WO2004038398A1

WO2004038398A1 - Organic molecule detection element and organic molecule detection device

Info

Publication number: WO2004038398A1
Application number: PCT/JP2003/013133
Authority: WO
Inventors: Takeshi Yagi
Original assignee: Nikon Corporation
Priority date: 2002-10-25
Filing date: 2003-10-14
Publication date: 2004-05-06
Also published as: AU2003271188A1; JP2004144630A

Abstract

An element used for detecting organic molecules, which can improve a work efficiency, downsize and simplify a detection device, and improve a detection sensitivity. The element comprises a pair of electrode areas (21, 22) provided on the main surface of a semiconductor substrate (11), insulation films (12, 13) formed on the main surface of the semiconductor substrate, a metal film (17) formed via insulation films so as to cover a specified area (11a) on the main surface side and between electrode areas, and an area (19) disposed on the surface of the metal film to fix organic molecules. A current route is formed in the specified area (11a) according to the electrification amount of those organic molecules that have been fixed in at least the fixing area (19).

Description

Description Organic molecule detection element and organic molecule detection device

The present invention relates to an organic molecule detection element and an organic molecule detection device used for detecting various organic molecules (for example, bases including nucleic acids and proteins such as DNA and RNA). Background art

Conventionally, detection of DNA using a DNA chip has been performed in order to analyze the base sequence and characteristics of DNA. DNA chip is probed on the glass plate surface

(Indicator DNA) is fixed. DNA analysis is performed by hybridizing a target (DNA to be detected) to which a fluorescent substance has been added to the probe of the DNA chip.

Here, when DNA having a known base sequence or property is immobilized as a probe, DNA having an unknown base sequence or property is hybridized to the probe as a target. Conversely, a DNA whose nucleotide sequence is unknown may be used as a probe and a known DNA as a target.

In any case, after the hybridization treatment, the DNA chip is sufficiently washed to remove the target other than the target adhered to the probe. As a result, on one DNA chip, there are scattered portions where the probe and the target are fixed. At each position where the probe and target are fixed, the probe 'or target is DNA whose base sequence or the like is known.

Since a fluorescent substance is added to the target in advance, this fluorescent substance can be used as a label to detect whether or not the probe and the target have hybridized and the position where the probe and the target are fixed.

Specifically, when analyzing DNA using a DNA chip, the DNA chip after hybridization is irradiated with excitation light such as ultraviolet light, and the excitation light is used to excite the DNA chip. The generated fluorescence from the fluorescent substance is visually observed by the imaging device, and it is detected whether or not the probe and the target have hybridized and the fixing position thereof.

Then, when information such as the position where the probe and the target are fixed to each other is obtained, the known base sequence and characteristics of the probe (or target) can be specified based on this information. The unknown base sequence and characteristics of the target (or prop) can be analyzed based on such information.

However, in order to detect DNA using a DNA chip, it is necessary to add a fluorescent substance for labeling to the target before hybridizing the target to the probe fixed on the surface of the glass plate. Work efficiency was poor.

In addition, in order to detect whether the probe and the target have hybridized or not, the position where the probe and the target are fixed, etc., a light source or an optical system that excites the fluorescent substance added to the target is necessary, and fluorescence from the fluorescent substance is observed. An optical system and an image sensor are also required. The optical system for observing fluorescence includes an optical filter and a microscope that block excitation light and transmit fluorescence. That is, the detection device was large and complicated.

By the way, a device for detecting DNA using a transistor has also been proposed (for example, Japanese Patent Application Publication No. 2001-511245). In this detector, a probe (DNA serving as an index) is immobilized on the gate of a MOS transistor, and a target (DNA serving as a detection target) is hybridized with the probe to detect a change in the amount of current between the source and the drain. To detect DNA.

Therefore, DNA can be easily detected without the need for fluorescent treatment (addition of a fluorescent substance for labeling) to the target or special analysis equipment (optical system for excitation, fluorescence observation, etc.).

However, in the test device described in the above-mentioned Japanese Translation of PCT Publication No. 2001-5111245, the detection sensitivity of DNA was lower than that in the case where a DNA chip was used. For this reason, if the number of probes and targets on the gate of the MO transistor was small, good detection results could not be obtained. Disclosure of the invention An object of the present invention is to provide an organic molecule detection element and an organic molecule detection device that can improve the working efficiency, reduce the size and simplification of the detection device, and can also improve the detection sensitivity. .

An organic molecule detection element according to the present invention includes: a pair of electrode regions provided on a main surface of a semiconductor substrate; an insulating film formed on the main surface; and the main surface side between the electrode regions via the insulating film. A metal film formed so as to cover the predetermined region, and an organic molecule fixing region disposed on the surface of the metal film, wherein the organic molecule is fixed to at least the fixing region in the predetermined region. Then, a current path is formed according to the charge amount of the fixed organic molecule.

Preferably, in the organic molecule detection element of the present invention, the surface area of the metal film is larger than the area of the predetermined region in the main surface.

Another organic molecule detecting element of the present invention is provided with a pair of electrode regions on a main surface of a semiconductor substrate, a metal film formed on the main surface, and a fixed region for organic molecules disposed on a surface of the metal film. Wherein the semiconductor substrate has a control electrode region on the main surface side between the electrode regions, the metal film is formed so as to cover the control electrode region, and The surface area is larger than the area of the control electrode region in the main surface, and the predetermined region adjacent to the control electrode region between the electrode regions includes at least the fixed region in which the organic molecules are fixed. · A current path is formed according to the charge amount of the fixed organic molecule.

Still another organic molecule detecting element of the present invention includes: a pair of electrode regions provided on a main surface of a semiconductor substrate; and a fixed region of organic molecules disposed on the main surface. The semiconductor substrate is provided between the electrode regions. Has a control electrode region on the main surface side thereof, and has a V-shaped recess toward the inside on the surface of the control electrode region, and the fixed region is disposed in the V-shaped recess. A current path is formed in the predetermined region adjacent to the control electrode region between the electrode regions, at least when the organic molecule is fixed to the fixed region, according to the charge amount of the fixed organic molecule. Is what is done.

