JP2005201682A - Element for microanalysis - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an element for microanalysis capable of manufacturing a variety of products at low cost while using a semiconductor substrate.
A semiconductor substrate 11 and a plate 12 bonded to one surface of the semiconductor substrate are provided. Between the semiconductor substrate and the plate, a flow path 13 for the liquid to be analyzed is formed. In the plate, the inlets 21 to 24 and the outlet 25 of the flow path are formed. On the surface of the semiconductor substrate, processing regions (31 to 38) used for a plurality of types of analysis assumed in advance are formed, and the flow path 13 is formed via a part (31, 34, 36) of all the processing regions. An inlet to an outlet are connected to form a desired analysis among a plurality of types of analysis.
[Selection] Figure 1

Description

  The present invention relates to a microanalytical element used for liquid analysis (liquid phase analysis), and in particular, analysis of a liquid containing organic molecules such as blood (for example, bases including nucleic acids and proteins such as DNA and RNA). The present invention relates to a microanalytical element suitable for the above.

In recent years, various proposals have been made for microanalytical elements called micro-TAS (μ-TAS; Micro-Total Analysis System), lab-on-a-chip (LOC), and the like (for example, patent documents). 1). This element is characterized in that a very small amount of liquid to be analyzed is required, and sequentially performs processing necessary for liquid phase analysis while moving a small amount of liquid along the flow path on the substrate. By using this element, the analysis time can be greatly shortened, and the liquid can be analyzed efficiently. Furthermore, when a micro-analysis element is configured using a semiconductor substrate such as a silicon substrate, a large amount of the same element can be easily obtained by utilizing an already established micro-processing technique (formation technique such as DRAM, LSI, or MEMS). Can be produced. If the same element is mass-produced, the manufacturing cost per element can be reduced.
JP-A-8-334505

  However, the elements as described above are not always required in large quantities. There are a wide variety of analysis types for liquids, and various types of microanalytical elements may be required little by little in accordance with various demands. If a large number of items are to be manufactured in small quantities, the above-described microfabrication technique requires a semiconductor substrate to be designed for each type, resulting in a very high manufacturing cost per element. For this reason, for example, in a general medical field, it is difficult in terms of cost to perform various analyzes of liquids containing organic molecules such as blood efficiently by using various types of microanalytical elements.

  An object of the present invention is to provide an element for microanalysis capable of manufacturing a variety of products at low cost while using a semiconductor substrate.

  The element for microanalysis according to claim 1 includes a semiconductor substrate and a plate bonded to one surface of the semiconductor substrate, and a liquid flow to be analyzed is interposed between the semiconductor substrate and the plate. A path is formed, the plate is formed with an inlet and an outlet of the flow path, the surface of the semiconductor substrate is formed with processing regions used for a plurality of types of analysis assumed in advance, and the flow path is In addition, the inlet is connected to the outlet through a part of the processing region, and the desired analysis is realized among the plurality of types of analysis.

According to a second aspect of the present invention, in the microanalysis element according to the first aspect, a groove for the flow path is formed on the surface of the semiconductor substrate so as to comprehensively connect the processing region. In the groove, a portion that blocks the inflow of the liquid is formed at a location that leads to a processing region unnecessary for the desired analysis.
According to a third aspect of the present invention, in the microanalysis element according to the first aspect, a groove for the flow path comprehensively connects the processing region to the surface on the semiconductor substrate side of the plate. In the groove, a portion that blocks the inflow of the liquid is formed at a location that leads to a processing area unnecessary for the desired analysis.

According to a fourth aspect of the present invention, in the microanalysis element according to the second or third aspect, the blocking portion is formed of a thermosetting resin or a photocurable resin.
According to a fifth aspect of the present invention, in the microanalysis element according to the second or third aspect, the plate is made of a thermoplastic resin or a thermoplastic resin, and the blocking portion is a plastic deformation of the plate. It is formed by.

According to a sixth aspect of the present invention, in the microanalysis element according to the second aspect of the present invention, a convex portion having a shape that matches the cross section of the groove is formed in advance on the surface of the semiconductor substrate on the plate. The blocking portion is formed by the convex portion of the plate.
According to a seventh aspect of the present invention, in the microanalysis element according to the first aspect of the present invention, the plate is provided with a groove for the flow path on the surface on the semiconductor substrate side, which is necessary for the desired analysis. It is formed so as to connect only the regions.

  According to the microanalytical element of the present invention, a variety of products can be manufactured at low cost while using a semiconductor substrate.

Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings.
(First embodiment)
The microanalysis element 10 according to the first embodiment includes a semiconductor substrate 11 and a plate 12 as shown in FIGS. 1 (plan view) and FIG. 2 (cross-sectional view), and the plate 12 is one surface of the semiconductor substrate 11. 11A. The semiconductor substrate 11 is made of a semiconductor material such as silicon or GaAs. The plate 12 is made of an insulating material such as glass or resin. As the resin, polyethylene terephthalate (PET), polyester, photocuring polymer, or the like is used. For example, an adhesive is used for joining the semiconductor substrate 11 and the plate 12. When the plate 12 is made of resin, the bonding may be performed by heating the semiconductor substrate 11 instead of the adhesive to melt the bonding interface of the plate 12.

  Further, in the microanalysis element 10, a flow path 13 for a liquid to be analyzed is formed between the semiconductor substrate 11 and the plate 12. The cross-sectional size of the flow path 13 is a micro scale. The liquid to be analyzed is a liquid containing organic molecules such as blood (for example, bases including nucleic acids and proteins such as DNA and RNA). The microanalytical element 10 has a feature that a very small amount of liquid to be analyzed is sufficient. Of the microanalyzer 10, the configuration of the plate 12 is shown in FIG. 3 (perspective view), and the configuration of the semiconductor substrate 11 is shown in FIGS. 4 to 6.

  In the plate 12, as shown in FIGS. 1 and 3, the inlets 21 to 24 and the outlet 25 of the flow path 13 are formed. The inlets 21 to 24 are openings for sequentially injecting various liquids (for example, liquid samples containing DNA or chemical liquids necessary for analysis). The outlet 25 is an opening for discharging liquid. The plate 12 is made of an inexpensive material (for example, glass or resin), and can be easily formed using a known injection molding method, stereolithography method, or the like. In FIG. 3, the lower surface 12 </ b> A of the plate 12 is a bonding surface with the surface 11 </ b> A of the semiconductor substrate 11.

The liquid injected from the inlets 21 to 24 of the plate 12 moves along the flow path 13 and is then discharged from the outlet 25. In addition, for the movement of the liquid, a method of applying pressure from the outside, a micro pump arranged near the flow path 13, a voltage gradient, or the like is used.
On the other hand, on the surface 11A of the semiconductor substrate 11, as shown in FIGS. 1, 4, and 5, all the processing regions (31 to 38) necessary for a plurality of types of analysis assumed in advance are formed in advance. Note that “all processing regions (31 to 38)” does not mean “all existing processing regions”, but “to complete each analysis (plural types) assumed in advance when designing the semiconductor substrate 11”. It means "all processing areas necessary for". For example, if two types of analysis are assumed in advance, a processing area (one or more) required to complete the first analysis and a processing area (one or more) required to complete the second analysis And “all processing areas”. “Analysis” described here includes not only detection, identification, and investigation of components contained in a liquid, but also liquid mixing (reaction) and separation.

  And as shown in FIG. 1, said flow path 13 is an entrance through some process areas (31, 34, 36) among all the process areas (31-38) formed in the semiconductor substrate 11. As shown in FIG. It is formed so as to connect from 21 to 24 to the outlet 25 and realize a desired analysis. Some of the processing areas (31, 34, 36) are necessary for the desired analysis. The processing contents in the processing area (31 to 38) will be described later.

  Further, as shown in FIGS. 4 and 5, the groove 41 for the flow path 13 (FIG. 1) comprehensively connects all the processing regions (31 to 38) to the surface 11 </ b> A of the semiconductor substrate 11. To be formed. Incidentally, the formation of all the processing regions (31 to 38) and the groove 41 is performed by using a well-known fine processing technique (a forming technique such as DRAM, LSI, MEMS (Micro Electro Mechanical System)).

  Then, as shown in FIGS. 6 and 7, the groove 41 formed in an exhaustive manner has a liquid in a place that communicates with a processing region unnecessary for the desired analysis (here, 32, 33, 35, 37, 38). Sites 42 to 45 that block inflow (hereinafter referred to as “blocking sites 42 to 45”) are formed. As a result, the inflow of the liquid is limited only to the portions that communicate with the processing regions (31, 34, 36) necessary for the desired analysis. Thus, in the microanalysis element 10 of the first embodiment, the flow path 13 (FIG. 1) is formed according to the positions of the blocking portions 42 to 45 in the comprehensive groove 41.

  The blocking portions 42 to 45 of the groove 41 are formed of, for example, a thermosetting resin such as polystyrene or epoxy. In this case, a liquid thermosetting resin may be injected into a necessary portion of the groove 41 by a dispenser or the like and temporarily cured, and then, when the plate 12 is joined, heat is applied to perform the main curing. The blocking portions 42 to 45 of the groove 41 can also be formed of a photocurable resin such as epoxy acrylate or urethane acrylate. In this case, similarly, liquid photo-curing resin may be injected and temporarily cured with a dispenser or the like, and thereafter, when the plate 12 is bonded, ultraviolet light is irradiated to perform main curing.

