JP4395616B2 - Biopolymer analysis support apparatus and control method thereof - Google Patents

Description

  The present invention relates to a biopolymer analysis support apparatus used for specifying the structure of a biopolymer and a control method thereof.

  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 the sample DNA is applied on the DNA microarray, the sample DNA is fixed 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 DNA microarray two-dimensionally with the beam, causes the condenser lens and photomal to follow the two-dimensional scanning of the beam, and emits the beam. The fluorescence is condensed onto a photomultiplier by a condensing lens, the fluorescence intensity is measured with the photomultiplier, and the fluorescence intensity distribution within 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, there is a problem that a small amount of DNA must be efficiently distributed on the DNA microarray.

  Accordingly, the present invention has been made to solve the above-described problems, and an object thereof is to provide a biopolymer analysis support apparatus capable of efficiently distributing DNA.

In order to solve the above problems, the biopolymer analysis support apparatus of the present invention is
An insulating substrate; a plurality of bottom gate lines arranged on the insulating substrate; a plurality of photosensitive semiconductor films arranged on the bottom gate lines along the bottom gate lines; A photosensor having a plurality of top gate lines opposed to each bottom gate line across the semiconductor film and provided along each bottom gate line, and a protective insulating film covering the plurality of top gate lines An array,
A plurality of spots made of known biopolymers and scattered on the surface of the protective insulating film,
And a top gate driver that applies a voltage for attracting an unknown biopolymer to the biopolymer to at least one of the plurality of top gate lines.

The control method of the biopolymer analysis support apparatus of the present invention includes:
An insulating substrate; a plurality of bottom gate lines arranged parallel to each other on the insulating substrate; and a plurality of photosensitive semiconductor films arranged on the bottom gate lines along the bottom gate lines. And a plurality of top gate lines facing each bottom gate line across the plurality of semiconductor films and parallel to each bottom gate line, and protective insulation covering the plurality of top gate lines A photosensor array having a film;
A method for controlling a biopolymer analysis support device comprising a known biopolymer and having a plurality of types of spots scattered on the surface of the protective insulating film,
A voltage for attracting an unknown biopolymer to the biopolymer is applied to at least one of the plurality of top gate lines.

  When using the biopolymer analysis support apparatus described above, a solution containing a fluorescently labeled sample is dispersed on the protective insulating film of the photosensor array. When a positive voltage is applied to at least one of the plurality of top gate lines by the top gate driver, the sample in the solution moves and the sample is concentrated into spots on the protective insulating film. This makes it easier for the sample to bind to specific (eg, complementary) spots. On the other hand, it does not bind to non-specific spots. Thereafter, the photosensor array performs an imaging operation. Here, if imaging is performed with the photosensor array in a state where the photosensor array is irradiated with excitation light, the spot portion bonded to the sample becomes brighter due to the fluorescence, and the spot portion not bonded to the sample becomes darker. .

  In this manner, unknown biopolymers (samples) can be efficiently attracted using the members constituting the photosensor array.

  ADVANTAGE OF THE INVENTION According to this invention, an unknown biopolymer can be attracted efficiently using the member which comprises a photosensor array.

  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 Support Device FIG. 1 is a block diagram of the biopolymer analysis support device 1, FIG. 2 is a circuit diagram of the photosensor array 3 and its peripheral circuits, and FIG. FIG. 4 is a schematic plan view of the photosensor array 3, and FIG. 4 is a cross-sectional view taken along line IV-IV shown in FIG. 3.

  As shown in FIGS. 1 to 4, the biopolymer analysis support apparatus 1 is roughly divided into a photosensor array 3 configured by two-dimensionally arranging a plurality of photosensors 20, 20,. .., A top gate driver 74, a bottom gate driver 75 and a drain driver 76 for driving the photosensor array 3 in cooperation with each other, and the photosensor array 3 The excitation light irradiation device 72 that irradiates the light receiving surface toward the light receiving surface, the controller 73 that controls the excitation light irradiation device 72, the top gate driver 74, the bottom gate driver 75, and the drain driver 76, and the drain driver 76 An A / D converter 78 for A / D converting the signal and outputting it to the controller 73; An output device 77 for outputting (displaying or printing) by the signal, and a.