Preferably, in the organic molecule detecting element according to the present invention, the electrode region is arranged near the main surface of the semiconductor substrate on the side opposite to the control electrode region.

An organic molecule detection device according to the present invention includes: the above-described organic molecule detection element; and the semiconductor substrate. And measuring means for measuring electric characteristics of the current path formed in the predetermined area. BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a cross-sectional view of the organic molecule detecting element 10.

FIG. 2 is a diagram showing a configuration of the organic molecule detection device 40.

FIG. 3 is a cross-sectional view of the organic molecule detecting element 70.

FIG. 4 is a cross-sectional view of the organic molecule detection element 80.

FIG. 5 is a cross-sectional view showing a manufacturing process of the organic molecule detecting element 80.

FIG. 6 is a cross-sectional view showing a manufacturing process of the organic molecule detecting element 80.

FIG. 7 is a cross-sectional view showing a manufacturing process of the organic molecule detecting element 80.

FIG. 8 is a cross-sectional view of the organic molecule detection element 90. BEST MODE FOR CARRYING OUT THE INVENTION

Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings.

(First Embodiment)

Here, detection of DNA, which is an example of an organic molecule, will be described. The organic molecule detection element 10 of the first embodiment has the same operating characteristics as an enhancement type MOS-FET, and detects DNA by utilizing the fact that DNA is negatively charged. It is a semiconductor element.

The configuration of the organic molecule detecting element 10 will be described. As shown in FIG. 1 (cross-sectional view), the organic molecule detection element 10 includes a silicon oxide film 12, 13, and a metal film 14, 15 for wiring on the main surface of the silicon substrate 11. A silicon oxide film 16 and a metal thin film 17 for fixing the DNA are formed in this order. Then, a region for fixing the index DNA 18 (hereinafter referred to as “DNA fixing region 19”) is arranged on the surface of the metal thin film 17. The formation of each film (12 to 17) is performed using a well-known semiconductor process technology.

The silicon substrate 11 (semiconductor substrate) of the organic molecule detecting element 10 has a pair of electrode regions 21 and 22 formed on the main surface side. The electrode regions 21 and 22 correspond to a source'drain. The conductivity type of the electrode regions 21 and 22 is the conductivity type of the silicon substrate 11 The opposite of the electric type.

The silicon oxide film 12, 13 (insulating film) has a film thickness D of a region sandwiched between the electrode regions 21, 22 of the silicon substrate 11, which is reduced to about 1θΑ to 100θΑ. Further, through holes 14a and 15a are provided in a part of the silicon oxide films 12 and 13. The through holes 14a and 15a are contact holes for electrically connecting the wiring metal films 14 and 15 to the electrode regions 21 and 22, respectively.

The silicon oxide film 16 is formed so as to cover the metal films 14 and 15. However, in order to electrically connect the measuring instruments (41, 42) described later, an exposed portion without the silicon oxide film 16 is secured in a part on the metal films 14, 15.

Further, the metal thin film 17 (metal film) for fixing the DNA is formed on the main surface side between the electrode regions 21 and 22 through the thinned portion of the silicon oxide film 12 and 13. It is formed to cover 1a. The metal thin film 17 corresponds to the gate portion of the MOS. The metal thin film 17 and the region 11 a of the silicon substrate 11 are insulated from each other via the thinned silicon oxide films 12 and 13.

Further, the metal thin film 17 is formed so as to extend not only into the concave portion formed by the silicon oxide films 12, 13, 16, but also to the periphery of the concave portion (on the silicon oxide film 16). Therefore, the area of the surface of the metal thin film 17, that is, the area of the DNA fixing region 19 is secured to be larger than the area in the main surface of the region 11 a of the silicon substrate 11. This is to improve the detection sensitivity without fail.

As a material of the metal thin film 17, for example, gold is preferably used. However, in addition to gold, any metal having excellent chemical resistance can be used (for example, Pt, W, A 1).

In the organic molecule detection element 10 having the above configuration, when the index DNA 18 is fixed to the DNA fixing area 19, a current path is formed in the area 11a of the silicon substrate 11 according to the charge amount of the index DNA 18. It is formed. The charge amount of the indicator DNA 18 is almost proportional to the amount immobilized.

When the DNA to be detected (not shown) is complementarily bound to the indicator DNA 18, the region 11a of the silicon substrate 11 has the quantity of the immobilized indicator DNA 18 (that is, the charged amount). , The total amount of the complementary bound DNA to be detected (that is, the amount of charge) Accordingly, a current path is formed.

And, the larger the width of the current path formed in the region 11 a of the silicon substrate 11, the more current flows between the electrode regions 21 and 22. Therefore, based on the amount of current flowing through the region 11a between the electrode regions 21 and 22, it is determined whether or not the index DNA 18 is immobilized on the DNA immobilization region 19, and the target DNA is detected on the index DNA 18 Can be detected whether or not has been complementary-bound.

Further, in the organic molecule detecting element 10 of the first embodiment, the area of the DNA fixing area 19 (the area of the surface of the metal thin film 17) is larger than the area of the area 11a of the silicon substrate 11. Therefore, the detection sensitivity is reliably improved as compared with the case where the areas of the DNA fixing region 19 and the region 11a are almost the same.

Since the potential change caused by the index DNA 18 and the DNA to be detected is proportional to the surface area of the metal thin film 1 Ί, securing a large area of the metal thin film 17 allows the index DNA 18 and the DN of the target to be detected. This is because A can cause a large potential change.

Here, as shown in FIG. 2, the organic molecule detecting device 40 including the organic molecule detecting element 10 includes a power source 41 and an ammeter 42 (measurement) in addition to the organic molecule detecting element 10. Means) are provided. The power supply 41 is a constant voltage source. The power supply 41 and the ammeter 42 are connected between the metal films 14 and 15 of the organic molecule detection element 10.

