JP2003262607A - Chemical concentration sensor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a chemical concentration sensor capable of speedily and quantitatively measuring a large number of samples by a single measuring system without replacing sensors. <P>SOLUTION: The chemical concentration sensor comprises a sensor chip 2 in which a two-dimension chemical concentration image sensor SL is formed on one flat surface, a plurality of recessed parts 3 formed on the sensor chip 2 as a bottom surface, and reference electrodes 4 each arranged in such a way as to face the inside surfaces of the recessed parts 3. It is possible to individually measure the chemical concentration of the samples S to be measured each housed in the recessed parts 3. <P>COPYRIGHT: (C)2003,JPO

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a chemical concentration sensor for measuring the chemical concentration of a liquid (solution or the like) contained in each recessed portion of a microplate, and more particularly, to improve the efficiency of the measurement. The present invention relates to an intended chemical concentration sensor.

[0002]

2. Description of the Related Art Conventionally, the chemical concentration of a test solution contained in each recess of a microplate (eg, pH of the solution)
When measuring, the small sensor is inserted into each recess in order.

FIG. 8 is a diagram for explaining a conventional chemical concentration sensor for measuring the pH of a test solution and a method of using the same. In FIG. 8, 50 is a recessed portion 50a in which the test solution is stored.
The microplate 51 on which the ridges are formed, 51 are the respective recessed portions 50a ...
It is a conventional chemical concentration sensor (pH sensor in the case of this example) having a sensor portion 51a which is formed small so that it can be inserted therein. That is, the user attaches the pH sensor 51 to each recess 50.
It was inserted into a ... and the chemical concentration of the solution in the recess 50a was measured.

[0004]

However, when the pH sensor 51 is used by using the conventional microplate 50, it is unavoidable that the physical size limit and the complicated operation occur. That is, in the conventional pH sensor 51 such as the microplate 50 that requires individual measurement, the sensor unit 51a is inserted into and removed from the recessed portion 50a at each measurement, or the sensor unit 51a after measurement is washed every time. Or it had to be replaced.

Further, the recessed portion 50 of the microplate 50
In order to be able to insert the sensor unit 51a into a,
Although it is necessary to reduce the size of the sensor unit 51a, there are physical limits (size of the glass electrode) and the like to make a small sensor. As a result, the recessed portion 50
There has been a limit in reducing the size of a.

On the other hand, LAPS (Light-Addressable Poten
tiometric Sensor) type pH sensor and Chemical-
By using a planar image sensor (referred to as a two-dimensional chemical concentration image sensor in this specification) that measures a two-dimensional chemical concentration distribution, such as a CCD, literally one sensor can be used at multiple points. However, when a plurality of liquid samples are placed on the two-dimensional chemical concentration image sensor, there is a problem that they are mixed.

That is, when the chemical concentration of each sample is measured without mixing a plurality of samples to be measured, it is necessary to have a recessed portion 50a for accommodating each sample separately like the microplate 50. Therefore, it was not possible to perform multiple points of a sample that requires individual measurement using the above-described two-dimensional chemical concentration image sensor.

The present invention has been made in consideration of the above, and provides a chemical concentration sensor capable of rapidly and quantitatively measuring a large number of samples without exchanging the sensors with a single measuring system. The purpose is to do.

[0009]

In order to achieve the above object, the chemical concentration sensor of the present invention comprises a sensor chip having a two-dimensional chemical concentration image sensor formed on one plane, and a sensor chip formed on the sensor chip. Consisting of a plurality of recesses formed so that the bottom surface, and a reference electrode respectively arranged so as to face the inner surface of each recess, the chemical concentration of the sample to be measured contained in each recess The feature is that it can be measured individually.

Therefore, since the chemical concentration of the sample can be measured without inserting the electrode into the sample housed in the recessed portion, there is no fear of contaminating the sample from the outside. Further, the liquid samples contained in the respective recesses do not mix with each other, and the chemical concentrations of the plurality of samples contained in the respective recesses are individually measured by a single measurement system formed on one plane. Can be measured. Since a plurality of samples can be measured with a single measurement system, the cost performance per recessed portion can be reduced, and a disposable chemical concentration sensor can be formed.

Further, unlike the conventional case, it is not necessary to change or wash the sensor chip for each measurement for each sample, and the two-dimensional chemical concentration image sensor is used to accommodate a plurality of recesses in a single measuring system. Since the chemical concentration of each sample can be sequentially measured, the signal processing circuit is simple and quick measurement can be performed on the microplate.

When the recessed portion is made of a photo-curing resin molded by a stereolithography method, the reference electrode can be easily miniaturized to face the recessed portion without changing the constitutional content of the reference electrode. In addition, each recess can be formed more accurately, and it is possible to reliably prevent leakage of each sample and form a recess that can be stored. Also, the size of the recessed portion can be easily reduced. That is,
By achieving miniaturization, it is also possible to form a chemical concentration sensor capable of measuring a minute amount such as μTAS.