[2] Photosensor Array The photosensor array 3 will be described in detail with reference to FIGS. Here, FIG. 5 is a plan view showing the electrode structure of the photosensor 20, and FIG. 6 is a cross-sectional view of the photosensor 20.

  3 to 6, the photosensor array 3 includes an insulating substrate 17, bottom gate lines 41, 41,... Arranged on the insulating substrate 17 so as to be parallel to each other, and these bottom gate lines 41. , 41, ..., the bottom gate insulating film 22, the photosensitive semiconductor films 23, 23, ... arranged along the bottom gate lines 41 on the bottom gate insulating film 22, and the bottom gate insulating film 22 , And the drain lines arranged alternately with the source lines 42, 42,... On the bottom gate insulating film 22. And the top gate insulating film 29 covering the source lines 42, 42,... And the drain lines 43, 43,. The top gate lines 44, 44,... Provided in parallel on the insulating film 29 along the respective bottom gate lines 41 and disposed so as to face the respective bottom gate lines 41 in plan view, , And a protective insulating film 31 covering the gate lines 44, 44,.

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

  On the bottom gate insulating film 22, the semiconductor films 23, 23,... Are arranged in a matrix of n rows and m columns, and the photosensors 20, 20,. . Here, n and m are both natural numbers of 2 or more, the number of the bottom gate lines 41 and the number of the top gate lines 44 are each n, the number of the source lines 42 and the number of the drain lines 43 are m and respectively. Become. Hereinafter, “row” is defined by the longitudinal direction of the bottom gate line 41 and the top gate line 44, and the longitudinal direction of the bottom gate line 41 and the top gate line 44 is referred to as a row direction. A “column” is defined by the longitudinal direction of the source line 42 and the drain line 43, and the longitudinal direction of the source line 42 and the drain line 43 is referred to as a column direction.

  As shown in FIG. 3 and FIG. 5, the bottom gate line 41 is provided with a wide width at the portion overlapping each semiconductor film 23, and the widened portion becomes the bottom gate 21 of the photosensor 20. The top gate line 44 is also provided with a wide width at a portion that overlaps each semiconductor film 23, and the widened portion becomes the top gate 30 of the photosensor 20. The source line 42 is provided wide at a position where it intersects with each bottom gate line 41 in plan view, and the widened portion becomes the source 27 of the photosensor 20. The drain line 43 is also provided with a wide width at a position where it intersects with each bottom gate line 41, and the widened portion becomes the drain 28 of the photosensor 20.

  The photosensor 20 is a double gate transistor type photoelectric conversion element. As shown in FIGS. 4 to 5, the photosensor 20 includes a bottom gate 21 formed on the insulating substrate 17, a semiconductor film 23 facing the bottom gate 21 with the bottom gate insulating film 22 interposed therebetween, and a semiconductor film 23. A channel protective film 24 formed on the central portion of the semiconductor film 23, impurity semiconductor films 25 and 26 formed on both ends of the semiconductor film 23 so as to be separated from each other, a source 27 formed on the impurity semiconductor film 25, A drain 28 formed on the impurity semiconductor film 26 and a top gate 30 facing the semiconductor film 23 with a top gate insulating film 29 interposed therebetween are configured.

  The bottom gate 21 is formed on the insulating substrate 17 for each photosensor 20. The bottom gates 21 of the photosensors 20, 20,... In the same row arranged in the row direction are formed integrally with a common bottom gate line 41. The bottom gate 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 insulating film 22 is formed on the entire surface common to all the photosensors 20, 20,..., And the bottom gate 21 and the bottom gate lines 41, 41,. Covered together. 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 ).

  A semiconductor film 23 is formed for each photosensor 20 on the bottom gate insulating film 22. 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 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 for each photosensor 20. The impurity semiconductor films 25 and 26 are made of amorphous silicon (n ⁺ silicon) containing n-type impurity ions.

  A source 27 patterned for each photosensor 20 is formed on the impurity semiconductor film 25. A drain 28 patterned for each photosensor 20 is formed on the impurity semiconductor film 26. The sources 27 of the photosensors 20, 20,... Arranged in the column direction are formed integrally with a common source line 42, and the photosensors 20, 20,. Each drain 28 is formed integrally with a common drain line 43. The source 27, the drain 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.

