JP2008039615A - Separation apparatus, analysis method and separation method - Google Patents

Abstract

A separation apparatus and a separation method that are easy to manufacture and suitable for downsizing are provided. In addition, a separation apparatus, a separation method, and the like that can improve separation efficiency and separation accuracy are provided.
A substrate S1 having flow paths 10a and 10b made of grooves formed on the surface thereof, an injection hole 3 connected to the flow path 10a, and a flow path 20a made of grooves formed on the surface thereof. The separation device includes a substrate S2 and a housing portion 5b connected to the flow path 20a, and the surface of the substrate S1 and the surface of the substrate S2 are in contact with each other so that the flow path 10a and the flow path 20a intersect each other. . As a result, the liquid component of the liquid flowing in the laminar flow state in the flow path 10a, for example, blood plasma can be introduced into the flow path 20a of the substrate S2, and the solid component and the liquid component in the liquid can be separated. it can.
[Selection] Figure 3

Description

  The present invention relates to a separation device, an analysis method, and a separation method, and more particularly to separation of a solid component or a liquid component of a liquid containing a solid component.

  Technology that integrates advanced chemical analysis, chemical synthesis, or bio-related analytical elements into a small microfluidic chip is drawing attention. These technologies are called μTAS (Micro-Total Analysis Systems) or Lab-on-a-chip, and medical diagnosis, health check, environment and food onsite. Applications are expected in a wide range of fields such as analysis, production of high value-added substances such as pharmaceuticals and chemicals, and high efficiency of bioanalysis, and in recent years its development has been regarded as important.

  According to such a technique, there are merits such that the required amount of the sample is smaller than that of the conventional apparatus, the reaction time is short, the amount of the test reagent used is small, and the waste is small.

  For example, when applied to blood tests in the medical field, the burden on the patient can be reduced by reducing the amount of specimen such as blood, and the test cost can be reduced by reducing the amount of reagent. . Furthermore, since the amount of the specimen and the reagent is small, the reaction time can be greatly shortened and the efficiency of the test can be improved.

Here, for example, Patent Document 1 below discloses a technique for obtaining plasma containing no cell components from whole blood in advance during a blood test.
JP-T-2005-505770

  As described above, various solid components are contained in blood. For precise examination, it is necessary to separate liquid components (plasma) in blood and measure various trace components in the liquid components. It is.

  A centrifugal separation method is used for such separation of liquid components (removal of solid components), but there is a problem that the apparatus is large and takes time for separation and inspection. Further, it is not suitable for a point of care (POC) test, that is, a clinical test performed on the patient side.

  On the other hand, there is a filter filtration method as a method that can be miniaturized, but it is difficult to set the filter material and the pore size, and there is a problem that the filter is clogged by proteins in the blood.

  As described above, there are the above problems in the treatment of blood before the test, and the above advantages of the μTAS technique may be impaired.

  Therefore, a separation technique as disclosed in Patent Document 1 has been studied. Here, in a separation module having an inlet channel (9), a first outlet channel (11) and a second outlet channel (12), a second outlet channel (12) through which fluid flows earlier than in the first outlet channel (11). A technique is disclosed in which a blood cell component is introduced into the blood cell and the blood cell component is separated from the blood. In addition, the code | symbol in the said literature is in a parenthesis.

  However, even if the technique disclosed in the above document is used, when the first discharge channel (11) and the second discharge channel (12) are formed in the same plane, the flow path (groove) is fine and deep. Is necessary. Therefore, in order to form the flow path on, for example, a glass substrate or a resin substrate, high-precision processing is required, which may increase the manufacturing cost of the separation module. In addition, there is a limit to improving separation efficiency and separation accuracy.

  Therefore, an object of the present invention is to provide a separation apparatus and a separation method that are easy to manufacture and suitable for downsizing. It is another object of the present invention to provide a separation apparatus and a separation method that can improve separation efficiency and separation accuracy.

  (1) A separation apparatus according to the present invention includes a first substrate having a first flow path formed by a groove formed on a first surface thereof, an injection portion connected to the first flow path, and a first surface thereof. A second substrate having a second flow path formed of a groove formed on the first substrate, and a first accommodating portion connected to the second flow path, wherein the first flow path and the second flow path intersect each other. Thus, the first surface of the first substrate and the first surface of the second substrate are brought into contact with each other.

