Sample seperating device and well plate, sample reaction device and sensor device for field diagnosing using the sample seperating device

Abstract

The present invention provides a sample separation device and a well plate, a sample reaction device, and a field diagnostic sensor device using the same, comprising: a lower substrate having a chamber for receiving a fluid; a membrane coupled to the upper part of the lower substrate and loaded with a sample; a filter coupled to the upper part of the membrane and allowing only specific components from the sample loaded on the membrane to pass through; and an upper substrate coupled to the upper part of the filter and fixing the filter, wherein the membrane is formed of an elastic material capable of expansion and contraction and is deformed to protrude toward the chamber by a negative pressure formed in the chamber, and deformed to contract in the opposite direction of the chamber by a reduction in the negative pressure formed in the chamber or a positive pressure formed in the chamber, thereby causing the loaded sample to come into contact with the filter and allowing specific components of the filter to pass through the filter.

Description

Technology Field

[0001] The present invention relates to a sample separation device, a well plate using the same, a sample reaction device, and a sensor device for on-site diagnosis. Background Technology

[0002] Various types of filters and peripheral devices with multiple holes of a specific size are used in diverse research and industrial fields, such as biology, medicine, chemistry, and the environment, to separate or concentrate particles, materials, or cells according to size.

[0003] For example, to separate plasma from blood, a filter with holes smaller in diameter than blood cells is used.

[0004] Meanwhile, a lab-on-a-chip is a device and technology that enables the handling of samples in microfluidic channels. It is gaining attention as a sensor-based technology capable of processing biological, chemical, and environmental samples for on-site diagnostics because of its small size and suitability for handling minute amounts of samples. In such lab-on-a-chips, filters are embedded and utilized to separate plasma from blood or to separate particles or cells based on size differences.

[0005] However, both these filters and lab-on-a-chip technologies currently require a structure to fix the filter, which generates dead volume during use and thus limits their ability to process ultra-trace amounts of samples.

[0006] Meanwhile, blood tests typically consist of blood cell counts and biochemical or immunological tests for various components, including various proteins and genetic biomarkers contained in plasma. To conduct accurate tests on biomarkers contained in plasma, it is important to obtain high-purity plasma free from blood cell contamination.

[0007] Known methods for extracting plasma from blood include centrifugation and extraction using filters and pressure; however, if hemolysis occurs during this process, components within red blood cells spread into the plasma, interfering with accurate biomarker analysis. In other words, measuring the degree of hemolysis prior to plasma extraction is crucial for disease diagnosis, but if hemolysis occurs during the extraction process, it can provide inaccurate information.

[0008] In addition, when extracting plasma using the centrifugation method, there is a problem that it requires high costs, specialized facilities, and personnel.

[0009] Recently, as the industrialization of point-of-care diagnostic sensors and diagnostic kits progresses, technologies for separating plasma with a simple configuration at the site are being developed, primarily using filters. However, these point-of-care diagnostic plasma separation technologies also have problems such as severe blood cell contamination, complex and difficult-to-handle configurations, severe hemolysis when separated by pressure, and low test reliability due to the relatively small amount of plasma obtained when using filters.

[0010] In addition, even when using a lab-on-a-chip, there are limitations to plasma separation from ultra-trace amounts of blood due to the insoluble volume problem, as mentioned above. Prior art literature

[0011] Republic of Korea Published Patent Application No. 10-2019-0113341 (Published Oct. 08, 2019) The problem to be solved

[0012] The present invention aims to solve the aforementioned problems by providing a sample separation device that can separate desired components even from ultra-trace samples by minimizing insoluble volume, and can be constructed at low cost with a simple configuration without using external power.

[0013] In addition, another objective of the present invention is to provide a sample separation device capable of simply and accurately separating a desired component from a sample without hemolysis.

[0014] In addition, another objective of the present invention is to provide a well plate, a sample reaction device, and a field diagnostic sensor device utilizing the principle of such a sample separation device. means of solving the problem

[0015] To solve the problem described above, the present invention provides a sample separation device comprising: a lower substrate having a chamber for receiving a fluid; a membrane coupled to the upper part of the lower substrate and loaded with a sample; a filter coupled to the upper part of the membrane and allowing only specific components from the sample loaded on the membrane to pass through; and an upper substrate coupled to the upper part of the filter and fixing the filter, wherein the membrane is formed of an elastic material capable of expansion and contraction and is deformed to protrude toward the chamber by negative pressure formed in the chamber, and deformed to contract in the opposite direction of the chamber by a decrease in negative pressure formed in the chamber or positive pressure formed in the chamber, thereby causing the loaded sample to come into contact with the filter and allowing specific components of the filter to pass through the filter.

[0016] Here, at least one opening may be formed in the lower substrate, which is a passage for injecting fluid into the chamber or discharging fluid from the chamber.

[0017] Additionally, a fluid communication means for injecting or discharging fluid is coupled to the opening, and the fluid is discharged to the outside of the chamber by the fluid communication means, thereby forming negative pressure inside the chamber, and the membrane can expand toward the chamber and protrude.

[0018] In addition, the filter can be closely bonded to the upper part of the membrane after the membrane is deformed and protrudes toward the chamber by the negative pressure formed in the chamber.

[0019] According to another aspect of the present invention, a sample separation device is provided comprising: a lower substrate having a chamber for receiving a fluid; a membrane coupled to the upper portion of the lower substrate and loaded with a sample; an expansion band coupled to the lower portion of the membrane; a filter coupled to the upper portion of the membrane and allowing only specific components from the sample loaded on the membrane to pass through; and an upper substrate coupled to the upper portion of the filter and fixing the filter, wherein the membrane is formed of an elastic material capable of expansion and contraction and is deformed to protrude toward the chamber by an external force applied to the expansion band in the direction opposite to the membrane, and is deformed to contract toward the chamber by removing the external force applied to the expansion band in the direction opposite to the membrane or by an external force applied toward the membrane, thereby causing the loaded sample to come into contact with the filter and allowing specific components of the filter to pass through the filter.

[0020] Here, the expansion member includes a coupling plate that is closely coupled to the lower surface of the membrane; and a connecting rod coupled to the coupling plate and directed toward the chamber, wherein the connecting rod can deform the membrane by moving toward the chamber by means of an external force applied to the connecting rod in the opposite direction of the membrane.

[0021] Additionally, an opening is formed in the lower substrate, and the connecting rod may be formed to be movable between the outside and inside of the chamber through the opening.

[0022] In addition, the filter can be closely bonded to the upper part of the membrane after the membrane is deformed to protrude toward the chamber by an external force applied to the expansion band in the opposite direction to the membrane.

[0023] Additionally, it may further include a lower stopper disposed inside the lower substrate and contacting the expansion band to restrict the movement of the membrane when the membrane is deformed to protrude toward the chamber.

[0024] According to another aspect of the present invention, a well plate is provided having a plurality of sample separation devices as described above, comprising: a single expansion band coupled to each of the expansion bands of the plurality of sample separation devices; and a lower stopper disposed inside the lower substrate of each of the plurality of sample separation devices, which contacts each of the expansion bands to restrict the movement of the membrane when the membrane protrudes in the direction of the chamber.

[0025] Here, at least some of the above-mentioned expansion bands can be formed from an elastic material capable of stretching.

