JP4576557B2 - Biopolymer analysis chip and analysis support device - Google Patents

Description

The present invention relates to a biopolymer analysis chip and an analysis support device used for specifying the structure of a biopolymer.

  In recent years, genetic information on living organisms has been used in a wide range of fields such as the medical field and the agricultural field. However, elucidation of the DNA structure is indispensable when using genes. DNA has two polynucleotide strands that are twisted in a spiral shape, and each polynucleotide strand is one-dimensionally composed of four types of bases (adenine: A, guanine: G, cytosine: C, thymine: T). Based on the complementarity of adenine and thymine and guanine and cytosine, the bases of one polynucleotide chain are bonded to the bases of the other polynucleotide chain.

  The elucidation of the structure of DNA is to specify the base sequence, and in order to specify the base sequence of DNA, a DNA microarray and its reader have been developed (Patent Document 1), and the DNA microarray and its reader are used. The base sequence of the sample DNA is specified as follows.

  First, a DNA microarray is prepared in which a plurality of types of cDNA having a known base sequence are aligned and fixed on a solid support such as a slide glass. Next, the sample DNA, which is an object to be detected, is denatured into single-stranded DNA, and a fluorescent substance or the like is bound to the denatured sample DNA.

  Next, when sample DNA is added onto the DNA microarray, the sample DNA is immobilized on the DNA microarray by hybridization. That is, the sample DNA is combined with complementary cDNAs among a plurality of types of cDNAs to form double strands. On the other hand, sample DNA does not bind to cDNA having no complementarity. Since the sample DNA is marked with a fluorescent substance, the cDNA combined with the sample DNA emits fluorescence. For example, sample DNA having a base sequence of TCGGGAA binds to cDNA having a base sequence of AGCCCTT, and the cDNA emits fluorescence.

Next, the DNA microarray is set in a reader and analyzed by the reader. The reader converges the excitation light emitted from the light source as a beam by a collimator lens, scans the beam two-dimensionally with respect to the DNA microarray, and also scans the condensing lens and the photomultiplier with the two-dimensional scan of the beam, The fluorescence emitted by the beam is condensed on a photomultiplier by a condensing lens, the fluorescence intensity is measured by the photomultiplier, and the fluorescence intensity distribution in the surface of the DNA microarray is measured by two-dimensional scanning. Thereby, the fluorescence intensity distribution on the DNA microarray is output as a two-dimensional image. In the output image, the portion having a high fluorescence intensity indicates that cDNA having a base sequence complementary to the base sequence of the sample DNA is included. Therefore, the base sequence of the sample DNA can be specified depending on which part of the two-dimensional image has a high fluorescence intensity.
JP 2000-1312237 A

  However, in order to analyze DNA using a conventional DNA microarray, a mechanism for scanning the DNA microarray with a beam, a photomultiplier or the like is required, and there is a problem that the entire reading apparatus is large.

Accordingly, the present invention has been made to solve the above-described problems, and provides a biopolymer analysis chip and an analysis support apparatus that can analyze a biopolymer without the need for a scanning mechanism. The purpose is to do.

In order to solve the above problems, a biopolymer analysis chip of the present invention includes a solid-state imaging device and an optical system in which a plurality of lenses are arranged in a plane so that the central axes of cylindrical lenses are parallel to each other An optical system that transmits an image from one surface to the other surface and forms one continuous image by the whole of the plurality of lenses , the one surface facing the light receiving surface of the solid-state imaging device. And a lens array placed on the light receiving surface of the solid-state imaging device so as to abut, an excitation light shielding film formed on the other surface of the lens array, and a known biopolymer, and the lens A plurality of spots scattered along the other surface of the array and spotted directly on the excitation light shielding film .

In the present invention, it is preferable that the lens array can be brought into contact with and separated from the light receiving surface of the solid-state imaging device .

In order to solve the above problems, an analysis support apparatus of the present invention is an optical system in which a solid-state imaging device and a plurality of lenses are arranged in a plane so that the central axes of cylindrical lenses are parallel to each other. An optical system that transmits an image from one surface to the other surface and forms one continuous image across the plurality of lenses , wherein the one surface faces the light receiving surface of the solid-state imaging device, and a lens array placed on the light receiving surface of the solid-state imaging device to abut, and the formed excitation light shielding film on the other surface of the lens array, made from known biopolymers, of the lens array A biopolymer analysis chip including a plurality of spots scattered along the other surface and directly spotted on the excitation light shielding film, and excitation for irradiating the biopolymer analysis chip with excitation light A light irradiation device is formed That.