  According to such a configuration, by introducing the liquid component of the liquid flowing in the laminar flow through the first flow path into the second flow path (first housing portion) of the second substrate, the solid component and the liquid component in the liquid Can be separated. In this manner, the components in the liquid can be separated by the structure in which two flow paths formed on the two substrates are crossed and bonded together. Therefore, the separator can be easily manufactured compared to the conventional method, and the size can be reduced.

  More preferably, the injection part is connected to one end of the first flow path, and has a second accommodating part at the other end of the first flow path. According to such a configuration, the solid component in the liquid can be introduced into the second housing portion.

  More preferably, a plurality of the second flow paths are formed. According to this configuration, since the liquid component of the liquid can be introduced by the plurality of second flow paths, the separation efficiency can be improved.

  More preferably, the width of the first channel is not less than 5 times its depth. According to such a configuration, the width of the second flow path can be secured wide, and the flow rate of the influent can be increased, so that the separation efficiency can be improved.

  For example, the separation device is a device for separating a liquid component in blood, and sample blood is injected into the injection hole, and a plasma component of the sample blood is introduced into the second flow path. According to this configuration, plasma components can be separated from the sample blood, which can contribute to highly accurate blood tests.

  (2) A separation apparatus according to the present invention includes a first substrate having a first flow path made of an opening, an injection part connected to the first flow path, and a groove formed on the first surface thereof. A second substrate having a second flow path; a third substrate having a third flow path formed by a groove formed on a first surface thereof; and a first housing connected to the second flow path and the third flow path. A first surface of the first substrate and the second substrate so that the first flow path and the second flow path, and the first flow path and the third flow path intersect each other. The first surface abuts, and the second surface of the first substrate abuts on the first surface of the third substrate.

  According to such a configuration, by introducing the liquid component of the liquid flowing in the laminar flow through the first flow path into the second and third flow paths (first housing part), the solid component and the liquid component in the liquid are removed. Can be separated. In this way, the structure in which the three substrates are laminated and the flow paths of the two substrates arranged above and below the first substrate are bonded to each other so as to intersect with the opening of the first substrate is used. Separation is possible. Therefore, the separator can be easily manufactured compared to the conventional method, and the size can be reduced.

  More preferably, the injection part is connected to one end of the first flow path, and has a second accommodating part at the other end of the first flow path. According to such a configuration, the solid component in the liquid can be introduced into the second housing portion.

  More preferably, a plurality of the second flow paths and the third flow paths are formed. According to this configuration, since the liquid component of the liquid can be introduced by the plurality of second and third flow paths, the separation efficiency can be improved.

  (3) The analyzer according to the present invention includes a separation unit and an inspection unit, and has the separation device as a separation unit.

  According to this configuration, it is possible to inspect the separated liquid component and the like. In particular, by incorporating the separation unit and the inspection unit in a single analyzer, it can be applied to a μTAS chip, and a small amount of sample or test agent can be used for a short time. Moreover, conveyance and storage are facilitated by downsizing the apparatus. Therefore, it is possible to perform inspection at the sample collection site such as POC inspection.

  (4) The analyzer according to the present invention includes a first substrate having a first flow path formed by a groove formed on the first surface, an injection portion connected to the first flow path, and a first surface thereof. A second substrate having a second flow path formed of a groove formed on the first substrate, and a first accommodating portion connected to the second flow path, wherein the first flow path and the second flow path intersect each other. In this case, the first substrate has a separation portion formed by contacting the first surface of the first substrate and the first surface of the second substrate.

  According to such a configuration, by introducing the liquid component of the liquid flowing in the laminar flow through the first flow path into the second flow path (first housing portion) of the second substrate, the solid component and the liquid component in the liquid Can be separated. In this manner, the components in the liquid can be separated by the structure in which two flow paths formed on the two substrates are crossed and bonded together. Therefore, the separator can be easily manufactured compared to the conventional method, and the size can be reduced. In addition, the analysis time can be shortened and the analysis accuracy can be improved. In addition, by incorporating the separation unit into the analyzer, the separated liquid component or the like can be inspected. In particular, the analysis device can be made into a μTAS chip, and a small amount of sample or test agent can be used, and a test can be performed in a short time. Moreover, conveyance and storage are facilitated by downsizing the apparatus. Therefore, it is possible to perform inspection at the sample collection site such as POC inspection.

