JP2005337755A - MULTI-pH SENSOR AND ITS MANUFACTURING METHOD - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a multi-pH sensor and its manufacturing method capable of three-dimensionally grasping a distribution state of pH of a sample, and measuring the distribution state of pH in a minute area with high measuring accuracy and superior response. <P>SOLUTION: In a multi probe-type sensor having a plurality of projections (probe) 2 formed by crystal growth on a semiconductor substrate 1 as a base, an amino group is fixed to surfaces of the probes 2 to have a function sensing hydrogen ion concentration (pH) in the sample. This multi-pH sensor is constituted by arranging the probes 2 of various heights. At least one or more amplification circuits or/and signal processing circuits 3 are formed on the semiconductor substrate 1. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a multi-pH sensor capable of three-dimensional measurement of a hydrogen ion concentration (pH) of a sample and a manufacturing method thereof.

    Conventionally, many measurement methods using a glass electrode have been used to measure the pH of a sample. On the other hand, in recent years, in various manufacturing processes such as the environment and semiconductors and chemical products, there is an increasing demand for grasping the distribution state of pH in a sample together with various physical or chemical phenomena such as concentration, temperature, magnetism and pressure. ing.

In response to such a demand, a method of measuring by arranging a plurality of glass electrodes is generally used (see, for example, Patent Document 1). Recently, detection means using an ion-sensitive field effect transistor (ISFET) is used. It is useful as various analysis / analysis samples by imaging the pH distribution state in the solution. Specifically, as illustrated in FIG. 4, a sensor array 23 in which a plurality of ISFETs 24 are arranged and a signal processing unit 25 including an analog multiplexer and an amplifier system are formed on one semiconductor substrate 22. A linear ISFET array chip 21 has been proposed (see, for example, Patent Document 2).
Japanese Patent Laid-Open No. 06-148124 Japanese Patent Laid-Open No. 2002-286691

  Today's pH measurement requires not only conventional planar measurement but also three-dimensional measurement information, and there is a strong demand for a method for obtaining three-dimensional information simultaneously as a measurement means. It was. In addition, three-dimensional information on minute parts is indispensable for grasping physical or chemical phenomena, and such requests are becoming stronger especially when information on materials or the inside of cells is to be obtained. Yes.

  However, it has been difficult to measure directly with the conventional method. That is, in the ion electrode method, even if the size of the electrode is small, it is on the order of mm, and there is a limit to the arrangement of the electrodes, and it is difficult to measure the pH of a micro area on the order of μm. In addition, ISFETs that can be used as a means for measuring the pH of a minute region can only be arranged two-dimensionally on a silicon wafer even if they are arrayed, and cannot cope with three-dimensional pH measurement. .

  Accordingly, an object of the present invention is to provide a multi-pH sensor capable of three-dimensionally grasping the pH distribution state of a sample and a method for manufacturing the same, and to measure the pH distribution state in a minute region with high measurement accuracy and An object of the present invention is to provide a multi-pH sensor that can be measured with excellent responsiveness and a method for manufacturing the same.

  As a result of intensive studies, the present inventors have found that the above object can be achieved by a multi-pH sensor and a manufacturing method thereof shown below, and have completed the present invention.

  That is, the present invention is a multi-probe type sensor having a plurality of protrusions (probes) crystal-grown with a semiconductor substrate as a base, wherein an amino group is fixed on the surface of the probe, and the hydrogen ion concentration (pH) in the sample It is characterized by having a function sensitive to.

  A probe produced by using a method for growing a crystal having a fine structure such as a VLS method described later makes it possible to produce a very fine probe, which has been difficult in the past, and provides a physical property of a fine region. It has become possible to obtain 2D or 3D information of phenomena or chemical phenomena. In other words, the present invention makes it possible to grasp the pH distribution state in a sample two-dimensionally or three-dimensionally by immobilizing an amino group having a very high sensitivity to pH on the surface of the probe by utilizing such characteristics of the probe. It has been found that this can be easily performed. In addition, the present invention adds a pH detection function to a very miniaturized portion of a plurality of probes, particularly the probe tip, which is effective for measurement of a fine region, and the tip of each probe is limited to a specific point. It is possible to easily detect at a specific point without affecting other points. Therefore, it is possible to provide a multi-pH sensor capable of measuring the pH distribution state in a minute region with high measurement accuracy and excellent responsiveness.