[0026] In addition, the sample separation device may further include a stopper disposed between the membrane and the filter to limit the range of shrinkage deformation of the membrane.

[0027] Additionally, the stopper may include a support member that is closely coupled to the membrane and the filter; a vertical bar that is coupled to the support member and extends for a predetermined length in the direction of the chamber; and a blocking plate formed at the bottom of the vertical bar that contacts the surface of the membrane when the membrane shrinks and deforms to restrict the movement of the membrane.

[0028] In addition, the length of the vertical bar may be variablely adjustable.

[0029] According to another aspect of the present invention, a well plate for sample separation is provided, comprising: a lower substrate having a plurality of chambers formed therein for receiving fluid; a base substrate coupled to the lower substrate and having a base chamber formed therein; a membrane coupled to the upper part of the lower substrate and having a sample loaded thereon; a filter coupled to the upper part of the membrane and allowing only specific components from the sample loaded on the membrane to pass through; and an upper substrate coupled to the upper part of the filter and fixing the filter, wherein a fluid communication channel capable of communicating fluid with the base chamber is formed in the plurality of chambers of the lower substrate, and the membrane is formed of an elastic material capable of expansion and contraction, and is deformed to protrude toward the plurality of chambers by a negative pressure formed in the base chamber and the plurality of chambers, and deformed to contract toward the opposite direction of the plurality of chambers by a reduction in the negative pressure formed in the base chamber and the plurality of chambers or a positive pressure formed in the base chamber and the plurality of chambers, thereby causing the loaded sample to come into contact with the filter, so that specific components of the sample pass through the filter.

[0030] According to another aspect of the present invention, a lower substrate having a plurality of chambers for receiving a fluid; a base substrate coupled to the lower substrate and having a base chamber formed therein; a membrane coupled to the upper part of the lower substrate and on which a sample is loaded; a plurality of expansion bands coupled to the lower surface of the membrane and disposed inside each of the plurality of chambers; and a filter coupled to the upper part of the membrane and allowing only specific components to pass through from the sample loaded on the membrane. The present invention provides a well plate for sample separation characterized by comprising an upper substrate that is coupled to the upper part of the filter and fixes the filter, wherein the membrane is formed of an elastic material capable of expansion and contraction, and is deformed to protrude toward the plurality of chambers by an external force applied to the plurality of expansion bands in the direction opposite to the membrane, and is deformed to contract toward the direction opposite to the plurality of chambers by removing the external force applied to the plurality of expansion bands in the direction opposite to the membrane or by an external force applied to the plurality of expansion bands in the direction of the membrane, thereby causing the loaded sample to come into contact with the filter, so that a specific component of the sample passes through the filter.

[0031] Here, a base expansion member may be further included that is combined with the plurality of expansion members and disposed within the base chamber.

[0032] According to another aspect of the present invention, a sample reaction device comprising a sample separation device as described above is provided, wherein the chamber is repeatedly alternately provided with i) the formation of negative pressure and the reduction of said negative pressure or the application of positive pressure; or ii) the application of an external force and the removal of said external force or the application of an external force in the opposite direction thereof, thereby causing said membrane to repeatedly alternately protrude and contract.

[0033] Here, the filter of the sample separation device can be excluded.

[0034] According to another aspect of the present invention, a sensor device for on-site diagnosis is provided, comprising: a sample separation device as described above; and at least one fluid channel coupled to an upper substrate of the sample separation device, wherein at least one biomarker probe material is disposed inside the fluid channel, and a fluid communication path is formed at one end of the fluid channel to allow a sample contained within the upper substrate to communicate, such that a specific component of the sample separated and extracted on the upper substrate of the sample separation device flows along the fluid channel through the fluid communication path and reacts with the biomarker probe material. Effects of the invention

[0035] According to the present invention, a sample separation device can be provided that minimizes the volume of insoluble material to separate desired components even from ultra-trace samples, and can be configured at low cost with a simple structure without using external power.

[0036] In addition, the present invention can provide a sample separation device capable of easily and accurately separating a desired component from a sample without hemolysis.

[0037] In addition, the present invention can provide a well plate, a sample reaction device, and a field diagnostic sensor device utilizing the principle of such a sample separation device. Brief explanation of the drawing

[0038] FIGS. 1 to 3 show a perspective view, an exploded perspective view, and a side cross-sectional view illustrating the configuration of a sample separation device (100) according to an embodiment of the present invention. FIGS. 4 and FIGS. 5 are drawings for explaining the process of separating and extracting specific components from a sample using a sample separation device (100). Figure 6 shows the absorbance at 540 nm of blood (Lysed), plasma, and plasma (M) obtained through a sample separation device (100), respectively. FIGS. 7 and FIGS. 8 are drawings for explaining a sample separation device (200) according to another embodiment of the present invention. FIG. 9 is a diagram illustrating the process of separating a specific component from a sample using a sample separation device (200). FIG. 10 is a drawing for explaining the lower stopper (17). FIG. 11 is a drawing for explaining the operation of a lower stopper (17) in a well plate equipped with a plurality of sample separation devices (200). FIG. 12 shows a perspective view of the upper stopper (60). FIG. 13 is a side cross-sectional view of a sample separation device (100) to explain the operation of the upper stopper (60). FIGS. 14 and FIGS. 15 are drawings for explaining a well plate (300) for sample separation according to an embodiment of the present invention. FIG. 16 is a drawing for explaining a well plate (400) according to another embodiment of the present invention. FIG. 17 shows a side cross-sectional view of a sample reaction device (500, 600). FIGS. 18 and 19 show a side view and a top view of a sensor device (700) for on-site diagnosis using a sample separation device (100, 200). Specific details for implementing the invention

[0039] Hereinafter, embodiments according to the present invention will be described in detail with reference to the attached drawings.

[0040] FIGS. 1 to 3 show a perspective view, an exploded perspective view, and a side cross-sectional view illustrating the configuration of a sample separation device (100) according to an embodiment of the present invention.

[0041] Referring to FIGS. 1 to 3, the sample separation device (100) of the present embodiment includes a lower substrate (10), a membrane (20), a filter (30), and an upper substrate (40), and performs the function of separating and extracting specific components from a sample, such as separating plasma from blood.

[0042] The lower substrate (10) has a chamber (11) in which fluid is received.

[0043] The lower substrate (10) has a side wall (13) and a lower plate (14), and the upper part of the lower substrate (10) is open.

[0044] A membrane (20) is coupled to the open upper portion of the lower substrate (10) to cover the open upper portion. Thus, the chamber (11) is defined by the membrane (20), the side wall (13), and the lower plate (14), and the chamber (11) provides a space to accommodate the deformed membrane (20) when the membrane (20) is deformed and protrudes toward the chamber (11) as described below.

[0045] The lower plate (14) can be formed in a flat shape, and the side wall (13) can be formed to extend vertically along the edge area of ​​the lower plate (14).

[0046] The side wall (13) has a preset height, and as described later, when the membrane (20) is deformed to protrude toward the chamber (11) due to negative pressure, it may have a height such that the lower surface of the membrane (20) does not come into contact with the lower plate (14), but if necessary, it may have a height such that the lower surface of the membrane (20) comes into contact with the lower plate (14).

[0047] Additionally, a fluid such as gas or liquid is contained in the chamber (11), and at least one opening (12) is formed in the lower substrate (10) as a passage for injecting fluid into the chamber (11) or discharging fluid from the chamber (11).