  (5) The analyzer according to the present invention includes a first substrate having a first flow path made of a groove formed on the first surface thereof, an injection portion connected to the first flow path, and a first surface thereof. A second substrate having a second flow path formed of a groove formed on the first substrate, and a first accommodating portion connected to the second flow path, wherein the first flow path and the second flow path intersect each other. The first surface of the first substrate and the first surface of the second substrate are in contact with each other, and further includes a sensor disposed in the first housing portion.

  According to such a configuration, by introducing the liquid component of the liquid flowing in the laminar flow through the first flow path into the second flow path (first housing portion) of the second substrate, the solid component and the liquid component in the liquid Can be separated. In this manner, the components in the liquid can be separated by the structure in which two flow paths formed on the two substrates are crossed and bonded together. Therefore, the separator can be easily manufactured compared to the conventional method, and the size can be reduced. Furthermore, it is possible to inspect the liquid component separated by the sensor disposed in the first housing portion. By arranging the sensors in this way, analysis time can be shortened and analysis accuracy can be improved. Further, the analyzer can be miniaturized, and can be applied to, for example, a μTAS chip. Therefore, it is possible to perform a test in a short time with a small amount of sample or test agent. Moreover, conveyance and storage are facilitated by downsizing the apparatus. Therefore, it is possible to perform inspection at the sample collection site such as POC inspection.

  (6) In the separation method according to the present invention, the liquid component containing the solid component and the liquid component injected into the first flow path formed on the first substrate is applied to the first surface of the first substrate. The solid component and the liquid component are separated by being introduced into the second flow path formed on the second substrate in contact with the first flow path and intersecting the first flow path.

  According to such a configuration, by introducing the liquid component of the liquid flowing in the laminar flow through the first flow path into the second flow path (first housing portion) of the second substrate, the solid component and the liquid component in the liquid Can be separated. In this manner, the components in the liquid can be separated by the structure in which two flow paths formed on the two substrates are crossed and bonded together. Therefore, the separation method is easier than the conventional method.

  The present embodiment will be described below with reference to the drawings. In addition, the same or related code | symbol is attached | subjected to what has the same function, and the repeated description is abbreviate | omitted.

  1-4 is a figure which shows the 1st separation apparatus of this Embodiment, FIG. 1 is a top view of the board | substrate which comprises the 1st separation apparatus of this Embodiment, FIG. It is a top view which shows the flow path of the 1st separation apparatus of this Embodiment. FIG. 3 is a cross-sectional view of the first separation device of the present embodiment, and FIG. 4 is a perspective view of the flow path portion of the first separation device of the present embodiment. 3A corresponds to the AA cross section of FIG. 2, and FIG. 3B corresponds to the BB cross section of FIG. FIG. 5 is a perspective view schematically showing the state of blood (sample blood) separation by the first separation device of the present embodiment.

  As shown in FIG. 3, the first separation apparatus (separation module, microdevice) 1 of the present embodiment has a stacked structure of a substrate S1 and a substrate S2. For example, the separation device 1 separates plasma components in blood.

  As shown in FIG. 1, two grooves extending in the x direction are formed on the surface (first surface) of the substrate S1, and flow paths (first flow paths) 10a and 10b are formed by these grooves. The In addition, five grooves extending in the y direction are formed on the surface (first surface) of the substrate S2, and a flow path (second flow path, branch flow path) 20a is formed by the grooves. These substrates are made of, for example, a glass substrate, a resin substrate, or a silicon substrate, and the groove is formed by, for example, etching. Further, the substrate S2 is formed with an opening penetrating from the front surface to the back surface (second surface), and this opening portion serves as an injection hole (injection part, particle dispersion liquid storage part) 3 and a storage part (particle concentrated liquid storage). Part) 5a and storage part (particle dilution liquid storage part) 5b. In addition to the substrate, a flexible sheet (film) material may be used. Note that a pump (syringe pump) (not shown) is connected to the injection hole 3 and the like via, for example, a silicon tube (tube).