  The processing region (31 to 38) of the semiconductor substrate 11 will be described. The processing regions (31 to 38) include, for example, three types of mixing regions 31 to 33 for mixing (reacting) the liquid, two types of separation regions 34 and 35 for separating the liquid, and any component ( For example, three types of detection regions 36 to 38 for detecting a DNA base sequence) are provided. Each region 31 to 38 has an electrode 39. However, the present invention can also be applied when the electrode 39 is omitted.

  As the mixing regions 31 to 33, for example, Y-shaped flow paths 13A to 13C can be used as shown in FIG. In this case, different types of liquids are merged through each of the flow paths 13A and 13B, and the two types of liquids are mixed by merging. In order to mix more uniformly, a small rod-like obstacle 45 (FIG. 8B) is arranged on the bottom surface of the flow path 13C after the merging, or stripe-like obstacles 46 and 47 in the oblique direction and the lateral direction (FIG. 8 ( It is preferable to arrange c), (d)), etc. to generate turbulent flow.

  Further, the flow path 13 in the mixing region may be heated via the electrode 39 (see FIG. 1) so that the liquid is uniformly mixed by convection. Further, it is conceivable that the magnetic stirrer is micromachined and installed in the flow path 13 in the mixing region so that the liquid is uniformly mixed by stirring. In this case, energization of the electrostatic actuator of the micromachine is performed via the electrode 39 (see FIG. 1).

As the separation regions 34 and 35, for example, as shown in FIG. 9, two electrodes 48 are arranged opposite to each other on the side surface of the flow path 13D, and a voltage is applied between them via the electrode 39 (see FIG. 1). Can be considered. In this case, liquid positive ions and negative ions can be guided to the separate branch channels 13E and 13F.
Also, for example, as shown in FIGS. 10A and 10B, an ion exchange resin 49 is disposed in the flow path 13G, and either one of liquid positive ions or negative ions is adsorbed thereto, and the other is A separation method in which the water is passed is also conceivable. Further, the liquid can be separated by utilizing reverse osmosis in the flow path 13 in the separation region. Further, a centrifuge that is micromachined by MEMS technology may be installed in the flow path 13 in the separation region.

  As the detection regions 36 to 38, for example, a current detection type DNA sensor may be installed in the flow path 13. Some current detection type DNA sensors have a structure similar to, for example, a MOS-FET or J-FET (Japanese Patent Laid-Open No. 2003-43010). In this case, by fixing the DNA in the portion corresponding to the gate and measuring the electrical characteristics of the portion corresponding to between the source and drain, it is possible to detect complementary binding between the index DNA and the DNA to be detected.

Other current detection type DNA sensors include an intercalator (an intercalator that specifically binds to a double-stranded site) after DNA complementary binding treatment, and measures the current value ( Toshiba review Vol.57 No.1 (2002) p.29-32 etc.). In this case, an electrode for DNA fixation and an electrode for current value measurement are arranged in the flow path 13 in the detection region.
Furthermore, the detection regions 36 to 38 are not limited to the current detection type DNA sensor, and a fluorescence detection type DNA sensor may be installed in the flow path 13. In the case of the fluorescence detection method, only the DNA trap site may be provided in the flow path 13 in the detection region, and the fluorescence of the DNA may be detected using an external optical microscope or the like. The detection target is not limited to DNA, and a sensor capable of detecting bases including nucleic acids such as RNA and proteins may be disposed in the flow path 13.

In addition, an ion sensitive field effect transistor (ISFET) may be installed in the flow path 13 to detect the pH, Na ⁺ , K ^+, etc. of plasma in the liquid. A sensor using surface plasmon resonance (SPR) may be installed in the flow path 13 to detect a change in the refractive index of the liquid. Further, a desired component may be detected after separation by liquid chromatography. A desired component may be detected after separation by capillary electrophoresis.

  In the micro-analysis element 10 of the first embodiment, when designing the semiconductor substrate 11, all the processing regions (here, for example, 3) necessary for a plurality of types of analysis assumed in advance from among the various processing regions described above. The types of mixed regions 31 to 33, the two types of separation regions 34 and 35, and the three types of detection regions 36 to 38) are selected and formed in advance on the surface 11A. Further, a groove 41 (see FIGS. 4 and 5) is formed so as to comprehensively connect all these processing regions (31 to 38). A well-known fine processing technique is used for the formation, and the semiconductor substrate 11 having the same configuration (that is, the processing region (31 to 38) and the comprehensive groove 41) can be easily mass-produced.

  Then, in order to realize a desired analysis (hereinafter referred to as “first analysis”) among a plurality of types of analysis, “a processing area unnecessary for the first analysis (for example, 32” in the groove 41 formed in an exhaustive manner). , 33, 35, 37, 38) are formed at blocking portions 42 to 45 (states of FIGS. 6 and 7). The blocking portions 42 to 45 can be easily formed using, for example, a thermosetting resin or a photocurable resin. For this reason, the flow path 13 (FIG. 1) required for the first analysis can be easily formed according to the positions of the blocking sites 42 to 45 in the comprehensive groove 41.

