JP5157523B2 - Biopolymer analysis chip - Google Patents

Description

  The present invention relates to a biopolymer analysis chip.

  In order to analyze gene expression and diagnose single nucleotide polymorphisms, biopolymer analysis chips such as DNA chips and readers thereof have been developed. The biopolymer analysis chip is obtained by aligning and fixing cDNA having a known base sequence serving as a probe on a solid support such as a slide glass in a matrix. For example, gene analysis using a DNA chip and its reader is performed as follows.

First, a DNA chip is prepared in which a plurality of types of cDNAs having known base sequences (hereinafter referred to as probe DNA) are aligned and fixed on a solid support such as a slide glass. Next, mRNA is extracted from the specimen, cDNA is synthesized using reverse transcriptase, and prepared by labeling with a labeling substance (hereinafter referred to as labeled DNA). Here, as the labeling substance, a fluorescent substance, a chemiluminescent substrate, an enzyme that emits light from the chemiluminescent substrate, or the like can be used.
Next, when the labeled DNA is added onto the DNA chip, the labeled DNA is immobilized on the DNA chip by hybridizing with the complementary probe DNA.

  Next, the DNA chip is set in a reader and analyzed by the reader. The reader condenses the light emitted by the labeling substance that scans the DNA chip with a condensing lens and a photomultiplier that moves two-dimensionally with respect to the DNA chip, and condenses the light intensity with the photomultiplier. By measuring the light intensity distribution in the surface of the DNA chip, the light intensity distribution on the DNA chip is output as a two-dimensional image. In the output image, the portion having a high light intensity indicates that a labeled DNA having a base sequence complementary to the base sequence of the probe DNA is included. Therefore, mRNA expressed in the specimen can be identified based on which part of the two-dimensional image has high fluorescence intensity.

Further, an invention has also been proposed in which a barcode seal that displays analysis information indicating the type, concentration, reaction time, and the like of DNA dropped on the DNA chip is attached to the DNA chip for identification (see, for example, Patent Document 1). ).
JP 2001-133464 A

  However, the conventional method of attaching a barcode seal to a DNA chip has a problem in that a manufacturing process is complicated since a process of placing a barcode is required in addition to the process of spotting DNA.

  An object of the present invention is to provide a biopolymer analysis chip that solves the above-described problems and can be easily manufactured and can identify a subject.

In order to solve the above problems, the invention described in claim 1 is a biopolymer analysis chip, wherein the first imaging device and the second imaging device each having a plurality of light receiving elements formed thereon, A storage device for storing image data captured by the first imaging device and the second imaging device, wherein the light receiving element of the first imaging device and the light receiving element of the second imaging device are have the same structure, said light-receiving surface of the first imaging device is provided with a probe to bind to particular biopolymers, wherein the light receiving surface of the second imaging device an electrostatic protective layer is provided It is characterized by being.

  The invention according to claim 2 is the biopolymer analysis chip according to claim 1, characterized in that the probe is a single-stranded DNA of a known base sequence.

  A third aspect of the present invention is the biopolymer analysis chip according to the first or second aspect, wherein the first imaging device is used for DNA detection.

  The invention according to claim 4 is the biopolymer analysis chip according to claim 3, wherein the second imaging device is used for biometric authentication other than DNA.

  The invention according to claim 5 is the biopolymer analysis chip according to any one of claims 1 to 4, wherein the storage device stores data for correcting the sensor value. It is characterized by.

  ADVANTAGE OF THE INVENTION According to this invention, the biopolymer analysis chip which can be manufactured simply and can identify a test subject can be provided.

  The best mode for carrying out the present invention will be described below with reference to the drawings. However, although various technically preferable limitations for implementing the present invention are given to the embodiments described below, the scope of the invention is not limited to the following embodiments and illustrated examples.

[First Embodiment]
[1] Overall Configuration of Biopolymer Analysis Chip FIG. 1 is a schematic plan view of a biopolymer analysis chip 1 according to an embodiment of the present invention. The biopolymer analysis chip 1 is a DNA chip that detects DNA, and includes a DNA detection region 2, a biometric authentication region 3, and a built-in storage device 4. The DNA detection region 2 and the biometric authentication region 3 are light receiving surfaces of the solid-state imaging devices 10 and 110, respectively.