In the organic molecule detection device 40, a predetermined voltage is applied between the metal films 14, 15 of the organic molecule detection element 10 by the power supply 41, and the metal film 14, 14 of the organic molecule detection element 10 is The amount of current flowing between 15 is measured. The amount of current flowing between the metal films 14 and 15 corresponds to the amount of current flowing between the electrode regions 21 and 22 of the silicon substrate 11 (FIG. 1).

Therefore, the organic molecule detection device 40 (FIG. 2) determines whether or not the index DNA 18 is fixed to the DNA fixing region 19 of the organic molecule detection element 10 based on the current value measured by the ammeter 42. It is possible to detect with high sensitivity whether or not the DNA to be detected is complementarily bound to the indicator DNA 18.

As described above, the first embodiment utilizes the fact that DNA is negatively charged, so that no label (fluorescent substance, etc.) is added in advance to the detection target: DNA. P hiring 13133

However, labeled DNA 18 and the DNA to be detected can be easily detected.

Furthermore, in the first embodiment, the area (the surface area of the metal thin film 17) of the DNA fixing region 19 of the organic molecule detection element 10 is larger than the area of the region 11a of the silicon substrate 11; Even if the charge amount of the indicator DNA 18 on the DNA immobilization region 19 or the DNA to be detected is very small, the width of the current path between the electrode regions 21 and 22 can be efficiently controlled by the charge amount. Sensitive detection can be performed.

Further, in the i-th embodiment, it is not necessary to add a label to the DNA to be detected, so that the working efficiency is improved. Furthermore, since the fluorescent substance is not used as a label, a light source and an optical system for exciting the fluorescent substance, and an optical system and an image sensor for observing the fluorescence from the fluorescent substance are not required. Since the measuring means (41, 42) is used, the size and simplification of the detecting device can be realized and the configuration can be made at a low cost.

In the above-described first embodiment, the organic molecule detecting element 10 having the same operating characteristics as the enhancement type MOS-FET has been described as an example. However, the present invention relates to a depletion type MOS transistor. — Can be applied to organic molecule detectors that have the same operating characteristics as FETs. In this case, a channel region of a conductivity type opposite to that of the silicon substrate 11 is formed on the main surface side between the electrode regions 21 and 22 of the silicon substrate 11.

In the first embodiment, the DNA fixing region 19 and the metal films 14 and 15 are formed on the same main surface side of the silicon substrate 11. However, the DNA fixing region 19 and the metal films 14 and 15 are formed. 5 may be formed on the opposite main surface of the silicon substrate 11. In this case, the electrode regions 21 and 22 are formed continuously and deeply from the main surface (front surface) on the side where the DNA fixing region 19 is formed or the vicinity thereof to the opposite main surface (rear surface). The insulating film of the region 11a may be a silicon nitride film or the like.

(Second embodiment)

Here, the detection of DNA, an example of an organic molecule, will be described. The organic molecule detecting element 70 according to the second embodiment is a semiconductor element that has the same operating characteristics as the J-FET and detects DNA using the fact that DNA is negatively charged.

The configuration of the organic molecule detecting element 70 will be described. As shown in FIG. 3 (cross-sectional view), the organic molecule detecting element 70 is provided on the main surface of the silicon substrate 71 as shown in FIG. A silicon oxide film 13, metal films 14 and 15, and a silicon oxide film 16 similar to the child 10 are formed, and a metal thin film 72 for immobilizing DNA is further formed.

Here, the description of each of the films 13 to 16 is omitted. The material of the metal thin film 72 is the same as that of the metal thin film 17 described above, and the description thereof is omitted. Hereinafter, the silicon substrate 71 and the metal thin film 72 will be described.

On the silicon substrate 71 (semiconductor substrate) of the organic molecule detecting element 7 ◦, a silicon layer 75 of the opposite conductivity type is formed on the silicon layer 74, and the surface of the silicon layer 75 (the silicon substrate 7 A source region 76, a drain region 77, and a gate region 78 are formed on the main surface side of FIG. The silicon layer 75 is an epitaxial layer.

The source region 76 and the drain region 77 (the pair of electrode regions) are of the same conductivity type as the silicon layer 75, and are formed through the through holes 14a and 15a of the silicon oxide film 13 respectively. Connected to the metal films 14 and 15. The gate region 78 (control electrode region) is disposed between the source region 76 and the drain region 77, has the same conductivity type as the silicon layer 74, and is connected to a wiring metal film (not shown). .

In addition, a region 71 a between the source region 76 and the drain region 77 of the silicon layer 75 and the gate region 78 of the silicon layer 75 and the silicon layer 74 (the predetermined region ) Is a region inside the silicon substrate 71 and is a region where a current path (channel) is formed.

Further, the gate region 78 of the silicon layer 75 and the silicon layer 74 are arranged to face each other with the region 71a interposed in the width direction of the current path. Like the gate region 78, the silicon layer 74 is also connected to a wiring metal film (not shown). This silicon layer 74 functions as a backgut.

Further, in the organic molecule detecting element 70, there is no thin silicon oxide film 12 unlike the organic molecule detecting element 10 described above. Therefore, the metal thin film 72 of the organic molecule detecting element 70 is formed so as to cover the gate region 78 of the silicon substrate 71. That is, the metal thin film 72 and the gate region 78 are electrically connected. Then, on the surface of the metal thin film 72, a region for fixing the index DNA 18 (hereinafter, referred to as a “DNA fixing region 73 J”) is arranged.

Further, the metal thin film 72 is formed by the silicon oxide films 13, 16 and the gate region 78. It extends not only inside the part but also around the recess (on the silicon oxide film 16). Therefore, the area of the surface of the metal thin film 72, that is, the area of the DNA fixing region 73 is ensured to be larger than the area in the main surface of the gate region 78 of the silicon substrate 71. This is to improve the detection sensitivity without fail.

In the organic molecule detection device 70 having the above-described configuration, when the indicator DNA 18 is fixed to the DNA fixing region 73, the charge amount of the indicator DNA 18 (in the region 71 a adjacent to the gut region 78 of the silicon substrate 71) A current path is formed according to <<: quantity. When the DNA to be detected is complementarily bound to the indicator DNA 18, a current path is formed in the region 71a in accordance with the total amount of the indicator DNA 18 and the DNA to be detected). You.