  In the element for microanalysis 10 of the first embodiment, a small amount of liquid injected from the inlets 21 to 24 of the plate 12 is moved along the flow path 13 and sequentially subjected to processing necessary for the first analysis (for example, mixing) Area 31 → separation area 34 → detection area 36), and the liquid after detection is discharged from the outlet 25 of the plate 12. Therefore, the analysis time can be greatly shortened, and the first analysis can be performed efficiently. Before injecting the liquid to be analyzed, it is preferable to inject a surfactant (for example, a micellar aqueous solution) or the like as necessary to chemically modify the flow path 13.

  Further, in order to realize an analysis different from the first analysis (hereinafter referred to as “second analysis”) among a plurality of types of analysis due to a request different from the above, the already designed semiconductor substrate 11 having the same configuration is used. A similar blocking portion may be formed in “a portion communicating with a processing region unnecessary for the second analysis” in the exhaustively formed groove 41 used. For this reason, according to the position of the interruption | blocking site | part in the comprehensive groove | channel 41, the flow path required for 2nd analysis (flow path different from said flow path 13 required for 1st analysis) can be formed easily. In this case, the second analysis for a small amount of liquid can be performed efficiently.

  As described above, in the first embodiment, the semiconductor substrate 11 having the same configuration including all the processing regions (31 to 38) necessary for a plurality of types of analysis assumed in advance and the comprehensive grooves 41 can be used. The semiconductor substrate 11 does not need to be designed for each type of analysis, and the manufacturing cost per one microanalytical element 10 can be reliably suppressed. The plate 12 of the microanalytical element 10 has to change the arrangement of the inlet and outlet of the flow path for each type of analysis, but the cost increase due to the design change is slight. Therefore, a variety of products can be manufactured at low cost while using the semiconductor substrate 11.

  For this reason, for example, in a general medical field, a liquid containing an organic molecule such as blood (for example, bases including nucleic acids and proteins such as DNA and RNA) is obtained by using a variety of inexpensive microanalytical elements 10. Various analyzes can be performed efficiently. The low-cost and wide variety of microanalytical elements 10 are effective not only in general medical practice but also in drug development, environmental analysis, and research applications. The processing necessary for the analysis is not limited to the above-described “mixing (reaction) → separation → detection”, and any processing including any one of mixing (reaction), separation, and detection may be used.

  Further, it is not necessary to arrange all of the mixed region, the separation region, and the detection region on the surface 11A of the semiconductor substrate 11, and according to a plurality of types of analysis assumed in advance at the time of design, necessary processing regions (mixed regions and What is necessary is just to arrange | position at least 1 type of a separation area | region and a detection area | region on the surface 11A of the semiconductor substrate 11. FIG. Two or more processing regions having the same configuration may be arranged. By connecting one flow path via the processing regions (two or more) having the same configuration, the analysis accuracy can be improved. Processing areas (two or more) having the same configuration can also be used for parallel processing.

  Further, when the detection region is arranged on the surface 11A of the semiconductor substrate 11 and the above-described current detection type DNA sensor is installed in the flow path in the detection region, the DNA sensor can also be used as a protein sensor. The detection region can be shared by the analysis of the liquid containing the protein and the analysis of the liquid containing the protein. In this case, in addition to the detection region, a treatment region suitable for a liquid containing DNA and a treatment region suitable for a liquid containing a protein are separately arranged in advance, and a detection region (DNA sensor) is formed by a flow path as desired. It is preferable to connect the

  Here, a specific application example of the microanalysis element 10 of the first embodiment will be described. This specific example assumes "analysis of DNA" and "analysis of plasma". In this case, as shown in FIG. 11 (schematic diagram), mixed regions 51, 52, 54, separation regions 53, 55, cleaning regions 56, and detection regions 57, 58 are arranged in advance on the surface of the semiconductor substrate 11. . Although not shown, a groove is formed on the surface of the semiconductor substrate 11 so as to comprehensively connect all these regions 51 to 58.

  Further, micromachined centrifuges are installed in the flow paths in the separation regions 53 and 55. This centrifuge can be used for both “DNA analysis” and “plasma analysis”. A current detection type DNA sensor is installed in the flow path in the detection region 57. An ion sensitive field effect transistor is installed in the flow path in the detection region 58. That is, sensors having different detection targets and detection methods are installed in the two detection areas 57 and 58, respectively.