[2] DNA detection region In the DNA detection region 2, a plurality of spots 60 are formed.
FIG. 2 is an enlarged view of one spot 60 in FIG. In the solid-state imaging device 10, a plurality of photosensors (hereinafter referred to as photosensors) 20 such as double gate type magnetic field effect transistors are arranged vertically and horizontally as photoelectric conversion elements. In FIG. 2, the spot 60 has a diameter of 0.5 mm, and the photosensors 20 are arranged at a pitch of 50 μm vertically and horizontally.

  Here, the solid-state imaging device 10 will be described with reference to FIGS. 3 is a plan view showing one photosensor 20, and FIG. 4 is a cross-sectional view taken along arrows IV-IV in FIG.

[2-1] Solid-State Imaging Device As shown in FIG. 4, the solid-state imaging device 10 includes a transparent substrate 11, a bottom gate insulating film 13, a top gate insulating film 21, a protective insulating film 23, and an optical filter 24. The spot fixing layer 25 is laminated. Between these layers, a plurality of bottom gate lines 12a, source lines 18a, drain lines 19a, top gate lines 22a, a bottom gate electrode 12 forming a photosensor 20, a semiconductor film 14, a channel protective film 15, an impurity semiconductor film 16, 17, source electrode 18, drain electrode 19, and top gate electrode 22 are provided.

  The transparent substrate 11 has a property of transmitting light emitted from a phosphor to be described later (hereinafter referred to as “light transmitting property”) and has an insulating property, for example, a glass substrate such as quartz glass, and a plastic substrate such as polycarbonate and PMMA. Etc.

In this solid-state imaging device 10, a photosensor 20 is used as a photoelectric conversion element, and a plurality of photosensors 20, 20,... Are arranged on a transparent substrate 11 in a two-dimensional array, particularly in a matrix, and these photosensors 20. , 20,... Are collectively covered with a protective insulating film 23 such as silicon nitride (SiN).
2 shows 100 photosensors 20, 20,... In 10 rows × 10 columns.

  As shown in FIGS. 3 and 4, each of the photosensors 20, 20,... Includes a semiconductor film 14 that is a light receiving portion, a channel protective film 15 formed on the semiconductor film 14, and a bottom gate insulating film 13. A bottom gate electrode 12 formed under the semiconductor film 14 with a sandwich, a top gate electrode 22 formed on the semiconductor film 14 with a top gate insulating film 21 in between, and a part of the semiconductor film 14 are formed. An impurity semiconductor film 16, an impurity semiconductor film 17 formed so as to overlap another part of the semiconductor film 14, a source electrode 18 overlapped with the impurity semiconductor film 16, and a drain electrode 19 overlapped with the impurity semiconductor film 17. , And outputs an electrical signal at a level according to the amount of light received by the semiconductor film 14.

  The bottom gate electrode 12 is formed on the transparent substrate 11 for each photosensor 20. Further, a plurality of bottom gate lines 12a, 12a extending in the horizontal direction are formed on the transparent substrate 11, and the bottoms of the photosensors 20, 20,... In the same row arranged in the horizontal direction are formed. The gate electrode 12 is formed integrally with a common bottom gate line 12a. The bottom gate electrode 12 and the bottom gate line 12a have conductivity and light shielding properties, and are made of, for example, chromium, a chromium alloy, aluminum, an aluminum alloy, or an alloy thereof.

The bottom gate electrode 12 and the bottom gate lines 12a, 12a,... Of the photosensors 20, 20,. That is, the bottom gate insulating film 13 is a film formed in common to all the photosensors 20, 20,. The bottom gate insulating film 13 has insulating properties and light transmittance, and is made of, for example, silicon nitride (SiN) or silicon oxide (SiO ₂ ).

  A plurality of semiconductor films 14 are formed on the bottom gate insulating film 13 so as to be arranged in a matrix. The semiconductor film 14 is formed independently for each photosensor 20, is disposed to face the bottom gate electrode 12 in each photosensor 20, and sandwiches the bottom gate insulating film 13 between the bottom gate electrode 12. It is out. The semiconductor film 14 has a substantially rectangular shape in plan view, and is a layer formed of amorphous silicon or polysilicon that generates electron-hole pairs in an amount corresponding to the amount of received fluorescence.