  The top gate insulating film 29 is formed on the entire surface common to all the photosensors 20, 20,..., And the channel protective film 24, the source 27 and the drain 28 of the photosensors 20, 20,. .. And the drain lines 43, 43,... Are collectively covered. 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 top gate 30 patterned for each photosensor 20 is formed on the top gate insulating film 29. The top gates 30 of the photosensors 20, 20,... Arranged in the row direction are formed integrally with a common top gate line 44. The top gate 30 and the top gate line 44 are conductive and light transmissive, for example, indium oxide, zinc oxide, tin oxide, or a mixture including at least one of them (eg, tin-doped indium oxide (ITO ), Zinc-doped indium oxide).

  The top gate 30 and the top gate lines 44, 44,... Of the photosensors 20, 20,... Are collectively covered with a protective insulating film 31 formed on the entire surface. The protective insulating film 31 has insulating properties and light transmissive properties, and is made of silicon nitride or silicon oxide.

  The photosensor array 3 configured as described above uses the surface of the protective insulating film 31 as a light receiving surface, and converts the amount of light received by the semiconductor film 23 of each photosensor 20 into an electrical signal.

An excitation light shielding film that shields excitation light and transmits visible light may be formed on the surface of the protective insulating film 31. The excitation light shielding film is made of, for example, TiO ₂ and has a property of shielding ultraviolet rays in particular as excitation light.

[3] Spot Next, the spot 60 will be described. 3, 4, and 6, a plurality of types of spots 60, 60,... Are separated from each other and arranged in a matrix on the light receiving surface of the photosensor array 3. One spot 60 is a cluster in which a large number of single-stranded probe DNAs 61 are gathered, and the many probe DNAs 61 included in one spot 60 have the same base sequence (nucleotide sequence). Further, the base sequence of the probe DNA 61 is different for each spot 60. Since bases such as polynucleotide nucleic acids constituting DNA only spirally bind or hybridize with a polymer having only a complementary base sequence, the probe DNA 61 of each spot 60 has hybridization characteristics corresponding to individual information. Have. Each spot 60 has a known base sequence. The probe DNA 61 is spotted on the light receiving surface of the photosensor array 3 by the surface coating material 32.

  Spots 60, 60,... Are arranged so that one photosensor 20 overlaps one spot 60. It should be noted that several adjacent photosensors 20, 20,... Per spot 60 may overlap, but in this case, the number of photosensors 20 overlapped at any spot 60 is the same.

[4] Photosensor Array Drive Circuit and Controller As shown in FIGS. 1 and 2, the photosensor array 3 is driven by a top gate driver 74, a bottom gate driver 75, and a drain driver 76.

  The top gate driver 74 is connected to the top gate lines 44, 44,..., And the bottom gate driver 75 is connected to the bottom gate lines 41, 41,. The drain driver 76 includes a column switch 81, a precharge switch 82, and an amplifier 83. The column switch 81 is connected to the drain lines 43, 43,.

  The photosensor array 3 is detachably provided to the top gate driver 74, the bottom gate driver 75, and the drain driver 76. When the photosensor array 3 is attached to the top gate driver 74, the bottom gate driver 75, and the drain driver 76, the source lines 42, 42,... Are connected to a constant voltage source, specifically, the source lines 42, 42,. Are connected to the ground of ± 0 [V].

  The top gate driver 74, the bottom gate driver 75, and the drain driver 76 are controlled by the controller 73. FIG. 7 is a timing chart of signals output from the top gate driver 74, the bottom gate driver 75, and the controller 73.

  The control signal φchm shown in FIGS. 1, 2, 7, etc. is a signal output from the controller 73 to the top gate driver 74 and the bottom gate driver 75, and the control signal φtg is output from the controller 73 to the top gate driver 74. The control signal φtb is a signal output from the controller 73 to the bottom gate driver 75, and the control signal φpg is a signal output from the controller 73 to the precharge switch 82 of the drain driver 76. is there. The controller 73 outputs the control signal φchm to the top gate driver 74 and the bottom gate driver 75 as a high level pulse, thereby operating the top gate driver 74 and the bottom gate driver 75 in the target movement mode M1.