  Further, the present invention is the multi-sensor, wherein probes having different heights are arranged.

  In order to grasp the distribution state of the pH in the sample three-dimensionally, it is preferable that information from pH detection ends arranged three-dimensionally can be obtained simultaneously and rapidly. According to the multi-probe according to the present invention in which the tip portions of a plurality of probes are arranged in a three-dimensional space, such a condition can be satisfied, and highly accurate three-dimensional information on the pH distribution state in the sample can be obtained. It can be easily obtained.

  3. The multi-pH sensor according to claim 1, wherein the multi-sensor includes at least one amplification circuit and / or signal processing circuit formed on the semiconductor substrate.

  As described above, in the multi-probe according to the present invention, the function may be concentrated in a very minimized part called the probe tip, so that the signal amount from the tip becomes very small. Therefore, when using the output from the multi-probe, it is preferable to adopt a configuration in which such an influence from the outside (hereinafter referred to as “disturbance”) is not affected as much as possible. In the present invention, at least one amplification circuit or / and signal processing circuit is formed on a semiconductor substrate, thereby converting a minute output from each probe into a pre-stabilized signal and transmitting the signal. -By outputting, it is possible to obtain highly accurate and stable output with little influence of disturbance.

The present invention is a method of manufacturing a multi-probe type sensor,
(1) Growing a plurality of protrusions (probes) on a semiconductor substrate as a base,
(2) A substrate is attached to the surface of the probe.
(3) fixing a substance having a thiol group to the substrate;
(4) immobilizing a substance having an amino group on the substance having a thiol group;
It is characterized by having each process.

  In order to detect a physical phenomenon or chemical phenomenon in a fine region, a probe having a very fine structure is required. As will be described later, a method for growing a crystal having a fine structure such as a VLS method has been developed, and the probe thus produced has a two-dimensional or three-dimensional physical or chemical phenomenon in a fine region, which has been difficult in the past. Detection was possible. On the other hand, conventionally, the detection end sensitive to pH with high sensitivity has been limited to very special conditions such as glass electrodes and ISFETs. As a result of studying how firmly the above-described probe material and amino group having a very high sensitivity to pH can be fixed, the present inventor found that the method of producing through the above-described process is very excellent. It is also advantageous in that a process linked to a manufacturing process such as the VLS method can be configured. In addition, it is easy to form a probe having an arbitrary height, and a multi-pH sensor in which a pH detection end is arranged at an optimum position can be manufactured.

  As described above, by using the multi-pH sensor according to the present invention, it is possible to easily perform three-dimensional measurement of pH in a minute region with high simultaneity and continuity, which has been difficult in the past. In addition, the multi-pH sensor manufacturing method according to the present invention forms a highly sensitive pH detection end firmly fixed to a probe made of a crystal having a fine structure, and has high measurement accuracy and excellent responsiveness. 3D measurement is possible. Therefore, it is particularly useful in a field where three-dimensional information such as a solution or a living body is required.

Hereinafter, embodiments of the present invention will be described with reference to the drawings.
FIG. 1 illustrates a basic configuration of a multi-pH sensor according to the present invention.

  In FIG. 1, a probe 2 made up of a large number of needle-like protrusions having different heights is formed on a semiconductor substrate (silicon substrate) 1. At this time, the formed probe 2 can have a high sensitivity function with respect to the pH of the sample by performing the following predetermined treatment on the surface thereof. Examples of the target sample include aqueous solutions, various ionic solutions (including organic substances), biological samples such as cell tissues, and gel-like substances.

  The predetermined treatment on the surface of the probe 2 refers to forming a pH sensitive film by a process to be described later. Specifically, it binds to Si—Au generated on the surface of the probe 2 during the crystal growth process using silicon as a substrate. It is formed by immobilizing a substance having an amino group A via a substance having a high property Au and a substance having a thiol group S thereon. Such a configuration makes it possible to obtain a very high pH sensitivity by being fixed very firmly and by a thin thin film.

  Here, the probe 2 can have not only the tip portion 4 having a pH detection function but also the side surface portion 5 of the probe 2 having a similar function or a different function. In addition, the shape of the probe 2 can be selected from any shape suitable for the purpose, such as a cylindrical shape or a tapered shape in which the outer diameter of the tip portion is small. Regarding the method for producing the probe 2, not only the VLS method described later, but also other liquid phase epitaxy methods and low-level probes are used to grow a crystal having a fine structure by using a vapor phase epitaxy method or the like. It is possible to apply the method.

