JP2009300272A - Ion sensor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an ion sensing structure in a semiconductor device in the field of an ion sensing system and a biosensing system which is subjected to simple surface treatment so as to properly guide an ionic substance in a specimen to an ion sensing part. <P>SOLUTION: The ion sensor includes: a semiconductor chip having a substrate and an insulator layer formed on the substrate; and a detection part for converting the change in electric potential energy of the interface between the semiconductor substrate and the insulator layer into an electric charge to detect the change as a change of current. In the ion sensor, the semiconductor chip has a sensing area including at least part of the surface of the insulator layer, and the ion sensing area is an area having an affinity for an ionic substance in a specimen. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to an ion sensor sensitive to an ionic substance in a specimen.

  Ion sensing systems and biosensing systems are applied to a wide range of fields such as food production, management, and environmental measurement. In particular, ion sensing systems, such as pH sensors, are widely used, and not only devices using conventional glass electrodes but also devices using semiconductor devices instead of conventional glass electrodes have been proposed. In addition, as for apparatuses using the semiconductor device, there is a movement to develop miniaturized apparatuses.

  Currently, there is an increasing trend to apply semiconductor devices in the field of ion sensing systems and biosensing systems (for example, International Publication No. 2004/017068 (Patent Document 1), JP 2003-202318 A). No. (Patent Document 2)). Patent Document 1 discloses a biosensing system in which a sample containing nucleic acid is allowed to act on a DNA microarray having a nucleic acid probe portion having a nucleic acid probe capable of hybridizing with a predetermined nucleic acid, and the nucleic acid in the sample is A nucleic acid detection device that can be quantified is described. Patent Document 2 discloses an ion sensing system, which describes a chemical property measuring apparatus capable of measuring ion concentration such as pH of wet hair.

Here, in particular, the ion sensing system has a very wide range of uses, and even if it is limited to pH sensing ([H ⁺ ] sensing), various uses such as cell activity and water quality determination can be considered. In recent years, in pH sensing, it is desired to make the device into a small chip. In addition, there is a demand for micromeasurement, multiple simultaneous measurement, and imaging. Thus, an ion sensing system is desired to improve functions and added values.

  As a conventional technique, an ion sensing system may include an apparatus using an ion sensitive field effect transistor (ISFET) having a layered structure including a silicon nitride film / a silicon oxide film / a silicon substrate. However, the ion sensing system using ISFET has not been made multi-device and miniaturized, and it is difficult to say that differentiation from a conventional apparatus using glass electrodes is achieved.

  In addition, ion sensing systems that are convenient to carry and easy to operate are currently in the development stage, and all of the reference electrodes, solution to be measured, potentiostats, etc. that are generally provided in ion sensing systems It is hard to say that it is small. Therefore, the ion sensing system tends to be large, and it is difficult to immediately deploy to various uses.

On the other hand, a device that applies semiconductor technology and does not use the above-described ISFET has been developed (see Japanese Patent Application Laid-Open No. 2002-098667 (Patent Document 3)). In the apparatus described in Patent Document 3, the above-described potentiostat control circuit can be integrated particularly when silicon is used as a semiconductor, and the sensing unit in the apparatus can be arrayed and viewed as a two-dimensional image. Therefore, an unprecedented ion sensing device is conceivable and very useful.
International Publication No. 2004/017068 Pamphlet JP 2003-202318 A JP 2002-098667 A

  However, in Patent Document 3, no consideration is given to the importance and contrivance of surface treatment for ion sensing. The inventors of the present invention have focused on problems such as malfunctions due to non-specific adsorption of biologically related substances and lowering of imaging resolution in parts other than the ion sensing site particularly in applications of ion sensing systems outside the chemical field. The present inventors have further paid attention to the lack of a structure that reliably leads the object to be measured to the ion sensing site. Accordingly, an object of the present invention is to provide a simple surface-treated ion sensing sensor for reliably guiding an ionic substance in a specimen to an ion sensing portion in a semiconductor device used in an ion sensing system and a biosensing system. That is.

  In order to solve the above-mentioned problems, the present inventor has intensively studied focusing on the structure of the semiconductor device, the chemical characteristics of the surface of the ion sensing portion, and the like. And the structure of the sensor which can contribute to high sensitivity and the expansion of a use was discovered. That is, the present invention is as follows.