Therefore, based on the amount of current flowing through the region 71a between the source region 76 and the drain region 77, whether or not the indicator DNA 18 is fixed in the DNA fixing region 73 and whether or not the indicator DNA 18 is detected It can be detected whether or not the target DNA has been complementarily bound. Furthermore, since the area of the DNA fixed region 73 (the area of the surface of the metal thin film 72) is larger than the area of the gate region 78 of the silicon substrate 71, the area of the DNA fixed region 73 and the gate region 78 are the same. The detection sensitivity is surely improved compared to the case of the degree. When DNA is detected using the organic molecule detection element 70, a power supply 41 and an ammeter 42 (FIG. 2) are connected to the organic molecule detection element 70. Then, a predetermined voltage is applied between the source region 76 and the drain region 77 of the organic molecule detection element 70, and the amount of current flowing through the region 71a of the silicon layer 75 is measured using the ammeter 42. At this time, the gate region 78 is kept in a state where the application of the voltage is cut off (floating). In addition, a reverse bias voltage (a voltage higher than that of the silicon layer 75) is applied to the silicon layer 74 opposed to the gate region 78.

Therefore, according to the organic molecule detection element 70, the above-described index DN A can be obtained based on the current value measured by the ammeter 42 without adding a label (such as a fluorescent substance) to the DNA to be detected in advance. 18 and the target DNA can be easily detected.

Furthermore, since the area of the DNA fixing region 73 of the organic molecule detection element 70 (the area of the surface of the metal thin film 72) is larger than the area of the gate region 78, the DNA fixing region 73 Even if the amount of charge on DNA 18 or the DNA to be detected is very small, the width of the current path between the source region 76 and the drain region 77 can be efficiently controlled by the charge amount, resulting in high sensitivity. Detection can be performed.

In addition, in the organic molecule detection element 70, even if nothing is fixed in the DNA fixing region 73, a current path is formed in the region 71a between the source region 76 and the drain region 77. Thus, it is also possible to investigate variations in the production of the organic molecule detecting element 70. After the indicator DNA 18 has been immobilized on the DNA immobilization region 73, the immobilized indicator DNA 18 can be quantitatively confirmed before the DNA to be detected is bound by capture.

Also in the second embodiment, it is not necessary to add a label to the DNA to be detected in advance, so that the working efficiency is improved. Furthermore, miniaturization and simplification of the detection device have been realized.

Therefore, it can be constructed at low cost.

Furthermore, in the organic molecule detection element 70, it is preferable that a positive voltage (for example, 5 V) be applied to the gate region 78 when the indicator DNA 18 is fixed to the DNA fixing region 73. As a result, the indicator DNA 18 can be attracted to the DNA fixing region 73, and the indicator DNA 18 can be effectively immobilized to the DNA fixing region 73 even if the indicator DNA 18 is in a trace amount. At this time, it goes without saying that the potential of the silicon substrate 71 is adjusted so that no current flows in the forward direction.

(Third embodiment)

Here, the detection of DNA, an example of an organic molecule, will be described. The organic molecule detecting element 80 of the third embodiment has the same operating characteristics as the J-FET as in the case of the organic molecule detecting element 70 described above. '

The configuration of the organic molecule detection element 80 will be described. As shown in FIG. 4 (cross-sectional view), the organic molecule detection element 80 has a silicon oxide film 13 and a metal film 14, similar to the organic molecule detection element 70 of FIG. 15 and a silicon oxide film 16 are formed, and a silicon nitride film 82 is formed thereon.

The silicon substrate 81 (semiconductor substrate) of the organic molecule detection element 80 is provided with a gate region 83 (control electrode region) instead of the gate region 78 of the silicon substrate 71 of the organic molecule detection element 70 (FIG. 3). And into the surface of this gate region 83 V-shaped recess 84 is provided.

On the surface of the V-shaped concave portion 84 (part of the main surface of the silicon substrate 81), a region for fixing the index DNA 18 (hereinafter, referred to as “DNA fixing region 85”) is arranged. The reason why the V-shaped concave portion 84 is provided on the surface of the gate region 83 and the DNA fixing region 85 is disposed therein is to surely improve the detection sensitivity. In addition, a region 81 a between the source region 76 and the drain region 77 of the silicon substrate 75 and between the gate region 83 of the silicon layer 75 and the silicon layer 74 (predetermined region) Is a region inside the silicon substrate 81 and a region for forming a current path (channel).

Next, a process of manufacturing the organic molecule detecting element 80 according to the third embodiment will be described with reference to FIGS. Here, an example will be described in which the silicon layer 74 is P-type and the silicon layer 75 is N-type.

First, as shown in FIG. 5 (a), a single-crystal silicon layer 75 is epitaxially grown on a single-crystal silicon layer 74 to form a silicon substrate 81. Then, a thin silicon oxide film 101 (FIG. 5 (b)) is formed on the main surface of the silicon substrate 81 (the surface of the silicon layer 75) using a thermal oxidation method or the like, and a resist is formed thereon. A top pattern 102 is formed.

Next, using the resist pattern 102 as a mask, an N-type impurity 103 is introduced at a high concentration by an ion implantation method. Thereafter, the resist pattern 102 is removed and purified, and an annealing process is performed, so that an N-type source region 76 and a drain region 77 having a high impurity concentration are formed in the silicon layer 75 of the silicon substrate 81. Is done.

As shown in Fig. 5 (b), the main surface (the surface of the silicon layer 75) of the silicon substrate 81 is protected by ion implantation through the thin silicon oxide film 101, so that a high-precision state is maintained. I can. The source region 76 and the drain region 77 may be formed by patterning a thick silicon oxide film, and using this as a mask by a vapor phase diffusion method using heat.

Further, another resist pattern 104 is formed on the silicon oxide film 101 (FIG. 5 (c)), and the silicon oxide film 101 is etched using the resist pattern 104 as a mask. . Next, after removing and cleaning the resist pattern 104, the main surface of the silicon substrate 81 (the surface of the silicon layer 75) is etched using the silicon oxide film 101 as a mask (FIG. 5). (d)).

