JPH01176934A - Ph sensor and glucose sensor - Google Patents

Abstract

PURPOSE:To simplify a manufacture process and to reduce cost on the whole by forming an n<+> layer and an electrode 4 in order on a glass substrate or plastic substrate coated with an amorphous silicon layer. CONSTITUTION:Then n<+> layer 3 and electrode 4 are formed in order on the glass substrate 1 or plastic substrate 1 coated with the amorphous silicon layer 2, and they are further coated with an amorphous silicon layer 2 to form an ISFET. The silicon layer 2 is used as a pH sensing layer and a hydroxy group is present in the surface of this amorphous silicon nitride, so surface charges vary with the hydrogen ion concentration in a solution and the interface potential also varies at the same time, so that the variation is measured by using a measuring instrument. Further, the substrate is constituted by using an inexpensive and nonbrittle glass plate or plastic sheet and an amorphous film is formed thereupon by using a plasma CVD device. Thus, the manufacture is facilitated and the cost is reduced.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a pH sensor and a glucose sensor. More specifically, the present invention relates to a pH sensor and a glucose sensor that can be easily and inexpensively produced.

[Conventional technology]

As a pH sensor using a field effect transistor (FET), an ion sensitive field effect transistor (ISFET) made of single crystal silicon has been known.

However, such 15FETs are expensive because they use single-crystal silicon substrates or SO8 substrates with a structure in which silicon single crystals are epitaxially formed on sapphire or spinel as element materials, and the manufacturing process is complicated and takes a long time. There are drawbacks.

Furthermore, since the 15FET must be cut by dicing after being manufactured using the above-mentioned substrate, even if the element itself can be miniaturized, there is a limit to the size of the finished product due to dicing.

Furthermore, since the substrate itself is fragile, there is also a problem in miniaturization from this point of view.

Further, one of the uses of a pH sensor using 15FET is a glucose sensor.

Conventionally, oxygen electrodes, hydrogen peroxide electrodes, pH electrodes, etc. have been used in the production of glucose sensors, and this is based on the fact that glucose detection utilizes the following enzymatic reaction.

GOD glucose + 02-11 → gluconic acid + H2O2, i.e.
Glucose undergoes the reaction described above due to the action of glucose oxidase (COD), but glucose is quantified by an indirect method of measuring O2, gluconic acid, and H2O2 among these.

Conventional glucose sensors are manufactured by attaching a membrane immobilized with glucose oxidase to the above electrode, but the electrodes used here are all old models, large in size, and time-consuming to manufacture. It also has the disadvantage of being expensive.

In order to improve these shortcomings, in recent years, lithography technology has been used to produce and use microgold electrodes that serve as oxygen electrodes and hydrogen peroxide electrodes, as well as field-effect transistors that serve as pH electrodes. There is. However, since both of these use silicon wafers as substrates, they are expensive, and the latter also requires a complicated manufacturing process.

Furthermore, although these microsensors are intended to be disposable, they still have the disadvantage of being too expensive due to the materials used to make them disposable.

[Problem to be solved by the invention]

In order to solve the above-mentioned problems encountered in pH sensors using 15FETs, the present inventor sequentially formed an aluminum electrode and an n+ layer on a glass substrate, and then deposited an amorphous silicon layer and an amorphous silicon nitride layer on the entire surface using plasma. By CVD method.

Furthermore, we previously proposed a pH sensor coated with silicon monoxide layers that were sequentially formed using a vacuum evaporation method (19
Collection of abstracts of the 54th Spring Annual Meeting of the Chemical Society of Japan in 1987 ■ No. 479
page).

In this pH sensor, when the pi characteristics are measured using a device that does not form a vacuum-deposited silicon oxide film,
A phenomenon of electrode dissolution was observed, and the desired pH characteristics could not be obtained. That is, in this case, the amorphous silicon layer through which the current flows is located below the amorphous silicon layer, which is considered to be the cause of the pinhole (leaf current).

Therefore, the inventor of the present invention formed an amorphous silicon layer and an amorphous silicon nitride layer on a glass substrate or a plastic substrate by plasma CVD method.
When creating ET and using it as a pH sensor,
- As a result of repeated studies in search of a device that does not require a vacuum-deposited silicon oxide film, we have created a structure in which an amorphous silicon layer is placed on an insulating substrate, so that no leakage current occurs and the electrodes do not melt. It has been found that this problem can be effectively solved by this method.

Further, the ion-sensitive field effect transistor configured in this manner can be used as a glucose sensor by immobilizing glucose oxidase on the uppermost layer thereof by a specific means.

[Means to solve the problem]

Accordingly, the present invention relates to a pH sensor, which consists of sequentially forming layers and electrodes on a glass or plastic substrate coated with an amorphous silicon layer, and further coated with an amorphous silicon nitride layer. Consists of a field effect transistor.

The present invention also relates to a glucose sensor using such an ion-sensitive field effect transistor, and the glucose sensor includes a photosensitive resin containing glucose oxidase on an amorphous silicon nitride layer. A cured film is formed.