  The present invention converts a change in electrical potential energy at the interface between a substrate and a semiconductor chip having a substrate, an insulator layer formed on the substrate, and the substrate into an electric charge, and detects it as a current change. The semiconductor chip has an ion sensing region composed of at least a part of the surface of the insulator layer, and the ion sensing region has an affinity for an ionic substance in the specimen. The present invention relates to an ion sensor that is a region having the same.

  As the “substrate”, there are glass, plastic, and the like. In this specification, the “substrate” will be described mainly using a semiconductor substrate.

  In the ion sensor of the present invention, the ion sensing region is preferably surface-treated with at least a hydrophilic group or a compound having a hydrophilic group.

  In the ion sensor of the present invention, the ion sensing region is surface-treated with an organosilane molecule having a hydrophilic group at least at one end and a linear hydrocarbon group having 3 to 20 carbon atoms. It is preferable.

  In the ion sensor of the present invention, the hydrophilic group preferably includes at least one of a hydroxyl group, an amino group, and a carboxyl group.

  In the ion sensor of the present invention, it is preferable that a region adjacent to the ion sensing region is surface-treated with a compound having a hydrophobic group in a region other than the ion sensing region on the surface of the insulator layer.

  In the ion sensor of the present invention, the compound having a hydrophobic group is an organic silane molecule having a linear alkyl group having 8 to 20 carbon atoms or an organic silane having a fluorinated linear alkyl group having 8 to 20 carbon atoms. It is preferably a molecule.

  In the ion sensor of the present invention, it is preferable that a region adjacent to the ion sensing region is subjected to a hydrophilic treatment in a region other than the ion sensing region on the surface of the insulator layer.

  In the ion sensor of the present invention, it is preferable that the surface of the insulator layer has an uneven structure at least partially.

  In ion sensors using semiconductor devices, it is possible to contribute to high sensitivity and expansion of applications.

  Embodiments of the present invention will be described with reference to the drawings. In the following drawings, the same or corresponding parts are denoted by the same reference numerals, and description thereof will not be repeated. In addition, dimensional relationships such as length, size, and width in the drawings are changed as appropriate for clarity and simplification of the drawings, and do not represent actual dimensions.

[First Embodiment]
FIG. 1 is a schematic diagram showing a configuration of an embodiment of an ion sensor of the present invention. FIG. 2 is a schematic diagram for illustrating the operation of the ion sensor of the present invention. FIG. 3 is a diagram for illustrating an operation at the time of measurement by the ion sensor of the present invention. FIG. 4 is a schematic diagram in which an ion sensing area in the ion sensor of the present invention is enlarged. Hereinafter, description will be given with reference to FIGS.

  First, it demonstrates based on FIG. The ion sensor of the present invention includes a semiconductor chip 20 and a detection unit 10. The semiconductor chip 20 includes a semiconductor substrate 11 and an insulator layer formed on the semiconductor substrate 11. In the present embodiment, the silicon oxide film 17 and the ion sensing unit 14 are substantially an insulator layer. Then, the detection unit 10 can convert a change in electrical potential energy at the interface between the semiconductor substrate 11 and the insulator layer into a charge and detect it as a current change.

  In the present embodiment, the semiconductor substrate 11 is p-type, and n-type diffusion layers 12 and 13 are formed on the surface of the semiconductor substrate 11. The n-type diffusion layer 12 has a drain electrode, and the n-type diffusion layer 13 has a source electrode. Further, a silicon oxide film 17 is formed on the surface of the semiconductor substrate 11 where the n-type diffusion layers 12 and 13 are not formed, and the ion sensing unit 14 formed of, for example, a silicon nitride film on the silicon oxide film 17. Gate metal electrode metals 15 and 16 are formed. Note that n-type, p-type, and the like can be selected as appropriate.

  The surface of the ion sensing unit 14 has an ion sensing region (not shown in FIG. 1), which is a region having an affinity for an ionic substance in a specimen to be measured by the ion sensor. In addition, the area | region which has affinity with an ionic substance shall mean an area | region where the contact angle with water is 90 degrees or less compared with the area | regions other than the ion sensing area | region in an ion sensing part. An ionic substance is an ionized substance, and the ionic substance is often dispersed and dissolved in water (including water vapor), and affinity with water is important.