  For example, the width of the channel 10a is about 200 μm, the depth is about 20 μm, the width of the channel 10b is about 200 μm, and the depth is about 12 μm. The width of the channel 20a is about 200 μm and the depth is about 200 μm. If it is a groove | channel of a magnitude | size like the flow path 20a, it is also possible to shape | mold by injection molding of a resin sheet (resin substrate), embossing, etc.

  The substrates S1 and S2 are aligned and bonded so that the flow paths 10a, 10b and the flow path 20a intersect, thereby forming the first separation device of the present embodiment. For bonding the substrates, the substrates may be aligned and bonded using an adhesive, or may be bonded by thermocompression bonding. As shown in FIG. 2, here, the flow paths 10a, 10b and the flow path 20a intersect so that the angle θ formed on the injection hole 3 side is approximately 90 °. Moreover, the injection hole 3 is connected to one end of the flow path 10a, and the accommodating part 5a is connected to the other end of the flow path 10a. One end of the flow path 10b is connected to the endmost flow path 20a, and the flow path 20a is sequentially connected to the flow path 10b at a fixed interval from this connection point. Furthermore, the other end of the flow path 10b is connected to the accommodating portion 5b.

  Therefore, the route of the liquid flowing from the injection hole 3 passes through the injection hole 3 through the flow channel 10a to the storage unit 5a, and sequentially passes from the injection hole 3 through the flow channel 10a, the flow channel 20a, and the flow channel 10b. 5b (see FIGS. 2 and 4).

  The sample solution can be separated using the separation device. Here, a case where blood is separated will be described. Blood tests are indispensable in medical settings. In blood, there are solid components such as red blood cells, white blood cells, and platelets (solid components, cell components, blood cell components, and formed components) and a liquid component called plasma (serum). Various substances in the body are dissolved in the blood (serum) that has circulated throughout the body as blood. By measuring these components, information for diagnosis, treatment, and prevention of diseases can be obtained. it can. Therefore, some tests can be performed using whole blood. However, in high-precision tests such as detection of trace components and concentration measurement, for example, there are many tests that must be performed after separating plasma. The diameter of red blood cells is about 8 μm, the diameter of white blood cells is about 10 to 25 μm, and the long diameter of platelets is about 2 to 3 μm.

  Therefore, according to the first separation device described above, plasma that is a liquid component in blood can be separated. That is, blood (whole blood) is injected into the injection hole 3 shown in FIG. 2, and a tube connector is connected to the accommodating portions 5a and 5b via packing. Furthermore, the accommodating parts 5a and 5b and the syringe pump are connected via a silicon tube. The pressure is reduced by a syringe pump, and blood is sent from the injection hole 3 to the flow path 10a and the like at a speed of 1 to 5 μl / min. For example, there is a four-fold difference in channel resistance between the channel 10a and the channel 10b. That is, the channel resistance of the channel 10b is four times the channel resistance of the channel 10a. On the other hand, the channel resistance of the channel 20a is negligibly small. In this case, it can be expected that about 25% of the plasma of the flow rate flows into the storage portion 5b. In the first separation device, since five flow paths 20a are provided, 5% of the volume (flow rate) flows into the flow path 20a. Here, the flow in the flow paths 10a, 10b, and 20a is a laminar flow, and 5% of the depth of 20 μm is 1 μm. Therefore, particles of 1 μm or more do not enter the flow path 20a. Therefore, the concentrated blood whose concentration of the solid component is increased can be introduced (separated) into the accommodating portion 5a by separating the plasma into the accommodating portion 5b.

  The reason why the separation is possible will be described with reference to FIG. First, the flow path through which a fluid flows is miniaturized, and in a flow path having a cross section (diameter, groove width, depth) on the order of several hundred μm, the influence of friction acting between the fluid and the wall of the flow path increases. Therefore, in such a microchannel, the Reynolds number, which is important for evaluating the flow, is 200 or less, and the flow is a laminar flow. These matters have also been confirmed in microvessels. Therefore, the flow resistance decreases from the vicinity of the channel wall to the center of the channel, and solid components such as erythrocytes (circled in FIG. 5) move to the center where the flow is fast. As a result, a thin layer (plasma layer, cell-free layer) of several μm through which only plasma as a liquid component flows is formed on the outer periphery (end portion, side wall portion) of the flow path.