When the reference electrode is formed so as to be sandwiched in the middle of the step of forming the recessed portion, it is possible to form an accurately downsized reference electrode by taking advantage of the optical molding method. .

The two-dimensional chemical concentration image sensor has a semiconductor substrate having a sensitive film formed on the surface thereof, and a light source capable of individually irradiating light from the rear surface of the semiconductor substrate to the positions corresponding to the respective recessed portions. A counter electrode corresponding to each reference electrode and arranged to face the inner surface of each recess, and a reference electrode and / or a reference electrode corresponding to the recess at the position where the light is irradiated.
Alternatively, by selecting the counter electrode and connecting it to the potentiostat, one of the recesses to be measured is selected from the plurality of recesses arranged on the semiconductor substrate, and the sensitive film in the recess is formed. In the case of having a multiplexer capable of individually measuring the photocurrent value as the measured value of the chemical concentration (that is, when the two-dimensional chemical concentration image sensor is a LAPS type sensor), a large number of samples are prepared by using the LAPS method. Can be measured.

In the case where the counter electrode and the miniaturized reference electrode are formed on the front surface and / or the back surface, and a highly insulating resin substrate is sandwiched in the recesses so that both electrodes face the inner surface of each recess. Can easily form a reference electrode and a counter electrode.

In the case where the light source is composed of a plurality of light emitting elements respectively arranged at positions corresponding to the recesses and a power supply section for selectively supplying power to one light emitting element to be measured. Can simplify the structure of the light source and can easily identify the recessed portion that is the measurement target.

In the case where a light shielding wall for guiding the light from each light emitting element to reach only the portion corresponding to the bottom surface of the corresponding recessed portion is located on the back surface of the semiconductor substrate,
It is possible to reliably correspond each light emitting element to each recessed portion and improve the measurement accuracy.

The two-dimensional chemical concentration image sensor has a plurality of ISFETs formed on a semiconductor substrate.
Each of the FETs is formed in a portion corresponding to the bottom surface of the concave portion, and the IS corresponding to the concave portion to be measured is
When it is possible to individually measure the chemical concentration of the sample to be measured in the recessed portion by the FET, a plurality of ISFETs can be formed at low cost at accurate positions by using a semiconductor manufacturing process. A chemical concentration sensor with high yield can be formed. Above all, ISFE
T has a simple electric circuit for signal processing, the time required for measurement is short, and the chemical concentration of each of a large number of samples can be quickly measured.

A multiplexer that selects an ISFET to be measured from a plurality of ISFETs, and the potential of the comparison electrode is controlled so that a constant current flows between the drain and the source of the ISFET selected by this multiplexer. However, when it has an operational amplifier capable of outputting the potential of the reference electrode as a measured value of the chemical concentration, one operational amplifier can be used to measure the chemical concentrations of a plurality of samples.

When there are a plurality of operational amplifiers for controlling the potentials of the corresponding comparison electrodes so that a constant current flows between the drain and the source of each ISFET, it is extremely easy to use the potentials of the respective comparison electrodes. A measurement of the chemical concentration of the sample in each recess can be obtained. Since this operational amplifier can be formed on the same semiconductor substrate as the ISFET using a semiconductor manufacturing process, the manufacturing cost can be reduced. However, the present invention is not limited to forming the operational amplifier on the same semiconductor substrate as the ISFET.

The two-dimensional chemical concentration image sensor has a plurality of CCDs for converting the chemical concentrations in a plurality of sensitive film portions on the semiconductor substrate into signal charges for detection, respectively.
The sensitive film of the CD is formed on the portion corresponding to the bottom surface of the recessed portion, and the chemical concentration of the sample to be measured in the recessed portion corresponding to the sensitive film is individually determined from the signal charge amount converted by each CCD. When it is possible to measure, the chemical concentration of the sample to be measured in each recess can be easily measured.
Since the CCD unit is formed on the same semiconductor substrate as the two-dimensional chemical concentration image sensor, its manufacturing cost can be reduced and its yield can be improved. Further, since the measured value of the chemical concentration converted into the signal charge can be easily transferred by the transfer CCD, the measured value by each CCD can be easily and sequentially detected.

[0022]

1 is a view showing a first embodiment of a chemical concentration sensor 1 of the present invention, and FIG. 2 is an enlarged view showing the essential parts of the chemical concentration sensor 1. As shown in FIG.

In FIG. 1, reference numeral 2 is a planar sensor chip using the LAPS method, which is an example of a two-dimensional chemical concentration image sensor, and 3 is two-dimensionally arranged on the sensor chip 2 so that it serves as the bottom surface. A plurality of recesses 4 are formed on the inner surface of each recess 3 so that the reference electrodes 5 are arranged so as to face the inner surface of each recess 3. It is the opposite pole provided.
That is, the two-dimensional chemical concentration image sensor S _L (hereinafter, referred to as the two-dimensional sensor S _L ) in this example is the member 2
Have ~ 5.