  If the ion sensing part 14 having the ion sensing region formed on the surface thereof is an insulator, it does not cause a problem in operation, but is preferably resistant to strong acid and strong alkali reagents. The ion sensing unit 14 is preferably made of silicon nitride or tantalum pentoxide. This is because it is known to show good pH responsiveness.

  Further, in the present embodiment, the ion sensing unit 14 is formed on the silicon oxide film 17, but there is no particular problem as long as an insulating material is disposed at the position of the silicon oxide film 17. , Can lead to a similar operation.

  In this embodiment, the insulator layer includes the silicon oxide film 17 and the ion sensing unit 14. However, as long as the ion sensing region can be formed on the outermost surface of the insulator layer on the silicon substrate 11. There is no particular limitation. Further, the area of the ion sensing region can be selected as appropriate.

Next, the operation of the ion sensor of the present invention will be described based on FIG. 1 and FIG.
The ion sensor of this embodiment can measure the trend of ionic substances in the liquid specimen 24. Therefore, although not shown in FIG. 1, a member that covers the ion sensing unit 14 is installed, and a flow path for allowing the ion sensing unit 14 and the specimen 24 to efficiently contact the inside of the member. It may be formed.

Further, for example, when the H ⁺ ions 25 in the specimen 24 come into contact with the surface of the ion sensing unit 14, the electrical potential energy 21 of the surface of the semiconductor substrate 11 changes via the insulator layer. In other words, this is a change in the electrical potential energy 21 at the interface between the insulator layer and the semiconductor substrate 11.

  This change in potential energy 21 is detected and analyzed by the detection unit 10. Specifically, for example, means for inputting the change value of the potential energy into the detection unit 10 and the change of the potential energy are converted into charges, and the charges are transferred to the floating diffusion region which has been reset in advance a plurality of times. There can be mentioned a configuration provided with means capable of charge transfer and means for inputting a change in potential of the floating diffusion region into the gate or base of the transistor and converting it into a change in current of the transistor. However, as long as the change of the potential energy 21 can be quantified, a known technique can be appropriately selected as the structure and function of the detection unit 10. As shown in FIG. 2, the semiconductor substrate 11 and the reference electrode 16 may be connected.

  FIG. 3 shows a specific mode of measurement of the ion sensor. The specimen 24 is placed by dropping at a predetermined location in the ion sensing unit 27 formed on the silicon substrate 30, and the reference electrode 26 is in contact with the specimen 24. In addition, an appropriately set voltage is applied to the gate metal electrodes 28 and 29.

  Next, a description will be given based on FIG. When a part of the ion sensing part of the ion sensor in the present embodiment is enlarged, the ion sensing region 1 and the hydrophobic molecular film 2 are formed. In this embodiment, the ion sensing area | region 1 is an area | region where the outermost surface of an ion sensing part (insulator layer) is surface-treated with a hydroxyl group. The hydrophobic molecular film 2 is a molecular film formed by surface treatment with a compound having a hydrophobic group.

The ion sensing region 1 in the ion sensing unit 14 of the present invention is preferably formed by surface treatment with at least a hydrophilic group or a compound having a hydrophilic group. As described above, the ion sensing region 1 is a region having an affinity for an ionic substance in a specimen. The ion-sensitive semiconductor sensing sensor of the present invention detects changes in electrical potential energy between the insulator layer and the semiconductor substrate 1, so that H ⁺ ions move on the surface of the semiconductor substrate 1 and the like. As a result, the electric potential energy fluctuates.

  In the present invention, the compound having a hydrophilic group is not particularly limited as long as the region surface-treated with the compound is hydrophilized. And the area | region hydrophilized in this invention shall show the area | region whose contact angle is 0-90 degree | times, More preferably, it is 0-30 degree | times. In the present invention, the hydroxyl group may be directly bonded to the ion sensing region 1 by bonding.

  The compound having a hydrophilic group is specifically a straight-chain hydrocarbon having 3 to 20 carbon atoms and having the hydrophilic group at least at one terminal on the side not bonded to the ion sensing region 1. Mention may be made of organosilane molecules having groups. If the number of carbon atoms is less than 3, the molecular modification density may be sparse. If the number of carbon atoms exceeds 20, the orientation and close-packed arrangement may be difficult due to steric hindrance of the molecules. Specifically, the hydrophilic group preferably contains at least one of a hydroxyl group, an amino group and a carboxyl group. This is because the presence of the hydrophilic group contributes to hydrophilicity.