  Therefore, as shown in FIG. 5, the whole blood flows into the flow channel 10a from the injection hole 3. However, since the flow channel 20a is arranged above the flow channel 10a in the intersecting direction, A plasma layer of several μm from the upper surface flows (extracts) into the flow path 20a. Therefore, the plasma component selectively flows into the flow path 20a (preferentially) and is stored in the storage portion 5b via the flow path 10b (see FIG. 4). On the other hand, the containing part 5a at the tip of the flow path 10a contains concentrated blood with reduced plasma components.

  Thus, according to this Embodiment, since the flow path 10a and the flow path 20a were arrange | positioned, the plasma component can be introduce | transduced into the flow path 20a, and a plasma component can be isolate | separated. Further, since the flow path 10a and the flow path 20a are formed on the substrate S1 and the substrate S2, respectively, the separation can be performed with a simple configuration in which these flow path formation surfaces are brought into contact with each other and the flow paths are crossed. The width of the flow path can be made relatively large with respect to the depth, and the cross area of the flow path 10a and the flow path 20a can be increased. Therefore, separation speed and separation accuracy can be improved, and separation efficiency can be improved. In addition, the manufacturing process of the separation apparatus is simple, and mass production is possible at a low cost. That is, since the aspect ratio of the grooves can be reduced, the substrate can be easily processed and the processing accuracy can be improved. In addition, since separation is possible with a fine flow path (groove) as described above, the separation device can be downsized. Therefore, the separation device can be formed as a micro device, and can be incorporated as a separation portion of the μTAS chip.

  Here, the ratio (width / depth) of the width and depth of the channel 10a is preferably 5 or more. In other words, the width of the flow path 10a is preferably 5 times or more the depth.

  Further, as shown in FIG. 2 and the like, the separation efficiency can be improved by intersecting the plurality of flow paths 20a with the flow paths 10a.

  In the present embodiment, the angle θ formed between the flow channel 10a and the flow channel 20a on the side of the injection hole 3 is approximately 90 °. However, the present invention is not limited to this value, and these flow channels intersect. Separation is possible. In the present embodiment, the flow velocity (flow rate) of the flow channel 10a and the flow channel 20a is adjusted using the difference in flow channel resistance. However, plasma can be separated by a method of adjusting the flow rate with a plurality of pumps. is there. The adjustment by the pump may be performed by pressurization from the injection hole 3 side in addition to the above-described suction from the accommodating portions 5a and 5b. In the case of suction, a pump can be connected to each of the accommodating portions 5a and 5b, and adjustment can be performed individually. Further, the pressurization and suction may be performed simultaneously.

  Further, in the present embodiment, the substrate S2 on which the flow path 20a for introducing plasma is formed is disposed on the substrate S1, but the vertical relationship of these substrates is not related to the separation of the plasma, and the flow is important. Substrate S1 and S2 should just contact | abut so that the path | route 10a and the flow path 20a may cross | intersect.

  6 to 8 are diagrams showing a second separation device of the present embodiment, FIG. 6 is a plan view of a substrate constituting the second separation device of the present embodiment, and FIG. FIG. 8 is a cross-sectional view of a second separation device of the present embodiment, and FIG. 8 is a perspective view of a flow path portion of the second separation device of the present embodiment. 7 corresponds to the AA cross section of FIG. In addition, the same code | symbol is attached | subjected to the same site | part as the 1st separation apparatus shown in FIGS. 1-4, and the detailed description is abbreviate | omitted.