[0048] In FIGS. 1 to 3, an opening (12) is shown formed in the side wall (13) of the lower substrate (10), but this is exemplary and may also be formed in the lower plate (14).

[0049] A fluid communication means (not shown) for injecting or discharging fluid is coupled to the opening (12), and fluid can be injected into the chamber (11) or discharged from the chamber (11) by the fluid communication means.

[0050] When fluid is discharged from the chamber (11) to the outside by the operation of such fluid communication means, negative pressure is formed inside the chamber (11), and as described below, the membrane (20) formed of an elastic material can expand toward the chamber (11) and protrude.

[0051] Additionally, when the negative pressure formed in the chamber (11) is reduced, fluid is introduced into the chamber (11), and the membrane (20) formed of an elastic material as described below may contract and deform toward the opposite side of the chamber (11) due to the recovery force attempting to return to a circular shape.

[0052] Here, the reduction of negative pressure can be achieved by using a fluid communication means or by separating the fluid communication means from the opening (11) so that an external fluid flows into the chamber (11).

[0053] In addition, even when positive pressure is applied to the chamber (11), fluid flows into the chamber (11), and a force is generated that pushes the membrane (20) toward the opposite side of the chamber (11). Along with this, the membrane (20) can contract and deform toward the opposite side of the chamber (11) due to the recovery force that causes the membrane (20) to return to its original shape.

[0054] Here, the fluid may be a gas or a liquid, and the fluid communication means may be a device such as a syringe or pump capable of injecting or discharging the gas or liquid.

[0055] The means of fluid communication itself is not the direct purpose of the present invention, and since any means known by prior art can be used as long as it allows fluid to be communicated into the chamber (11) and can control negative pressure or provide positive pressure within the chamber (11), a detailed description is omitted.

[0056] The membrane (20) is bonded to the upper part of the lower substrate (10), and a sample is loaded on its surface.

[0057] The membrane (20) is joined to the side wall (13) of the lower substrate (10) to cover the open upper part of the chamber (11) of the lower substrate (10).

[0058] The membrane (20) may have a flat shape, but is formed of a material having elasticity that can expand or contract due to pressure or external force.

[0059] For example, the membrane (20) can be formed of PDMS (polydimethylsiloxane).

[0060] As described above, when fluid is discharged to the outside from the chamber (11) of the lower substrate (10) through the opening (12) by means of a fluid communication means, negative pressure is formed inside the chamber (11), and thereby the elastic membrane (20) is subjected to pressure toward the chamber (11), and thus the membrane (20) is deformed and protrudes toward the chamber (11) (see FIG. 4 (b)).

[0061] Accordingly, a concave space is formed on the surface of the membrane (20) toward the lower substrate (10) when viewed from the side, and a sample can be loaded into this concave space.

[0062] In this case, the sample may be loaded after the membrane (20) is deformed to protrude toward the chamber (11), but it is also possible to load the sample onto the membrane (20) first and then deform the membrane (20) to protrude toward the chamber (11).

[0063] Additionally, as described above, when the negative pressure formed in the chamber (11) is reduced or positive pressure is applied to the chamber (11), the membrane (20), which was deformed to protrude toward the chamber (11), is deformed to contract toward the opposite side of the chamber (11) (see FIG. 5 (e)).

[0064] Since the membrane (20) shrinks and deforms toward the opposite side of the chamber (11), that is, toward the filter (30) described later, a force is generated that pushes the sample loaded on the membrane (20) toward the filter (30), and thus the sample comes into contact with the filter (30), and a specific component of the sample passes through the filter (30).

[0065] In this case, the membrane (20) may have a material and thickness that provide enough elasticity to shrink and deform in the opposite direction of the chamber (11) and make close contact with the filter (30), but the material or thickness of the membrane (20) may be different so that the pressure for separating specific components from the sample can be adjusted as needed.

[0066] The filter (30) is attached to the upper part of the membrane (20) and performs the function of allowing only specific components to pass through from the sample loaded on the membrane (20).

[0067] The filter (30) can be formed in a flat shape and can have a size corresponding to the size of the membrane (20).

[0068] The filter (30) can be placed on the upper part of the membrane (20) and closely coupled with the membrane (20) after the sample is loaded onto the membrane (20) and the membrane (20) is deformed to protrude toward the chamber (11) by the negative pressure formed in the chamber (11).

[0069] At least one pore (31) is formed in the filter (30) having a size that allows a specific component to be separated from the sample to pass through.

[0070] For example, if the sample separation device (100) is a device for separating plasma from blood, at least one pore (31) is formed in the filter (30) with a size such that red blood cells and white blood cells do not pass through, for example, 1 to 2 μm or less, or a size such that platelets do not pass through, for example, 100 to 500 nm or less.

[0071] As described above, when the membrane (20) is deformed to protrude toward the chamber (11) and then the membrane (20) is deformed to contract toward the opposite side of the chamber (11) due to a decrease in negative pressure formed in the chamber (11) or positive pressure formed in the chamber (11), the filter (30) comes into contact with a sample loaded on the membrane (20), and thereby a specific component of the sample passes through the filter (30) through the pores (31) of the filter (30) (see FIG. 5 (e)).

[0072] The upper substrate (40) is coupled to the upper part of the filter (30) and performs the function of fixing the filter (30).

[0073] In addition, the upper substrate (40) performs the function of collecting specific components of the sample that has passed through the filter (30) as described above.

[0074] The lower and upper portions of the upper substrate (40) are open and are coupled to the filter (30) by the side wall (41).

[0075] The side wall (41) also has a predetermined height, and by this side wall (41), a space of a predetermined height is formed inside the upper substrate (40), and a specific component of the sample that has passed through the filter (30) can be prevented from leaking out to the outside in this space.

[0076] FIGS. 4 and FIGS. 5 are drawings for explaining the process of separating and extracting specific components from a sample using a sample separation device (100).

[0077] The following explanation uses the example of a case where the sample is blood and plasma is separated from the blood.

[0078] First, as shown in FIG. 4 (a), the lower substrate (10) and the membrane (20) are combined, and as shown in FIG. 4 (b), when negative pressure is formed in the chamber (11) through the opening (12) of the lower substrate (10), the elastic membrane (20) is deformed and protrudes toward the chamber (11) of the lower substrate (10).

[0079] In this state, blood is loaded onto the surface of the membrane (20) as shown in (c) of Fig. 4.

[0080] After the blood is loaded, the filter (30) is closely bonded to the upper part of the membrane (20) as shown in Fig. 5 (d), and the upper substrate (40) is bonded on the filter (30).

[0081] In this state, as shown in FIG. 5 (e), when the negative pressure formed in the chamber (11) through the opening (12) of the lower substrate (10) is reduced or positive pressure is applied to the chamber (11), the membrane (20) contracts and deforms in the opposite direction of the chamber (11), thereby generating a force that pushes the blood loaded on the membrane (20) toward the filter (30).

[0082] Therefore, the blood comes into contact with the filter (30), and only the plasma in the blood passes through the pores (31) of the filter (30) and is collected on the upper surface of the filter (30), so that the plasma can finally be separated and extracted from the blood.

[0083] Meanwhile, in the above embodiment, the sample separation device (100) is shown as being cylindrical in shape overall, but this is exemplary and it is obvious that it may be formed in other shapes such as a cube.