  In addition, the compound having a hydrophilic group and the ion sensing region may be joined by either a chemical bond or a physical bond. Examples of the chemical bond include a covalent bond and an ionic bond. Examples include hydrophobic interaction and electrostatic adsorption.

  More specifically, the ion sensing region 1 is preferably covered with a molecular film made of an organosilane molecule having a hydrophilic group. The thickness of the molecular film is not particularly limited, but is preferably 5 to 30 mm. This is from the viewpoint of molecular orientation. Although the form of a molecular film is not specifically limited, For example, it can be set as a monomolecular film. In the case of a monomolecular film, the molecule forming the molecular film may be one kind or a mixture of two or more kinds.

  The length of the organic molecules forming the molecular film is preferably in the range of 0.5 nm to 3 nm. The length is derived from the molecular weight of the organic molecules forming the organic molecular film 7. The surface state of the molecular film can be confirmed with an electron microscope or the like.

  In a region other than the ion sensing region 1 on the surface of the insulator layer, at least a region adjacent to the ion sensing region 1 is surface-treated with a compound having a hydrophobic group. The compound having a hydrophobic group is not particularly limited as long as the region surface-treated with the compound is hydrophobized. In the present invention, the hydrophobized region refers to a region having a contact angle of 90 degrees and 180 degrees or less.

  The compound having a hydrophobic group is specifically an organic silane molecule having a linear alkyl group having 8 to 20 carbon atoms or an organic silane molecule having a fluorinated linear alkyl group having 8 to 20 carbon atoms. Can be mentioned. If the compound having a hydrophobic group has less than 8 carbon atoms, the hydrophobicity may not increase, and if it has more than 20, the alignment may be difficult due to steric hindrance of the molecule. . The compound having a hydrophobic group is a compound in which one end is bonded to the surface of the sensing unit 14 and the other end toward the outside is a hydrophobic group. The compound having a hydrophobic group and the ion sensing unit 14 may be bonded by either chemical bond or physical bond. Examples of the chemical bond include covalent bond and ionic bond. Examples include interaction and electrostatic adsorption.

  In this embodiment, it is preferable that the film is covered with a molecular film composed of organosilane molecules having a linear alkyl group. The thickness of the molecular film is not particularly limited, but is preferably 5 to 30 mm. This is because the molecular density is high and it can be chemically modified. Although the form of a molecular film is not specifically limited, For example, it can be set as a monomolecular film. In the case of a monomolecular film, the molecule forming the molecular film may be one kind or a mixture of two or more kinds.

  The length of the organic molecules forming the molecular film is preferably in the range of 5 to 30 mm. The length is derived from the molecular weight of the organic molecules forming the organic molecular film 7. The surface state of the molecular film can be confirmed with an electron microscope or the like.

  According to this embodiment, since the molecular film is very thin, the surface form of the semiconductor chip can be maintained after the molecular film is formed, and the characteristics of the surface form itself can be utilized to the maximum.

  Examples of the surface treatment method include film formation in liquid in an organic solvent or chemical vapor deposition in which an organic silane agent is heated to form a film on a semiconductor chip.

The ion sensor of the present invention can be applied to uses such as food management, oral cavity monitoring, plant management, environmental measurement, soil management, and observation of cell ion access. It is also possible to produce a sensor configured by arraying semiconductor chips. In addition to H ⁺ ions, it is also possible to examine trends in Ca ions, Mg ions, etc. in the specimen.

[Second Embodiment]
FIG. 5 is a schematic diagram in which an ion sensing area in the ion sensor in the present embodiment is enlarged. Hereinafter, a description will be given based on FIG.

  In this embodiment, the configuration and members such as the semiconductor substrate and the insulator layer can be the same as those in the first embodiment, but only the surface treatment in the ion sensing unit 14 is different from that in the first embodiment. In the present embodiment, specifically, the ion sensing region 3 is surface-treated with a compound having an amino group at the terminal, and regions other than the ion sensing region 3 in the ion sensing unit 14 are covered with the hydrophobic molecular film 2. It is hydrophobized.

  According to this embodiment, there exists an advantage which is easy to perform pH monitoring of a biomolecule, for example.