  A channel protective film 15 is formed on the semiconductor film 14. The channel protective film 15 is patterned independently for each photosensor 20, and is formed on the central portion of the semiconductor film 14 in each photosensor 20. The channel protective film 15 has insulating properties and light transmittance, and is made of, for example, silicon nitride or silicon oxide. The channel protective film 15 protects the interface of the semiconductor film 14 from an etchant used for patterning. When light enters the semiconductor film 14, an amount of electron-hole pairs according to the amount of incident light is generated around the interface between the channel protective film 15 and the semiconductor film 14. In this case, holes are generated as carriers on the semiconductor film 14 side, and electrons are generated on the channel protective film 15 side.

An impurity semiconductor film 16 is partially formed on one end portion of the semiconductor film 14 so as to overlap the channel protective film 15, and an impurity semiconductor film 17 is partially formed on the other end portion of the semiconductor film 14. The channel protective film 15 is formed so as to overlap. The impurity semiconductor films 16 and 17 are patterned independently for each photosensor 20. The impurity semiconductor films 16 and 17 are made of amorphous silicon (n ⁺ silicon) containing n-type impurity ions.

  A source electrode 18 is formed on the impurity semiconductor film 16, and a drain electrode 19 is formed on the impurity semiconductor film 17. The source electrode 18 and the drain electrode 19 are formed for each photosensor 20. A plurality of source lines 18 a and 18 a and drain lines 19 a and 19 a extending in the vertical direction are formed on the bottom gate insulating film 13. The source electrodes 18 of the photosensors 20, 20,... In the same row arranged in the vertical direction are formed integrally with the common source line 18a, and the photosensors 20, 20 in the same row arranged in the vertical direction. ,... Are formed integrally with a common drain line 19a. The source electrode 18, the drain electrode 19, the source line 18a, and the drain line 19a have conductivity and light shielding properties, and are made of, for example, chromium, a chromium alloy, aluminum, an aluminum alloy, or an alloy thereof.

  The source electrode 18 and the drain electrode 19 of the photosensors 20, 20,... And the source lines 18a, 18a and the drain lines 19a, 19a are collectively covered with a top gate insulating film 21. The top gate insulating film 21 is a film formed in common to all the photosensors 20, 20,. The top gate insulating film 21 has insulating properties and light transmissive properties, and is made of, for example, silicon nitride or silicon oxide.

  A plurality of top gate electrodes 22 are formed for each photosensor 20 on the top gate insulating film 21. The top gate electrode 22 is disposed to face the semiconductor film 14 in each photosensor 20, and the top gate insulating film 21 and the channel protective film 15 are sandwiched between the top gate electrode 22 and the semiconductor film 14. A plurality of top gate lines 22a and 22a extending in the horizontal direction are formed on the top gate insulating film 21, and the top gate electrodes of the photosensors 20 and 20 in the same row arranged in the horizontal direction are formed. 22 is formed integrally with a common top gate line 22a. The top gate electrode 22 and the top gate line 22a are conductive and light transmissive, for example, indium oxide, zinc oxide, tin oxide, or a mixture containing at least one of them (for example, tin-doped indium oxide ( ITO) and zinc-doped indium oxide).

  The top gate electrode 22 and the top gate lines 22a, 22a of the photosensors 20, 20,... Are collectively covered with a protective insulating film 23, and the protective insulating film 23 is formed in common to all the photosensors 20, 20,. Film. The protective insulating film 23 has insulating properties and light transmittance, and is made of silicon nitride or silicon oxide.

  In the DNA detection region 2, an excitation light filter 24 is provided on the upper surface of the protective insulating film 23. The excitation light filter 24 is a low-pass filter or a band-pass filter that transmits a fluorescence wavelength emitted from a phosphor described later but does not transmit the excitation light wavelength.

  Such an excitation light filter is formed by patterning a dielectric multilayer film on the surface of the protective insulating film 23 in a checkered pattern by, for example, vapor deposition such as vapor deposition, sputtering, PVD, or CVD. be able to.

  A spot fixing layer 25 is provided on the surface of the excitation light filter 24. The spot fixing layer 25 fixes the spot by covalent bonding or electrostatic coupling with a probe to be described later that becomes the spot 60.