In this case, the etching is performed using an anisotropic etching solution such as a TMAH solution (a tetramethylammonium-oxide solution). As a result, a V-shaped concave portion 84 is formed on the main surface (the surface of the silicon layer 75) of the silicon substrate 81 toward the inside.

Next, another resist pattern 105 is formed on the silicon oxide film 101 (FIG. 6A), and using this resist pattern 105 as a mask, a P-type impurity 106 is formed by ion implantation. Introduce to concentration. By subsequent aerating, a P-type gate region 83 with a high impurity concentration is formed in the silicon layer 75 (V-shaped recess 84 between the source region 76 and the drain region 77) of the silicon substrate 81. Is done. It is preferable to form a thin silicon oxide film on the surface of the concave portion 84 before the ion implantation. This is because, if ions are implanted through a thin silicon oxide film, the main surface of the silicon substrate 81 (the surface of the silicon layer 75) can be protected and maintained in a highly accurate state. The gate region 83 may be formed by a vapor phase diffusion method using heat using a patterned silicon oxide film as a mask.

Next, after removing and cleaning the resist pattern 105, a silicon oxide film 101 is further grown by a thermal oxidation method or the like, and as shown in FIG. To form At this time, the silicon oxide film 13 is also formed on the surface of the gate region 83.

Thereafter, a resist pattern 107 is formed on the silicon oxide film 13 (FIG. 6C), and a part of the silicon oxide film 13 is etched using the resist pattern 107 as a mask. Through this etching, through holes 14a and 15a are formed in the silicon oxide film 13, and the above-described source region 76 and drain region 77 are exposed.

Next, after removing and cleaning the resist pattern 107, a metal film for wiring is formed on the entire surface using a sputtering device or the like. Then, using a resist pattern (not shown) as a mask, a part of the metal film is etched to form the metal films 14 and 15 shown in FIG. 7A. The metal films 14 and 15 are connected to the source region 76 and the drain via the through holes 14a and l5a. It is electrically connected to the rain area 77.

Then, after removing and cleaning a resist pattern (not shown) on the metal films 14 and 15, a silicon oxide film 16 is formed on the entire surface (FIG. 7 (b)). A silicon nitride film 82 is formed on the entire surface. Then, a resist pattern 108 is formed on the silicon nitride film 82 (FIG. 7C), and a part of the silicon nitride film 82 and a part of the silicon oxide film 13, 16 are used as a mask. Etch. The silicon oxide film 16 is a protective film made of PSG or the like.

Through this etching, a through hole 109 is formed in the silicon nitride film 82 and the silicon oxide films 13 and 16, and the gate region 83 is exposed. Then, after removing and cleaning the resist pattern 108, a concave portion is formed by the surface of the gate region 83, the silicon nitride film 82, and the silicon oxide films 13 and 16. The bottom surface of this concave portion is V-shaped, and serves as a DNA fixing region 85 (FIG. 4).

Finally, the surface of the V-shaped concave portion 84 (DNA fixing region 85) is subjected to a plasma treatment or the like, thereby completing the organic molecule detecting element 80 of the third embodiment. Incidentally, the periphery of the DNA fixing region 85 is covered with a silicon nitride film 82 and a silicon oxide film 13, 16.

The silicon nitride film 82 has a denser film structure than the silicon oxide film, is less likely to take in alkali metal (eg, sodium) atoms, and has excellent chemical resistance, and thus functions reliably as a protective film '. With the silicon nitride film 82, deterioration of the metal films 14, 15 can be reliably prevented.

In addition, the silicon nitride film 82 has a feature that DNA is less likely to adhere to the silicon oxide film than the silicon oxide film. Therefore, it is possible to prevent the DNA from being attached unnecessarily around the DNA fixing region 85, and to efficiently attach the DNA only to the DNA fixing region 85.

In the organic molecule detection element 80 having the above configuration, when the indicator DNA is fixed to the DNA fixing region 85, the charge amount of the indicator DNA (the region 81a adjacent to the gate region 83 of the silicon substrate 81) The current path is formed according to the quantity. When the DNA to be detected is complementarily bound to the indicator DNA, a current path is formed in the region 81a according to the total amount of the indicator DNA and the DNA to be detected). Therefore, based on the amount of current flowing in the region 81a between the source region 76 and the drain region 77, whether or not the indicator DNA is fixed in the DNA anchoring region 85, and the DN to be detected is indicated in the indicator DNA. It can be detected whether or not A has been complementarily bound.

Furthermore, the shape of the DNA fixing region 85 (the shape of the surface of the gate region 83) is V-shaped with the inside facing, so that the 0 fixing region 85 (the surface of the gate region 83) has a flat shape. As a result, the detection sensitivity is surely improved. Due to the concentration of the electric field, the channel of the gate region 83 changes even with a slight potential change, and the source region 76 and the drain region

This is because the amount of current flowing in the region 81a during 77 greatly changes.

When DNA is detected using the organic molecule detection element 80, a power supply 41 and an ammeter 42 (FIG. 2) are connected to the organic molecule detection element 80. And organic molecule detection element

A predetermined voltage is applied between the source region 76 and the drain region 77 of 80, and the amount of current flowing in the region 81 a of the silicon layer 75 is measured using the ammeter 42. At this time, the gate region 83 is kept in a state where the application of the voltage is cut off (floating). A reverse bias voltage (when the silicon layer 75 is N-type and the silicon layer 74 is P-type) is applied to the silicon layer 74 with a reverse bias voltage.

Therefore, according to the organic molecule detection element 80, even if a label (such as a fluorescent substance) is not added in advance to the DNA to be detected, the above-described index DNA can be obtained based on the current value measured by the ammeter 42. And the DNA to be detected can be easily detected.

Furthermore, since the shape of the DNA fixing region 85 (the shape of the surface of the gate region 83) of the organic molecule detecting element 80 is formed in a V shape toward the inside, the index DNA on the DNA fixing region 85 and the DNA to be detected are determined. Even if the charge amount is very small, the width of the current path between the source region 76 and the drain region 77 can be efficiently controlled by the charge amount, and highly sensitive detection can be performed.