  The controller 73 outputs the control signal φtg to the top gate driver 74 to operate the top gate driver 74 in the sensor detection mode M2 after the target movement mode M1. Further, the controller 73 operates the bottom gate driver 75 in the sensor detection mode M2 by outputting a control signal φbg to the bottom gate driver 75. Here, the controller 73 outputs a control signal φchm, a control signal φtg, and a control signal φbg.

2 and 7, signals φT <b> 1 to φTn are signals output to the top gate lines 44 by the top gate driver 74. The numbers given to the signals φT1 to φTn represent the row numbers of the top gate lines 44. That is, for example, the output voltage to the top gate line 44 in the first row is the signal φT1, and the output voltage to the top gate line 44 in the second row is the signal φT2. The signals φB1 to φBn are signals output to the bottom gate lines 41 by the bottom gate driver 75. The numbers given to the signals φB1 to φBn represent the row numbers of the bottom gate lines 41.
The top gate driver 74 selects and takes in the switch that switches the input control signal φchm for a predetermined period in the target movement mode M1, and deselects the switch that switches the input control signal φtg (high impedance state). And the control signal φchm is set to be output to a predetermined top gate line 44 for a predetermined period in the target movement mode M1. Thereafter, during the sensor detection mode M2, the top gate driver 74 selects the switch that switches the input control signal φtg without taking in the switch that switches the input control signal φchm by deselecting (high impedance state). The shift pulse (reset pulse) of the control signal φtg is sequentially output to each top gate line 44.

  Specifically, as shown in FIG. 2 and FIG. 7, the top gate driver 74 to which the control signal φchm is input has a high level pulse voltage exceeding ± 0 [V] in the target movement mode M1 (in FIG. 7, , +15 [V] as an example) is applied to at least one of the top gate lines 44, 44,. Of course, a pulse voltage may be applied to all the top gate lines 44, 44,.

  The top gate driver 74 that appropriately takes in the control signal φtg receives high-level reset pulses φT1 to φTn exceeding ± 0 [V] (in FIG. 7, as an example, +15 [V]) as the top gate line 44, 44,... When the signals φT1 to φTn are at a low level, the top gate lines 44, 44,... Of the first row to the nth row are respectively −15 [V].

  The bottom gate driver 75 that appropriately takes in the control signal φbg applies high-level read pulses φB1 to φBn to the bottom gate lines 41, 41,. When the signals φB1 to φBn are at a low level, the bottom gate lines 41, 41,... Of the first to nth rows are ± 0 [V], respectively.

  The timing of the reset pulse and the read pulse will be described with reference to FIGS. Here, FIG. 8 shows that in the sensor detection mode M2, the top gate driver 74 applies a high-level reset pulse to the i-th top gate line 44 and the bottom gate driver 75 then applies the (i + 1) -th bottom gate. 4 is a timing chart of signals output by a top gate driver 74, a bottom gate driver 75, and a drain driver 76 until a high level read pulse is applied to a line 41; Note that i is an arbitrary number from 1 to n.

  As shown in FIGS. 7 and 8, after the top gate driver 74 applies a high level reset pulse to the top gate line 44 of any row, the bottom gate driver 75 passes the bottom gate line 41 of the same row after a predetermined time. The top gate driver 74 and the bottom gate driver 75 shift the output signal so that a high level read pulse is applied to the output signal. That is, in each row, the timing at which the high level read pulse is output is delayed from the timing at which the high level reset pulse is output.

  In FIG. 8, the reset time Treset is the time during which a high level reset pulse is applied, the read time Tread is the time during which a high level read pulse is applied, and the storage time Te is a high level. This is the time from the end of applying the reset pulse to the start of applying a high level read pulse.

  As shown in FIG. 8, the control signal φpg is an amplitude signal that becomes a high level during the storage time Te of any row in the sensor detection mode M2. When the control signal φpg goes high, the precharge switch 82 is turned on, and the precharge voltage Vpg is applied to all the drain lines 43, 43,. When the control signal φpg is at a low level, the precharge switch 82 is off, so that the precharge voltage Vpg is not applied to any of the drain lines 43, 43,. In FIG. 8, a precharge time Tprch is a time during which the control signal φpg is at a high level.

  The column switch 81 outputs the voltages of the drain lines 43, 43,... To the amplifier 83 in the column order after application of the precharge voltage Vpg. The voltage amplified by the amplifier is converted into a digital image signal by the A / D converter 78, and the A / D converted image signal is input to the controller 73.

  The controller 73 has a function of turning on the excitation light irradiation device 72. Further, the controller 73 has a function of causing the top gate driver 74 to operate in the target movement mode M1 by outputting the control signal φchm and causing the photosensor array 3 to move DNA.

  In addition, the controller 73 outputs the control signal φtg, the control signal φbg, and the control signal φpg to operate the top gate driver 74, the bottom gate driver 75, and the drain driver 76 in the sensor detection mode M2, thereby capturing the image of the photosensor array 3. It has a function to perform the operation. Thus, the controller 73 has a function of acquiring the light intensity distribution along the light receiving surface of the photosensor array 3 as two-dimensional image data by inputting the image signal input from the drain driver 76 through the A / D converter 78. Have.

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

[5] DNA analysis method, control method of biopolymer analysis support device, operation of biopolymer analysis support device

  Next, a method for analyzing the base sequence of DNA using the biopolymer analysis support apparatus 1 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 biopolymer analysis support device 1. As the fluorescent material, for example, Cy2 of CyDye (Amersham). The obtained single-stranded DNA is contained in the solution. Hereinafter, this single-stranded DNA is referred to as sample DNA.

  The photosensor array 3 is set, the photosensor array 3 is connected to the top gate driver 74, the bottom gate driver 75, and the drain driver 76, and the excitation light irradiation device 72 is opposed to the light receiving surface of the photosensor array 3.

  Next, a solution containing the sample DNA is applied to the light receiving surface of the photosensor array 3. At this time, the solution containing the sample DNA is heated so that the single strand does not become a double strand.

  Next, when the controller 73 is activated, the controller 73 outputs a control signal φchm to the top gate driver 74 and the bottom gate driver 75. Then, the top gate driver 74 and the bottom gate driver 75 operate in the target movement mode M1. That is, as shown in FIG. 7, the top gate driver 74 applies a high level pulse voltage to at least one of the top gate lines 44, 44,.

  The movement of the sample DNA 99 in the target movement mode M1 will be described with reference to the schematic diagrams of FIGS. As shown in FIG. 9, when a high level pulse is not applied to the top gate lines 44, 44,..., The sample DNA 99 is floating in the solution on the light receiving surface of the photosensor array 3. After that, as shown in FIG. 10, since a high level pulse voltage is applied to at least one of the top gate lines 44, 44,..., In the photosensors 20 of those rows, the top gate 30 is applied. A positive voltage is applied. As a result, the sample DNA 99 that has floated migrates so as to be concentrated in the spot 60 corresponding to the photosensor 20. Therefore, the concentration of the sample DNA 99 is concentrated around the spot 60 corresponding to the row of the top gate line 44 to which a positive voltage is applied. Therefore, the sample DNA 99 is easily hybridized to the probe DNA 61 of the spot 60 in a short time.

  When a high-level pulse voltage is applied by the top gate driver 74, if there is a spot DNA complementary to the sample DNA in the spots 60, 60,..., The sample DNA 99 is complementary to the probe DNA 61 of the spot 60. And bind by hybridization. On the other hand, if none of the spots 60, 60,... Is complementary to the sample DNA 99, the sample DNA does not bind to any of the spots 60, 60,.

  When the pulse voltage by the top gate driver 74 ends, the dense sample DNA 999 dissociates and floats in the solution.

  Thereafter, the sample DNA applied to the light receiving surface of the photosensor array 3 that has not been hybridized is removed when washed away, and the hybridized DNA remains on the photosensor array 3.

  Thereafter, 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 light receiving surface of the photosensor array 3.