  The solid-state imaging device 10 configured as described above has the surface of the spot fixing layer 25 as a light receiving surface, and is provided so as to convert the amount of light received by the semiconductor film 14 of the photosensor 20 into an electric signal.

[2-2] Spot As shown in FIGS. 1 and 2, a spot 60 is formed on the imaging surface of the solid-state imaging device 10. Each spot 60 is formed by dropping a solution of cDNA (probe DNA 61) having a known base sequence serving as a probe onto the DNA detection region 2 and drying it.

5 is a cross-sectional view taken along the line V-V in FIG. In one spot 60, a crowd of many single-stranded probe DNAs 61 having the same base sequence is immobilized, and the probe DNA 61 has a different base sequence for each spot 60. As the probe DNA 61, a DNA having a nucleotide sequence identical to or complementary to a known mRNA nucleotide sequence or a part thereof is used. Specifically, for example, a cDNA library prepared from the same cell specimen as that used for fluorescently labeled DNA described later can be used.
As shown in FIG. 2, one spot 60 is formed so as to overlap a plurality of photosensors 20.

[3] Biometric Authentication Area FIG. 6 is a cross-sectional view showing the solid-state imaging device 110 in the biometric authentication area 3. The solid-state imaging device 110 is different from the solid-state imaging device 10 in that an electrostatic protection layer 26 is provided instead of the excitation light filter 24 and the spot fixing layer 25, but the transparent substrate 11, the bottom gate insulating film 13, and the top. Since the gate insulating film 21, the protective insulating film 23, and the photosensor 20 can be simultaneously formed on the same substrate as the solid-state imaging device 10, the manufacturing process can be facilitated. Note that the configuration of the solid-state imaging device 110 other than the electrostatic protection layer 26 is the same as that of the solid-state imaging device 10, and thus the description thereof is omitted.

The electrostatic protection layer 26 is formed so as to cover the protective insulating film 21 and protects the photosensor 3 from static electricity. The electrostatic protective layer 26 is a transparent conductor such as a light-transmitting metal oxide, for example, indium oxide, zinc oxide, tin oxide, or a mixture containing at least one of these (for example, tin-doped Indium oxide (ITO), zinc-doped indium oxide) is used.
The solid-state imaging devices 10 and 110 may share the source line 18a and the drain line 19a. Alternatively, the bottom gate line 12a and the top gate line 22a may be shared.

[4] Driver The biopolymer analysis chip 1 further includes a top gate driver 41, a bottom gate driver 42, and a drain driver 43 that drive the solid-state imaging devices 10 and 110. FIG. 7 is a block diagram showing a configuration of an analyzer 70 (described later) to which the biopolymer analysis chip 1 is connected.
The top gate driver 41, the bottom gate driver 42, and the drain driver 43 cooperate to drive the solid-state imaging device 10. Are the terminals of the top gate driver 41, the bottom gate lines 12a, 12a,... Are the terminals of the bottom gate driver 42, and the drain lines 19a, 19a,. The driver 43 is connected to each terminal.
The top gate driver 41, the bottom gate driver 42, and the drain driver 43 are connected to a signal line of the computer 71 when connected to an analyzer 70 described later.
Note that the source lines 18a, 18a,... Of the solid-state imaging devices 10 and 110 are connected to a constant voltage source when connected to an analyzer 70 described later.

[5] Internal Storage Device The internal storage device 4 includes a memory cell 51 such as a flash memory and a memory control circuit 52 inside. The memory cell 51 and the memory control circuit 52 can be formed simultaneously with the solid-state imaging devices 10 and 100.

FIG. 8A is a schematic diagram illustrating a configuration of data stored in the storage device. The data stored in the storage device includes the biopolymer analysis chip 1 ID (4 bytes), the year (2 bytes), the month (1 byte), and the day (1 byte) when the biopolymer analysis chip 1 was manufactured. , Hour (1 byte), minute (1 byte), second (1 byte), number of the machine that manufactured the biopolymer analysis chip 1 (2 bytes), manufacturing location code (2 bytes), and diagnosed flag (described later) 1 byte), data for correcting the sensor value (128 bytes), fixed DNA data for detection, and biometric data including any one of fingerprint, vein, iris, and the like are stored.
Furthermore, the light intensity distribution along the light receiving surface of the solid-state imaging device 110 may be stored as two-dimensional image data.