Further, in the organic molecule detection element 80, even when nothing is fixed to the DNA fixing region 85, a current path is formed in the region 81a between the source region 76 and the drain region 77, In this state, variations in the production of the organic molecule detection element 80 can be investigated. After the indicator DNA is immobilized on the DNA fixing region 85, the immobilized indicator DNA can be quantitatively confirmed before the DNA to be detected is complementarily bound. Also in the third embodiment, it is not necessary to add a label to the DNA to be detected in advance, so that the working efficiency is improved. Further, downsizing and simplification of the detection device are realized, and the configuration can be made at a low cost.

Further, in the organic molecule detection element 80, it is preferable to apply a positive voltage (for example, 5 V) to the gate region 83 when fixing the indicator DNA to the DNA fixing region 85. As a result, the index DNA can be attracted to the DNA fixed region 85, and even if the index DNA is very small, it can be effectively immobilized to the DNA fixed region 85. At this time, it goes without saying that the potential of the silicon substrate 81 is adjusted so that no current flows in the forward direction.

In addition, in the organic molecule detection element 80, since a current path is formed in the area 81a inside the silicon substrate 81 (that is, the bulk part), noise is generated in the current path due to the influence of the element surface and the like. Nothing happens. As a result, the above-described DNA detection can be performed accurately.

Furthermore, even if the DNA immobilization region 85 (the surface of the gate region 83) is contaminated by chemical treatment such as hybridization, etc., the region 81a (the region where the current path is formed) inside the balta is altered. There is almost no possibility of deterioration, and accurate DNA detection can always be performed.

In the third embodiment, as shown in FIGS. 5D and 6A, after the silicon layer 75 is etched to form a V-shaped concave portion 84, the V-shaped concave portion 84 is formed. The gate region 83 was formed, but this procedure may be reversed.

Further, similarly to the organic molecule detecting element 70 of the second embodiment described above, a metal thin film for fixing DNA may be formed on the DNA fixing region 85. In this case, the DNA fixing region 85 is disposed on the surface of the metal thin film. As a result, the detection sensitivity is further improved. (Fourth embodiment)

Here, the detection of DNA, an example of an organic molecule, will be described. The organic molecule detecting element 90 of the fourth embodiment has the same operating characteristics as the J-FET, similarly to the organic molecule detecting elements 70 and 80 described above.

The configuration of the organic molecule detection element 90 will be described. As shown in FIG. 8 (cross-sectional view), the organic molecule detecting element 90 has a main surface of a silicon substrate 91 (here, the silicon layer 74 The front surface) is provided with a concave portion 92 similar to the concave portion 84 of the organic molecule detecting element 80 in FIG. 4, and on the side opposite to the main surface, a silicon oxide similar to the organic molecule detecting element 70 in FIG. A film 13, metal films 14 and 15, and a silicon oxide film 16 are formed.

In the surface of the silicon layer 74 (control electrode region), the position of the concave portion 92 is a position facing the gate region 78 of the silicon layer 75. The concave portion 92 of the organic molecule detecting element 90 is also V-shaped toward the inside. Then, on the surface of the silicon layer 74 (including the surface of the V-shaped concave portion 92), a region for fixing the index DNA (hereinafter, referred to as “DNA fixing region 93”) is arranged.

Therefore, in the organic molecule detecting element 90 of the fourth embodiment, the source region 76, the drain region 77, the gate region 78 (transistor portion) formed in the silicon layer 75 of the silicon substrate 91 This means that it is located near the main surface on the opposite side from 93.

In addition, a V-shaped recess 92 is provided at a position facing the gate region 78 on the main surface of the silicon substrate 91 (the surface of the silicon layer 74), and the silicon layer including the surface of the loop 92 is provided. The reason why the DNA fixing region 93 is arranged on the surface of 74 is to surely improve the detection sensitivity.

In addition, a silicon oxide film 94 and a silicon nitride film 95 are formed around the DNA fixing region 93 on the main surface of the silicon substrate 91 (the surface of the silicon layer 74), and a wide DNA is fixed. Area 93 is reserved.

A region 91 a (predetermined region) sandwiched between the source region 76 and the drain region 77 of the silicon layer 75 and between the gut region 78 and the silicon layer 74 of the silicon layer 75 is formed of silicon. This is an area inside the circuit board 91 and an area for forming a current path (channel).

In addition, the metal films 14, 15, and 96 connected to the source region 76, the drain region 77, and the gut region 78 of the organic molecule detection element 90 are all formed by the silicon oxide film 16 as a whole. Covered in. Furthermore, a thick protective substrate (not shown) (for example, a silicon wafer or a glass substrate) is bonded on the silicon oxide film 16. Further, inside the silicon substrate 91 of the organic molecule detection element 90, the dielectric separation layer 9 is continuously formed from the main surface (front surface) on the DNA fixing region 93 side to the main surface (back surface) on the opposite side. 7 is Is formed. The dielectric isolation layer 97 is a thermal oxide film or the like, and is a layer for electrically isolating the silicon layers 91 (74 and 75) (control electrode regions).

Here, a process of manufacturing the organic molecule detecting element 90 of the fourth embodiment will be briefly described. Here, the description will be given by taking an example in which the silicon layer 74 is P-type and the silicon layer 75 is N-type.

(1) The state after the formation of a normal J-FET (that is, the source region 76, the drain region 77, the gate region 78, and the dielectric isolation layer 97 are formed on the silicon substrate 91, and After the silicon oxide film 13, the metal films 14 and 15, and the silicon oxide film 16 have been formed, a protective substrate (not shown) is bonded on the silicon oxide film 16. In this state, the silicon layer 74 of the silicon substrate 81 is polished and thinned.

(2) Then, a silicon oxide film 94 is formed on the entire surface of the polished silicon layer 74, and a silicon nitride film 95 is formed on the entire surface. Further, a resist pattern is formed on the silicon nitride film 95, and the silicon oxide film 94 and a part of the silicon nitride film 95 are etched using the resist pattern as a mask.