  In this case, as shown in FIG. 7, the substrate S1 is disposed on the substrate S2. As shown in FIG. 1, two grooves extending in the x direction are formed on the surface (first surface) of the substrate S1, and flow paths (first flow paths) 10a and 10b are formed by these grooves. The In addition, five grooves extending in the y direction are formed on the surface (first surface) of the substrate S2, and a flow path (second flow path) 20a is configured by the grooves. Here, an opening penetrating from the front surface to the back surface is formed in the substrate S1, and the injection hole 3, the accommodating portion 5a, and the accommodating portion 5b are configured by this opening portion. In addition, the top view which shows the flow path of this 2nd separation apparatus 1 is the same as that of FIG.

  In the second separation device, as in the first separation device, whole blood flows from the injection hole 3 into the flow channel 10a, but the flow channel 20a is arranged below the flow channel 10a in the intersecting direction. Therefore, a plasma layer of several μm flows (extracts) from the upper surface of the flow channel 10a into the flow channel 20a. Therefore, the plasma component selectively flows into the flow path 20a (preferentially) and is stored in the storage portion 5b through the flow path 10b (see FIGS. 5 and 8). On the other hand, the containing part 5a at the tip of the flow path 10a contains concentrated blood with reduced plasma components.

  In the first and second separation devices, two substrates are stacked, but the separation device 1 may be configured by stacking three substrates. 9 and 10 are diagrams showing a third separation apparatus according to the present embodiment, FIG. 9 is a plan view of a substrate constituting the third separation apparatus according to the present embodiment, and FIG. FIG. 5 is a cross-sectional view of a third separation device of the present embodiment. FIG. 10 corresponds to the AA cross section of FIG. In addition, the same code | symbol is attached | subjected to the same site | part as the 1st separation apparatus shown in FIGS. 1-4, and the detailed description is abbreviate | omitted.

  In this case, as shown in FIG. 10, the substrate S1 is disposed on the substrate S3, and the substrate S2 is disposed on the substrate S1. As shown in FIG. 9, the substrate S1 is formed with two slits (openings) extending from the front surface to the back surface and extending in the x direction, and the slits (first flow channel) 10a. 10b are configured. In addition, five grooves extending in the y direction are formed on the surface (first surface) of the substrate S2, and a flow path (second flow path) 20a is configured by the grooves. Further, the substrate S2 is further formed with an opening penetrating from the front surface to the back surface, and the opening portion constitutes the injection hole 3, the accommodating portion 5a, and the accommodating portion 5b. Further, five grooves extending in the y direction are formed on the surface (first surface) of the substrate S3, and a flow path (third flow path) 30a is configured by the grooves. This flow path 30a is arrange | positioned so that the plane pattern may be located between the flow paths 20a so that it may not overlap with the flow path 20a.

  In the third separation device, as in the first separation device, the whole blood flows into the flow channel 10a from the injection hole 3, but is arranged above the flow channel 10a in the direction in which the flow channel 20a intersects. Furthermore, since the flow path 30a is arranged below the flow path 10a in the intersecting direction, a plasma layer of several μm flows into the flow paths 20a and 30a from the upper surface or the lower surface of the flow path 10a (extracted). ) Therefore, plasma components selectively flow into the flow paths 20a and 30a (preferentially) and are stored in the storage portion 5b via the flow path 10b. On the other hand, the containing part 5a at the tip of the flow path 10a contains concentrated blood with reduced plasma components.

  In the third separation device, in addition to the effects of the first and second separation devices, the separation efficiency is improved because the number of flow paths 20a and 30a intersecting the flow path 10a is large. Further, since the flow path 10a is formed by the slits in the substrate S1 and the flow paths 20a and 30a are disposed above and below the slit, the flow paths can be highly integrated, and the apparatus can be further miniaturized.

  In the first to third separation apparatuses, the separation apparatus has been described as a main process. However, similar components may be incorporated into an analysis apparatus such as a μTAS device as a separation unit. Moreover, it is good also as an analyzer which can provide a test | inspection part connected to said accommodation part (especially 5b) in a board | substrate, and it can react with a test reagent etc. and can perform a test | inspection (determination).

  In addition, as shown in FIG. 11, the sensor 40 may be arranged in the housing portion 5 b of the analyzer 50, and the inspection result may be taken out as an electrical signal through the electrode (wiring) 43. FIG. 11 is a plan view and a cross-sectional view showing the analyzer of the present embodiment. The cross-sectional view corresponds to the BB cross section of the plan view. Moreover, since it is the same structure as the 2nd separation apparatus except the structure of the sensor 40 and the electrode 43, the same code | symbol is attached | subjected to a corresponding site | part and the detailed description is abbreviate | omitted.