  FIG. 8B is a schematic diagram showing the structure of the detection fixed DNA data. The detection fixed DNA data stores a simple code for identifying each probe DNA 61 fixed for each spot 60, the number of constituent bases, and base sequence data, together with the number of bytes of the entire detection fixed DNA data. Yes. In the base sequence data, four types of bases are distinguished by 2-bit data.

[5] Data Writing Flow at Manufacturing FIG. 9 is a data writing flow to the built-in storage device 4 that is performed when the biopolymer analysis chip 1 is manufactured. Data is written by a spotter (not shown) that drops the probe DNA 61.

  First, a chip to be the biopolymer analysis chip 1 is attached to the spotter. Then, the spotter writes the year, month, day, hour, minute and second for manufacturing the biopolymer analysis chip 1 in the memory cell 51 (step S1). Further, the spotter writes a spotter number (step S2) for identifying the spotter itself, a manufacturing place code (step S3), and sensor value correction data (step S4) in the memory cell 51. Thereafter, the spotter initializes the DNA fixing position (step S5).

  Next, the spotter drops a solution containing the probe DNA 61 having the base sequence in the DNA detection region 2 to form one spot 60 (step S6). Then, the spotter writes the identification code (step S7), the number of constituent bases (step S8), and the base sequence data (step S9) of the probe DNA 61 contained in the dropped solution into the memory cell 51.

  Next, the spotter determines whether or not all the spots 60 have been formed (step S10), and if not completed (step S10 → No), advances the DNA fixing position by one and probes with different base sequences. A solution containing DNA 61 is dropped to form one spot 60 (step S6), and the identification code (step S7), the number of bases (step S8), and the base sequence data (step S9) of the probe DNA 61 are stored in the memory cell 51. Write. Thereafter, steps S6 to S10 are repeated until the formation of all the spots 60 is completed.

  When the formation of all the spots 60 is completed (step S10 → Yes), the spotter writes the number of bytes of all the DNA information data (step S11), and the manufacture of the biopolymer analysis chip 1 is completed.

[6] Analysis Device Next, an analysis device 70 to which the biopolymer analysis chip 1 is attached will be described with reference to FIG.
The analysis device 70 is connected to the biopolymer analysis chip 1, a computer 71 that controls the biopolymer analysis chip 1 and the entire analysis device 70, a storage device 72, and an excitation light irradiation device 73 that is controlled by the computer 71. , An output device 77 that performs output (printing) using a signal output from the computer 71, a display device 78 that performs display using a signal output from the computer 71, and an illumination device 79.

The computer 71 outputs control signals to the top gate driver 41, the bottom gate driver 42, and the drain driver 43, thereby driving the solid-state imaging devices 10 and 110 to the top gate driver 41, the bottom gate driver 42, and the drain driver 43. Has the function to perform.
The computer 71 has a function of causing the output device 77 to output an image according to the two-dimensional image data stored in the built-in storage device 4 or the storage device 72. The output device 77 is, for example, a plotter, a printer, or a display. The display device 78 is a display device such as a liquid crystal display.

Further, the computer 71 has a function of acquiring the light intensity distribution along the light receiving surface of the solid-state imaging device 10 in the storage device 72 as two-dimensional image data by A / D converting the electrical signal input from the drain driver 43. Have. It may be stored in the built-in storage device 4.
In addition, the computer 71 performs A / D conversion on the electrical signal input from the drain driver 43, thereby acquiring the light intensity distribution along the light receiving surface of the solid-state imaging device 110 in the internal storage device 4 as two-dimensional image data. Have

In the storage device 72, the light intensity distribution along the light receiving surfaces of the solid-state imaging devices 10 and 110 input from the drain driver 43 to the computer 71 and subjected to A / D conversion is stored as two-dimensional image data.
The excitation light irradiation device 73 irradiates the biopolymer analysis chip 1 with excitation light that excites the phosphor. For example, when using Cy2, Cy3, and Cy5 as phosphors, the biopolymer analysis chip 1 is irradiated with excitation light including these absorption wavelengths (Cy2: 491 nm, Cy3: 553 nm, Cy5: 645 nm).
The illumination device 79 emits near-infrared light and irradiates a finger 80 disposed on the solid-state imaging device 110. An LED or the like can be used as the light source of the illumination device 79. The illumination device 79 is disposed below the solid-state imaging device 110.