  Since the sample DNA is labeled, the spot 60 hybridized with the sample DNA out of the spots 60, 60,... Emits fluorescence (mainly in the visible light wavelength region), and from the spot 60 that does not bind to the sample DNA. Does not emit fluorescence. Therefore, high intensity fluorescence is incident on the photosensor 20 corresponding to the spot 60 bonded to the sample DNA, and almost no fluorescence is incident on the photosensor 20 corresponding to the spot 60 not bonded to the sample DNA. Since the spots 60, 60,... Are fixed on the light receiving surface of the photosensor array 3, the fluorescence emitted from the spot 60 combined with the sample DNA is not attenuated so much and enters the photosensor 20 corresponding to the spot 60. Thus, electron-hole pairs are generated. Therefore, even if the sensitivity of the photosensors 20, 20,... Is low, the intensity can be sufficiently detected. When the phosphorescent material is bonded to the sample DNA, phosphorescence (mainly in the visible light wavelength region) continues to be emitted from the spot 60 hybridized with the sample DNA even when the excitation light irradiation device 72 is turned off.

  After that (after a predetermined time has elapsed since the high-level pulse voltage has ended), when the fluorescent substance or the optical resonance scattering substance is bound to the sample DNA, the phosphorescent material is applied to the sample DNA while the excitation light irradiation device 72 is lit. When the excitation light irradiation device 72 is turned off after being turned on, the controller 73 outputs the control signal φtg, the control signal φbg, and the control signal φpg to the top gate driver 74, the bottom gate driver 75, and the drain driver 76, respectively. Thus, the top gate driver 74, the bottom gate driver 75, and the drain driver 76 drive the photosensor array 3 in the sensor detection mode M2.

  In the sensor detection mode M2, as shown in FIG. 7, the top gate driver 74 applies a reset pulse to the top gate lines 44, 44,... Sequentially from the top gate line 44 of the first row. Thus, the top gate driver 74 scans the top gate lines 44, 44,. Further, the bottom gate driver 75 applies a read pulse to the bottom gate lines 41, 41, 41,... Sequentially from the bottom gate line 41 of the first row. As a result, the bottom gate driver 75 scans the bottom gate lines 41, 41, 41,. The scanning frequency by the top gate driver 74 is the same as the scanning frequency by the bottom gate driver 75, but the scanning period by the bottom gate driver 75 is delayed from the scanning period by the top gate driver 74.

  During the precharge time Tprch of each row during scanning, the control signal φpg input to the precharge switch 82 of the drain driver 76 is at a high level, so that the precharge voltage Vpg is set during the precharge time Tprch of each row. It is applied to all the drain lines 43, 43,.

  The operation of each i-th photo sensor 20 will be described in detail. As shown in FIG. 8, the top gate driver 74 applies a reset pulse to the i-th top gate line 44. In the reset time Treset of the i-th row, carriers (here, holes) accumulated in the semiconductor film 23 of each photosensor 20 in the i-th row and in the vicinity of the interface between the semiconductor film 23 and the channel protective film 24. ) Is repelled and discharged by the voltage of the top gate 30.

  In the storage time Te from when the reset pulse applied to the i-th top gate line 44 ends to when the read pulse is applied to the i-th bottom gate line 41, the amount according to the amount of incident light Electron-hole pairs are generated in the semiconductor film 23, of which 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 30.

  Next, the drain driver 76 applies the precharge voltage Vpg to all the drain lines 43, 43,... During the precharge time Tprch in the latter half of the storage time Te. In the precharge time Tprch, the voltage of the top gate 30 of each photosensor 20 in the i-th row is a negative voltage (−15 [V]), and the voltage of the bottom gate 21 is ± 0 [V]. 23, the gate-source voltage is low only by the charge of holes accumulated in the vicinity of the interface between the semiconductor film 23 and the channel protective film 24, so that no channel is formed in the semiconductor film 23, and the drain 28, source 27, During this period, no current flows. Since no current flows between the drain 28 and the source 27 during the precharge time Tprch, the precharge voltage Vpg applied to the drain lines 43, 43,... Charged.

  Next, the application of the precharge voltage Vpg by the drain driver 76 is finished, and the bottom gate driver 75 applies a read pulse to the bottom gate line 41 of the i-th row. In the read time Tread in which the bottom gate driver 75 applies the read pulse to the i-th bottom gate line 41, the voltage of the bottom gate 21 of each photosensor 20 in the i-th row is a positive voltage (+10 [V]). Therefore, each photo sensor 20 in the i-th row is turned on.

  In the read time Tread, the carriers accumulated in the storage time Te work to alleviate the negative electric field of the top gate 30, so that an n channel is formed in the semiconductor film 23 by the positive electric field of the bottom gate 21, and the drain 28 A current flows through the source 27. Therefore, at the read time Tread, 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 increases during the storage time Te, the number of accumulated carriers increases, and as the number of accumulated carriers increases, the current flowing from the drain 28 to the source 27 increases during the read time Tread. Become. Therefore, the change tendency of the voltage of the drain lines 43, 43,... During the read time Tread depends on the amount of light incident on the semiconductor film 23 during the storage time Te. That is, as the amount of light incident on the semiconductor film 23 increases during the storage time Te, the voltage change rate of the drain lines 43, 43,. Therefore, the drain line 43, 43 after a predetermined time has elapsed from the start of the column switch 81 and the read time Tread between the read time Tread of the i-th row and the precharge time Tprch of the next (i + 1) -th row. ,... Are sequentially output to the amplifier 83 by the column switch 81, amplified by the amplifier 83, and further A / D converted by the A / D converter 78. Thereby, it converts into the intensity | strength of light. Note that the time until the predetermined threshold voltage is reached may be detected via the column switch 81 between the read time Tread of the i-th row and the precharge time Tprch of the next (i + 1) -th row. Even in this case, the light intensity is converted.

  The above-described series of image reading operations is set as one cycle, and the same processing procedure is repeated for each photosensor 20 in all rows, so that the photosensor array 3 detects the amount of light by each of the photosensors 20, 20,. The light intensity distribution along the light receiving surface is acquired as a two-dimensional image. The controller 73 inputs an image acquired by the photosensor array 3 and outputs the image to the output device 77. And the process of the controller 73 is complete | finished.

  The operator confirms the presence or absence of hybridization from the image 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.

  As described above, according to the present embodiment, the sample DNA moves to each spot 60 on the surface of the photosensor array 3 only by applying a positive voltage to the top gate lines 44, 44,. Therefore, it is not necessary to separately provide the photosensor array 3 with an electrode for moving the sample DNA. Therefore, unknown sample DNA can be attracted efficiently using the drain lines 44, 44,... Constituting the photosensor array 3.

  Further, since the spots 60, 60,... Are scattered on the light receiving surface of the photosensor array 3, a two-dimensional image can be obtained only by imaging with the photosensor array 3. Furthermore, since a clear image can be obtained by the photosensor array 3 without providing a lens in the biopolymer analysis support apparatus 1, the biopolymer analysis support apparatus 1 can have a simple structure. Furthermore, since light emitted from the spot 60 is incident on the light receiving surface of the photosensor array 3 without being attenuated, the sensitivity of the photosensor array 3 may not be high.

[Modification 1]
The present invention is not limited to the above-described embodiments, and various improvements and design changes may be made without departing from the spirit of the present invention.
For example, as shown in FIGS. 12 and 13, a bathtub 101 having a rectangular frame shape surrounding the light receiving surface of the photosensor array 3 is provided on the light receiving surface of the photosensor array 3. An anode 102 and a cathode 103 are provided on the inner surface of the side wall parallel to the gate line 44, respectively. When the electrophoresis medium 104 such as a gel is accommodated in the bathtub 101 and sample DNA is injected into the electrophoresis medium 104, the sample DNA can be migrated from the cathode 103 to the anode 102.