Reference numeral 6 denotes a plurality of light emitting diodes (hereinafter referred to as LEDs) arranged at positions corresponding to the recessed portions 3 as an example of a light source for irradiating light from the back surface side of the two-dimensional sensor S _L , and 7 denotes each LED 6 An electric power supply unit for selectively supplying alternating current electric power to 8 ... An analog for switchingably selecting the reference electrode 4 so that the chemical concentration of the sample to be measured contained in each recess 3 can be individually measured. A multiplexer (multiplexer for switching analog signals), 9 is an error amplifier connected to the analog multiplexer 8. Note that 8a to 8n are input buffer amplifiers, and C is a connector for detachably connecting the two-dimensional sensor S _L, for example.

Reference numeral 10 is an arithmetic processing unit of this chemical concentration sensor 1, 11 is a DA converter, 12 is an ohmic contact,
Reference numeral 13 is a preamplifier, 14 is a signal processing circuit, 15 is an AD converter, and 16 is a display unit for displaying measurement results. Also,
An address signal A for switching the recessed portion 3 to be measured is input to the power supply unit 7 and the multiplexer 8 to switch the LED 6 for flashing and emitting, and an appropriate action in the recessed portion 5 to be measured. Each unit 7 to 12 is configured to be controllable so that an electric current is passed. Reference numeral 18 denotes an external IT equipment connection connector, and the measurement value obtained by the arithmetic processing device 10 may be transmitted to the external IT equipment via the connector 18.

That is, since the analog multiplexer 8 is provided after the input voltage buffer amplifier 8a of the comparison electrode 4, the address A and the control address A of the power supply unit are made the same, and the LED 6 in the LED array 6A is lit by AC. The signal from the comparison electrode 4 attached to the recessed portion 3 is guided to the amplification calculation circuit 9, so that a voltage whose error is corrected in comparison with the set bias voltage is applied to the counter electrode 5. That is, the current supplied through the counter electrode 5 can be adjusted so that the potential difference between the reference electrode 4 and the sensor chip 2 in the recessed portion 3 which is the measurement target has a predetermined value.

Further, in the chemical concentration sensor 1 of this example, since the two-dimensional sensor S _L is a LAPS type sensor, one concave portion is measured at a time, and the counter electrode 5 has all the concave portions 3 ... Can be common in.

A more detailed structure of the two-dimensional sensor S _L is, as shown in FIG. 2, a concave portion 3 formed by a stereolithography method on a sensor chip (LAPS sensor) 2 made of, for example, a silicon semiconductor. It has a wall surface 3a constituting it and a wall surface 3b formed on the lower surface of the sensor chip 2 by an optical molding method.

Regarding the shape of the wall surface 3a, the bottom surface of each recessed portion 3 formed thereby serves as the surface of the sensor chip 2, and an appropriate amount of sample S to be measured is accommodated by each recessed portion 3 without leaking. It is possible. Also,
The shape of the wall surface 3b is such that the light introducing portions 3 '... Are formed at the positions on the back surface side of the sensor chip 2 corresponding to the recessed portions 3. Therefore, the wall surface 3b for constructing the light introducing portions 3 '... In this example functions as a wall for preventing stray light from the adjacent LEDs 6, and is opaque to the emission wavelength of the LEDs 6. It is preferable that it is made of transparent resin.

Reference numeral 17 denotes a highly insulating resin substrate formed so as to be sandwiched between the wall surfaces 3a during molding, and the substrate 17 of the present example has the front surface and the back surface thereof with the comparison electrode 4 respectively.
Further, a miniaturized counter electrode 5 is formed so that the both electrodes 4 and 5 face the inner side surfaces of the recessed portions 3.

Also, the ohmic contact 1 of the present example.
Reference numeral 2 is for connecting the sensor chip 2 and the wiring pattern on the substrate 17, and the two-dimensional sensor S _L can be replaced by inserting and removing the substrate 17 and the connector C.
That is, the disposable two-dimensional sensor S _L by can be installed two-dimensional sensor S _L replacement freely relative to the LED array 6A composed of a plurality of LED 6 ... which are arranged two-dimensionally. On the other hand, the LEDs 6 ... Are arranged in a two-dimensional direction on a substrate 7a forming a part of the power supply unit 7 to form the LED array 6A.

The present invention is not limited to the detailed structure described above. For example, it is not necessary to limit the two-dimensional sensor S _L to be replaceable by the connector C or the like. Alternatively, each of the buffers 8a, 9, 13 detailed in FIG.
It is also possible to appropriately provide the multiplexer 8, the signal processing circuit 14, and the like.

In addition, as described above, the wall surface 3b is continuously provided on the back surface side of the sensor chip 2 to form the light introducing section 3 ', so that the light introducing section 3' ... also functions as a sensor base. It is also possible to use each LED 6 as a guide for corresponding to each recessed portion 3, but the wall surface 3b (sensor base) is continuously provided on the substrate 7a side, and the replaceable two-dimensional sensor is provided. The structure of S _L may be simplified.

In this case, it is advisable to provide an appropriate positioning mechanism between the two-dimensional sensor S _L and the substrate 7a. Alternatively, a wall surface functioning as a sensor base is continuously provided on the substrate 7a side, and a wall surface functioning as a guide and a stray light prevention wall is continuously provided on the back surface side of the two-dimensional sensor S _L so that both wall surfaces can be easily aligned. Good.

Further, although the above-mentioned example shows an example using the LED array 6A, the light source of the two-dimensional sensor S _L is LE.
It goes without saying that the light source is not limited to D6, and other light sources such as a laser light source can be used.

FIG. 3 shows the two-dimensional sensor S _L shown in FIGS.
It is a figure which shows the manufacturing method of. FIG. 3A shows a first stage of manufacturing, and shows a step of forming the plate body 3A by a stereolithography method. At this time, the LEDs 6 on the plate 3A
The wall surface 3b is formed by forming the through hole 3c at a position corresponding to the position.

The photocurable resin used here is transparent to the wavelength of light for curing, but the resin after photocuring is a resin material that is opaque to the emission wavelength of the LED 6. As a result, a sufficient function as a stray light prevention wall can be obtained. That is, it is not necessary to care about the radiation characteristics of the LED 6, which is advantageous in manufacturing the device. However, the present invention need not be limited to forming the plate 3A by photo-curing.

FIG. 3B is a diagram showing the second stage of manufacturing. That is, the sensor chip 2 is placed on the plate 3A. This sensor chip 2 is formed by forming an oxide film and a sensitive film on a silicon semiconductor, and is provided with an ohmic contact 12 in advance. Further, the plate body 3A forming the sensor base may be placed horizontally even if it is not sufficiently cured. By mounting the sensor chip 2 in a state where the plate body 3A is not sufficiently cured, the sensor chip 2 is placed and then photocured again to strengthen the bond between the plate body 3A and the sensor chip 2. Is possible.

FIG. 3C is a diagram showing a third stage of manufacturing. That is, the stray light prevention wall 3d is optically formed on the side of the sensor chip 2. As a result, the adjacent LEDs 6
It is possible not only to prevent stray light from the outside.

FIG. 3D is a diagram showing a fourth stage of manufacturing. That is, the recessed portions 3 of the microplate are optically formed on the sensor chip 2. At this time, the recessed portions 3 ... Are formed at the positions corresponding to the light guide portions 3 ′ ...

FIG. 3E is a diagram showing the fifth stage of manufacturing. In FIG. 3 (E), 17a is a through hole which is provided at a position corresponding to the recessed portions 3 ... Of the substrate 17 made of a resin plate (FPC) and has a diameter equal to or smaller than the diameter of the recessed portions 3. The substrate 17 is provided with the reference electrodes 4 ... And the counter electrode 5 formed around the through hole 17 a, and the reference electrode 4 and the counter electrode 5 are formed so as to project from the inner peripheral surface of the recess 3. That is, the counter electrode 5 is similarly attached to the back surface of the reference electrode 4, and the resin substrate 17 having a high insulating property is provided in the middle.
Is located so that each pole 4, 5 is electrically isolated.

The board 17 has a connecting portion 17b which can be connected to the connector C. In addition, the substrate 1
7 is placed on the recesses 3 ... Formed in the fourth step, and the ohmic contact 12 is placed on the substrate 17
It is connected to the upper wiring (for ease of wiring). In addition,
The substrate 17 may be a wiring resin plate having a multilayer structure that shields the power distribution of the comparison electrode 4 by the electrode voltage of the counter electrode 5 in order to improve noise resistance.

Although the detailed structure of the reference electrode 4 is not shown, the reference electrode 4 is formed by miniaturizing a general reference electrode by, for example, an optical molding method. Alternatively, the comparison electrode 4 may be composed of a simplified silver wire or the like. In any case, the reference electrodes 4 and the counter electrodes 5 are formed so as to face the inner surface of the recess 3. Further, in this example, the counter electrode 5 is common, and only the reference electrodes 4 are wired corresponding to the recessed portions 3, respectively, but the present invention is not limited to this point, and the reference electrode 4 is not limited to this. Is common to all the recessed portions 3 ... and the counter electrode 5 ...
May be provided corresponding to each recess 3.

In this example, the substrate 17 is made of a resin having high insulation.
The configuration is not limited to 7. That is, the fourth
It is also possible to omit the substrate 17 (wiring resin plate) by wiring on the wall surface 3a already formed in the step, forming an insulating layer by the optical molding method, and stacking wiring.

FIG. 3F is a diagram showing a sixth stage of manufacturing. That is, the two-dimensional sensor S _L having the recessed portions 3 ... With the substrate 17 sandwiched therebetween is configured by further forming the recessed portions 3 ... On the substrate 17.

By using the chemical concentration sensor 1 of the present example described in detail above, the measurement electrode has a concave portion 3 ...
It is not necessary to insert the measurement target sample S from above, and the chemical concentration of the measurement target sample can be measured. Therefore, it is possible to perform measurement without worrying that the solution is contaminated from the outside, and it is not necessary to wash and reuse the electrode, and it is possible to reduce extra labor and cost.

Further, since the two-dimensional sensor S _L used to form the chemical concentration sensor 1 is formed by using one silicon substrate, the manufacturing by the optical molding method is a relatively inexpensive and highly accurate modeling. Is something that can be done in. Therefore, the manufacturing cost of the two-dimensional sensor S _L can be reduced, and the two-dimensional sensor S _L can be a disposable structure. This makes it possible to carry out chemical concentration measurement without any fear of contamination.

It is needless to say that the two-dimensional sensor S _L can be cleaned and reused, and in this case as well, the plurality of samples S contained in the microplate having the plurality of recesses 3 ... It is possible to measure the chemical concentration at once. Therefore, unlike the conventional case, it is not necessary to perform cleaning each time the measurement target sample S in each recessed portion 3 is measured, so that it is possible to reduce extra cost as compared with the conventional case. Therefore, it becomes possible to quickly perform the measurement.

Next, FIGS. 4 and 5 are views showing the construction and manufacturing method of another chemical concentration sensor 20 of the present invention. Figure 4,
5, the same reference numerals are given to the same or equivalent portions as those in the example shown in FIGS. 1 to 3, and the detailed description thereof is omitted.

In FIG. 4, reference numeral 21 denotes a sensor chip formed on a plane of one semiconductor substrate so as to be two-dimensionally arranged (in this example, 4 × 4 in the vertical and horizontal directions) so as to be aligned with the recessed portions 3. ISFET (this ISFET2
1 is a group of a plurality of ISFET arrays 21A), 22 and 23 are multiplexers (analog switches) for selecting one from a plurality of ISFETs 21, 24 is a constant voltage source for supplying a constant voltage Vd, 25 is a constant current source for supplying a constant current Is, 26 is an operational amplifier, 27
Is a voltage source that supplies a predetermined set voltage Vs to the operational amplifier 26, and 28 is a capacitor.

That is, the two-dimensional sensor S _I in this example
Is composed of the members 21 to 28.

The ISFET 21 has a drain D, a source S, and a comparison electrode 4 in contact with the sample S to be measured. The constant voltage source 24 is arranged through the multiplexer 22 in the horizontal direction of the ISFET array 21A. Common ISFET 21 drain parts D
Connect to. The constant current source 25 is the multiplexer 23.
Through the ISFET array 21A, the sources S of the ISFET 21 having a common vertical arrangement are connected.

Therefore, the signals A ₁ and A ₂ can be sent from the arithmetic processing unit 10 to the respective multiplexers 22 and 23 to select the ISFET 21 corresponding to the recessed portion 3 to be measured. ISFE selected by this
A measuring circuit system connecting the drain D, the source S of T21 and the comparison electrode 4 is formed, and the potential of the comparison electrode 4 is set by the operational amplifier 10 so that the constant current Is flows through the ISFET.

Then, it becomes possible to obtain the detection value by converting the set value of the potential supplied to the comparison electrode 4 into a digital signal by the ADC 15 and taking it into the arithmetic processing unit 10. Further, the arithmetic processing unit 10 measures the potential of the reference electrode 4 at a constant chemical concentration in advance, compares this with a calibration value, and compares it with the detection value in the case of the measurement target sample S to determine the concentration of the measurement target sample S. Is calculated as a measured value and displayed on the display unit 16.

In the case of this example, the arithmetic processing unit 10 has an external I
It has a T device connection connector 18. Therefore, the measured value may be transmitted to an external IT device via this connector 18.

In the above example, the sample S to be measured is
Since one ISFET 21 corresponding to the recessed portion 3 that accommodates is switched by the multiplexers 22 and 23 and one ISFET 21 is selected for measurement, the wiring to the reference electrode 4 is the same for each ISFET 21. Good.

However, a measuring circuit system having an operational amplifier 26 may be provided in a one-to-one relationship with each ISFET 21. In this case, ISFET of multiple points
21, it is possible to measure the chemical concentrations of a plurality of measurement target samples S at the same time, and more rapid measurement can be performed. Further, it is possible to reduce the production cost by forming an electronic circuit such as the operational amplifier 26 on the silicon substrate forming the ISFET 21.

Further, the ISFETs 21 ... Which are selected by the multiplexers 22 and 23 are divided into some blocks so that a plurality of ISFETs selected in each of the plurality of blocks can be measured at the same time. The measurement time per (one microplate) may be shortened. At this time, the wiring to the comparison electrode 4 should be one in each block.

[0059] Conversely, in the present embodiment constitutes a two-dimensional sensor S _I as a single unit what including multiplexers 22, 23 and operational amplifier 26 to ISFET21, processor the two-dimensional sensor S _I by a connector C 1
However, the multiplexers 22 and 23 or the operational amplifier 26 may be separated from the two-dimensional sensor S _I. In this case, the two-dimensional sensor S _I
The configuration can be simplified, the manufacturing cost can be reduced as much as possible, and the cost when the two-dimensional sensor S _I is disposable can be reduced.

FIG. 5 is a diagram showing a method of manufacturing the two-dimensional sensor S _I in the chemical concentration sensor 20 of this example. Figure 5
FIG. 3A is a diagram showing a first step in the method of manufacturing the two-dimensional sensor S _I , in which the ISFET array 21A is manufactured on the semiconductor substrate 29 using a normal manufacturing process, and at the same time, the ISF
Wiring of ET array 21A and multiplexers 22 and 2
3 shows the step of forming the operational amplifier circuit 26 and the like in the same manufacturing process as above.

In FIG. 5A, 30 is ISF.
Sensitive membrane corresponding to Ged G of ET21, 31 is each ISF
It is a barrier formed during ET21. Next, the semiconductor substrate 29 is diced into a predetermined size.

FIG. 5B is a diagram showing a second stage of the method of manufacturing the two-dimensional sensor S _I , and each I is manufactured by the optical molding method.
The step of forming the wall surfaces 3a ... From the upper surface of the semiconductor substrate 29 sequentially upward is shown so that the sensitive film 30 corresponding to the gate G of the SFET 21 becomes the bottom surface of each recess 3.

Next, as shown in FIG. 5 (C), the reference electrode 4 is formed at an appropriate position so as to face the inner peripheral surface of each recess 3, and the wall surface 3a is subsequently formed. The recessed portions 3 are completed, and finally, a portion other than the connection electrodes of the semiconductor substrate 29 is packaged by a stereolithography method or the like to form a resin coating layer 32. By forming this resin coating layer 32, moisture resistance,
Although chemical resistance can be improved, it goes without saying that this step may be omitted.

In the example shown in FIG. 5 (C), the reference electrode 4 is attached at a substantially intermediate position in the height direction of the recessed portions 3 ,. However, the present invention does not limit the height position to the intermediate position. That is, the reference electrode 4 is separated from the sensitive film 30 and is attached so as to face the inner peripheral surface of the recessed portions 3 ... At a height position where the reference electrode 4 does not contact the measurement target sample S reliably. .

Next, FIGS. 6 and 7 are views showing the construction, manufacturing method and measurement concept of another chemical concentration sensor of the present invention. 6 and 7, the same reference numerals are given to the same or equivalent portions as those in the examples shown in FIGS. 1 to 5, and detailed description thereof will be omitted.

The chemical concentration sensor of this example converts the chemical concentration in each sensitive film (sensitive film) 40a into a signal charge as an example of a sensor chip of a two-dimensional chemical concentration image sensor (hereinafter referred to as a two-dimensional sensor S _C ). A plurality of CCDs 40 (hereinafter, each CCD 40 is referred to as a unit element 40, and the plurality of unit elements 40 are combined to form the chemical CCD array 4).
0A) is used. The detailed configuration and operation of the chemical CCD array 40A shown in this example are described in detail in, for example, "Method and apparatus for measuring physical or chemical phenomenon" described in JP-A-10-332423. And will be omitted from the following description.

FIG. 6 (A) is a diagram showing a first step of manufacturing the two-dimensional sensor S _C , in which the unit elements 40 ... Wiring to the CCD array 40A, transfer C for sequentially transferring the converted signal charges in the direction of arrow A
A process of incorporating a CD 42 (hereinafter, referred to as a charge transfer unit 42), a multiplexer (not shown), an operational amplifier circuit and the like in the same manufacturing process is shown. Then, the semiconductor substrate 41 is diced into a predetermined size.

FIG. 6B is a diagram showing a second step of manufacturing the two-dimensional sensor S _{C so} that the sensitive films 40a of the unit elements 40 are on the bottom surface of the recesses 3. 7 shows a forming step of forming a microplate by a stereolithography method. As in this example, the sensitive films 40a of the unit elements 40 ...
Are formed on the surface of the semiconductor substrate 41 in order so as to be the bottoms of the recessed portions 3 ... It can be formed so as to surely come into contact with the sensitive films 40a ... And to prevent leakage.

FIG. 6C is a diagram showing a second step of manufacturing the two-dimensional sensor S _{C. The} reference electrode 4 is formed in each recess 3 at an appropriate time during the step of forming the wall surface 3a. It shows the state of being attached to. Then, the protective layer 43 is formed by resin-molding the parts other than the connecting electrodes by using an optical molding method. As described in detail above, the formation position of the comparison electrode 4 is located at the position facing the recess 3 ...
It can be set to an arbitrary position as long as it is away from.

FIG. 7 is a diagram showing a measurement conceptual diagram of the chemical CCD array 40A formed by the manufacturing process. The chemical CCD array 40A shown in FIG. 7 exemplifies an array of 10 × 5 in length and width. Then, a constant bias voltage is applied to the comparison electrode 4.

In the first stage of measurement, each unit element 40
The chemical concentration of the sample S to be measured contained in each recess 3 is sensed by each sensitive film 40a and converted into a signal charge. Then, the signal charge proportional to the chemical concentration is sequentially transferred by the transfer CCD 42 as shown by an arrow A, and is output via the output transistor 44. Then, it is converted into a digital signal by an AD converter 15 (see FIGS. 1 and 4) (not shown) and taken into the arithmetic processing unit 10.

Before the main measurement, a standard sample having a constant chemical concentration is measured in advance, and the measured value is compared with the above value as a calibration value to calculate the concentration of the sample S to be measured as the measured value. , Display or sent to IT related equipment.

On the other hand, since the wiring to the comparison electrode 4 is measured at the same time, the wiring common to the recessed portions 3 ... Can be performed.

When the chemical CCD array 40A is used as the two-dimensional sensor S _C as in this example, the chemical concentrations of the sample S to be measured contained in the plurality of recesses 3 ... Since the measurement can be performed and the measured values can be individually detected, quick measurement can be performed. In particular, since a large number of CCDs 40 and 42 can be formed on the semiconductor substrate 41 at a relatively low cost by using the CCD structure, the manufacturing cost can be easily reduced.

In each of the above examples, the two-dimensional chemical concentration image sensors 2, 21A, 40A are formed by forming the recessed portions 3 ... Using a stereolithography method to form the shape more accurately. , It is possible to dramatically reduce the size of the recessed portions 3 ...
The present invention is not limited to forming by the stereolithography method. That is, it may be realized by a combination of resin molded products and processed products.

Further, it goes without saying that the sample S to be measured in each of the above-mentioned examples is not limited to a liquid sample and may be a gel. In addition, the sensitive film in each of the above examples uses, for example, a nitride film (Si ₃ N ₄ ), a tantalum oxide film (Ta ₂ O ₃ ), an alumina film (Al ₂ O ₃ ) according to the sample S to be measured. However, by modifying the sensitive film which reacts to the chemical substance to be measured, any sensitive film corresponding to the concentration measurement of various specific chemical substances can be formed.

Further, it is also possible to measure a plurality of chemical concentrations at once by modifying various responsive films on the sensitive film corresponding to the bottom surface of each recess 3.

Then, as in the above example, the ISFET is
When using an array sensor such as the array 21A or the chemical CCD array 40A, an FE that replaces the reference electrode 4
The T structure (generally called REFET) is called IS
The same semiconductor substrate 29, 4 as the FET 21 or CCD 40
They may be formed adjacent to each other.

[0079]

As described above, according to the chemical concentration sensor of the present invention, it is possible to use a single two-dimensional chemical concentration image sensor formed on one plane to replace a large number of samples. Can be measured quickly and quantitatively. That is, it is not necessary to insert the measurement electrode into the sample housed in the recessed portion as in the conventional case, and only by storing the measurement target sample in each recessed portion forming the microplate, the chemical concentration of each measurement target sample is Since it can be measured, there is no worry of contaminating the sample from the outside.

Further, the liquid sample contained in each recess can be individually measured in a completely separated state, and a plurality of samples can be measured by a single measuring system. The cost performance per hit can be reduced and a disposable chemical concentration sensor can be formed.

[Brief description of drawings]

FIG. 1 shows LAPS as an example of a chemical concentration sensor of the present invention.
It is a figure which shows the whole structure at the time of using a two-dimensional type sensor.

FIG. 2 is an enlarged view of a main part showing a configuration of a two-dimensional sensor of the chemical concentration sensor.

FIG. 3 is a diagram illustrating a method for manufacturing the two-dimensional sensor of the chemical concentration sensor.

FIG. 4 is an ISF as another example of the chemical concentration sensor of the present invention.
It is a figure which shows the whole structure at the time of using the two-dimensional sensor by ET.

FIG. 5 is a diagram illustrating a method for manufacturing the two-dimensional sensor of the chemical concentration sensor shown in FIG.

FIG. 6 is a CCD as another example of the chemical concentration sensor of the present invention.
FIG. 6 is a diagram showing a manufacturing method and a main part configuration when the two-dimensional sensor according to is used.

7 is a diagram showing a planar configuration of the two-dimensional sensor shown in FIG.

FIG. 8 is a diagram illustrating a conventional method for measuring a chemical concentration using a microplate.

[Explanation of symbols]

1,20 ... chemical concentration _{sensors, S L, S I, S} C ... two-dimensional chemical concentrations image sensor, 2 and 21a, 40A ... sensor chip, 2,29,41 ... semiconductor substrate, 3 ... recess, 3
b ... light-shielding wall, 4 ... comparison electrode, 5 ... counter electrode, 6 ... light emitting element (light source), 7 ... power supply unit (light source), 8, 22, 23 ...
Multiplexer, 30 ... Sensitive film, 17 ... Resin substrate, 26
... operational amplifier, 40a ... sensitive film, S ... sample to be measured.

   ─────────────────────────────────────────────────── ─── Continued front page    (72) Inventor Tsuyoshi Nakanishi             2 Higashimachi, Kichijoin-miya, Minami-ku, Kyoto-shi, Kyoto             HORIBA, Ltd. (72) Inventor Tanabe Yuki             2 Higashimachi, Kichijoin-miya, Minami-ku, Kyoto-shi, Kyoto             HORIBA, Ltd.

Claims (11)

[Claims] 1. A sensor chip having a two-dimensional chemical concentration image sensor formed on one plane, a plurality of recessed portions formed on the sensor chip so as to form the bottom surface, and each recessed portion. And a reference electrode arranged so as to face the inner surface of the sample, and the chemical concentration of the sample to be measured contained in each recess can be individually measured. 2. The chemical concentration sensor according to claim 1, wherein the recessed portion is made of a photocurable resin molded by a stereolithography method. 3. The chemical concentration sensor according to claim 2, wherein the reference electrode is formed so as to be sandwiched during the step of forming the recess. 4. The two-dimensional chemical concentration image sensor,
A semiconductor substrate having a sensitive film formed on the front surface, a light source capable of individually irradiating light from the back surface of the semiconductor substrate to a position corresponding to each recessed portion, and a recessed portion of each recessed portion corresponding to each reference electrode. A plurality of counter electrodes arranged on the semiconductor substrate are formed by selecting a counter electrode arranged to face the inner surface and a reference electrode and / or counter electrode corresponding to the recessed portion at the position where the light is irradiated and connecting to the potentiostat. A multiplexer for selecting one of the concave portions to be measured from among the concave portions, and individually measuring the photocurrent value generated in the sensitive film in the concave portion as the measured value of the chemical concentration. Item 4. The chemical concentration sensor according to any one of Items 1 to 3. 5. The counter electrode and the miniaturized reference electrode are formed on the front surface and / or the back surface, and a highly insulating resin substrate is sandwiched in the recessed portions so that both electrodes face the inner side surfaces of the recessed portions. The chemical concentration sensor according to claim 4. 6. The light source comprises a plurality of light emitting elements respectively arranged at positions corresponding to the recesses, and a power supply section for selectively supplying electric power to one light emitting element as a measurement object. The chemical concentration sensor according to claim 4 or 5. 7. A light shielding wall for guiding the light from each light emitting element to reach only a portion corresponding to the bottom surface of the corresponding recessed portion on the back surface of the semiconductor substrate.
The chemical concentration sensor described in. 8. The two-dimensional chemical concentration image sensor has a plurality of ISFETs formed on a semiconductor substrate, each IFET
The SFETs are formed in the respective portions corresponding to the bottom surface of the recessed portion, and I corresponding to the recessed portion to be measured
The chemical concentration sensor according to any one of claims 1 to 3, wherein the SFET can individually measure the chemical concentration of the sample to be measured in the recessed portion. 9. A multiplexer for selecting an ISFET to be measured from a plurality of ISFETs, and a potential of a comparison electrode so that a constant current flows between the drain and the source of the ISFET selected by the multiplexer. 9. The chemical concentration sensor according to claim 8, further comprising an operational amplifier capable of controlling the electric potential of the reference electrode and outputting the potential of the reference electrode as a measured value of the chemical concentration. 10. The chemical concentration sensor according to claim 8, further comprising a plurality of operational amplifiers that control the potentials of the corresponding reference electrodes so that a constant current flows between the drain and the source of each ISFET. 11. The two-dimensional chemical concentration image sensor has a plurality of CCDs that detect chemical concentrations in a plurality of sensitive film portions on a semiconductor substrate by converting them into signal charges, respectively.
The sensitive film of each CCD is formed in a portion corresponding to the bottom surface of the recessed portion, and the chemical concentration of the sample to be measured in the recessed portion corresponding to this sensitive film is individually determined from the signal charge amount converted by each CCD. The chemical concentration sensor according to claim 1, which is measurable.