  The analysis device 70 is used for acquiring biometric data including any one of fingerprints, veins, irises, etc., and detecting DNA. Hereinafter, the operation of the analyzer 70 in these operations will be described.

[7] Acquisition of Biometric Data FIG. 10 is a schematic diagram illustrating a method for acquiring fingerprint data by the solid-state imaging device 110. First, the biopolymer analysis chip 1 is set in the analyzer 70, and the top gate driver 41, the bottom gate driver 42, and the drain driver 43 are set to the top gate lines 22a, 22a,..., The bottom gate lines 12a, 12a,. Connected to the drain lines 19a, 19a,. Further, the source lines 18a, 18a,... Are connected to a constant voltage source. Thereafter, the computer 71 is activated.

  Next, as shown in FIG. 10, a finger 80 is placed on top of the solid-state imaging device 110. Thereafter, the light source 79 is turned on by the computer 71, and the top gate driver 41, the bottom gate driver 42, and the drain driver 43 are caused to cooperate by the computer 71 while irradiating the finger 80 with near infrared light from the back surface of the solid-state imaging device 110. Then, the solid-state imaging device 110 is driven to acquire image data.

  Here, the light incident on the semiconductor film 14 of the photosensor 20 is light emitted from the light source 79 to the finger 80, scattered in the finger 80, and emitted from the surface of the finger 80. Therefore, in the semiconductor film 14 of the photosensor 3 in which the ridge 81 of the finger 80 is disposed on the upper side, the distance between the surface of the finger 80 and the semiconductor film 14 is short, so that more carriers are generated and acquired. The data has high brightness.

On the other hand, in the semiconductor film 14 of the photosensor 20 with the finger valley line 82 disposed on the upper side, the distance between the surface of the finger 80 and the semiconductor film 14 is long, so that the number of generated carriers is small, and the acquired image data has low luminance. It becomes.
The computer 71 stores the luminance distribution of each photosensor 20 of the solid-state imaging device 110 in the built-in storage device 4 as two-dimensional image data. As described above, fingerprint data is acquired.

[8] Detection of DNA [8-1] Preparation of fluorescently labeled DNA As a sample to be analyzed by the biopolymer analysis chip 1, DNA can be used. As the sample DNA, for example, DNA obtained by PCR reaction from genomic DNA extracted from white blood cells in blood (hereinafter referred to as sample DNA) can be used. Sample DNA is labeled with a fluorophore. A phosphor that is excited by the excitation light emitted from the excitation light irradiation device of the analyzer and emits fluorescence by the excitation light is selected. As the phosphor, for example, GE Healthcare Bioscience Co., Ltd. Company-made Cy2 (absorption wavelength 491 nm, fluorescence wavelength 509 nm), Cy3 (absorption wavelength 553 nm, fluorescence wavelength 569 nm), Cy5 (absorption wavelength 645 nm, fluorescence wavelength 664 nm), and the like can be used.

  In order to label the sample DNA with a phosphor, for example, an RT-PCR reaction may be carried out using an oligo dT primer labeled with a phosphor or a labeled dNTP mix. Hereinafter, this labeled sample DNA is referred to as fluorescently labeled DNA.

[8-2] Hybridization Hereinafter, a method of hybridizing the fluorescently labeled DNA with the probe DNA 61 will be described with reference to FIGS.

FIG. 11 is a schematic diagram showing a state in which a solution containing fluorescently labeled DNAs 62 and 63 (hereinafter referred to as a fluorescently labeled DNA solution) is dropped onto the DNA detection region 2 of the biopolymer analysis chip 1. The fluorescently labeled DNAs 62 and 63 have different base sequences.
First, as shown in FIG. 11, the operator drops a fluorescently labeled DNA solution onto the DNA detection region 2 of the biopolymer analysis chip 1. It should be noted that the fluorescently labeled DNA solution may be dropped on each of the spots 60, 60,. At this time, the fluorescently labeled DNA solution is heated so that the DNA becomes a single strand.