  When the “DNA analysis” is realized using the semiconductor substrate 11 having the configuration shown in FIG. 11, a processing region (that is, the detection region 58) unnecessary for the “DNA analysis” in the comprehensive groove (not shown). As shown in FIG. 12 (a), a blocking portion is formed. As shown in FIG. 12 (a), “inlet 50 → mixing region 51 → mixing region 52 → separating region 53 → mixing region 54 → separating region 55 → cleaning region 56 → detecting region 57 → A flow path (illustrated by an arrow here) is formed like the outlet 59 "to complete the microanalysis element. In this element, “DNA analysis” is performed as follows. Note that DNA serving as an index is fixed in advance to the DNA sensor installed in the flow path in the detection region 57.

  The collected blood (0.5 ml) is taken from the inlet 50. In the mixing region 51, 1 ml of DNAzol BD (Invitrogen, USA) is added to the blood and mixed to produce a mixed solution. In the mixing region 52, isopropanol is added to the mixed solution to precipitate DNA, thereby generating a mixed solution of DNA and impurities. In the separation region 53, DNA is separated by a centrifuge. In the mixing region 54, 0.5 ml of the same DNAzol BD as described above is added to and suspended in the DNA after centrifugation to produce a mixed solution of DNA and DNAzol BD. In the separation region 55, DNA is separated by a centrifuge. In the washing region 56, the separated DNA is washed with 75% ethanol to obtain DNA to be detected. In the detection region 57, the complementary binding between the index DNA and the DNA to be detected is detected by a current detection type DNA sensor. The liquid after detection is discharged from the outlet 59. The addition of a chemical solution such as DNAzol BD may be performed in order from the inlet 50, or another inlet (not shown) may be used. According to the microanalytical element shown in FIG. 12 (a), by simply injecting blood from the inlet 50, complementary binding between the DNA to be detected and the indicator DNA contained therein can be easily detected. Can be performed efficiently.

  On the other hand, when the “plasma analysis” is realized by using the semiconductor substrate 11 having the configuration shown in FIG. 11, a processing region (that is, the mixing region 51, 52, 54, separation region 55, washing region 56, detection region 57), a blocking part is formed, and “inlet 50 → separation region 53 → detection region 58 → outlet 59” as shown in FIG. Thus, a flow path (shown here by an arrow) is formed to complete a microanalysis element. In this device, “plasma analysis” is performed as follows.

The collected blood is taken from the inlet 50. In the separation region 53, plasma is separated by a centrifuge. In the detection region 58, plasma pH, Na ⁺ , K ^{+ and the} like are detected by an ion sensitive field effect transistor installed in the flow path. The liquid after detection is discharged from the outlet 59. According to the microanalytical element shown in FIG. 12 (b), by simply injecting blood from the inlet 50, it is possible to easily detect the pH, Na ⁺ , K ^+, etc. of plasma contained therein. It can be done efficiently.

  According to the above specific example, all the processing regions (51-58) necessary for “DNA analysis” and “plasma analysis” and the same configuration with exhaustive grooves (not shown) (FIG. 11). By reusing the semiconductor substrate 11, it is not necessary to design the semiconductor substrate 11 for each type of analysis, and the manufacturing cost per element can be surely suppressed. The plate of each element has to change the arrangement of the inlet (50) and outlet (59) of the flow path for each type of analysis, but the cost increase due to the design change is slight. Therefore, a variety of products can be manufactured at low cost while using the semiconductor substrate 11.

  In the above specific example, the indicator DNA is fixed in advance to the DNA sensor in the detection region 57. However, for example, by injecting a chemical solution from another inlet directly connected to the detection region 57, the indicator DNA is fixed. Processing may be performed. In this case, after immobilization, the collected blood is injected from the inlet 50 to detect DNA. The same detection can be repeated by introducing a stripping solution after one DNA detection and removing the DNA in the detection region 57.

In the above specific example, DNA was extracted from blood inside the device and led to the detection region 57. However, the process of extracting DNA from blood was performed outside the device in advance, and the obtained DNA to be detected was detected. It may be introduced into the region 57.
Furthermore, in the first embodiment described above, the comprehensive groove 41 (FIGS. 4 and 5) of the semiconductor substrate 11 has a blocking portion made of a thermosetting resin or a photocurable resin (for example, the blocking portion of FIGS. 6 and 7). 42 to 45) are provided, and processing regions necessary for the desired analysis (for example, the mixing region 31, the separation region 34, and the detection region 36 in FIG. 1) are connected by the flow path 13, but the present invention is not limited to this.

  For example, as shown in FIG. 13, convex portions 61 to 64 having a shape matching the cross section of the groove 41 are formed on the surface 12A of the plate 12 on the semiconductor substrate 11 side (that is, the bonding surface with the surface 11A of the semiconductor substrate 11). Alternatively, the protrusions 61 to 64 may be fitted into the groove 41 and brought into close contact with each other when the plate 12 is bonded to the semiconductor substrate 11 in advance. In this case, a blocking portion of the groove 41 is formed by the convex portions 61 to 64.