[0084] Next, a specific experimental example of the sample separation device (100) described with reference to FIGS. 1 to 5 will be described.

[0085] First, as shown in FIG. 4 (a), a lower substrate (10) and a membrane (20) are prepared and combined.

[0086] Here, the membrane (20) is formed of PDMS (polydimethylsiloxane) and has a thickness of 500 μm. In addition, the diameter of the opening (12) of the lower substrate (10) is 8 mm.

[0087] In this state, as shown in FIG. 4 (b), a syringe connected to a tygon tube is attached to the opening (12), and as described above, negative pressure is formed in the chamber (11) to deform the membrane (20) so that it protrudes toward the chamber (11), and then blood, which is a sample, is loaded onto the surface of the membrane (20) as shown in FIG. 4 (c).

[0088] Here, the amount of blood was set to 100 μL, consisting of concentrated red blood cells and plasma supplied by the Ulsan Blood Center of the Korean Red Cross mixed in a ratio of 4.5:5.5.

[0089] In this state, as shown in FIG. 5 (d), a filter (30) is bonded onto a membrane (20), and an upper substrate (40) is bonded thereon. Here, the diameter of the pores (31) of the filter (30) is 0.4 μm.

[0090] Next, when the negative pressure applied to the chamber (11) is reduced, as shown in FIG. 5 (e), plasma passes through the pores (31) of the filter (30) and collects on the filter (30).

[0091] The plasma collected on the filter (30) is extracted using a micropipette to obtain plasma (M).

[0092] Meanwhile, Triton X-100 is mixed with the blood previously loaded on the membrane (20) at a ratio of 0.1% (w / v) and reacted at 37°C for 30 minutes to obtain the treated blood (Lysed), and the absorbance at 540 nm of this blood (Lysed), plasma supplied by the Ulsan Blood Center of the Korean Red Cross, and plasma (M) obtained through the sample separation device (100) are each measured and compared. Here, a NanoQ (K-Lab) spectrometer was used.

[0093] FIG. 6 shows the absorbance at 540 nm of blood (Lysed), plasma, and plasma (M) obtained through a sample separation device (100), respectively.

[0094] As shown in Figure 6, it can be seen that in the blood treated with Triton X-100 (Lysed), the absorbance at a wavelength of 540 nm is significantly higher due to hemolysis than in the case of plasma (Plasma) and plasma (M).

[0095] In addition, it can be seen that the absorbance of the plasma (M) extracted by the sample separation device (100) is not significantly different from the absorbance of the plasma (Plasma) not mixed with concentrated red blood cells. Therefore, from these experimental results, it can be confirmed that no significant hemolysis occurred during the plasma extraction process by the sample separation device (100) according to the present invention.

[0096] In addition, after extracting the plasma extracted by the sample separation device (100) four times, it was placed in a hemocytometer and analyzed for contamination of blood cells under an optical microscope, and it was confirmed that the amount of blood cells contained in the plasma was 0%.

[0097] Meanwhile, in the above embodiment, a sample separation device (100) using negative pressure formed in a chamber (11) was described, but other methods may be used instead of negative pressure.

[0098] FIGS. 7 and FIGS. 8 are for explaining a sample separation device (200) according to another embodiment of the present invention, FIG. 7 is a side cross-sectional view of the sample separation device (200), and FIG. 8 is a side cross-sectional view of a lower substrate (10-1) and a membrane (20) combined.

[0099] FIGS. 7 and FIGS. 8 are different in that they have the same basic principle as the sample separation device (100) of FIGS. 1 to 5, but the membrane (20) is deformed by using an expansion band (50).

[0100] Referring to FIGS. 7 and 8, the expansion band (50) is coupled to the lower surface of the membrane (20), and when an external force is applied to the expansion band (50) in the opposite direction to the membrane (20) by user operation or other driving means, it performs the function of protruding the membrane (20) toward the chamber (11).

[0101] Additionally, when the external force applied to the expansion band (50) is removed or an external force is applied in the direction of the membrane (20), the membrane (20) shrinks and deforms in the opposite direction of the chamber (11).

[0102] The expansion plate (50) may include a connecting plate (51) and a connecting rod (52).

[0103] The connecting plate (51) is formed in a flat shape and is closely connected to the lower surface of the membrane (20).

[0104] The center of the connecting plate (51) can be connected so as to be positioned on the same vertical line as the center of the membrane (20).

[0105] The connecting rod (52) is connected to the connecting plate (51) and extends in the direction of the chamber (11).

[0106] The connecting rod (52) can be connected to the center of the connecting plate (51).

[0107] An opening (12-1) is formed in the lower substrate (10-1), and a connecting rod (52) is formed to be movable between the outside and inside of the chamber (11) through the opening (12-1).

[0108] The opening (12-1) may be formed in the lower plate (14) or in the side wall (13).

[0109] The connecting rod (52) moves toward the chamber (11) by an external force applied in the opposite direction of the membrane (20) by user operation or other driving means, and moves toward the opposite direction of the chamber (11) by the removal of such external force or an external force applied toward the membrane (20).

[0110] For example, when a user holds the connecting rod (52) with their hand and pulls it toward the chamber (11), the membrane (20) protrudes toward the chamber (11) (see FIG. 8 (a)), and when the external force is removed by releasing the hand holding the connecting rod (52), the membrane (20) can contract in the opposite direction of the chamber (11) due to the elasticity of the membrane (20).

[0111] In this case, even when the user applies an external force by pushing the connecting rod (52) toward the membrane (20), the membrane (20) can be deformed by shrinking in the opposite direction of the chamber (11).

[0112] Additionally, an external force may be applied to or removed from the connecting rod (52) by other driving means such as a motor, a pump, etc. For example, an external force may be applied to the connecting rod (52) by rotating the motor in a specific direction so that the connecting rod (52) may move in the opposite direction of the membrane (20), and the connecting rod (52) may move in the direction of the membrane (20) by rotating the motor in the opposite direction.

[0113] The expansion band (50) may be made of a material that has elasticity, but may also be made of a material that does not have elasticity, and may be formed by combining an elastic material and a non-elastic material.

[0114] In addition, the expansion band (50) may be formed of the same material as the membrane (20).

[0115] Additionally, the expansion band (50) may be formed integrally with the membrane (20).

[0116] The other configurations of the sample separation device (200) are the same as those of the sample separation device (100) described in FIGS. 1 to 5, so a detailed description is omitted.

[0117] FIG. 9 is a diagram illustrating the process of separating a specific component from a sample using a sample separation device (200).

[0118] First, as shown in Fig. 8, the lower substrate (10-1) and the membrane (20) are combined.

[0119] Here, an expansion band (50) is attached to the lower surface of the membrane (20).

[0120] In this state, as shown in FIG. 8 (a), when an external force is applied to the expansion band (50) in the opposite direction to the membrane (20) and the expansion band (50) moves toward the outside of the chamber (11) through the opening (12-1) of the lower substrate (10-1), the elastic membrane (20) is deformed and protrudes toward the chamber (11) of the lower substrate (10) as described above.

[0121] In this state, as previously shown in FIG. 4 (c) and FIG. 5 (d), blood is loaded onto the surface of the membrane (20), a filter (30) is closely bonded to the upper part of the membrane (20), and an upper substrate (40) is bonded on top of the filter (30).