  Similar to the second separation device, the concentrated blood with reduced plasma components is accommodated in the accommodating portion 5a at the end of the flow path 10a. Here, with respect to the plasma component stored in the storage unit 5b, the detection target component or concentration measurement is performed by a sensor. For example, the presence / absence or concentration of the component to be inspected is converted into an electric signal and detected as an electric signal via the electrode 43.

  Examples of blood test sensors include electrochemical sensors, QCM sensors, SPR sensors, and optical sensors. The illustrated sensor 40 is a kind of electrochemical sensor, and is an enzyme sensor (enzyme electrode) that measures blood glucose level and the like.

  For example, if an enzyme electrode containing glucose oxidase and potassium ferricyanide is prepared in the sensor, it reacts specifically with glucose in the blood to generate gluconic acid and electrons. This electron turns potassium ferricyanide into potassium ferrocyanide, and when a certain voltage is applied thereto, it becomes potassium ferricyanide again, and then a current is generated. Since this current is proportional to the glucose concentration in the blood, the blood glucose level can be measured by measuring the current value.

  Of course, other sensors described above may be incorporated. Hereinafter, the SPR sensor and the QCM sensor will be described.

  Since an antibody has the property of selectively adsorbing a specific molecule, when the reflected light is monitored by arranging the antibody on a metal thin film, the intensity of the reflected light or the reflected intensity is reduced when molecules that bind only to that antibody bind. The peak position changes. This is because the refractive index generated by the electron cloud in the metal thin film changes. A sensor that detects this change is an SPR (Surface Plasma Resonance) sensor.

  A sensor that utilizes regular vibration transmission of quartz is a QCM (Quartz Crystal Microbalance) sensor. That is, when a substance adheres to the electrode surface of a crystal resonator, a very small amount (nanogram order) of mass change can be measured by utilizing the property that the frequency varies (decreases) according to the mass.

  In this way, the first to third separation devices can be incorporated as a separation unit in the analysis device, or a detection unit such as a sensor can be provided in the first to third separation devices to be used as the analysis device. . With such an analyzer, the separated plasma can be efficiently examined (analyzed), and analysis time can be shortened and analysis accuracy can be improved. Further, the analyzer can be miniaturized, and can be applied to, for example, a μTAS chip. Therefore, it is possible to perform inspection in a short time with a small amount of sample (sample) or test agent. Moreover, conveyance and storage are facilitated by downsizing the apparatus. Therefore, it is possible to perform inspection at the sample collection site such as POC inspection.

  In the analyzer, in addition to the detection unit, a purification unit (coagulation precipitation unit) that removes unnecessary proteins (particularly proteins having coagulation properties) from plasma and other processing units (reagent mixing unit, heating unit and reaction unit, Other separation units and the like may be provided.

  In the above embodiment, blood has been described as an example. However, the present invention is not limited to blood, and can be widely applied to dispersion liquids (sample liquid, specimen, suspension) containing a solid component and a liquid component. For example, the separation device or the like may be used to separate a solid component and a liquid component of a suspension of cultured cells. In this case, it is important to separate the high-concentration cell liquid (solid component) stored in the storage unit 5a. Therefore, in order to efficiently collect cells, the separation from the injection hole 3 to the accommodating portions 5a, 5b is performed a plurality of times, that is, a plurality of separation units from the injection hole 3 to the accommodating portions 5a, 5b are prepared, The concentration of cell components may be increased sequentially.

  Moreover, in the said embodiment, although the groove | channel was provided in the board | substrate S2, for example, you may comprise by the slit which provided this groove | channel in the board | substrate, and the other board | substrate and film | membrane which covers the one surface of the board | substrate.

  Moreover, in the said embodiment, although the injection hole and the accommodating part were provided in the upper part of the separation apparatus, you may perform injection | pouring and accommodation from the side surface or bottom face (lower surface) of an apparatus.