  In addition to the method of previously forming the convex portions 61 to 64 on the plate 12 as shown in FIG. 13, the following method is also conceivable. That is, the plate 12 may be made of a thermoplastic resin or a thermoplastic resin, and when the plate 12 is bonded to the semiconductor substrate 11, the plate 12 may be plastically deformed by applying pressure by heating or irradiating light to a necessary portion. . In this case, the blocking portion of the groove 41 is formed by plastic deformation of the plate 12.

Further, in the first embodiment described above, the example in which the arrangement of the inlet and outlet of the flow path is changed for each type of analysis in the plate 12 has been described, but the present invention is not limited to this. For example, as shown in FIG. 14, openings 26 are provided in advance at all locations assumed as inlets and outlets of the flow channel (16 locations in FIG. 14), and the openings 26 corresponding to the corresponding types are analyzed according to the type of analysis. It may be used as an entrance or exit. In this case, the opening 26 unnecessary for the desired analysis may be left unattended, but contamination of dust can be prevented by closing the unnecessary opening 26. As described above, when all the assumed openings 26 are provided in advance, the plate 12 may be designed only once as in the semiconductor substrate 11. Therefore, a variety of microanalytical elements can be manufactured at a lower cost.
(Second Embodiment)
The microanalytical element of the second embodiment is composed of a semiconductor substrate 71 shown in FIG. 15 and a plate 72 shown in FIGS. 16 to 19, and the comprehensive groove 41 (FIG. 4, FIG. 4) of the first embodiment described above. An exhaustive groove 73 similar to 5) is formed on one surface 72A of the plate 72. Moreover, the opening 72 similar to the opening 26 of FIG. 14 is previously formed in the plate 72 in all the places (16 places in FIG. 16) assumed as the entrance and exit of the flow path mentioned later. The material and forming method of the plate 72 are the same as those of the plate 12 described above.

  As shown in FIG. 15, in the semiconductor substrate 71, all processing regions (31 to 38) necessary for a plurality of types of analysis assumed in advance are formed in advance on one surface, and electrodes 39 are formed in the respective regions 31 to 38. Provided. Note that the processing contents in the processing areas (31 to 38) are the same as those in the first embodiment, and thus the description thereof is omitted here. The material and forming method of the semiconductor substrate 71 are the same as those of the semiconductor substrate 11 described above. Also in the second embodiment, the semiconductor substrate 71 having the same configuration (that is, having the processing regions (31 to 38)) can be easily mass-produced.

  In the microanalysis element according to the second embodiment, a processing region (for example, FIG. 15) unnecessary for the desired analysis among the comprehensive grooves 73 (FIGS. 16 and 17) formed on the surface 72 </ b> A of the plate 72. 18 and 19 are formed at locations that communicate with the processing regions 33, 35, 37, and 38) (8 locations in FIG. 18). As a result, it is possible to restrict the inflow of liquid only to portions that communicate with the processing areas necessary for the desired analysis (for example, the processing areas 31, 32, 34, and 36 in FIG. 15). The formation of the blocking site 75 is the same as the blocking sites 42 to 45 described above.

  After temporarily curing the thermosetting resin or the photocurable resin as the blocking part 75, the surface 72A of the plate 72 is joined to one surface of the semiconductor substrate 71 (formation surface of the processing region (31 to 38)), When this resin is fully cured, the flow path 76 shown in FIGS. 20 and 21 is formed between the plate 72 and the semiconductor substrate 71, and the microanalysis element 70 of the second embodiment is completed. The joining method of the plate 72 and the semiconductor substrate 71 is the same as that of the first embodiment.

  As shown in FIG. 20, the flow path 76 of the liquid to be analyzed is one of all the processing regions (31 to 38) depending on the position of the blocking part 75 in the comprehensive groove 73 (FIGS. 16 and 17). It forms so that a desired analysis may be implement | achieved through the process area | region (31,32,34,36) of a part. Of the plurality of (in the figure, 16) openings 74 of the plate 72, those required for analysis are used as the inlet and outlet of the flow path 76.

  Accordingly, in the microanalytical element 70 of the second embodiment, a small amount of liquid (for example, liquid containing DNA such as blood) injected from the inlet (74) of the plate 72 is moved along the flow path 76. Processing necessary for a desired analysis can be performed in order (for example, mixing region 31 → mixing region 32 → separation region 34 → detection region 36), and the liquid after detection is discharged from the outlet (74) of the plate 72. Therefore, the analysis time can be greatly shortened, and desired analysis can be performed efficiently.

  Further, in order to realize an analysis different from the above among a plurality of types of analysis due to a request different from the above, the semiconductor substrate 71 (FIG. 15) having the same structure already designed is used to comprehensively form the analysis. A similar blocking portion may be formed in “a portion communicating with a processing area unnecessary for the analysis” in the groove 73 (FIGS. 16 and 17). For this reason, according to the position of the interruption | blocking site | part in the comprehensive groove | channel 73, the flow path required for the said analysis (flow path different from said flow path 76) can be formed easily. In this case, another analysis with respect to a very small amount of liquid can be performed efficiently.

  As described above, in the second embodiment, the semiconductor substrate 71 having the same configuration including all the processing regions (31 to 38) necessary for a plurality of types of analysis assumed in advance is used, so that the semiconductor for each type of analysis. There is no need to design the substrate 71, and the manufacturing cost per micro-analyzing element 70 can be surely suppressed. Further, since the comprehensive groove 73 is provided on the surface 72A of the plate 72, the configuration of the semiconductor substrate 71 is simplified and the manufacture thereof is facilitated. Furthermore, since openings 74 are provided in advance in all the locations of the plate 72 that are supposed to be the entrances and exits of the flow paths 76, the design of the plate 72 is sufficient once as in the semiconductor substrate 71. Therefore, various types of microanalytical elements can be manufactured at low cost while using the semiconductor substrate 71.

In the second embodiment described above, the blocking portion 75 made of a thermosetting resin or a photocurable resin is provided in the comprehensive groove 73 of the plate 72, but the present invention is not limited to this. For example, when the plate 72 is made of a thermoplastic resin or a thermoplastic resin, and the plate 72 is joined to the semiconductor substrate 71, pressure is applied by heating or irradiating a necessary portion, and the groove 73 portion of the plate 72 is plasticized. It may be deformed. In this case, the blocking portion 75 of the groove 73 is formed by plastic deformation of the plate 72.
(Third embodiment)
The element for microanalysis according to the third embodiment includes the semiconductor substrate 71 (described above) shown in FIG. 15 and the plate 82 shown in FIGS. In the plate 82, a groove 83 for a flow path 86 to be described later is formed on one surface 82A (that is, a bonding surface with the semiconductor substrate 71), for example, a processing region necessary for a desired analysis (for example, the processing region 31, FIG. 32, 34, 36) only. Further, the plate 82 has openings 84 that serve as inlets and outlets of the flow path 86 at the ends (five places) of the groove 83. The material and forming method of the plate 82 are the same as those of the plate 12 described above.

When the surface 82A of the plate 82 is bonded to one surface of the semiconductor substrate 71 (the formation surface of the processing regions (31 to 38) in FIG. 15), the plate 82 and the semiconductor substrate 71 are connected to each other as shown in FIGS. The micro-analysis element 80 of the third embodiment is completed. The method for joining the plate 82 and the semiconductor substrate 71 is the same as that in the first embodiment.
As shown in FIG. 24, the flow path 86 of the liquid to be analyzed is a part of all the processing regions (31 to 38) according to the shape of the groove 83 (FIGS. 22 and 23). 32, 34, 36) to achieve the desired analysis. In addition, a plurality (five in the figure) of openings 84 in the plate 82 are used as inlets and outlets of the flow path 86.

  Therefore, in the microanalysis element 80 of the third embodiment, while moving a small amount of liquid (for example, liquid containing DNA such as blood) injected from the inlet (84) of the plate 82 along the flow path 86, Processing necessary for a desired analysis can be performed in order (for example, mixing region 31 → mixing region 32 → separation region 34 → detection region 36), and the liquid after detection is discharged from the outlet (84) of the plate 82. Therefore, the analysis time can be greatly shortened, and desired analysis can be performed efficiently.

  Further, in order to realize an analysis different from the above among a plurality of types of analysis due to a request different from the above, the semiconductor substrate 71 (FIG. 15) having the same configuration that has already been designed is used. What changed the shape of the groove | channel 83 and arrangement | positioning of the opening 84 according to (position of the process area | region required for an analysis) should just be used. For this reason, according to the shape of the groove | channel after a change, the flow path (flow path different from said flow path 86) required for the said analysis can be formed easily. In this case, another analysis with respect to a very small amount of liquid can be performed efficiently.

As described above, in the third embodiment, the semiconductor substrate 71 having the same configuration including all the processing regions (31 to 38) necessary for a plurality of types of analysis assumed in advance is used, so that the semiconductor for each type of analysis. It is not necessary to design the substrate 71, and the manufacturing cost per micro-analyzing element 80 can be reliably suppressed. The plate 82 of the microanalysis element 80 has to change the shape of the groove and the arrangement of the inlet and outlet of the flow path for each type of analysis, but the cost increase due to the design change is slight. Therefore, various types of microanalytical elements can be manufactured at low cost while using the semiconductor substrate 71.
(Modification)
In the above-described embodiment, the example in which the channel groove 41 is provided in the semiconductor substrate 11 and the example in which the channel grooves 73 and 83 are provided in the plates 72 and 82 have been described. However, the present invention is not limited thereto. Not. The channel groove may be provided on both the semiconductor substrate and the plate.