Examples of the surface treatment method include the above-described methods.
[Third Embodiment]
FIG. 6 is a schematic diagram in which an ion sensing region in the ion sensor according to the present embodiment is enlarged. Hereinafter, a description will be given with reference to FIG.

  In the present embodiment, the configuration and members such as the semiconductor substrate and the insulator layer can be the same as those in the first embodiment, but only the surface treatment in the ion sensing unit 14 is different from the first embodiment. In the present embodiment, specifically, the ion sensing region 5 is surface-modified with a compound having an amino group at the terminal, and regions other than the ion sensing region 3 in the ion sensing unit 14 are subjected to hydrophilic treatment, It is a hydrophilic region 4. Specifically, an OH group is bonded.

  According to the present embodiment, for example, non-specific adsorption of a biomolecule with a hydrophobized region such as a protein is prevented, and there is an advantage that it is difficult to affect pH measurement.

Examples of the surface treatment method include the above-described methods.
[Fourth Embodiment]
FIG. 7 is a schematic diagram in which an ion sensing area in the ion sensor in the present embodiment is enlarged. This will be described below with reference to FIG.

  In the present embodiment, the configurations and members such as the semiconductor substrate and the insulator layer can be the same as those in the first embodiment. However, the surface shape of the ion sensing unit 14 has an uneven structure, and the region other than the ion sensing region 7 in the ion sensing unit 14 does not need to be surface-treated.

  Here, the concavo-convex structure is preferably a concavo-convex structure having an interval of 100 μm or less, preferably 50 nm to 50 μm, and a height of 100 μm or less, preferably 1 to 50 μm. In the present embodiment, the concavo-convex structure is provided in a region other than the ion sensing region 7 in the ion sensing unit 14 so that the region can be made hydrophobic. Further, by providing a concavo-convex structure on the surface of the ion sensing region 7, the hydrophilicity can be further enhanced.

  According to this embodiment, for example, there is an advantage that the hydrophobicity of the hydrophobized region can be stabilized and promoted, and disturbance factors other than the ion sensing unit can be reduced.

Examples of the surface treatment method include the above-described methods.
[Fifth Embodiment]
FIG. 8 is a schematic diagram in which an ion sensing area in the ion sensor according to the present embodiment is enlarged. Hereinafter, a description will be given based on FIG.

  In the present embodiment, the configurations and members such as the semiconductor substrate and the insulator layer can be the same as those in the first embodiment. However, the surface shape of the ion sensing unit has an uneven structure, and the region other than the ion sensing region 9 in the ion sensing unit 14 is covered with a hydrophobic molecular film by being surface-treated.

Examples of the surface treatment method include the above-described methods.
[Other Embodiments]
In addition to the above, a configuration may be employed in which a concavo-convex structure is provided only in the ion sensing region in the ion sensing unit, or a concavo-convex structure is provided only in a region other than the ion sensing region in the ion sensing unit. In addition, if the ion sensing region in the ion sensing unit and the adjacent surface treatment in other regions are different and the ion sensing region in the sample describes the ionic substance to be measured, The content is not limited.

  Further, the detection unit is not particularly limited, and can be appropriately selected and used.

  As described above, there is an advantage that the ion sensitivity of the ion sensing unit and the ion sensing of the specimen can be accurately performed.

  EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated in detail, this invention is not limited to these.

[Example 1]
An ion sensor was manufactured in which the ion sensing region on the surface of the insulator layer of the semiconductor chip was surface-treated with a compound having an amino group in order to have an affinity with an ionic substance in the specimen. In addition, the region adjacent to the ion sensing region was surface-treated with a compound having a hydrophobic group.

Hereinafter, a description will be given with reference to FIGS. 1 and 5.
First, a p-type silicon substrate 11 having n-type diffusion layers 12 and 13 shown in FIG. 1 was prepared, and a silicon oxide film 17 was formed on one surface thereof. Then, an ion sensing unit 14 including an ion sensing region made of a silicon nitride film was formed on the silicon oxide film 17. Further, gate metal electrodes 15 and 16 made of Al were formed so as to sandwich the ion sensing unit 14.

  The surfaces of the gate metal electrodes 15 and 16 and the ion sensing unit 14 were subjected to hydrophilic treatment by irradiating oxygen plasma. This is a process performed to ensure molecular modification.

Next, as shown in FIG. 5, a fluoroalkylsilane molecule (CF ₃ (CF ₂ ) ₇ (CH ₂ ) ₂ Si) having a hydrophobic group is formed on the surface of the chip on the side including the ion sensing unit 14 by a gas phase reaction. A hydrophobic molecular film 2 made of (OCH ₃ ) ₃ ) was formed.

  Next, the surface of the chip on which the hydrophobic molecular film 2 was formed was coated with an ultraviolet resist. Then, only the resist in the region corresponding to the ion sensing region 3 was provided with an opening. The hydrophobic molecular film 2 in the ion sensing region 3 was removed by irradiating oxygen plasma through the resist.

Next, aminosilane molecules (NH ₂ (CH ₂ ) ₃ Si (OCH ₂ CH ₃ ) ₃ having a hydrophilic group are formed by a solution reaction in which a semiconductor chip is immersed in aminosilane diluted in a toluene solution on the surface of the ion sensing region _3. The ion sensing region 3 covered with the molecular film formed in (1) was formed.

  The semiconductor chip in the present invention was formed by the above process. An ion sensor was completed by electrically connecting the semiconductor chip to a detection unit that converts a change in potential energy at the interface between the semiconductor substrate and the insulator layer into a charge and detects the change as a current.

  Using the ion sensor according to this example, the pH of a predetermined solution was measured. As the solution for measuring pH, pH buffer solutions of pH 4, 7, and 9 were used. First, a pH 7 pH buffer solution as the specimen 24 was dropped on the semiconductor chip as shown in FIG. Then, the reference electrode 26 was disposed so as to be in contact with the specimen 24. Then, the specimen 24 was sequentially changed from pH 7 buffer solution to pH 4 → pH 7 → pH 9 → pH 7, and voltage fluctuation and drift characteristics at that time were confirmed.

  FIG. 9 is a diagram illustrating voltage fluctuations in the ion sensor according to the present embodiment. As shown in FIG. 9, no voltage fluctuation was observed at the same pH. In addition, (DELTA) V = 8.5V in a figure shows the fluctuation value of pH7-> 4, and (DELTA) V = 7.0V shows the fluctuation value of pH7-> 9.

  In addition, in the ion sensor having the same configuration except that the semiconductor chip on which the ion sensing region 3 and the hydrophobic molecular film 2 are not formed is provided, the measurement using pH buffer solutions of pH 4, 7, and 9 is similarly performed. I did it. Also in this case, the same result as the ion sensor in Example 1 was obtained. In pH measurement, the drain and source electrodes of the semiconductor chip were used as working electrodes. An Ag / AgCl electrode is used as the gate electrode.

  From the above, it was found that the semiconductor chip after molecular modification surface treatment showed good pH responsiveness.

[Example 2]
An ion sensor was manufactured in which the ion sensing region on the surface of the insulator layer of the semiconductor chip was surface-treated with an OH group in order to have affinity with the ionic substance in the specimen. In addition, the structure adjacent to the ion sensing region has an uneven structure.

  Hereinafter, a description will be given with reference to FIGS. 1 and 8. However, in the present example, as will be described later, the uneven structure is not formed in the ion sensing region 9 in FIG.

  First, a p-type silicon substrate 11 having n-type diffusion layers 12 and 13 shown in FIG. 1 was prepared, and a silicon oxide film 17 was formed on one surface thereof. Then, an ion sensing unit 14 including an ion sensing region made of tantalum pentoxide was formed on the silicon oxide film 17. Further, gate metal electrodes 15 and 16 made of Al were formed so as to sandwich the ion sensing unit 14.

  Next, a region corresponding to the ion sensing region 9 in the ion sensing unit 14 is protected with a metal mask, and lithography and reactive ion etching are performed on the region adjacent to the ion sensing region 7 to form a concavo-convex structure with a height of 3 μm at intervals of 6 μm. Formed.

  Next, the metal mask was peeled off, and the surfaces of the gate metal electrodes 15 and 16 and the ion sensing unit 14 were subjected to a hydrophilic treatment by irradiating oxygen plasma.

Next, as shown in FIG. 8, a fluoroalkylsilane molecule (CF ₃ (CF ₂ ) ₇ (CH ₂ ) ₂ Si) having a hydrophobic group is formed on the surface of the chip having the ion sensing unit 14 by a gas phase reaction. A hydrophobic molecular film 6 made of (OCH ₃ ) ₃ ) was formed.

  Next, the surface of the chip on which the hydrophobic molecular film 2 was formed was coated with an ultraviolet resist. Then, only the resist in the region corresponding to the ion sensing region 3 was provided with an opening. The hydrophobic molecular film 6 in the ion sensing region 9 was removed by irradiating oxygen plasma through the resist. Further, the surface of the ion sensing region 9 was surface-treated with OH groups by irradiating oxygen plasma.

  The semiconductor chip was formed by the above process. An ion sensor was completed by electrically connecting the semiconductor chip to a detection unit that converts a change in potential energy at the interface between the semiconductor substrate and the insulator layer into a charge and detects the change as a current.

  Using the ion sensor according to this example, the same pH measurement as in Example 1 was performed with pH buffer solutions of pH 4, 7, and 9. As a result, as in Example 1, no voltage fluctuation was observed at the same pH. As a result, the ion sensing region 9 is surface-treated with OH groups, the effect of inducing the ionic substance in the specimen, the uneven structure other than the ion sensing region 9 in the ion sensing part, and the superposition due to the hydrophobic molecular film 6 It was found that the water repellent structure has an effect of suppressing induction (adsorption) of ionic substances in the specimen.

  Further, after the measurement using the pH buffer, the protein-containing solution was dropped on the chip as shown in FIG. 3 and left for 30 minutes. And after rinsing the place where this solution was dripped with pH buffer solution, pH measurement was again performed with the same buffer solution. As a result, no change in pH was observed. If impurities adhere to the surface on which the protein-containing solution is dropped, the surface potential changes, and thus erroneous recognition occurs as if the pH has changed. However, in the ion sensor of the present example, since no pH fluctuation was observed, it was shown that no protein was attached to a region other than the ion sensing region 9. FIG. 10 is a diagram showing that the above pH fluctuation was not observed.

  Furthermore, after the same experiment was performed using a solution containing a fluorescently labeled protein, the surface was observed with a fluorescence microscope. As a result, protein-derived fluorescence was not confirmed in the ion sensing unit 14.

[Example 3]
An ion sensor was manufactured in which the ion sensing region on the surface of the insulator layer of the semiconductor chip was surface-treated with a compound having an amino group in order to have an affinity with an ionic substance in the specimen. Moreover, in the present Example, the area | region adjacent to an ion sensing area | region was surface-treated with OH group.

Hereinafter, a description will be given with reference to FIGS. 1 and 6.
First, a p-type silicon substrate 11 having n-type diffusion layers 12 and 13 shown in FIG. 1 was prepared, and a silicon oxide film 17 was formed on one surface thereof. Then, an ion sensing unit 14 including an ion sensing region made of tantalum pentoxide was formed on the silicon oxide film 17. Further, gate metal electrodes 15 and 16 made of Al were formed so as to sandwich the ion sensing unit 14.

Then, a region other than the ion sensing region 5 on the surface of the semiconductor chip where the ion sensing unit 14 is formed was coated with a resist. Then, the solution reaction of immersing the semiconductor chips aminosilane diluted in toluene solution to the surface of the ion sensing region 5, aminosilane molecule having a hydrophilic group _{(NH 2 (CH 2) 3} Si (OCH 2 CH 3) 3) The ion sensing region 3 covered with the molecular film formed in (1) was formed.

  Next, the surface of the region adjacent to the ion sensing region 5 was modified with OH groups by coating only the ion sensing region 5 with a resist and irradiating the semiconductor chip with oxygen plasma.

  The semiconductor chip was formed by the above process. An ion sensor was completed by electrically connecting the semiconductor chip to a detection unit that converts a change in potential energy at the interface between the semiconductor substrate and the insulator layer into a charge and detects the change as a current.

  In the ion sensor in Example 3, the pH measurement using the pH buffer solution and the pH measurement using the pH buffer solution after leaving the protein-containing solution on the surface of the semiconductor chip are the same as those in Example 1 and Example 2. Similar results were shown.

  Moreover, in the ion sensor in a present Example, the cell suspension containing a plant cell (epidermal cell) was dripped at the ion sensing part 14, and it was tried whether it could apply to cell activity measurement.

  Since the cells easily adhere to the amino group surface, it was expected that the cells adsorb only to the ion sensing region 5 described above. Actually, the cell turbid solution is dropped onto the surface of the semiconductor chip, and then the surface is washed with physiological saline. When the surface is observed with an optical microscope, the cells are selectively present only in the ion sensing region 5. Adsorption was confirmed. FIG. 12 is a diagram showing a state observed with an optical microscope in Example 3. FIG. It is considered that cell adsorption is unlikely to occur because regions other than the ion sensing region 5 in the ion sensing unit 14 are surface-treated with OH groups.

  In addition, as shown in FIG. 11, regarding the potential response, a change in threshold voltage (ΔV = 3 V) was observed before and after cell adsorption, so that the presence of adsorbate on the surface could be confirmed even by observation other than by microscopic observation.

  It should be understood that the embodiments and examples disclosed herein are illustrative and non-restrictive in every respect. The scope of the present invention is defined by the terms of the claims, rather than the description above, and is intended to include any modifications within the scope and meaning equivalent to the terms of the claims.

It is a typical figure showing composition of one embodiment of an ion sensor of the present invention. It is a typical figure for showing operation of an ion sensor of the present invention. It is a figure for showing operation at the time of measurement by the ion sensor of the present invention. It is the schematic diagram which expanded the ion sensing area | region in the ion sensor of this invention. It is the typical figure which expanded the ion sensing area | region in the ion sensor in 2nd Embodiment in this invention. It is the schematic diagram which expanded the ion sensing area | region in the ion sensor in 3rd Embodiment in this invention. It is the schematic diagram which expanded the ion sensing area | region in the ion sensor in 4th Embodiment in this invention. It is the schematic diagram which expanded the ion sensing area | region in the ion sensor in 5th Embodiment in this invention. It is a figure which shows the voltage fluctuation in the ion sensor in Example 1. FIG. It is a figure which shows that pH fluctuation was not recognized in Example 2. It is a figure which shows the change of the threshold voltage before and behind adsorption | suction of a cell in Example 3. FIG. It is the figure which showed a mode that it observed with the optical microscope in Example 3. FIG.

Explanation of symbols

1, 3, 5, 7, 9 Ion sensing region, 2, 6 Hydrophobic molecular film, 4 Hydrophilization region, 10 Detection unit, 11 Semiconductor substrate, 12, 13 Diffusion layer, 14, 27 Ion sensing unit, 15, 16, 28, 29 Gate metal electrode, 17 Silicon oxide film, 20 Semiconductor chip, 21 Potential energy, 24 specimen, 25 H ⁺ ion, 26 Reference electrode, 30 Silicon substrate.

Claims (8)

A semiconductor chip having a substrate and an insulator layer formed on the substrate;
A detection unit that converts a change in electrical potential energy at the interface between the substrate and the insulator layer into a charge and detects the change as a current;
An ion sensor comprising:
The semiconductor chip has an ion sensing region composed of at least a part of the surface of the insulator layer,
The ion sensing region is a region having affinity with an ionic substance in a specimen.
Ion sensor.   The ion sensor according to claim 1, wherein the ion sensing region is surface-treated with at least a hydrophilic group or a compound having a hydrophilic group.   The ion sensor according to claim 1, wherein the ion sensing region is surface-treated with an organosilane molecule having a hydrophilic group at least at one end and a linear hydrocarbon group having 3 to 20 carbon atoms. .   The ion sensor according to claim 2, wherein the hydrophilic group includes at least one of a hydroxyl group, an amino group, and a carboxyl group.   The ion according to any one of claims 1 to 4, wherein a region adjacent to the ion sensing region is surface-treated with a compound having a hydrophobic group in a region other than the ion sensing region on the surface of the insulator layer. Sensor. The compound having a hydrophobic group is
The ion sensor according to claim 5, which is an organic silane molecule having a linear alkyl group having 8 to 20 carbon atoms or an organic silane molecule having a fluorinated linear alkyl group having 8 to 20 carbon atoms.   The ion sensor according to any one of claims 1 to 4, wherein a region adjacent to the ion sensing region in a region other than the ion sensing region on the surface of the insulator layer is subjected to a hydrophilic treatment.   The ion sensor according to claim 1, wherein a surface of the insulator layer has an uneven structure at least partially.