As a result, small through holes are formed in the silicon oxide film 94 and the silicon nitride film 95, and a part of the silicon layer 74 is exposed. The exposed portion at this time is a narrow region facing only the gate region 78 of the silicon layer 75, and is used for forming the V-shaped concave portion 92.

(3) After that, the resist pattern is removed and cleaned, and the main surface (the surface of the silicon layer 74) of the silicon substrate 91 is etched using the silicon nitride film 95 as a mask. Etching in this case is performed using an anisotropic etching solution such as a TMAH solution. As a result, a V-shaped concave portion 92 is formed on the main surface of the silicon substrate 91 (the surface of the silicon layer 74) toward the inside.

(4) Next, a thin silicon oxide film is formed on the surface of the concave portion 92, another resist pattern is formed on the silicon nitride film 95, and using this as a mask, a P-type impurity is ion-implanted. Introduce to high concentration. By a subsequent annealing process, a P-type region having a high impurity concentration is formed in the concave portion 92 of the silicon layer 74 of the silicon substrate 91.

(5) After that, the resist pattern is removed and cleaned at the time of ion implantation. Another resist pattern is formed on the silicon nitride film 95, and the silicon oxide film 94 and a part of the silicon nitride film 95 are etched using this as a mask.

As a result, large through holes are formed in the silicon oxide film 94 and the silicon nitride film 95, and a part of the silicon layer 74 is further exposed. Then, after removing and cleaning the resist pattern, a concave portion is formed by the surface of the silicon layer 74, the silicon oxide film 94, and the silicon nitride film 95. The bottom of the recess also includes a V-shaped recess 92, and the entire exposed portion at this time is used as a DNA fixing region 93.

(6) Finally, by subjecting the DNA fixing region 93 (the surface of the silicon layer 74 including the surface of the V-shaped concave portion 92) to plasma treatment or the like, the organic molecule of the fourth embodiment is obtained. The detection element 90 is completed. Incidentally, the periphery of the DNA fixing region 93 is covered with a silicon nitride film 95 and a silicon oxide film 94.

The reason that the silicon layer 74 is thinned by polishing in the manufacturing process of the organic molecule detection element 90 is that the distance between the DNA fixing region 93 and the region 91 a (current path forming region) is reduced, so that the DNA layer is thinned. This is for improving the detection sensitivity.

In this organic molecule detection element 90, the silicon layer 74 functions as a gate, and the gate region 78 functions as a back gate. Therefore, at the time of DNA detection using the organic molecule detection element 90, the silicon layer 74 is kept in a state where the application of the voltage is cut off (floating). A reverse bias voltage (a voltage lower than that of the silicon layer 75) is applied to the gate region 78.

Therefore, even with the organic molecule detection element 90, it is possible to confirm whether or not an appropriate amount of the index DNA is fixed in the DNA fixing area 93 by using the same operating characteristics as the J-FET, or to complement the DNA to be detected with complementary binding. It can be detected whether or not it has been performed.

Further, since the shape of the portion of the DNA fixing region 93 facing the gate region 78 (the shape of the surface of the silicon layer 74) is formed in a V shape toward the inside, the DNA fixing region 93 (the surface of the silicon layer 74) is formed. ) The detection sensitivity is surely improved as compared with the case where is flat.

In other words, even if the amount of charge of the indicator DNA or the DNA to be detected on the DNA fixing region 93 is very small, the concentration of the electric field causes the source region 76 and the drain region 77 (region The width of the current path in the area 9 la) can be controlled efficiently, and highly sensitive detection can be performed.

In addition, when nothing is fixed to the DNA fixing region 93, it is possible to investigate the variation in manufacturing the organic molecule detecting element 90. With the indicator DNA fixed to the DNA fixing region 93 (before the complementary binding of the DNA to be detected), the indicator DNA can be quantitatively confirmed.

In the fourth embodiment as well, since it is not necessary to add a label to the DNA to be detected in advance, the working efficiency is improved. Further, downsizing and simplification of the detection device are realized, and the configuration can be made at a low cost.

Further, in the organic molecule detection element 90, when fixing the indicator DNA to the DNA fixing region 93, a positive voltage (for example, 5 V) is applied to the silicon layer 74 using a wiring circuit (not shown). It is preferable to keep it. As a result, the index DNA can be attracted to the DNA fixed region 93, and even if the amount of the index DNA is very small, it can be effectively immobilized to the DNA fixed region 93. At this time, it is needless to say that the bias voltage applied to the silicon layer 75 should be paid so that the current does not flow in the forward direction.

Also, in the organic molecule detection element 90, since a current path is formed in the region 91a inside the silicon substrate 91 (that is, inside the balta), noise is generated in the current path due to the influence of the element surface and the like. This does not occur, and the above-mentioned DNA detection can be performed accurately.

Furthermore, even if the DNA fixed region 93 (the surface of the silicon layer 74) is contaminated by chemical treatment such as hybridization, the region 91a inside the balta (current path forming region) is deteriorated. It does not cause deterioration and can always perform accurate DNA detection.

In addition, the main surface of the organic molecule detecting element 90 on the transistor section (76 to 78) side is sealed with a protective substrate (not shown), and is not contaminated by chemical treatment such as hybridization. Therefore, the durability of the organic molecule detection element 90 against chemicals is significantly improved.

Furthermore, since a silicon nitride film 95 is formed around the DNA fixing region 93, it is possible to prevent DNA from being attached unnecessarily around the DNA fixing region 93, and it is possible to efficiently use DNA only in the DNA fixing region 93. Can adhere well. The bonding agent for the wiring metal films 14, 15 and 96 and the protective substrate is a high melting point that can withstand high-temperature steps such as annealing and oxidation in the manufacturing process of the organic molecule detection element 90. It is preferable to select the material described above. For example, it is preferable to use Ti (titanium) or W (tungsten) for the metal films 14, 15 and 96, and to use an inorganic adhesive as a bonding agent. Further, the bonding of the protective substrate may be performed using an anodic bonding method. Further, instead of the protection substrate, the main surface on the transistor section (76 to 78) side may be covered with a resin after the heating step.