  When using the above biopolymer analysis chip, a labeled sample is applied on the other surface of the optical transmission unit. The sample then binds to specific (eg, complementary) spots and not to non-specific spots. If excitation light is irradiated toward the other surface of the optical transmission unit, a fluorescence intensity distribution appears on the other surface of the optical transmission unit, and this fluorescence intensity distribution is displayed as an image from the other surface to the one surface. Is transmitted. For this reason, when imaging is performed with a solid-state imaging device, a portion with a spot bonded to the sample becomes brighter due to fluorescence, and a portion with a spot not bonded to the sample becomes darker. By using the biopolymer analysis chip manufactured as described above, a two-dimensional image can be obtained simply by imaging with a solid-state imaging device without performing scanning of a beam or the like, and analysis of a sample from the obtained image. It can be performed.

  According to the present invention, a two-dimensional image can be obtained simply by performing imaging with a solid-state imaging device without performing scanning, and biopolymers can be analyzed.

  In addition, since the optical transmission unit is mounted on the solid-state imaging device, the solid-state imaging device can be reused as it is by removing the optical transmission unit after using the biopolymer analysis chip.

  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.

[1] Overall Configuration of Biopolymer Analysis Chip FIG. 1 is a schematic plan view of a biopolymer analysis chip 1 according to an embodiment to which the present invention is applied, and FIG. 2 is an arrow of a cut surface II-II in FIG. FIG.

  The biopolymer analysis chip 1 includes a solid-state imaging device 3 in which photoelectric conversion elements are arranged in a matrix, a SELFOC lens array 33 as an optical transmission unit placed on the light-receiving surface of the solid-state imaging device 3, The excitation light shielding film 32 formed on the incident surface of the Selfoc lens array 33, and spots 60, 60,... Scattered in a matrix along the surface of the excitation light shielding film 32 are provided. Here, the excitation light is light in a wavelength region that excites a fluorescent material, phosphorescent material, or optical resonant scattering material, which will be described later, and the fluorescence is a fluorescent material, phosphorescent material, or optical resonant scattering material excited by the excitation light. The wavelength range of the excitation light is different from the wavelength range of the fluorescence. Specifically, the excitation light is light in the ultraviolet wavelength range, and the fluorescence is light in the visible wavelength range.

[2] Solid-State Imaging Device The solid-state imaging device 3 will be described in detail with reference to FIGS. Here, FIG. 2 is a plan view showing an electrode structure of a photoelectric conversion element that is a pixel of the solid-state imaging device 3, and FIG. 3 is a cross-sectional view of the photoelectric conversion element of the solid-state imaging device 3.

  In the solid-state imaging device 3, a double gate type field effect transistor (hereinafter referred to as a double gate transistor) 20 is used as a photoelectric conversion element. A plurality of double gate transistors 20, 20,... Are arranged in a matrix along the insulating substrate 17.

  The insulating substrate 17 has a property of transmitting light (hereinafter referred to as light transmitting property) and is electrically insulating, and is a glass substrate such as quartz glass or a plastic substrate such as polycarbonate or PMMA.

  Each of the double gate transistors 20, 20,... Includes a semiconductor film 23 that is a light receiving portion, a bottom gate electrode 21 formed under the semiconductor film 23 with the bottom gate insulating film 22 interposed therebetween, and a top gate insulating film 29. The top gate electrode 30 formed on the semiconductor film 23 with the sandwich, the impurity semiconductor film 25 formed so as to overlap with part of the semiconductor film 23, and the impurity formed so as to overlap with another part of the semiconductor film 23 A semiconductor film 26, a source electrode 27 overlapping the impurity semiconductor film 25, and a drain electrode 28 overlapping the impurity semiconductor film 25, and converting the electrical signal to a level according to the amount of light received by the semiconductor film 23 It is.

  A bottom gate electrode 21 is formed for each double gate transistor 20, and a plurality of bottom gate electrodes 21 are arranged in a matrix on the insulating substrate 17. Further, a plurality of bottom gate lines 41, 41,... Extending in the horizontal direction are formed on the insulating substrate 17, and the double gate transistors 20, 20,... In the same row arranged in the horizontal direction are formed. These bottom gate electrodes 21 are formed integrally with a common bottom gate line 41. The bottom gate electrode 21 and the bottom gate line 41 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 21 and the bottom gate lines 41, 41,... Of the double gate transistors 20, 20,. That is, the bottom gate insulating film 22 is a film formed in common to all the double gate transistors 20, 20,. The bottom gate insulating film 22 has insulating properties and light transmissive properties, and is made of, for example, silicon nitride (SiN) or silicon oxide (SiO ₂ ).