  In addition, the examples and application examples described through the above-described embodiments of the present invention can be used in combination as appropriate according to the application, or can be used with modifications or improvements, and the present invention is limited to the description of the above-described embodiments. Is not to be done.

FIG. 1 is a plan view of a substrate constituting the first separation apparatus of the present embodiment. FIG. 2 is a plan view showing a flow path of the first separation device of the present embodiment. FIG. 3 is a cross-sectional view of the first separation device of the present embodiment. FIG. 4 is a perspective view of the flow path portion of the first separation device of the present embodiment. FIG. 5 is a perspective view schematically showing a blood separation state by the first separation device of the present embodiment. FIG. 6 is a plan view of a substrate constituting the second separation apparatus of the present embodiment. FIG. 7 is a cross-sectional view of the second separation device of the present embodiment. FIG. 8 is a perspective view of the flow path portion of the second separation device of the present embodiment. FIG. 9 is a plan view of a substrate constituting the third separation apparatus of the present embodiment. FIG. 10 is a cross-sectional view of the third separation device of the present embodiment. FIG. 11 is a plan view and a cross-sectional view showing the analyzer of the present embodiment.

Explanation of symbols

  DESCRIPTION OF SYMBOLS 1 ... Separation apparatus, 3 ... Injection hole, 5a, 5b ... Accommodating part, 10a, 10b ... Flow path, 20a ... Flow path, 30a ... Flow path, 40 ... Sensor, 43 ... Electrode, 50 ... Analytical apparatus, S1, S2 , S3 ... substrate

Claims (11)

A first substrate having a first flow path made of a groove formed in the first surface;
An injection part connected to the first flow path;
A second substrate having a second flow path made of a groove formed in the first surface;
A first accommodating portion connected to the second flow path,
A separation apparatus, wherein the first surface of the first substrate and the first surface of the second substrate are brought into contact with each other so that the first channel and the second channel intersect.   The separation apparatus according to claim 1, wherein the injection part is connected to one end of the first flow path, and has a second storage part at the other end of the first flow path.   The separation apparatus according to claim 1, wherein a plurality of the second flow paths are formed.   The separation apparatus according to any one of claims 1 to 3, wherein the width of the first flow path is not less than five times the depth.   The separation device is a device for separating a liquid component in blood, wherein sample blood is injected into the injection hole, and the liquid component of the sample blood is introduced into the second flow path. The separation device according to any one of claims 1 to 4. A first substrate having a first flow path comprising an opening;
An injection part connected to the first flow path;
A second substrate having a second flow path made of a groove formed in the first surface;
A third substrate having a third flow path made of a groove formed on the first surface;
A first housing connected to the second flow path and the third flow path,
Contacting the first surface of the first substrate and the first surface of the second substrate so that the first channel and the second channel, and the first channel and the third channel cross each other, A separation apparatus, wherein the second surface of the first substrate and the first surface of the second substrate are brought into contact with each other.   The separation device according to claim 6, wherein the injection part is connected to one end of the first flow path, and has a second accommodating part at the other end of the first flow path.   The separation apparatus according to claim 6 or 7, wherein a plurality of the second flow paths and the third flow paths are formed. A first substrate having a first flow path made of a groove formed in the first surface;
An injection part connected to the first flow path;
A second substrate having a second flow path made of a groove formed in the first surface;
A first accommodating portion connected to the second flow path,
An analyzer comprising: a separation unit formed by contacting the first surface of the first substrate and the first surface of the second substrate so that the first channel and the second channel intersect each other. A first substrate having a first flow path made of a groove formed in the first surface;
An injection part connected to the first flow path;
A second substrate having a second flow path made of a groove formed in the first surface;
A first accommodating portion connected to the second flow path,
The first surface of the first substrate and the first surface of the second substrate are in contact with each other so that the first channel and the second channel intersect,
Furthermore, it has a sensor arrange | positioned at the said 1st accommodating part, The analyzer characterized by the above-mentioned.   A second substrate in which a liquid component of a liquid containing a solid component and a liquid component injected into a first channel formed on the first substrate is in contact with a first surface of the first substrate, A separation method for separating the solid component and the liquid component by introducing the second substrate into the second channel of the second substrate having a second channel intersecting with the one channel.

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