[0122] In this state, as shown in Fig. 9 (b), when the external force applied to the expansion band (50) is removed or the external force is not applied in the direction of the membrane (30), the membrane (20) shrinks and deforms in the opposite direction of the chamber (11) due to elasticity or the external force in the direction of the membrane (20), and thereby a force is generated to bring the blood loaded on the membrane (20) into contact with the filter (30).

[0123] Accordingly, as previously described regarding the sample separation device (100), blood comes into contact with the filter (30), and only the plasma in the blood passes through the filter (30) through the pores (31) of the filter (30) and is collected on the upper surface of the filter (30), so that the plasma can finally be separated and extracted from the blood.

[0124] Meanwhile, the sample separation device (100, 200) may further include a lower stopper (17) for limiting the range in which the membrane (20) protrudes and deforms.

[0125] FIG. 10 is a drawing for explaining the lower stopper (17), FIG. 10 (a) is a side cross-sectional view of the lower substrate (10-1) of the sample separation device (200) and the membrane (20) combined, FIG. 10 (b) is a side cross-sectional view showing the membrane (20) being deformed and protruding in the direction of the chamber (11) when an external force is applied to it.

[0126] Referring to FIG. 10 (a) and (b), the lower stopper (17) is placed inside the lower substrate (10-1) and performs the function of restricting the movement of the membrane (20) by contacting the expansion band (50) when the membrane (20) is deformed to protrude toward the chamber (11) by an external force as described above.

[0127] In FIG. 10, the lower stopper (17) is formed to protrude into the chamber (11) at the edge of the lower substrate (10-1) and is configured to contact the lower surface of the connecting plate (51) of the expansion band (50) when the membrane (20) protrudes.

[0128] According to this configuration, the protruding deformation range of the membrane (20) can be limited, so there is an advantage in that the space where the sample is loaded on the surface of the membrane (20) can be kept constant.

[0129] In addition, when applied to a well plate in which a plurality of sample separation devices (200) are arranged, the protruding deformation range of each sample separation device (200) can be consistently secured by the lower stopper (17).

[0130] FIG. 11 is a drawing for explaining the operation of a lower stopper (17) in a well plate equipped with a plurality of sample separation devices (200).

[0131] Referring to FIG. 11, the sample separation devices (200) described with reference to FIG. 7 to 9 are arranged side by side, and the expansion band (50) of each of these sample separation devices (200) is combined with a single expansion band (50-1) outside the opening (12-1) of the lower substrate (10-1).

[0132] In this state, as indicated by the red arrow, when an external force is applied to a single expansion band (50-1) in the opposite direction to the membrane (20), each expansion band (50) moves simultaneously toward the chamber (11), and the membrane (20) also protrudes and deforms toward the chamber (11). At this time, as described above, since a lower stopper (17) is placed on the lower substrate (10-1), each expansion band (50) comes into contact with the lower stopper (17), thereby limiting the protruding deformation range of the membrane (20).

[0133] In this case, as illustrated, since the external force applied to a single expansion band (50-1) may not be applied uniformly to the expansion bands (50), if at least a portion of the connecting rod (52) of each expansion band (50) is formed from an elastic material (53) that can be stretched, the extension range of the connecting rod (52) will vary depending on the external force applied to each expansion band (50), and thus the protruding deformation range (a, b, c) of the membrane (20) can be maintained uniformly.

[0134] Meanwhile, the sample separation device (100, 200) may further include an upper stopper (60) to limit the range in which the membrane (20) shrinks and deforms.

[0135] FIG. 12 is a perspective view of the upper stopper (60), and FIG. 13 is a side cross-sectional view of the sample separation device (100) to explain the operation of the upper stopper (60).

[0136] FIG. 13 (a) shows a state in which the membrane (20) is deformed and protrudes toward the chamber (11), and FIG. 13 (b) shows a state in which the membrane (20) is deformed and contracted toward the opposite direction of the chamber (11). It should be noted that for convenience of explanation, blood is excluded from FIG. 13.

[0137] Referring to FIGS. 12 and 13, the upper stopper (60) is positioned between the membrane (20) and the filter (30) and performs the function of limiting the shrinkage range of the membrane (20) when the membrane (20) shrinks in the opposite direction of the chamber (11).

[0138] The upper stopper (60) includes a support member (61) that is closely coupled to the membrane (20) and filter (30), and a vertical bar (62) that is coupled to the support member (61) and extends in a predetermined length toward the chamber (11).

[0139] Additionally, it includes a blocking plate (63) formed at the bottom of the vertical bar (62) that contacts the surface of the membrane (20) when the membrane (20) shrinks and deforms, thereby restricting the movement of the membrane (20).

[0140] The support portion (61) is formed in a shape corresponding to the edge portion of the membrane (20) and filter (30), and a plurality of horizontal bars (64) are formed extending from the support portion (61) toward the center of the vertical bar (62).

[0141] The vertical bar (62) is formed to extend downward from where the horizontal bars (64) meet, that is, in the direction of the chamber (11).

[0142] The length of the vertical bar (62) determines the range of movement of the membrane (20) when the membrane (20) is deformed. This means that the amount of sample passing through the filter (30) is determined according to the length of the vertical bar (62). In other words, the amount of sample passing through the filter (30) can be controlled to a constant level by the length of the vertical bar (62).

[0143] For example, in the case of plasma separation, the amount of plasma passing through the filter (30) can be controlled as desired when the amount of blood initially loaded is constant by causing the membrane (20) to contract and deform to a desired degree by the length of the vertical bar (62). By doing so, hemolysis caused by excessive pressure can be prevented by taking hematocrit into account.

[0144] Considering these points, it is also desirable to form the vertical bar (62) in a variable shape so that the length of the vertical bar (62) can be adjusted variably.

[0145] FIGS. 12 and FIGS. 13 show a case where a stopper (60) is placed in a sample separation device (100), but this is exemplary and it is obvious that a stopper (60) can likewise be placed in a sample separation device (200).

[0146] FIGS. 14 and FIGS. 15 are drawings for explaining a well plate (300) for sample separation according to an embodiment of the present invention, showing a case where the principle of the sample separation device (100) of FIGS. 1 to 5 is used.

[0147] FIG. 14 shows the state before the filter (30) is coupled to the membrane (20), and FIG. 15 shows the operating state after the filter (30) and upper substrate (40) of the well plate (300) are coupled to the membrane (20), and after blood is loaded, plasma is separated through the filter (30).

[0148] Referring to FIGS. 14 and 15, a well plate for sample separation (300, hereinafter simply referred to as "well plate (300)") comprises a lower substrate (10-2), a base substrate (70), a membrane (20), a filter (30), and an upper substrate (40).

[0149] The lower substrate (10-2) is basically the same as the lower substrate (10) described in the sample separation device (100), but differs in that it has multiple chambers (11A, 11B, 11C) formed therein.

[0150] Here, multiple chambers (11A, 11B, 11C) can be arranged in a two-dimensional array form when viewed from above the well plate (300), and each chamber (11A, 11B, 11C) is separated from each other by a barrier wall (15).

[0151] Each of the multiple chambers (11A, 11B, 11C) contains a fluid as described above.

[0152] In each of the multiple chambers (11A, 11B, 11C), a passage (16-1, 16-2, 16-3) is formed to communicate fluid with the base chamber (71) of the base substrate (70) described later.

[0153] The passage (16-1, 16-2, 16-3) can be formed in the lower plate (14) of the plurality of chambers (11A, 11B, 11C).

[0154] The base substrate (70) is combined with the lower substrate (10-2) and a base chamber (71) is formed.

[0155] The base substrate (70) is coupled to the lower part of the lower substrate (10-2), and the base chamber (71) is connected to a plurality of chambers (11A, 11B, 11C) by the aforementioned passages (16-1, 16-2, 16-3).

[0156] The base substrate (70) has a size corresponding to the lower substrate (10-2) overall and has a side wall (73) and a base plate (74).

[0157] At least one base opening (72) is formed in the base substrate (70), which is a passage for injecting fluid into the base chamber (71) or discharging fluid from the base chamber (71).

[0158] In FIGS. 14 and 15, a base opening (72) is shown formed in the base plate (74) of the base substrate (70), but this is exemplary and may be formed in the side wall (73).

[0159] A fluid communication means as described in the sample separation device (100) is coupled to the base opening (72), and fluid can be injected into the base chamber (71) or discharged from the base chamber (71) by the fluid communication means.

[0160] As a result, negative pressure can be formed inside the base chamber (71) and simultaneously in the plurality of chambers (11A, 11B, 11C). Therefore, as previously explained, the membrane (20) can expand toward the plurality of chambers (11A, 11B, 11C) and protrude.

[0161] In addition, as previously described in the sample separation device (100), negative pressure may be reduced or positive pressure may be formed in the plurality of chambers (11A, 11B, 11C) by the reduction of negative pressure formed in the base chamber (71) or the positive pressure formed in the base chamber (71). Accordingly, as previously described, the membrane (20) may contract and deform toward the opposite side of the plurality of chambers (11A, 11B, 11C).

[0162] FIG. 14 shows a state in which negative pressure is formed in the base chamber (71) and, accordingly, negative pressure is also formed in the plurality of chambers (11A, 11B, 11C), causing the membrane (20) to protrude and deform in the direction of the plurality of chambers (11A, 11B, 11C).

[0163] Meanwhile, the membrane (20), filter (30), and upper substrate (40) are identical to those in the sample separation device (100) described with reference to FIGS. 1 to 5, except that the membrane (20) is formed to cover the entire plurality of chambers (11A, 11B, 11C) of the lower substrate (10-2) and the upper substrate (40) has a barrier wall (45) corresponding to the barrier wall (15) of the plurality of chambers (11A, 11B, 11C), so a detailed description is omitted.

[0164] However, in FIG. 14, the membrane (20) is shown as being formed to cover the entire plurality of chambers (11A, 11B, 11C) of the lower substrate (10-2), but this is exemplary, and the membrane (20) may be formed to cover each of the plurality of chambers (11A, 11B, 11C).

[0165] FIG. 15 shows the state in which, after the filter (30) and upper substrate (40) of the well plate (300) are combined with the membrane (20), a sample is loaded and the membrane (20) is deformed in the opposite direction of the chamber (11A, 11B, 11C) due to a decrease in negative pressure or the formation of positive pressure.

[0166] In a state as shown in Fig. 14, blood is loaded onto the surface of the membrane (20), a filter (30) is closely bonded to the upper part of the membrane (20), and an upper substrate (40) is bonded on top of the filter (30).

[0167] In this state, when negative pressure is reduced or positive pressure is applied through the base opening (72) of the base substrate (70) as previously described, as shown in FIG. 15, negative pressure is reduced or positive pressure is formed in the plurality of chambers (11A, 11B, 11C) through the passage (16-1, 16-2, 16-3), and the membrane (20) is deformed in the opposite direction of the plurality of chambers (11A, 11B, 11C), and a force is generated to push the blood loaded on the membrane (20) toward the filter (30).

[0168] Therefore, as the blood comes into contact with the filter (30), only the plasma in the blood passes through the filter (30) via the pores (31) of the filter (30) and is collected on the upper surface of the filter (30), and finally, the plasma can be separated and extracted from the blood.

[0169] FIG. 16 is a drawing for explaining a well plate (400) according to another embodiment of the present invention, showing a case where the principle of the sample separation device (200) of FIG. 7 to 9 is used.

[0170] The well plate (400) of FIG. 16 has the same basic principle as the well plate (300) of FIG. 14 and FIG. 15, but differs in that it uses expansion bands (50A, 50B, 50C) to deform the membrane (20) into protruding or contracting deformations.

[0171] Referring to FIG. 16, the well plate (400) includes a lower substrate (10-2), a base substrate (70), a membrane (20), a plurality of expansion bands (50A, 50B, 50C), a filter (30), and an upper substrate (40).

[0172] Here, the lower substrate (10-2), base substrate (70), membrane (20), filter (30), and upper substrate (40) are identical to the well plate (300) of FIGS. 12 and FIGS. 13, so a detailed description is omitted.

[0173] The multiple expansion plates (50A, 50B, 50C) are identical to the expansion plates (50) of the sample separation device (200) of FIGS. 7 to 9, but differ in that they are placed inside each of the multiple chambers (11A, 11B, 11C) and are coupled to the lower surface of the membrane (20).

[0174] A plurality of expansion bands (50A, 50B, 50C) are combined with a base expansion band (75) disposed in the base chamber (71) of the base substrate (70) through a passage (16-1, 16-2, 16-3) formed in a plurality of chambers (11A, 11B, 11C).

[0175] The base expansion member (75) is formed to be movable between the outside and inside of the base chamber (71) through a base opening (72) formed in the base substrate (70), and the base expansion member (75) moves the multiple expansion members (80) toward the multiple chambers (11A, 11B, 11C) by means of an external force applied in the opposite direction of the membrane (20) by user operation or other driving means in the same manner as described above, thereby performing the function of protruding the membrane (20) toward the multiple chambers (11A, 11B, 11C).

[0176] In addition, the base expansion unit (75) performs the function of shrinking and deforming the membrane (20) in the opposite direction of the multiple chambers (11A, 11B, 11C) by removing an external force in the opposite direction of the membrane (20) or applying an external force in the direction of the membrane (30) in the same manner as described above.

[0177] That is, the base expansion unit (75) performs the same function as the expansion unit (50) of FIGS. 7 to 9, but differs only in that it is not directly connected to the membrane (20), so a detailed description of other components is omitted.

[0178] Referring again to FIG. 16, the operation of the well plate (400) is explained as follows: as indicated by the red arrow, an external force is applied to the base expansion member (75) in the opposite direction to the membrane (20), and when the base expansion member (75) moves toward the outside of the base chamber (71) through the opening (72) of the base substrate (70), the multiple expansion members (50A, 50B, 50C) move toward the multiple chambers (11A, 11B, 11C), and thus the membrane (20) is deformed while protruding toward the multiple chambers (11A, 11B, 11C).

[0179] In this state, blood is loaded onto the surface of the membrane (20), the filter (30) is closely attached to the upper part of the membrane (20), and the upper substrate (40) is attached to the filter (30). Then, as indicated by the blue arrow in FIG. 15, when the external force applied to the base expansion unit (75) in the opposite direction of the membrane (20) is removed or an external force is applied in the direction of the membrane (20), the base expansion unit (75) moves into the base chamber (71), and the multiple expansion units (50A, 50B, 50C) move in the opposite direction of the multiple chambers (11A, 11B, 11C), and thus the membrane (20) is deformed while contracting in the opposite direction of the multiple chambers (11A, 11B, 11C).