  On the bottom gate insulating film 22, a plurality of semiconductor films 23 are arranged in a matrix. The semiconductor film 23 is formed independently for each double gate transistor 20, and is disposed opposite to the bottom gate electrode 21 in each double gate transistor 20, and the bottom gate insulating film 22 is interposed between the bottom gate electrode 21. Is sandwiched. The semiconductor film 23 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 24 is formed on the semiconductor film 23. The channel protective film 24 is patterned independently for each double gate transistor 20, and is formed on the central portion of the semiconductor film 23 in each double gate transistor 20. The channel protective film 24 has insulating properties and light transmissive properties, and is made of, for example, silicon nitride or silicon oxide. The channel protective film 24 protects the interface of the semiconductor film 23 from an etchant used for patterning. When light enters the semiconductor film 23, an amount of electron-hole pairs according to the amount of incident light is generated around the interface between the channel protective film 24 and the semiconductor film 23. In this case, holes are generated as carriers on the semiconductor film 23 side, and electrons are generated on the channel protective film 24 side.

An impurity semiconductor film 25 is formed on one end portion of the semiconductor film 23 so as to partially overlap the channel protective film 24, and an impurity semiconductor film 26 is partially channeled on the other end portion of the semiconductor film 23. It is formed so as to overlap the protective film 24. The impurity semiconductor films 25 and 26 are patterned independently for each double gate transistor 20. The impurity semiconductor films 25 and 26 are made of amorphous silicon (n ⁺ silicon) containing n-type impurity ions.

  A source electrode 27 is formed on the impurity semiconductor film 25, and a drain electrode 28 is formed on the impurity semiconductor film 26. The source electrode 27 and the drain electrode 28 are formed for each double gate transistor 20. A plurality of source lines 42, 42,... And drain lines 43, 43,... Extending in the vertical direction are formed on the bottom gate insulating film 22. The source electrodes 27 of the double gate transistors 20, 20,... In the same column arranged in the vertical direction are formed integrally with the common source line 42, and the double gate transistors 20 in the same column arranged in the vertical direction. , 20,... Are formed integrally with a common drain line 43. The source electrode 27, the drain electrode 28, the source line 42, and the drain line 43 have conductivity and light shielding properties, and are made of, for example, chromium, a chromium alloy, aluminum, an aluminum alloy, or an alloy thereof.

  .. Of the double gate transistors 20, 20,... And the source lines 42, 42... And the drain lines 43, 43,. That is, the top gate insulating film 29 is a film formed in common to all the double gate transistors 20, 20,. The top gate insulating film 29 has insulating properties and light transmissive properties, and is made of, for example, silicon nitride or silicon oxide.

  A plurality of top gate electrodes 30 are arranged in a matrix on the top gate insulating film 29. The top gate electrode 30 is formed independently for each double gate transistor 20. The top gate electrode 30 is disposed opposite to the semiconductor film 23 in each double gate transistor 20, and the top gate insulating film 29 is interposed between the semiconductor film 23. It is sandwiched. Further, a plurality of top gate lines 44, 44,... Extending in the horizontal direction are formed on the top gate insulating film 29, and the double gate transistors 20, 20,. The top gate electrode 30 is formed integrally with a common top gate line 44. The top gate electrode 30 and the top gate line 44 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 30 and the top gate lines 44, 44,... Of the double gate transistors 20, 20,... Are collectively covered with a protective insulating film 31, and the protective insulating film 31 is common to all the double gate transistors 20, 20,. It is the film | membrane formed in this way. The protective insulating film 31 has insulating properties and light transmissive properties, and is made of silicon nitride or silicon oxide.

  The solid-state imaging device 3 configured as described above has the surface of the protective insulating film 31 as a light receiving surface, and is provided so as to convert the amount of light incident on the semiconductor film 23 of each double gate transistor 20 into the level of an electric signal. It has been.

[3] Selfoc Lens Array The Selfoc lens array 33 is an optical system in which the Selfoc lenses 34 are arranged so that the central axes of the plurality of cylindrical Selfoc lenses 34 are parallel to each other. This is an optical system that forms one continuous image with the entire lens 34. The refractive index of the Selfoc lens 34 continuously changes along the radial direction from the central axis of the Selfoc lens 34 to the cylindrical surface of the Selfoc lens 34.

  The Selfoc lens array 33 is placed on the light receiving surface of the solid-state imaging device 3 such that the emission surface (a set of circular lower surfaces of the Selfoc lens 34) faces and contacts the light receiving surface of the solid-state imaging device 3. In the Selfoc lens array 33 placed in this way, the center axis of the Selfoc lens 34 is perpendicular to the light receiving surface of the solid-state imaging device 3. The Selfoc lens array 33 can be brought into contact with and separated from the light receiving surface of the solid-state imaging device 3.

[4] Excitation light shielding film An excitation light shielding film 32 that shields excitation light and transmits fluorescence is formed on the incident surface of the Selfoc lens array 33 (a set of circular upper surfaces of the Selfoc lens 34). . The excitation light shielding film 32 is made of, for example, TiO ₂ .

[5] Spots As shown in FIGS. 1, 2, and 4, a plurality of types of spots 60, 60,... Are directly spotted on the excitation light shielding film 32, and the SELFOC lens array is interposed via the excitation light shielding film 32. 33 are scattered along the light receiving surface. These spots 60, 60,... Are spaced apart from each other and arranged in a matrix. The spot 60 is a cluster in which a large number of single-stranded probe DNAs 61 are gathered, and the multiple single-stranded probe DNAs 61 included in one spot 60 have the same base sequence (nucleotide sequence). Further, the base sequence of the single-stranded probe DNA 61 is different for each spot 60. Each spot 60 has a known base sequence.

  As shown in FIG. 1, spots 60, 60,... Are arranged so that one double gate transistor 20 overlaps one spot 60. It should be noted that several adjacent double gate transistors 20, 20,... Per spot 60 may overlap, but in this case, the number of double gate transistors 20 overlapped at any spot 60 is the same.

[6] DNA Analysis Method and Analysis Support Device Next, a method for analyzing a DNA base sequence using the biopolymer analysis chip 1 will be described.

  Since the biopolymer analysis chip 1 is set in the analysis support apparatus 70 shown in FIGS. 5 and 6 and the biopolymer analysis chip 1 is used, the analysis support apparatus 70 will be described first. FIG. 5 is a block diagram showing a configuration of the analysis support apparatus 70, and FIG. 6 is a side view when the biopolymer analysis chip 1 is set in the analysis support apparatus 70. In FIG. 6, the biopolymer analysis chip 1 is shown broken.

  The analysis support device 70 includes an analysis table 71 on which the biopolymer analysis chip 1 is set, an excitation light irradiation device 72 that emits excitation light from the light receiving surface of the solid-state imaging device 3 toward the light receiving surface, and solid-state imaging. A top gate driver 74, a bottom gate driver 75 and a drain driver 76 for driving the device 3, a controller 73 for controlling the excitation light irradiation device 72, the top gate driver 74, the bottom gate driver 75 and the drain driver 76, and an output from the controller 73 And an output device 77 that outputs (displays or prints) the received signal.

  The biopolymer analysis chip 1 can be attached to and detached from the analysis table 71. When the biopolymer analysis chip 1 is set on the analysis table 71, the top gate lines 44, 44,... Of the solid-state imaging device 3 are connected to the terminals of the top gate driver 74, respectively. Similarly, the bottom gate lines 41, 41,... Of the solid-state imaging device 3 are connected to the terminals of the bottom gate driver 75, respectively, and the drain lines 43, 43,. The When the biopolymer analysis chip 1 is set on the analysis table 71, the source lines 42, 42,... Of the solid-state imaging device 3 are connected to a constant voltage source, and in this example, the source lines 42, 42,. It has come to be.

  The excitation light irradiation device 72 is opposed to the analysis table 71 with a predetermined interval between the excitation table 72 and the analysis table 71. When the biopolymer analysis chip 1 is mounted on the analysis table 71, the excitation light irradiation device 72 irradiates the biopolymer analysis chip 1 with excitation light in a planar shape. The excitation light emitted from the excitation light irradiation device 72 is light in a wavelength region that excites a fluorescent material, phosphorescent material, or optical resonance scattering material described later. Note that the excitation light irradiation device 72 may be capable of changing the wavelength range of the emitted excitation light.

  The output device 77 is a plotter, a printer, or a display.

  The top gate driver 74, the bottom gate driver 75, and the drain driver 76 cooperate to drive the solid-state imaging device 3. The top gate driver 74 is a shift register. That is, as shown in FIG. 7, the top gate driver 74 sequentially outputs reset pulses to the top gate lines 44, 44,. The level of the reset pulse is a high level of +5 [V]. On the other hand, the top gate driver 74 applies a low level potential of −20 [V] to each top gate line 44 when no reset pulse is output.

  The bottom gate driver 75 is a shift register. That is, as shown in FIG. 7, the read pulses are sequentially output to the bottom gate lines 41, 41,. The level of the read pulse is a high level of +10 [V], and the level when the read pulse is not output is a low level of ± 0 [V].

  The top gate driver 74 outputs a read pulse to the bottom gate line 41 of the same row after the carrier accumulation period after the top gate driver 74 outputs the reset pulse to the top gate line 44 of any row. 74 and bottom gate driver 75 shift the output signal. That is, in each row, the timing at which the read pulse is output is delayed from the timing at which the reset pulse is output. The period from the start of reset pulse input to the top gate line 44 of any row to the end of read pulse input to the bottom gate line 41 of the same row is the selection period of that row. is there. The level of the reset pulse is a high level of +5 [V], and the level when the reset pulse is not output is a low level of −20 [V].

  As shown in FIG. 7, the drain driver 76 precharges all the drain lines 43, 43,... Between the reset pulse output and the read pulse output in the selection period of each row. Output a pulse. The level of the precharge pulse is a high level of +10 [V], and the level when the precharge pulse is not output is a low level of ± 0 [V]. In addition, the drain driver 76 amplifies the voltages of the drain lines 43, 43,...

  The controller 73 has a function of turning on the excitation light irradiation device 72. Further, the controller 73 outputs a control signal to the top gate driver 74, the bottom gate driver 75 and the drain driver 76, thereby driving the solid-state imaging device 3 to the top gate driver 74, the bottom gate driver 75 and the drain driver 76. Has the function to perform. In addition, the controller 73 has a function of acquiring the fluorescence intensity distribution along the light receiving surface of the solid-state imaging device 3 as two-dimensional image data by A / D converting the electric signal input from the drain driver 76. The controller 73 has a function of causing the output device 77 to output an image according to the input two-dimensional image data.

  The operation of the biopolymer analysis chip 1 and the analysis support device 70 and the DNA analysis method (identification method) will be described.

  First, an operator collects DNA from a specimen, denatures the collected double-stranded DNA into single-stranded DNA, and optionally performs PCR amplification. The obtained single-stranded DNA is subjected to fluorescent material, phosphorescent material or The optical resonance scattering material is bound, and the single-stranded DNA is labeled with a fluorescent material, a phosphorescent material, or an optical resonance scattering material. The fluorescent material, phosphorescent material, or optical resonance scattering material is selected from those excited by the excitation light emitted from the excitation light irradiation device 72 of the analysis support device 70. As the fluorescent material, for example, CyDye Cy2 (Amersham) Made). The obtained single-stranded DNA is contained in the solution. Hereinafter, this single-stranded DNA is referred to as sample DNA.

  Next, the operator applies a solution containing the sample DNA to the surface of the biopolymer analysis chip 1 (the surface of the excitation light shielding film 32). Here, in order to distribute the sample DNA to the biopolymer analysis chip 1, the sample DNA may be electrophoresed. A solution containing the sample DNA may be dropped on the spots 60, 60,... Sequentially or simultaneously. At this time, the solution containing the sample DNA is heated so that the single strand does not become a double strand.

  Thereafter, the biopolymer analysis chip 1 is cooled to a predetermined temperature in order to cause hybridization of the sample DNA. Thus, if any of the spots 60, 60,... Is complementary to the sample DNA, the sample DNA is bound to the probe DNA 61 of the complementary spot 60 by hybridization. On the other hand, if none of the spots 60, 60,... Is complementary to the sample DNA, the sample DNA will not bind to any of the spots 60, 60,.

  Thereafter, the sample DNA applied to the surface of the biopolymer analysis chip 1 that has not been hybridized is removed when washed away, and the hybridized DNA remains on the solid-state imaging device 3.

  Next, the operator sets the biopolymer analysis chip 1 on the analysis table 71, the biopolymer analysis chip 1 is made to face the excitation light irradiation device 72, and the top gate driver 74, the bottom gate driver 75 and the drain driver 76 are placed on the living body. The polymer analysis chip 1 is connected.