One embodiment of the pH sensor according to the present invention is shown in a plan view (
a) and its sectional view taken along line I-1 (b).

Hereinafter, the present invention will be described in detail with reference to this drawing.

Generally, a glass plate is used as the glass substrate, and a polyester sheet, a Teflon sheet, etc. are used as the plastic substrate.While masking a part, for example, half of these insulating substrates 1 with a glass plate, SiH4
By applying a plasma CVD method using uzfi gas, an amorphous silicon layer 2 that partially covers the substrate is generally formed with a film thickness of about 100 to 4000 nm. The processing conditions at this time are a pressure of approximately 10 to 1000 m1.
00O, preferably about 80-120 mTorr, time about 5-60 minutes, preferably about 10-30 minutes, power about 0
．． 1-100w, preferably about 1-20w.

Next, a plasma CVD method using a mixed gas of PH4 (phosphine), SiH4 and H2 is applied to the entire surface of the substrate partially covered with an amorphous silicon layer,
n) Layer 3 is generally formed to a thickness of about 1000 to 4000 layers. The processing conditions at this time are a pressure of approximately 1 to 1000 m1.
00O, preferably about 10-150mTorr, time about 1-60 minutes, preferably about 5-20 minutes, power about 0.
1 to 100 seconds, preferably about 4 to 10 seconds, temperature about 250 degrees
-350°C, preferably about 280-320°C.

After that, aluminum vacuum evaporation method 5 sputtering method etc. is applied on the n+ layer to form a film with a thickness of about 1000 to 400 nm.
After forming 00 electrodes, etching together n''M.
By applying patterning.

The electrodes to become the source 4 and drain 5 are generally formed in the same shape as the n1 layer, together with these electrode lead-out portions 4' and 5'.

The substrate parts on the source and drain electrode sides are formed by applying plasma CVD to the electrode extraction part by applying a plasma CVD method there using a mixed gas of SiH4, NH, and H2 while masking the substrate on the electrode extraction part side with a glass plate or the like. An amorphous silicon nitride layer 6, typically about 1000 to 4000 thick, is deposited to form an ion-sensitive field effect transistor. The processing conditions at this time are a pressure of approximately 10 to 1
000m100O, preferably about 100-200ffI
Torr, time about 10-120 minutes, preferably about 30
~90 minutes, power approximately 0.1~100W, preferably approximately 1
~201i1.

The ion-sensitive field effect transistor constructed in this way can be used as a pH sensor as is, but
As shown in FIG. 4, a glucose sensor can be formed by forming a photocured film 7 of a photosensitive resin containing glucose oxidase on the amorphous silicon nitride wafer.

Photosensitive resins include polyvinyl alcohol, cyclized polyisoprene, and polyvinyl cinnamate.

Polymethyl methacrylate-based and polymethyl isopropyl ketone-based materials are used, but water-soluble polyvinyl alcohol-based materials are preferably used.

When a polyvinyl alcohol-based photosensitive resin is used, the glucose oxidase-containing photosensitive resin is prepared as an aqueous solution, for example, a photosensitive resin aqueous solution with a concentration of about 3 to 7% 1
Approximately 0.5 to 100 m of glucose oxidase per mQ
Prepared by adding g.

The prepared aqueous solution is spread onto the amorphous silicon nitride layer by, for example, mounting a field effect transistor on a spinner, dropping the solution onto the amorphous silicon nitride layer, and spinning the solution. Next, using a mask aligner, the water-soluble photosensitive resin is photocured by irradiating it with light at a wavelength that does not deactivate glucose oxidase, for example, 300nrn, for about 10 to 120 seconds, and the photocured film is coated with glucose oxidase. Make it fixed.

[Function] and [Effects of the Invention] The FET-type pi (sensor) of the present invention constructed in this manner uses an amorphous silicon nitride layer as a pH-sensitive layer, and since hydroxyl groups exist on the surface of this amorphous silicon nitride, Since the surface charge changes depending on the hydrogen ion concentration in the solution and the interfacial potential changes at the same time, this can be measured using a measuring device as shown in FIG.

Moreover, the pH sensor according to the present invention does not use an expensive silicon wafer as a substrate, but uses an inexpensive and non-brittle glass plate or plastic sheet as a substrate, and uses a plasma CVD device to form an amorphous (nitride) silicon film thereon. The manufacturing process is also easier than that of the conventional method because it only involves forming a , and therefore the overall cost can be effectively reduced.

In addition, regarding glucose sensors, whereas conventional types detect glucose using an enzymatic reaction, glucose concentration can be directly quantified as an output voltage with selectivity to other substances, which improves accuracy. You also get benefits.

〔Example〕

Next, the present invention will be explained with reference to examples.

Example 1 A glass plate (Corning 7059, manufactured by Dow Corning) that had been sequentially washed with trichlorethylene, acetone, and ethanol was used, and after masking half of its area, it was placed in a plasma CVD apparatus, and Sin,
-H2 (volume ratio 1:9) mixed gas was injected at a pressure of 100 mTorr, and a high frequency of 13.56 MHz was irradiated under conditions of a plasma output of 6 W and a time of 20 minutes to form an amorphous silicon layer (film) on a glass plate. Thickness 3000
people).