[0180] This generates a force that pushes the blood loaded on the membrane (20) toward the filter (30), and thus the blood comes into contact with the filter (30), causing the plasma to pass through the filter (30) via the pores (31) of the filter (30) and accumulate on the upper surface of the filter (30), and finally, the plasma can be separated and extracted from the blood.

[0181] According to these well plates (300, 400), a large amount of samples can be processed quickly, accurately, and efficiently through multiple wells.

[0182] In addition, a bead with a biomarker probe material fixed thereon may be provided in advance within the upper substrate (40), or a biomarker probe material may be provided on the upper surface of the filter (30) or the upper surface of the membrane (20), and plasma biomarker analysis may be performed simultaneously with plasma extraction as described above.

[0183] In addition, the upper substrate (40) can be separated after extracting plasma and used later for biomarker analysis.

[0184] In addition, it is also possible to use one or more other substances as probes, detection substances, or reaction substances, rather than biomarker probes.

[0185] In addition, although the above example describes the case of separating plasma from blood, this is exemplary and applicable to various samples including all substances, particles, and cells, and of course applicable to various fields such as biology, medicine, chemistry, and environment.

[0186] Meanwhile, the principle of the sample separation device (100, 200) described above can also be applied to a device that mixes samples or promotes a reaction.

[0187] FIG. 17 shows a side cross-sectional view of a sample reaction device (500, 600).

[0188] Figure 17 (A) shows a sample reaction device (500) using a sample separation device (100).

[0189] The sample reaction device (500) is identical to the sample separation device (100), but is characterized by repeatedly alternating the formation and reduction of negative pressure or the application of positive pressure to the chamber (11) of the lower substrate (10-1), thereby causing the membrane (20) to repeatedly protrude and contract in the up and down direction.

[0190] When the membrane (20) is deformed to the maximum protrusion toward the chamber (11) by such repeated formation and reduction of negative pressure or application of positive pressure, the height of the sample becomes h1, and when the membrane (20) is deformed to the maximum contraction toward the chamber (11), the height of the sample becomes h2. Accordingly, the sample flows in the up and down direction within the range of h1 to h2, and the mixing, reaction, washing, etc. of the materials within the sample can be effectively performed.

[0191] In this case, a separate blocking plate (not shown) may be placed between the membrane (20) and the filter (30) so that the membrane (20) and the filter (30) are spaced apart from each other.

[0192] Figure 17 (B) shows another sample reaction device (600) using a sample separation device (100), which is identical to Figure 17 (A), but differs in that the filter (30) is removed.

[0193] According to the configuration of (B) in FIG. 17, since the filter (30) is removed, the membrane (20) can move upward higher than the original position of the filter (30) as illustrated. Therefore, when the membrane (20) undergoes maximum shrinkage deformation in the opposite direction of the chamber (11), the height h2 of the sample is higher than in the case of (A) in FIG. 16. This means that the membrane (20) can move over a wider range in the vertical direction, thus having the advantage of allowing greater reactivity in the sample.

[0194] As shown in FIG. 17, when two or more different liquids or substances are contained in a sample within an upper substrate (40) by repeatedly protruding and contracting the membrane (20) in the up and down directions, mixing, reaction, and washing of these substances can be effectively performed.

[0195] As shown on the right side of (B) in FIG. 17, if material B is fixed to the inner surface of the side wall (41) of the upper substrate (40) and material A is present in the sample, then the operation of the membrane (20) as described above causes a corresponding repeated flow of fluid within the sample, thereby increasing the probability of contact between material A and material B. Thus, the reaction between material A and material B can be promoted.

[0196] Even when both material B and material A are present in the sample, the probability of contact between the two materials can be increased and the reaction can also be promoted by the fluid flow induced in the sample by the repeated deformation of the membrane (20).

[0197] Effective washing is also possible because a repetitive flow of the washing solution is induced when a washing process is required to fix, bind, or induce a reaction by a probe on the inner surface of the side wall (41) of the upper substrate (40).

[0198] In addition, all the effects described above can be obtained in the same way when performing bead essay inside the upper substrate (40).

[0199] Figure 17 shows a case using a sample separation device (100), but this is exemplary and can be applied in the same way to a sample separation device (200).

[0200] FIGS. 18 and 19 show a side view and a top view of a sensor device (700, hereinafter simply referred to as "sensor device (700)") for on-site diagnosis using a sample separation device (100, 200).

[0201] FIGS. 18 and 19 show a sensor device (700) using a sample separation device (100), but this is exemplary and can be applied to a sample separation device (200) as well.

[0202] Referring to FIGS. 18 and 19, the sensor device (700) includes a sample separation device (100) and fluid channels (710A to 710D) as previously described.

[0203] The fluid channels (710A~710D) are coupled to the upper substrate (40) of the sample separation device (100).

[0204] A top plate (711) covering the upper portion of the fluid channels (710A~710D) may be formed, and the top plate (711) may be formed integrally to cover the upper substrate (40) and the fluid channels (710A~710D) simultaneously.

[0205] At one end of the fluid channels (710A~710D), a fluid passage (720) is formed to allow a sample contained within the upper substrate (40) to communicate.

[0206] Accordingly, as described above, when a specific component that has passed through the filter (30) is extracted on the upper substrate (40) of the sample separation device (100), the extracted specific component, such as plasma, flows along the fluid channels (710A~710D) through the fluid communication path (720).

[0207] At least one fluid channel (710A to 710D) may be formed, and at least one biomarker probe material is disposed inside the fluid channel (710A to 710D). If there are multiple fluid channels (710A to 710D) as illustrated, different biomarker probe materials may be disposed in each fluid channel (710A to 710D).

[0208] Here, biomarker probe materials may include antibodies, oligonucleotides, aptamers, etc., but this is merely an example and various other biomarker materials may be used.

[0209] Accordingly, plasma that has passed through the filter (30) is extracted to the upper substrate (40), and at the same time, the plasma flows along the fluid channels (710A~710D) through the fluid communication path (720) and comes into contact with and reacts with biomarker probe materials, thereby allowing various biomarkers to be analyzed simultaneously.

[0210] According to this sensor device (700), it has the advantage of being able to perform analysis with only a much smaller amount of sample than the amount of sample required in conventional sensor devices such as biosensors based on microfluidic channels.

[0211] Of course, this sensor device (700) can be applied not only to the sample separation device (100, 200), but also to the well plate (300, 400) and sample reaction device (500, 600).

[0212] Although the present invention has been described above with reference to preferred embodiments, the invention is not limited to the above embodiments, and it is understood that various modifications and variations are possible within the scope of the invention as understood by the appended claims and drawings.

[0213] For example, although the above examples mainly described cases where the sample is blood, they are not limited thereto and various other biological, chemical, and environmental samples may be used, and various probe materials other than those mentioned above may also be used. Explanation of the symbols

[0214] 100, 200... Sample separation device 300, 400...well plate 500, 600... Sample reaction device 700...Field diagnostic sensor device 10...Lower board 20...membrane 30...Filter 40...Upper board

Claims

Claim 1 A sample separation device comprising: a lower substrate having a chamber for receiving a fluid; a membrane coupled to the upper portion of the lower substrate and loaded with a sample; a filter coupled to the upper portion of the membrane and allowing only specific components from the sample loaded on the membrane to pass through; and an upper substrate coupled to the upper portion of the filter and fixing the filter, wherein the membrane is formed of an elastic material capable of expansion and contraction and is deformed to protrude toward the chamber by negative pressure formed in the chamber, and deformed to contract in the opposite direction of the chamber by a reduction in negative pressure formed in the chamber or positive pressure formed in the chamber, thereby causing the loaded sample to come into contact with the filter and allowing specific components of the filter to pass through the filter. Claim 2 A sample separation device according to claim 1, characterized in that the lower substrate has at least one opening formed therein, which is a passage for injecting fluid into the chamber or discharging fluid from the chamber. Claim 3 A sample separation device according to claim 2, wherein a fluid communication means for injecting or discharging fluid is coupled to the opening, and the fluid is discharged to the outside of the chamber by the fluid communication means, thereby forming negative pressure inside the chamber and causing the membrane to expand toward the chamber and protrude. Claim 4 A sample separation device according to claim 3, wherein the filter is closely coupled to the upper part of the membrane after the membrane is deformed to protrude toward the chamber by negative pressure formed in the chamber. Claim 5 A sample separation device comprising: a lower substrate having a chamber for receiving a fluid; a membrane coupled to the upper portion of the lower substrate and loaded with a sample; an expansion band coupled to the lower portion of the membrane; a filter coupled to the upper portion of the membrane and allowing only specific components from the sample loaded on the membrane to pass through; and an upper substrate coupled to the upper portion of the filter and fixing the filter, wherein the membrane is formed of an elastic material capable of expansion and contraction and is deformed to protrude toward the chamber by an external force applied to the expansion band in the direction opposite to the membrane, and is deformed to contract toward the chamber by removing the external force applied to the expansion band in the direction opposite to the membrane or by an external force applied toward the membrane, thereby causing the loaded sample to come into contact with the filter and allowing specific components of the filter to pass through the filter. Claim 6 A sample separation device according to claim 5, wherein the expansion member comprises: a coupling plate that is closely coupled to the lower surface of the membrane; and a connecting rod coupled to the coupling plate and directed toward the chamber, wherein the connecting rod moves toward the chamber by means of an external force applied to the connecting rod in the opposite direction to the membrane, thereby causing the membrane to protrude toward the chamber. Claim 7 A sample separation device according to claim 6, wherein an opening is formed in the lower substrate, and the connecting rod is formed to be movable between the outside and inside of the chamber through the opening. Claim 8 A sample separation device according to claim 5, wherein the filter is closely coupled to the upper part of the membrane after the membrane is deformed to protrude toward the chamber by an external force applied to the expansion band in the opposite direction to the membrane. Claim 9 A sample separation device according to claim 5, further comprising a lower stopper disposed inside the lower substrate and contacting the expansion band to restrict the movement of the membrane when the membrane is deformed to protrude toward the chamber. Claim 10 A well plate having a plurality of sample separation devices according to claim 5, comprising: a single expansion band coupled to each of the plurality of sample separation devices; and a lower stopper disposed inside the lower substrate of each of the plurality of sample separation devices, which contacts each of the expansion bands to restrict the movement of the membrane when the membrane is deformed to protrude toward the chamber. Claim 11 A well plate according to claim 10, characterized in that at least a portion of each expansion band is formed of a stretchable elastic material. Claim 12 A sample separation device according to claim 1 or claim 5, further comprising a stopper disposed between the membrane and the filter to limit the range of shrinkage deformation of the membrane. Claim 13 A sample separation device according to claim 12, wherein the stopper comprises: a support member that is closely coupled to the membrane and the filter; a vertical bar that is coupled to the support member and extends for a predetermined length in the direction of the chamber; and a blocking plate formed at the bottom of the vertical bar that contacts the surface of the membrane when the membrane is contracted and deformed to restrict the movement of the membrane. Claim 14 A sample separation device according to claim 13, characterized in that the length of the vertical bar is variablely adjustable. Claim 15 A well plate for sample separation comprising: a lower substrate having a plurality of chambers formed therein for receiving fluid; a base substrate coupled to the lower substrate and having a base chamber formed therein; a membrane coupled to the upper part of the lower substrate and on which a sample is loaded; a filter coupled to the upper part of the membrane and allowing only specific components from the sample loaded on the membrane to pass through; and an upper substrate coupled to the upper part of the filter and fixing the filter, wherein a fluid communication channel capable of communicating fluid with the base chamber is formed in the plurality of chambers of the lower substrate, and the membrane is formed of an elastic material capable of expansion and contraction, and is deformed to protrude toward the plurality of chambers by negative pressure formed in the base chamber and the plurality of chambers, and deformed to contract in the opposite direction of the plurality of chambers by a reduction in negative pressure formed in the base chamber and the plurality of chambers or positive pressure formed in the base chamber and the plurality of chambers, thereby causing the loaded sample to come into contact with the filter, so that specific components of the sample pass through the filter. Claim 16 A well plate for sample separation comprising: a lower substrate having a plurality of chambers formed therein for receiving fluid; a base substrate coupled to the lower substrate and having a base chamber formed therein; a membrane coupled to the upper part of the lower substrate and on which a sample is loaded; a plurality of expansion bands coupled to the lower surface of the membrane and disposed inside each of the plurality of chambers; a filter coupled to the upper part of the membrane and allowing only specific components from the sample loaded on the membrane to pass through; and an upper substrate coupled to the upper part of the filter and fixing the filter, wherein the membrane is formed of an elastic material capable of expansion and contraction, and is deformed to protrude toward the plurality of chambers by an external force applied to the plurality of expansion bands in the direction opposite to the membrane, and is deformed to contract toward the direction opposite to the plurality of chambers by removing the external force applied to the plurality of expansion bands in the direction opposite to the membrane or by an external force applied to the plurality of expansion bands in the direction of the membrane, thereby causing the loaded sample to come into contact with the filter and allowing specific components of the sample to pass through the filter. Claim 17 A well plate for sample separation according to claim 16, further comprising a base expansion member coupled to the plurality of expansion members and disposed within the base chamber. Claim 18 A sample reaction device comprising a sample separation device according to either claim 1 and claim 5, wherein the chamber is repeatedly alternately provided with: i) the formation of negative pressure and the reduction of said formed negative pressure or the application of positive pressure; or ii) the application of an external force and the removal of said external force or the application of an external force in the opposite direction thereof, thereby causing said membrane to repeatedly alternately protrude and contract. Claim 19 A sample reaction apparatus according to claim 18, characterized by excluding the filter of the sample separation apparatus. Claim 20 A sample separation device according to any one of claims 1 and 5; and a field diagnostic sensor device comprising at least one fluid channel coupled to an upper substrate of the sample separation device, wherein at least one biomarker probe material is disposed inside the fluid channel, and a fluid communication path is formed at one end of the fluid channel to allow a sample contained within the upper substrate to communicate, wherein a specific component of the sample separated and extracted on the upper substrate of the sample separation device flows along the fluid channel through the fluid communication path and reacts with the biomarker probe material.

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