  Next, the biopolymer analysis chip 1 is cooled to a predetermined temperature at which DNA forms a double strand. Then, as shown in FIG. 12, of the fluorescently labeled DNA in the fluorescently labeled DNA solution, the fluorescently labeled DNA 62 complementary to the probe DNA 61 of the spot 60 hybridizes with the probe DNA 61. On the other hand, the fluorescently labeled DNA 63 that is not complementary to the probe DNA 61 does not bind to the spot 60.

  Thereafter, the fluorescently labeled DNA solution on the biopolymer analysis chip 1 is washed away with a washing buffer solution, and the non-hybridized fluorescently labeled DNA is removed from the biopolymer analysis chip 1.

[8-3] Detection of fluorescently labeled DNA Next, a method of detecting the fluorescently labeled DNA 62 will be described with reference to FIG.
After performing the above processing, the biopolymer analysis chip 1 is set in the analyzer 70, and the top gate driver 41, the bottom gate driver 42, and the drain driver 43 are respectively connected to the top gate lines 22a, 22a,. , 12a,..., Drain lines 19a, 19a,. Further, the source lines 18a, 18a,... Are connected to a constant voltage source. Thereafter, the computer 71 is activated.

  Next, the excitation light irradiation device 73 is controlled by the computer 71 to irradiate the biopolymer analysis chip 1 with the excitation light L of the phosphor 64. The excitation light irradiation device 73 may irradiate the excitation light L from the upper surface of the biopolymer analysis chip 1 or may irradiate the excitation light L from the lower surface.

  Fluorescence F (mainly in the visible light wavelength region) is emitted from the spot 60 where the fluorescently labeled DNA 62 is bonded to the probe DNA 61 when the phosphor 64 excited by the excitation light transitions from the excited state to the ground state.

As shown in FIG. 13, the emitted fluorescence F passes through the excitation light filter 24 and enters the photosensor 20.
Electron-hole pairs are generated in the photosensor 20 where the fluorescence is incident. Since the excitation light L does not pass through the excitation light filter, the excitation light L does not enter the photosensor 20 to generate electron-hole pairs, and noise due to the excitation light L can be reduced.

  Next, the computer 71 performs the above-described imaging operation, and acquires light amount data of each of the photosensors 20, 20,... Of the solid-state imaging device 10. Thereafter, the computer 71 adjusts the light amount data acquired by each photosensor 20 according to the sensor value correction data read from the built-in storage device 4, and then stores it in the storage device 72.

  The computer 71 causes the display device 78 to display the light amount data of each of the photosensors 20, 20,... Stored in the storage device 72 according to the operation of the operator.

  The portion corresponding to the spot 60 where the fluorescently labeled DNA is hybridized with the probe DNA is displayed brightly on the screen. On the other hand, the portion corresponding to the spot 60 where the fluorescently labeled DNA has not hybridized is displayed in a dark color on the screen.

  As described above, by looking at the brightness of each of the spots 60, 60,..., It can be determined whether or not DNA complementary to the probe DNA exists in the genomic DNA in the specimen.

  It should be noted that the image data displayed on the display device 78 may be output by the image output device 77, and the presence or absence of hybridization in each of the spots 60, 60,.

[9] Diagnosis Flow Next, gene diagnosis using the biopolymer analysis chip 1 will be described.
FIG. 14 is an operation flow performed by the analyzer 70 when the biopolymer analysis chip 1 is used for diagnosis.
First, in the analyzer 70 to which the biopolymer analysis chip 1 is attached, the computer 71 reads the year, month, day, hour, minute, and second when the biopolymer analysis chip 1 is manufactured from the built-in storage device 4 (step) S21). Next, the computer 71 determines whether or not the biopolymer analysis chip 1 is within the expiration date (step S22). For example, the expiration date is obtained by comparing the current year, month, day, hour, minute, and second with a value obtained by adding a predetermined expiration date to the read year, month, day, hour, minute, and second. It can be determined whether it is within or not. When it is determined that the expiration date has been exceeded (step S22 → No), ERROR is displayed.

  When it is determined that the expiration date has passed (step S22 → Yes), the computer 71 reads the spotter number (step S23) and the manufacturing location code (step S24) for manufacturing the biopolymer analysis chip 1 from the internal storage device 4. Then, it is determined whether or not the spotter number and the manufacturing location are appropriate (step S25). If it is determined that it is not appropriate (step S25 → No), ERROR display is performed.