  Further, by covering the portion other than the tip portion or side surface portion of the probe 2 having a specific function with an insulator or a protective film, the probe 2 is prevented from being contaminated or deteriorated, or from the influence of disturbance. It can be performed.

  In addition, various circuits can be formed on the semiconductor substrate 1, but when used as a multi-pH sensor, it is preferable to form at least one amplifier circuit and / or signal processing circuit. By converting a minute output from each probe into a pre-stabilized signal and transmitting / outputting it, an output with high accuracy and stability with little influence of disturbance can be obtained. In particular, the formation of an impedance conversion circuit using an amplifier circuit (op-amp) is a condition in which various disturbances are likely to occur because the object has a variable element of charge, such as solution measurement and intracellular measurement. It is very effective. In addition, the formation of the signal processing circuit can increase not only the stable output but also the independence of the multi-sensor, and the versatility of the configuration of the measuring apparatus such as wireless transmission.

  FIG. 2 illustrates the overall configuration of such a multi-pH sensor. In the probe 2, a predetermined voltage is applied from the power supply unit V to the distal end portion (pH detection end) 4 (may be applied to the side surface portion 5 in some cases), and the potential change of each distal end portion 4 at that time Can be taken out by the detection means D as a change in the current value, and the change in the pH of the object can be grasped.

  FIG. 3 illustrates a manufacturing process of a microprobe constituting a multi-pH sensor. Here, a process of forming a microprobe on a substrate on which a semiconductor circuit is already formed will be described. However, various processes can be selected, such as when a semiconductor circuit is formed after forming a microprobe first. FIG. 3 shows a case where a probe is formed on the drain 6 made of n + (high concentration diffusion layer).

(A) A signal processing circuit is formed on a p-type silicon substrate 1 and is further covered with an oxide film (SiO ₂ ) 7. In this step, steps such as formation of a protective film used for normal circuit formation are omitted, but it goes without saying that various steps can be added and the order can be changed as necessary.

(B) By performing an etching process, an opening 8 reaching the silicon substrate 1 is formed at the center position of the SiO ₂ film 7 and the drain 6. The size of the opening 7 needs to be larger than the thickness of the probe 2 to be formed. However, by setting the size of the probe 2 to about 1.1 to 50 times the cross-sectional area of the probe 2, a suitable positional accuracy of the probe 2 is ensured. can do.

  (C) Further, an Au thin film 9 is formed on the opening surface of the drain 6 of the silicon substrate 1. The thickness of the Au thin film 9 formed here needs to be changed depending on the film forming temperature and the thickness of the probe 2 to be grown. For example, the film forming temperature of the Au thin film 9 is 700 ° C. and the probe 2 having a diameter of several μm is used. When forming, it is appropriate that the thickness of the Au thin film 9 is 10 to 100 nm. The Au thin film 9 can be formed after a resist film is formed on the entire silicon substrate 1 and then removed together with the resist film by a lift-off method, leaving only the Au thin film 9 formed on the opening surface of the drain 6. is there.

(D) Silicon is epitaxially grown on the Au thin film 9 portion of the drain 6 by the VLS growth method. That is, the silicon substrate 1 is heated to a temperature higher than the eutectic point of the Au—Si alloy in an atmosphere of a gas containing silicon such as SiH ₄ or Si ₂ H ₆ . Thereby, first, a droplet made of a mixed solution of Au and n + silicon forming the drain 6 is generated in the central portion of the Au thin film 9. Next, silicon atoms generated by the thermal decomposition of the gas are taken into the droplet, and the silicon concentration in the droplet becomes excessive. This excess silicon is epitaxially grown from the surface of the drain 6. As a result, a protrusion made of single crystal silicon is obtained. At this time, a hemispherical alloy portion 10 made of an Au—Si alloy is formed at the tip of the protrusion by solidification of the droplet. Since this protrusion is grown from n + silicon forming the drain 6, it has higher conductivity than that directly grown from the silicon substrate 1. Therefore, this protrusion can be used as a conductive probe as it is. Further, subsequent impurity diffusion can also be used depending on the purpose.