  Thereafter, when the controller 73 is activated, when the controller 73 controls the excitation light irradiation device 72 to turn on the excitation light irradiation device 72, excitation light is emitted from the excitation light irradiation device 72 toward the surface of the biopolymer analysis chip 1. Exit.

  Since the sample DNA is labeled, fluorescence is emitted from the spot 60 hybridized with the sample DNA among the spots 60, 60,..., And no fluorescence is emitted from the spot 60 that is not bound to the sample DNA. Spots 60, 60,... Are scattered on the entrance surface of the Selfoc lens array 33, and among them, there are spots 60 that emit fluorescence and spots 60 that do not emit fluorescence. Shows the distribution of fluorescence intensity. This fluorescence intensity distribution is transmitted as an image to the emission surface by the SELFOC lens array 33 and formed on the light receiving surface of the solid-state imaging device 3. When a phosphorescent material is bound to the sample DNA, fluorescent afterglow (phosphorescence) continues to be emitted from the spot 60 hybridized with the sample DNA even when the excitation light irradiation device 72 is turned off.

  Thereafter, when the fluorescent substance or the optical resonance scattering substance is bonded to the sample DNA, the excitation light irradiation device 72 is turned on. When the phosphorescent material is bonded to the sample DNA, the excitation light irradiation device 72 is turned off after being turned on. In this state, the controller 73 controls the top gate driver 74, the bottom gate driver 75, and the drain driver 76 to cause the solid-state imaging device 3 to perform an imaging operation. As a result, the solid-state imaging device 3 detects the light intensity or the amount of light with each of the double gate transistors 20, 20,..., And acquires the fluorescence intensity distribution along the light receiving surface as two-dimensional image data. The controller 73 inputs image data acquired by the solid-state imaging device 3 and outputs the image to the output device 77. Then, the controller process ends.

  The operator confirms the presence / absence of hybridization from the image data output by the output device 77, and specifies the base sequence of the sample DNA if hybridization has occurred. That is, since the base sequence of the sample DNA is a sequence complementary to the spot 60 that overlaps the pixel that emitted fluorescence by hybridization in the image, which part of the output image data emitted fluorescence. Thus, the base sequence of the sample DNA can be specified.

Here, the operation of the solid-state imaging device 3 by the top gate driver 74, the bottom gate driver 75, and the drain driver 76 will be described.
The top gate driver 74 sequentially outputs reset pulses from the top gate line 44 of the first row to the top gate line 44 of the last row, and the bottom gate driver 75 sequentially reads the read pulses to the bottom gate lines 41, 41, 41,. Is output. At that time, the drain driver 76 outputs a precharge pulse to all the drain lines 43, 43,... Between the reset period in which the reset pulse is output in each row and the period in which the read pulse is output in each row. .

  The operation of each double gate transistor 20 in an arbitrary i-th row from the first row to the last row will be described in detail. As shown in FIG. 7, when the top gate driver 74 outputs a reset pulse to the i-th top gate line 44, the i-th top gate line 44 goes to a high level. While the i-th top gate line 44 is at a high level (this period is referred to as a reset period), in each double-gate transistor 20 in the i-th row, the semiconductor film 23 and the channel protective film 24 The carriers (here, holes) accumulated near the interface with the surface are repelled and discharged by the voltage of the top gate electrode 30.

  Next, the top gate driver 74 finishes outputting the reset pulse to the i-th top gate line 44. The amount of light depends on the amount of light during the period from when the reset pulse of the top gate line 44 in the i-th row ends to when the read pulse is output to the bottom gate line 41 in the i-th row (this period is referred to as a carrier accumulation period). An amount of electron-hole pairs is generated in the semiconductor film 23, and the holes are accumulated in the semiconductor film 23 or in the vicinity of the interface between the semiconductor film 23 and the channel protective film 24 by the electric field of the top gate electrode 30. The

  Next, during the carrier accumulation period, the drain driver 76 outputs a precharge pulse to all the drain lines 43, 43,. While the precharge pulse is output (referred to as a precharge period), in each double gate transistor 20 in the i-th row, the potential applied to the top gate electrode 30 is −20 [V], and the bottom Since the potential applied to the gate electrode 21 is ± 0 [V], even if only the charge of holes accumulated in the semiconductor film 23 or in the vicinity of the interface between the semiconductor film 23 and the channel protective film 24 is gate-source. Since the interpotential is low, no channel is formed in the semiconductor film 23, and no current flows between the drain electrode 28 and the source electrode 27. Since no current flows between the drain electrode 28 and the source electrode 27 during the precharge period, the drain electrode 28 of each double gate transistor 20 in the i-th row is output by the precharge pulse output to the drain lines 43, 43,. Is charged.

  Next, the drain driver 76 finishes outputting the precharge pulse, and the bottom gate driver 75 outputs a read pulse to the i-th bottom gate line 41. While the bottom gate driver 75 outputs a read pulse to the i-th bottom gate line 41 (this period is referred to as a read period), +10 is applied to the bottom gate electrode 21 of each i-th double gate transistor 20. Since the potential of [V] is applied, each double gate transistor 20 in the i-th row is turned on.

  In the read period, the carriers accumulated in the carrier accumulation period work so as to alleviate the negative electric field of the top gate electrode 30, so that an n channel is formed in the semiconductor film 23 by the positive electric field of the bottom gate electrode 21, and the drain electrode Current flows from 28 to the source electrode 27. Therefore, in the read period, the voltages of the drain lines 43, 43,... Tend to gradually decrease with time due to the drain-source current.

  Here, as the amount of light incident on the semiconductor film 23 in the carrier accumulation period increases, the number of accumulated carriers also increases. As the number of accumulated carriers increases, the current flowing from the drain electrode 28 to the source electrode 27 in the read period is increased. The level also increases. Therefore, the voltage change tendency of the drain lines 43, 43,... During the read period is deeply related to the amount of light incident on the semiconductor film 23 during the carrier accumulation period. Then, during the period from the read period of the i-th row to the precharge period of the next i + 1-th row (however, if the i-th row is the last row, the i + 1-th row is the first row) Via the driver 76, the voltage of the drain lines 43, 43,... After a predetermined time has elapsed since the start of the read period is detected and A / D converted. Thereby, it converts into the intensity | strength of light. Note that the time required to reach a predetermined threshold voltage may be detected via the drain driver 76 between the i-th read period and the next (i + 1) -th precharge period. Even in this case, the light intensity is converted. In FIG. 7, the rising timing of the reset pulse of the (i + 1) -th row of the top gate driver 74 is after the read pulse of the i-th row of the bottom gate driver 75 falls. The rising timing of the reset pulse of the (i + 1) -th row of the gate driver 74 is from immediately after the falling edge of the reset pulse of the i-th row of the top gate driver 74 to the falling edge of the read pulse of the i-th row of the bottom gate driver 75. It may be. However, the output of the precharge pulse output to the drain lines 43, 43,... For the double gate transistor 20 in the (i + 1) -th row is after the falling edge of the read pulse in the i-th row of the bottom gate driver 75. Is set to

  The above-described series of image reading operations is set as one cycle, and the same processing procedure is repeated for each double gate transistor 20 in all rows, whereby the light intensity distribution on the biopolymer analysis chip 1 is acquired as an image. . Then, an image representing the fluorescence intensity distribution is input to the controller.

  As described above, according to the present embodiment, since the spots 60, 60,... Are scattered on the Selfoc lens array 33 placed on the solid-state imaging device 3, the solid-state imaging device is not scanned. A two-dimensional image can be obtained simply by taking an image at 3. Furthermore, since the clear image can be obtained with the solid-state imaging device 3 without providing a lens in the analysis support apparatus 70, the analysis support apparatus 70 can be downsized. Further, since the spots 60, 60,... Are scattered on the SELFOC lens array 33, the light emitted from the spot 60 is incident on the light receiving surface of the solid-state imaging device 3 without being attenuated. Therefore, the sensitivity of the solid-state imaging device 3 does not have to be high.

  Further, since the Selfoc lens array 33 is mounted on the solid-state imaging device 3, the solid-state imaging device 3 can be reused by removing the Selfoc lens array 33 after using the biopolymer analysis chip 1.

[Modification 1]
In the biopolymer analysis chip 1, the solid-state imaging device 3 using the double gate transistors 20, 20,... As the pixels is used as the photoelectric conversion element, but the solid-state imaging using another type of photoelectric conversion element as the pixel. The device may be used for a biopolymer analysis chip. For example, a solid-state imaging device such as a CCD image sensor or a CMOS image sensor using a photodiode as a pixel may be used. In a CCD image sensor, photodiodes are arranged in a matrix on a substrate, and around each photodiode, a vertical CCD and a horizontal CCD for transferring an electrical signal photoelectrically converted by the photodiode. Is formed. In a CMOS image sensor, photodiodes are arranged in a matrix on a substrate, and a CMOS circuit for amplifying an electric signal photoelectrically converted by the photodiodes is provided around each photodiode. Yes.