  When it is determined that the spotter number and the manufacturing location are appropriate (step S25 → Yes), the computer 71 reads the DNA identification code from the built-in storage device 4 (step S26), and includes the DNA identification code used for genetic diagnosis. It is determined whether the chip is an appropriate chip (step S27). When it is determined that it is not appropriate (step S27 → No), ERROR display is performed.

If it is determined that the chip is appropriate (step S27 → Yes), the computer 71 writes 1 in the diagnosed flag (step S28).
Thereafter, using the biopolymer analysis chip 1 that has been diagnosed, biometric authentication data (fingerprint data) is acquired (step S29) and DNA data is acquired (step S30). As biometric authentication data, for example, fingerprint data can be obtained when blood is collected from a patient, and then the extracted and amplified DNA can be analyzed to obtain DNA data. Since fingerprint data is acquired at the time of blood collection and stored in the biopolymer analysis chip 1, it is possible to prevent the biopolymer analysis chip 1 from being mistaken by checking the fingerprint data, and further prevent leakage of personal information. can do. Furthermore, DNA data and fingerprint data may be stored in the built-in storage device 4 of the biopolymer analysis chip 1 for centralized management.
In addition, after collecting blood and acquiring DNA data, you may acquire fingerprint data from a patient.
In addition, fingerprint data is acquired as biometric authentication data in the present embodiment, but biometric authentication data including any one of vein data, iris data, and the like may be acquired.

1 is a schematic plan view of a biopolymer analysis chip 1 according to an embodiment of the present invention. It is the figure which expanded one spot 60 in FIG. 2 is a plan view showing one photosensor 20. FIG. FIG. 4 is a cross-sectional view taken along the line IV-IV in FIG. 3. It is a VV arrow sectional view of Drawing 2. 2 is a cross-sectional view showing a solid-state imaging device 110 in a biometric authentication area 3. FIG. 3 is a block diagram showing a configuration of an analysis device 70. FIG. (A) is a schematic diagram which shows the structure of the data memorize | stored in the memory | storage device, (b) is a schematic diagram which shows the structure of the fixed DNA data for a detection. 4 is a flow of writing data into the internal storage device 4 performed when the biopolymer analysis chip 1 is manufactured. 4 is a schematic diagram illustrating a method for acquiring fingerprint data by the solid-state imaging device 110. FIG. It is a schematic diagram which shows the state which dripped the fluorescence labeled DNA solution in the DNA detection area | region 2 of the biopolymer analysis chip | tip 1. FIG. FIG. 5 is a schematic diagram showing a state in which only fluorescently labeled DNA 62 is hybridized with probe DNA 61. It is a schematic diagram which shows the detection method of the fluorescence labeled DNA62. It is the operation | movement flow performed by the analyzer 70 when using the biopolymer analysis chip | tip 1 for a diagnosis.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Biopolymer analysis chip 4 Built-in memory | storage device 10,110 Solid-state imaging device (imaging apparatus)
20 Photosensor (light receiving element)
61 Probe DNA (probe)

Claims (6)

A first imaging device and a second imaging device each having a plurality of light receiving elements;
A storage device for storing image data captured by the first imaging device and the second imaging device;
The light receiving element of the first imaging device and the light receiving element of the second imaging device have the same structure,
The light receiving surface of the first imaging device is provided with a probe that binds to a specific biopolymer ,
A biopolymer analysis chip, wherein an electrostatic protective layer is provided on a light receiving surface of the second imaging device .   The biopolymer analysis chip according to claim 1, wherein the probe is a single-stranded DNA of a known base sequence.   The biopolymer analysis chip according to claim 1 or 2, wherein the first imaging device is used for detection of DNA.   The biopolymer analysis chip according to claim 3, wherein the second imaging device is used for biometric authentication other than DNA.   The biopolymer analysis chip according to any one of claims 1 to 4, wherein data for correcting the sensor value is stored in the storage device. The light receiving element has a source electrode, a drain electrode, a bottom gate electrode, a top gate electrode,
The first imaging device and the second imaging device have a common source line connected to the source electrode and a drain line connected to the drain electrode, or a bottom gate line connected to the bottom gate electrode. The biopolymer analysis chip according to claim 1, wherein a top gate line connected to the top gate electrode is common.

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