  In the above-described embodiment, the protrusion used as the probe 2 is crystal-grown from the drain 6. However, the crystal may be grown from another part on the substrate. The base for crystal growth of the protrusions to be used as the probe 2 may be a high-concentration diffusion layer of an element constituting the signal processing circuit of the sensor if possible. In addition to the NMOSFET portion, the source or drain of PMOSFET or CMOSFET, Bi− Examples include CMOS or bipolar transistor emitters or collectors, diode n + layers or p + layers. It can also be formed in the gate circuit portion of the MOS transistor.

  Further, in the crystal growth, it is preferable to form the probe 2 by controlling the length of the protrusion at least one by one or at least for each probe having the same height. By performing such control, it becomes easy to form a probe having an arbitrary height, and a desired multi-probe can be produced.

  Next, a process for forming a pH sensitive film on the tip 4 of the probe 2 will be described.

  (1) An Au film is produced as a substrate on the tip 4 of the probe 2 by the same method as in FIG. As described above, since there is an alloy portion made of an Au—Si alloy at the tip of each projection of the multi-probe, Au, Pt, Ir, or the like can be easily fixed. In particular, for Au, it is possible to ensure a very strong bonding state with such an alloy.

  (2) A substance having a thiol group is fixed to the substrate. The thiol group plays the role of an intermediate binding material between the base Au and the pH-sensitive amino group, and can be firmly fixed to the tip 4 of the probe 2. Specific examples of the substance having a thiol group include tetramercaptobiphenyl and pentanethiol. The thickness of the substance is suitably 10 to 100 nm.

  (3) Immobilizing a substance having an amino group on the substance having a thiol group. The amino group is highly useful as a pH detection end because of its high pH-sensitive function and high selectivity, and has a strong binding force with a specific reactive group such as a thiol group, and has a surface shape like the probe 2. It is also useful in that it can be easily fixed. Specific examples of the substance having an amino group include various amino acids. At this time, the thickness of the material is suitably 10 to 100 nm.

  The pH detection end can be formed at the distal end portion 4 of the probe 2 by the processing as described above. In addition, by performing such a process on a plurality of probes having different heights, a multi-pH sensor having a high pH sensitivity and a multi-probe with very fine needles can be formed. Therefore, by using the multi-pH sensor according to the present invention, the pH distribution state in the sample can be easily obtained as three-dimensional information even in a minute region.

As described above, the present invention can be suitably used for three-dimensional distribution measurement of ion concentration of a sample such as a solution, and can also be applied to the following fields.
(1) Application field as chemical microscope; pH measurement / electrochemical field, gas distribution measurement field, two-dimensional dynamic observation and analysis of titration (2) Environmental measurement / environment; Application to bioremediation (3) Food Inspection / food, microorganisms (4) ME field / medicine / ecological tissue; tissue cell surface and internal pH measurement, DNA measurement (5) bio field (6) animal and plant field / plant; callus surface and internal potential distribution measurement / biology -Front view animals (7) Corrosion measurement field-Metal; Metal corrosion and painting-Coating (8) Surface analysis such as zeta potential-Zeta potential of powder and ceramics.

Explanatory drawing which shows the basic structure of the multi-pH sensor which concerns on this invention. Explanatory drawing which shows the whole structure of the multi-pH sensor which concerns on this invention. Explanatory drawing which shows the manufacturing process of the microprobe based on this invention. Explanatory drawing of the conventional multi-pH sensor.

Explanation of symbols

1 Semiconductor substrate (silicon substrate)
2 Probe 3 Signal processing circuit 4 Tip (pH detection end)
5 Sides

Claims (4)

  A multi-probe type sensor having a plurality of protrusions (probes) grown on a semiconductor substrate as a base, the amino group being fixed on the surface of the probe, and a function sensitive to the hydrogen ion concentration (pH) in the sample A multi-pH sensor characterized by that.   The multi-pH sensor according to claim 1, wherein the multi-pH sensors are formed by arranging probes having different heights.   3. The multi-pH sensor according to claim 1, wherein at least one amplification circuit and / or signal processing circuit is formed on the semiconductor substrate. A method of manufacturing a multi-probe type sensor,
(1) Growing a plurality of protrusions (probes) on a semiconductor substrate as a base,
(2) A substrate is attached to the surface of the probe.
(3) fixing a substance having a thiol group on the substrate;
(4) fixing a substance having an amino group on the substance having a thiol group;
A method for producing a multi-pH sensor, comprising: each process.

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