  Further, in the above-described embodiment, one flow path is formed so as to realize one type among a plurality of types of analysis assumed in advance, but two or more streams are formed so as to realize two or more types of analysis at the same time. A path may be formed.

It is a plane schematic diagram which shows the structure of the element 10 for microanalysis of 1st Embodiment. It is a cross-sectional schematic diagram which shows the structure of the element 10 for microanalysis of 1st Embodiment. 4 is a perspective view showing a configuration of a plate 12. FIG. 2 is a schematic plan view showing a configuration of a semiconductor substrate 11. FIG. 2 is a schematic cross-sectional view showing a configuration of a semiconductor substrate 11. FIG. 4 is a schematic plan view illustrating a configuration of a semiconductor substrate 11 having blocking portions 42 to 45. FIG. 4 is a schematic cross-sectional view showing a configuration of a semiconductor substrate 11 having blocking portions 42 to 45. FIG. It is a figure explaining an example of the mixing area | regions 31-33. It is a figure explaining an example of the isolation | separation area | regions 34 and 35. FIG. It is a figure explaining the other example of the isolation | separation area | regions 34 and 35. FIG. 3 is a block diagram illustrating a specific example of a semiconductor substrate 11. FIG. It is a block diagram explaining the flow path (liquid flow) in the case of realizing “analysis of DNA” and “analysis of plasma”. It is a perspective view explaining the plate 12 of a modification. It is a top view explaining plate 12 of another modification. It is a plane schematic diagram which shows the structure of the semiconductor substrate 71 of the element for microanalysis of 2nd Embodiment. It is a plane schematic diagram which shows the structure of the plate 72 of the element for microanalysis of 2nd Embodiment. It is a cross-sectional schematic diagram which shows the structure of the plate 72 of the element for microanalysis of 2nd Embodiment. FIG. 6 is a schematic plan view showing a configuration of a plate 72 having a blocking part 75. It is a cross-sectional schematic diagram which shows the structure of the plate 72 which has the interruption | blocking site | part 75. FIG. It is a plane schematic diagram which shows the structure of the element 70 for microanalysis of 2nd Embodiment. It is a cross-sectional schematic diagram which shows the structure of the element 70 for microanalysis of 2nd Embodiment. It is a plane schematic diagram which shows the structure of the plate 82 of the element for microanalysis of 3rd Embodiment. It is a cross-sectional schematic diagram which shows the structure of the plate 82 of the element for microanalysis of 3rd Embodiment. It is a plane schematic diagram which shows the structure of the element 80 for microanalysis of 3rd Embodiment. It is a cross-sectional schematic diagram which shows the structure of the element 80 for microanalysis of 3rd Embodiment.

Explanation of symbols

10, 70, 80 Micro analysis element 11, 71 Semiconductor substrate 12, 72, 82 Plate 13, 76, 86 Channel 21-24 Inlet 25 Outlet 26, 74, 84 Opening 31-33, 51, 52, 54 Mixed region 34, 35, 53, 55 Separation region 36-38, 57, 58 Detection region 39 Electrode 41, 73, 83 Groove 42-45, 75 Blocking region 56 Washing region 61-64 Projection

Claims (7)

A semiconductor substrate;
A plate bonded to one surface of the semiconductor substrate,
Between the semiconductor substrate and the plate, a flow path of the liquid to be analyzed is formed,
The plate is formed with an inlet and an outlet of the flow path,
On the surface of the semiconductor substrate, processing regions used for a plurality of types of analysis assumed in advance are formed,
The flow path is formed so as to realize a desired analysis among the plurality of types of analysis by connecting from the inlet to the outlet through a part of the processing region. Element. In the microanalysis element according to claim 1,
A groove for the flow path is formed on the surface of the semiconductor substrate so as to comprehensively connect the processing region,
A portion for blocking the inflow of the liquid is formed in the groove at a location leading to a processing region unnecessary for the desired analysis. In the microanalysis element according to claim 1,
In the plate, a groove for the flow path is formed on the surface on the semiconductor substrate side so as to comprehensively connect the processing region,
A portion for blocking the inflow of the liquid is formed in the groove at a location leading to a processing region unnecessary for the desired analysis. In the element for microanalysis according to claim 2 or claim 3,
The part for blocking is formed of a thermosetting resin or a photocurable resin. In the element for microanalysis according to claim 2 or claim 3,
The plate is made of a thermoplastic resin or a thermoplastic resin,
The portion for blocking is formed by plastic deformation of the plate. The microanalytical element according to claim 2,
On the surface of the semiconductor substrate side, a convex portion having a shape that matches the cross section of the groove is formed on the plate in advance.
The portion for blocking is formed by the convex portion of the plate. In the microanalysis element according to claim 1,
The microanalysis element, wherein the plate is formed with a groove for the flow path on the surface on the semiconductor substrate side so as to connect only a processing region necessary for the desired analysis.

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