[Modification 2]
In the biopolymer analysis chip 1, the spot 60 is made of single-stranded DNA with a known base sequence. However, other known biopolymers such as proteins with known amino acid sequences and peptide sequences, known What consists of a cell etc. may be sufficient. Therefore, the biopolymer analysis chip 1 can analyze the amino acid sequence and peptide sequence of the protein.

[Modification 3]
In the above embodiment, the excitation light emitted from the excitation light irradiation device 72 is ultraviolet light, and the fluorescence emitted from the sample DNA by the excitation light is visible light. However, the wavelength range of such light is not limited. However, the excitation light emitted from the excitation light irradiation device 72 is light in a wavelength range that excites the labeling substance bonded to the sample DNA, and the wavelength range of the light emitted from the labeling substance by the excitation light is the wavelength range of the excitation light. It is necessary to be different. Moreover, it is necessary for the solid-state imaging device 3 to exhibit sensitivity to light emitted from the labeling substance.

[Modification 4]
In the analysis support apparatus 70, the controller 73 outputs an image according to the image data input from the solid-state imaging device 3 to the output apparatus 77, and the operator specifies the sequence of the sample DNA from the output image. The controller 73 may specify the sequence of the sample DNA. That is, the controller identifies which part in the image data emits fluorescence by the feature extraction process, identifies the spot 60 corresponding to the part emitting fluorescence, and a base complementary to the identified spot 60 Output the array from the output device.

[Modification 5]
Further, the excitation light shielding film 32 may not be formed on the incident surface of the Selfoc lens array 33, and the spots 60, 60,... May be directly spotted on the incident surface of the Selfoc lens array 33. In that case, each Selfoc lens 34 of the Selfoc lens array 33 may be formed of a material (for example, TiO ₂ ) having excitation light shielding properties and fluorescence transmission.

1 is a schematic plan view of a biopolymer analysis chip 1 in an embodiment of the present invention. It is sectional drawing along the cut surface II of FIG. 3 is a plan view of one pixel of the solid-state imaging device 3. FIG. FIG. 4 is a cross-sectional view taken along a cutting plane IV in FIG. 3. 3 is a block diagram showing a circuit configuration of an analysis support apparatus 70. FIG. 3 is a schematic side view of an analysis support apparatus 70. FIG. 6 is a timing chart showing the transition of the level of an electric signal output to the solid-state imaging device 3 by a driver.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 ... Biopolymer analysis chip 3 ... Solid-state imaging device 32 ... Excitation light shielding film 33 ... Selfoc lens array (optical transmission part)
60 ... spot

Claims (3)

A solid-state imaging device;
An optical system in which a plurality of the lenses are arranged in a plane so that the central axes of the cylindrical lenses are parallel to each other, and an image is transmitted from one surface to the other surface, and one entire continuous lens A lens array placed on the light receiving surface of the solid-state imaging device so that the one surface faces and contacts the light-receiving surface of the solid-state imaging device;
An excitation light shielding film formed on the other surface of the lens array;
A biopolymer analysis comprising a plurality of types of spots made of known biopolymers, scattered along the other surface of the lens array , and spotted directly on the excitation light shielding film Chip. The biopolymer analysis chip according to claim 1, wherein the lens array is capable of contacting and separating from the light receiving surface of the solid-state imaging device.   An optical system in which a plurality of lenses are arranged in a plane so that the central axes of a solid-state imaging device and a cylindrical lens are parallel to each other, and an image is transmitted from one surface to the other surface, and the plurality of lenses An optical system that forms one continuous image as a whole, wherein the one surface faces the light receiving surface of the solid-state imaging device and is placed on the light-receiving surface of the solid-state imaging device An array, an excitation light shielding film formed on the other surface of the lens array, and a known biopolymer, interspersed along the other surface of the lens array, and directly on the excitation light shielding film A plurality of spotted spots, a biopolymer analysis chip comprising:
  An analysis support apparatus, comprising: an excitation light irradiation device configured to irradiate the biopolymer analysis chip with excitation light.

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