In the above embodiment, a silicon nitride film is used. However, if there is a film (DNA separation film) having a property of repelling DNA in addition to the silicon nitride film, this DNA separation film is replaced with a silicon nitride film. The same effect can be obtained by forming instead.

Further, similarly to the above-described organic molecule detection element 70, a metal thin film for fixing DNA may be formed on the DNA fixing region 93. In this case, the DNA fixing region 93 is disposed on the surface of the metal thin film. As a result, the detection sensitivity is further improved.

(Modification)

In the embodiment described above, the DNA fixing region (for example, 19), the corresponding current path forming region (for example, 11a), the transistor unit (for example, 21 and 22), and the metal film for wiring (for example, For example, although an organic molecule detection element (for example, 10) in which only one cell having (14, 15) is provided has been described as an example, a plurality of cells may be two-dimensionally arranged in a matrix.

However, in this case, in order to electrically separate the individual cells on the silicon substrate, a dielectric separation layer such as a thermal oxide film (for example, see 97 in FIG. 8) must be provided inside the silicon substrate. Is preferred.

According to the organic molecule detection device having a plurality of cells, a plurality of DNAs can be detected at the same time, and thus the working time and cost can be reduced. In this case, the same type of DNA or different types of DNA may be attached to a plurality of cells.

If different types of DNA are to be attached to multiple cells, they must be attached one by one, so that a positive voltage should be applied to the DNA fixed region of a specific cell to which a certain type of DNA is to be attached. , Minor DNA fixation region in other cells It is preferable to apply a voltage of the source. As a result, DNA can be attracted only to the DNA fixing region to which the positive voltage has been applied, and a trace amount of DNA can be selectively immobilized on a specific cell.

In addition, in an organic molecule detection device equipped with multiple cells, by measuring the amount of current flowing through the current path formation region (for example, 11a) with nothing attached to the DNA fixed region of each cell. The individual difference (variation) between cells can be confirmed. Then, by applying a desired voltage in consideration of individual differences between cells to the region functioning as a back gate, the individual differences can be corrected. By this correction, the width of the current path can be controlled appropriately (eg, uniformly) in advance. Note that an appropriate voltage value (for example, an average value) to be applied to the back gate may be obtained in consideration of individual differences between cells, and this may be applied as a whole.

Further, in the above-described second to fourth embodiments, two gate regions (for example, a silicon layer 74 and a gate region 78) are opposed to each other with the current path forming region interposed therebetween. The gate regions may likewise be opposed. Further, the gate region may be formed in a cylindrical shape.

Further, in all the embodiments described above, the organic molecule detecting element using the silicon substrate has been described, but various semiconductor substrates can be used instead of the silicon substrate (for example, GaAs).

Furthermore, if a label (fluorescent substance, radioisotope, etc.) is added to the DNA to be detected before the DNA to be detected is complementarily bound to the indicator DNA, the timing may be the same as or different from the electrical measurement described above By using other devices (such as a fluorescence microscope, a fluorescence measurement device, and a radioisotope detection device), the added state of the label can be optically measured, and the detection accuracy of DNA is improved.

In all the above embodiments, the measurement was performed using the power supply 41 and the ammeter 42. However, instead of using the power supply 41 (constant voltage source), a constant current source was used. A similar analysis can be performed when a voltage is measured between the wiring metal films 14 and 15 using a voltmeter instead of the voltmeter.

Further, in all of the embodiments described above, examples of detecting DNA have been described.However, for other charged organic molecules such as RNA, proteins, nucleic acids, and bases, A similar test can be performed. Industrial potential

ADVANTAGE OF THE INVENTION According to this invention, while improving an operation efficiency and miniaturizing and simplifying a detection apparatus, it is also possible to improve detection sensitivity.

Claims

.The scope of the claims

(1) providing a pair of electrode regions on the main surface of the semiconductor substrate,

An insulating film formed on the main surface;

A metal film formed so as to cover a predetermined region on the main surface side between the electrode regions via the insulating film;

Including a fixed region of organic molecules disposed on the surface of the metal film,

When the organic molecule is fixed to at least the fixed region, a current path is formed in the predetermined region according to the charge amount of the fixed organic molecule.

An organic molecule detecting element, characterized by comprising:

(2) The organic molecule detecting element according to claim 1,

An organic molecule detection element, wherein an area of a surface of the metal film is larger than an area of the predetermined region in the main surface.

(3) providing a pair of electrode regions on the main surface of the semiconductor substrate,

A metal film formed on the main surface;

The semiconductor substrate has a control electrode region on the main surface side between the electrode regions, the metal film is formed so as to cover the control electrode region, and the surface area of the metal film is Larger than the area of the control electrode region in the main surface,

In the predetermined region adjacent to the control electrode region between the electrode regions, at least when the organic molecule is fixed to the fixed region, a current path is formed according to the charge amount of the fixed organic molecule. To

An organic molecule detecting element, characterized by comprising:

(4) providing a pair of electrode regions on the main surface of the semiconductor substrate,

Including a fixed region of organic molecules arranged on the main surface,

The semiconductor substrate has a control electrode region on the main surface side between the electrode regions, and has a V-shaped concave portion facing inward on a surface of the control electrode region,

The fixing region is disposed in the V-shaped recess,

A predetermined area adjacent to the control electrode area between the electrode areas includes at least a front area. When the organic molecules are fixed to the fixed region, a current path is formed according to the charge amount of the fixed organic molecules.

An organic molecule detecting element, characterized by comprising:

(5) The organic molecule detecting element according to claim 4,

The electrode region is disposed near a main surface of the semiconductor substrate opposite to the control electrode region.

An organic molecule detecting element, characterized by comprising:

(6) The organic molecule detection element according to any one of claims 1 to 5, further comprising: a measuring unit configured to measure an electric characteristic of the current path formed in the predetermined region of the semiconductor substrate. Was

An organic molecule detection device, comprising: