirmed that the biomarker can be accurately detected through the lab-on-a-chip manufactured according to the present embodiment.

13 is a human total PSA ELISA standard curve that quantitatively analyzes the amount of human total PSA in a conventional well plate method as reference data.

As an analysis system, an ELISA system capable of linearly quantifying a PSA concentration of 2000 pg / mL to several pg / mL was used.

13 shows the detection dynamic range shown by the antibody-antigen-detection antibody system used in the Examples. The dynamic range of detection has a range similar to the concentration of PSA detected in patients with prostate cancer at about 0.5 to 2 ng / mL.

Accordingly, when the ELISA system performed in the reference (well plate) is implemented in the lab-on-a-chip of the present embodiment, it can be expected to exhibit a similar detection range.

As described above, although exemplary embodiments of the present invention have been illustrated and described, various modifications and other embodiments may be made by those skilled in the art. These modifications and other embodiments are all contemplated and included in the appended claims, and will not depart from the true spirit and scope of the invention.

10: platform 12: channel
14: home 20: supply
21: filter 22: micro flow
23: substrate 24: cover plate
25: Hall 26: Exit
30: reagent receiving section 31: receiving line
32: reagent 33: intermediate layer
34: buffer solution 40: drive unit
41: drive chamber 50: analysis unit
55: analysis line 56: micro groove
57: antibody particle 70: waste portion
80: magnet 100: lab on a chip

Claims (25)

A platform on which a channel through which a fluid is transferred is formed, a supply unit for supplying a sample to the channel of the platform, at least one analysis unit arranged along the channel to detect biomarkers included in the sample, and connected to the channel to supply the analysis unit A reagent receiving unit for receiving the reagent, and a driving unit for transferring the reagent and the sample along the channel to the analysis unit,
The analysis unit includes an analysis line through which a fluid flows, a plurality of micro grooves arranged on the bottom surface of the analysis line, and antibody particles accommodated in each of the micro grooves to detect a biomarker of a sample,
The driving part is a lab-on-a-chip comprising a driving chamber connected to the receiving line of the reagent accommodating part, and a thermal expansion material accommodated in the driving chamber and expanded by heat. According to claim 1,
The micro-groove is formed in a size corresponding to the size of the antibody particles accommodated therein, a lab-on-a-chip in which one antibody particle is inserted into each microgroove and fixed. According to claim 2,
The analysis unit is a lab-on-a-chip having a plurality of serially arranged serially connected channels. The method of claim 3,
Each of the analysis units is a lab-on-a-chip containing different antibody particles. According to claim 1,
The antibody particle is a lab-on-a-chip having a structure in which a capture antibody is attached to the surface of a magnetic bead. According to claim 1,
The reagent accommodating part is connected to a channel, and a lab-on-a-chip including an accommodating line in which reagents are accommodated, a plurality of reagents sequentially accommodated in the accommodating line, and an intermediate layer formed between each reagent to prevent interference between reagents. According to claim 1,
The depth of the micro-groove, d <h <2d wrap-on-a-chip.
Here, h = depth of the microcavity, d = diameter of the antibody particle. According to claim 1,
The micro groove is a lab-on-a-chip having a structure formed in a direction perpendicular to a fluid transfer direction from the bottom surface of the analysis line. delete According to claim 1,
The drive unit is installed on a platform, the lab on a chip further comprising a heating unit for applying heat to the drive chamber. According to claim 1,
The supply unit is a lab-on-a-chip including a filter for filtering and supplying a sample. The method of claim 11,
The supply part is formed on the filter outlet side of the platform and is connected to the channel further comprises a micro-channel for transferring the sample through the filter lab on a chip. According to claim 1,
The supply part is provided separately from the platform, a lab-on-a-chip structure that is detachably coupled to a groove formed in the platform. The method of claim 13,
The supply unit is formed with a micro-channel spaced at the surface and a substrate having an outlet through which the sample is discharged through communication with the micro-channel at the tip, a filter provided in contact with the surface of the substrate to filter the sample, and the filter interposed therebetween A lab-on-a-chip that is attached to the surface of the substrate and includes a cover plate with a hole for supplying a sample at a position corresponding to the filter. The method of claim 14,
The substrate or / and the cover plate is a wrap-on-a-chip formed of an elastic material or a plastic material including an elastomer. The method of claim 12,
The micro flow path is a lab-on-a-chip having a structure in which a buffer solution for reducing surface tension between the filter exit side and the micro flow path is accommodated as a wetting agent. The method of claim 16,
A lab-on-a-chip further comprising a wax layer installed on the filter outlet surface or the micro-channel to selectively block between the buffer solution and the filter outlet surface. Prepare a lab-on-a-chip equipped with an analysis unit in which a plurality of micro-grooves are arranged on the bottom surface of the analysis line through which the fluid flows, and insert antibody particles with capture antibodies attached to magnetic beads on each micro-groove. Method of manufacturing a wrap-on-a-chip of claim 1, comprising the step of fixing. The method of claim 18,
In the fixing process, the antibody particle is accommodated in the assay line, a magnetic force is applied to the antibody particle outside the bottom surface of the assay line, and the magnetic force is moved along the analysis line to move the antibody particle along the magnetic force while the antibody particle is moved. Method comprising the step of inserting the antibody particles in the micro groove. The method of claim 19,
A method further comprising removing the remaining antibody particles from the analysis line in addition to the antibody particles fixed in the micro groove by transferring the fluid to the analysis line. A sample supply process for preparing a lab-on-a-chip of any one of claims 1 to 8 and supplying a sample to a channel formed on a platform of the lab-on-a-chip,
Moving process for moving the sample to the analysis unit provided on the platform,
Reagent supply process for supplying a reagent to the analysis unit, and
A method of analyzing a biomarker to provide information for diagnosis using a lab-on-a-chip comprising detecting a biomarker of a sample with an antibody particle accommodated in the microgroove arranged along the analysis unit and labeling it with a reagent. The method of claim 21,
The method of supplying the sample, further comprising the step of filtering the sample with a filter. The method of claim 22,
The method of supplying the sample further includes wetting the filter outlet with a buffer solution before filtering the filter. The method of claim 21,
The moving process includes the step of pushing the sample by applying pressure to the channel to move the sample. The method of claim 21,
The moving process includes the step of applying heat to the drive chamber of the platform containing the reagent.

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