Then, PI(,-5in4-H2(volume ratio 10-'
: 1 : 9) was injected at a pressure of 130 mTorr,
High frequency was irradiated under the conditions of a plasma output of 6W, a temperature of 300°C, and a time of 10 minutes to form an N4 layer (thickness of 1000 layers). Thereafter, vacuum evaporation of aluminum was carried out rapidly on the N4 layer to a thickness of 1,000 layers using a vapor deposition apparatus, and patterning including etching was performed on the N+ layer to form electrode portions.

Next, the substrate portion on the source and drain electrode sides is
While masking the substrate on the electrode extraction part side with a glass plate, 5iH4-NH,-H, (volume ratio 0.33:0.
67:9) Mixed gas was injected at a pressure of 15 On + Torr, and high frequency was irradiated under the conditions of a plasma output of 6Ii and a time of 50 minutes, and the electrode was coated with amorphous silicon nitride with a thickness of 3000 nm, and the wire at the electrode extraction part was Perform bonding to create an ion-sensitive field effect transistor (
An ISFET (channel width: 500 pm, channel length: 10 μm) was formed.

The sensor constructed in this way can be measured using the measuring device shown in FIG.
13 and the silver/silver chloride reference electrode 14 were immersed in the measurement liquid (20mM Tris adjusted to each pH value).
-H (, Q buffer) 15 in a constant temperature cell 16 at a constant temperature (2
The potential response was measured while keeping the source-drain current (500 μA) and voltage (4 V) constant using an apparatus maintained at 0° C.). As shown in the graph in Figure 2, this result shows linearity within the pH range of 1 to 12, and its sensitivity is approximately 50 mV per pH, which confirms its effectiveness as a pH sensor. Ta.

Example 2 In order to examine the response characteristics of the PH sensor of Example 1, the PH sensor was immersed in distilled water Loom Q at 20°C, and then immersed in INH (l or IN NaOH) at 0.
When applied to 1m12, the potential reached a steady value in about 30 seconds, and it was found that the response characteristics were also excellent.

Example 3 In Example 1, a Teflon sheet (thickness 1 mm) was used instead of the glass plate as the substrate, and 15FET
was formed.

This 15FET was placed on a spinner, and a polyvinyl alcohol photosensitive resin with a concentration of 5% (photosensitive stilbazolium group content: 1.4 mol, saponification degree of 88%, polymerization degree of 140%) was placed on a spinner.
0) Add glucose oxidase to an aqueous solution
ml of aqueous solution was added dropwise and spin-coated.

Next, the photosensitive resin is photocured by irradiating ultraviolet rays with a wavelength of 300 nm using a mask aligner,
A glucose sensor was created by immobilizing glucose oxidase.

This glucose sensor was measured using the measuring device shown in FIG.
(concentration 20 to 900 mg)
/ρ glucose aqueous solution, pH 7.0) 15 was kept at a constant temperature (37°C) in a constant temperature cell 16, and the source-drain current (500 μA) and voltage (4 V
) were kept constant, and the potential responses were measured.

The obtained results are shown in the graph of FIG. 5, and the results show that there is a correlation between the logarithmic value of the glucose concentration and the steady value of the output voltage, and that when the glucose concentration is 50~BOOrng/
It was found that quantification was possible within the range of Q.

Example 4 In the measurement of Example 3, instead of the glucose aqueous solution,
Using an aqueous solution of glycine, albumin, or sucrose with a concentration of 200 mg/Q, respectively, and measuring their output potentials and comparing them with the output potential of an aqueous glucose solution with the same concentration, the response is the same as the signal-to-noise ratio with respect to the aqueous glucose solution. 2
It was confirmed that only glucose could be selectively quantified.

[Brief explanation of the drawing]

FIG. 1 is a plan view of one embodiment of the pH sensor according to the present invention (
They are a) and a sectional view taken along the line I-1 (b). FIG. 2 is a graph showing the measurement results of Example 1, and FIG. 3 is a schematic diagram of the measuring device used for the measurement. FIG. 4 is a plan view (a) and a sectional view (b) taken along the line ■-■ of one embodiment of the glucose sensor according to the present invention. Moreover, FIG. 5 is a graph showing the measurement results of Example 3. (Explanation of symbols) 1...Insulating substrate 2...Amorphous silicon layer 3...N layer 4...Source electrode 5...Drain electrode

Claims (1)

[Claims] 1. Consisting of an ion-sensitive field effect transistor in which an n^+ layer and an electrode are sequentially formed on a glass substrate or plastic substrate covered with an amorphous silicon layer, and further covered with an amorphous silicon nitride layer. pH
sensor. 2. In the ion-sensitive transistor according to item 1,
A glucose sensor comprising a photocured film of a photosensitive resin containing glucose oxidase formed on an amorphous silicon nitride layer.