[Modification 2]
In the above embodiment, the excitation light irradiation device 72 irradiates the excitation light from the light receiving surface of the photosensor array 3 toward the photosensor array 3, but the bottom gate 21 is a material that blocks the excitation light. The excitation light may be irradiated toward the photosensor array 3 by being arranged on the back surface (the surface opposite to the light receiving surface) of the insulating substrate 17. Since the photosensor array 3 is light transmissive except for the bottom gate 21, bottom gate line 41, source 27, source line 42, drain 28, and drain line 43, excitation light is emitted from the photosensors 20, 20,. The light is emitted upward from the light receiving surface of the photosensor array 3. In such a layout, the irradiated excitation light can be prevented from being directly incident on the semiconductor film 23, and the excitation light traveling between the photosensors 20 and 20 is incident on the spot 60. Since the sensitivity characteristic can be prevented from being lowered and the fluorescence due to hybridization can be received, the fluorescence can be detected normally. In this case, no excitation light shielding layer is formed on the light receiving surface of the photosensor array 3.

[Modification 3]
In the above embodiment, the spot 60 is made of single-stranded DNA of a known base sequence, but is made of other known biopolymers, for example, proteins of known amino acid sequence or peptide sequence, known cells, etc. Things can be used. Therefore, the amino acid sequence and peptide sequence of the protein can be analyzed by the biopolymer analysis support apparatus 1.

[Modification 4]
In the above embodiment, the excitation light emitted from the excitation light irradiation device 72 is ultraviolet light, and the light emitted from the sample DNA by the excitation light is fluorescence (visible light). However, the present invention is not limited to the wavelength range of such light. 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 photosensor array 3 to be sensitive to light emitted from the labeling substance.

[Modification 5]
In the above embodiment, the controller 73 outputs an image according to the image data input from the photosensor array 3 to the output device 77, and the operator specifies the sequence of the sample DNA from the output image. May specify the sequence of the sample DNA. That is, the controller 73 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 is complementary to the identified spot 60. The base sequence is output from the output device.

1 is a block diagram of a biopolymer analysis support apparatus 1. FIG. FIG. 3 is a circuit diagram of the photosensor array 3 and its peripheral circuits. 2 is a plan view of a photosensor array 3. FIG. FIG. 4 is a cross-sectional view taken along the line IV-IV shown in FIG. 3. 3 is a plan view of one pixel of the photosensor array 3. FIG. FIG. 6 is a cross-sectional view taken along the line VI-VI shown in FIG. 5. 7 is a timing chart of signals output by a top gate driver 74, a bottom gate driver 75, and a controller 73. 7 is a timing chart of signals output by a top gate driver 74, a bottom gate driver 75, and a drain driver 76. It is drawing for demonstrating the motion of sample DNA. It is drawing for demonstrating the motion of sample DNA. It is drawing for demonstrating the motion of sample DNA. It is a schematic plan view of the photosensor array 3 in a modification. It is a schematic side view of the photosensor array 3 in a modification.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Biopolymer analysis support apparatus 3 Photo sensor array 17 Insulating substrate 23 Semiconductor film 31 Protective insulating film 41 Bottom gate line 44 Top gate line 60 Spot 74 Top gate driver 75 Bottom gate driver

Claims (2)

An insulating substrate; a plurality of bottom gate lines arranged on the insulating substrate; a plurality of photosensitive semiconductor films arranged on the bottom gate lines along the bottom gate lines; A photosensor having a plurality of top gate lines opposed to each bottom gate line across the semiconductor film and provided along each bottom gate line, and a protective insulating film covering the plurality of top gate lines An array,
A plurality of spots made of known biopolymers and scattered on the surface of the protective insulating film,
A biopolymer analysis support device, comprising: a top gate driver that applies a voltage for attracting an unknown biopolymer to the biopolymer to at least one of the plurality of top gate lines. . An insulating substrate; a plurality of bottom gate lines arranged parallel to each other on the insulating substrate; and a plurality of photosensitive semiconductor films arranged on the bottom gate lines along the bottom gate lines. And a plurality of top gate lines facing each bottom gate line across the plurality of semiconductor films and parallel to each bottom gate line, and protective insulation covering the plurality of top gate lines A photosensor array having a film;
A method for controlling a biopolymer analysis support device comprising a known biopolymer and having a plurality of types of spots scattered on the surface of the protective insulating film,
A control method for a biopolymer analysis support apparatus, wherein a voltage for attracting an unknown biopolymer to the biopolymer is applied to at least one of the plurality of top gate lines.

Images