Back irradiation type imaging element, flow path unit for biological sample analysis, and biological sample analysis system

Abstract

The purpose of the present invention is to provide a technique for improving the accuracy of fluorescence detection in biological sample analysis. The present disclosure provides a back surface irradiation type imaging element including a plurality of pixel units, each pixel unit including at least: an analyte holding portion configured to hold an analyte; and a fluorescence detection unit that detects fluorescence caused by irradiation of the analyte with the excitation light. The present disclosure also provides a flow path unit for biological sample analysis, the flow path unit having the back irradiation type imaging element. The present disclosure also provides a biological sample analysis system for analyzing a biological sample using the flow path unit for biological sample analysis.

Description

Technical Field

[0001] The present invention relates to a back-illuminated imaging element, a flow path unit for biological sample analysis, and a biological sample analysis system. Background Art

[0002] Various devices for detecting or analyzing biological materials have been proposed. In such devices, light from the biological material is often detected. This light is typically weak, necessitating improved detection accuracy. Regarding such a device, for example, Patent Document 1 below discloses "a chip for detecting biologically derived materials, the chip comprising a plurality of pixels, each pixel comprising at least a holding surface for holding the biologically derived material and a photoelectric conversion unit disposed below the holding surface and on a semiconductor substrate, with a color mixing suppression unit disposed between the pixels." (Claim 1).

[0003] DNA is often the target of detection. Examples of devices used for DNA base sequence analysis include DNA sequencers. For example, a DNA sequencer uses fluorescence to identify the types of bases that make up DNA. A DNA sequencer is configured to radiate excitation light and can also include a detection unit, such as a transparent glass that transmits the excitation light, a flow path through which the sample flows, a nanowell, an optical filter, and a photodiode. The nanowell has, for example, a well shape that is sized to accommodate fragmented DNA. List of citations Patent Literature

[0004] Patent Document 1: Japanese Patent Application Laid-Open No. 2020-85666 Summary of the Invention Technical problem to be solved by the invention

[0005] To increase the processing speed of a DNA sequencer, for example, one approach might be to increase the number of pixels in the imaging element that detects fluorescence. However, increasing the size of the imaging element is undesirable, for example, from a cost perspective. Therefore, reducing the size of the unit pixel (particularly the photodiode) is a viable option.

[0006] However, as the pixel size decreases, the distance between pixels becomes closer, which causes optical crosstalk to generate noise, and the fluorescent signal from DNA is buried in the noise, resulting in a decrease in fluorescence detection accuracy. Furthermore, thick filters used to block excitation light can also reduce fluorescence detection accuracy due to optical crosstalk. For example, thick filters increase the distance between the detection unit and the phosphor. Consequently, fluorescence that diffuses obliquely into adjacent pixels becomes noise, reducing the signal-to-noise ratio. Furthermore, the excitation light used to generate fluorescence can also reduce the accuracy of fluorescence detection. For example, if the main beam of excitation light directly strikes the sensor, the excitation light component becomes noise, which can also reduce the accuracy of fluorescence detection.

[0007] Therefore, an object of the present invention is to provide a technique for improving the accuracy of fluorescence detection in biological sample analysis. Solutions to technical problems

[0008] The present invention provides A back-illuminated imaging element comprising: A plurality of pixel units, each pixel unit comprising at least: an analyte retaining portion configured to retain an analyte; and A fluorescence detection section detects fluorescence generated by irradiating the analyte with excitation light. The analyte holding portion may have a well shape, and The detection portion may be provided so as to cover not only the bottom of the well but also the side surfaces of the well. In the back-illuminated image sensor, grooves may be provided between the pixel units. In the image pickup element, two or more wells may be connected to each other so as to form a column-like structure. Each pixel unit may be provided with an electrode pair, and a voltage is applied to the electrode pair in such a manner as to adjust the position of the analyte. Each pixel unit may be provided with an excitation light blocking portion that prevents the excitation light from reaching the detection portion. The excitation light blocking portion may include a multilayer film reflection filter. The multilayer film reflection filter may be provided between the analyte holding portion and the detection portion. Each of the pixel units may further include an excitation light detection portion for detecting the excitation light. The back-illuminated image pickup element may be configured to process a signal obtained by the fluorescence detection section using a signal obtained by the excitation light detection section. The excitation light blocking portion may include a polarizer, a plasmon filter, a metamaterial, or a multilayer film having a Fabry-Perot structure. The excitation light blocking portion may be configured to transmit the fluorescent light. The excitation light blocking portion may include a polarizer, and The excitation light may be polarized light. The excitation light blocking portion may include a polarizer, and One polarizer may be provided so as to cover two or more of the pixel-based detection sections. The fluorescence detection section may include two or more photodiodes. The two or more photodiodes may be arranged to form a vertical stack structure between the analyte retaining portion and the wiring layer. The photodiode closer to the wiring layer among the two or more photodiodes may be configured to detect fluorescence of a longer wavelength. The two or more photodiodes may form a two-layer structure or a three-layer structure. In addition, the present invention also provides a flow path unit for biological sample analysis, the flow path unit comprising: A back-illuminated imaging element comprising a plurality of pixel units, each of the pixel units comprising at least: an analyte holding portion configured to hold an analyte; and a fluorescence detecting portion detecting fluorescence generated by irradiating the analyte with excitation light; and A flow channel supplies the biological sample to the analyte holding portion. In addition, the present invention also provides a biological sample analysis system, which uses a flow path unit for biological sample analysis to analyze the biological sample, wherein the flow path unit includes: A back-illuminated imaging element comprising a plurality of pixel units, each of the pixel units comprising at least an analyte holding portion configured to hold an analyte; and a fluorescence detecting portion detecting fluorescence generated by irradiating the analyte with excitation light; and A flow channel supplies the biological sample to the analyte holding portion. BRIEF DESCRIPTION OF THE DRAWINGS

[0009] Figure 1 : is a schematic diagram showing a configuration example of a back-illuminated image pickup element according to the present invention. Figure 2A It is a diagram for explaining the sizes of wells and pixel units. Figure 2B This is another diagram for explaining the sizes of wells and pixel units. Figure 2C : is a schematic diagram showing a configuration example of an electronic reading section. Figure 3 : is a schematic diagram showing another configuration example of the back-illuminated image pickup element according to the present invention. Figure 4A : is a schematic diagram showing another configuration example of the back-illuminated image pickup element according to the present invention. Figure 4B : is a schematic diagram showing another configuration example of the back-illuminated image pickup element according to the present invention. Figure 4C: is a schematic diagram showing another configuration example of the back-illuminated image pickup element according to the present invention. Figure 5 : is a schematic diagram showing another configuration example of the back-illuminated image pickup element according to the present invention. Figure 6 1 is a schematic diagram showing a configuration example of a back-illuminated image pickup element including a multilayer film reflection filter according to the present invention. Figure 7A A schematic diagram for explaining an example of the structure of a multilayer film reflection filter. Figure 7B is another schematic diagram for explaining an example of the configuration of a multilayer film reflection filter. Figure 8 1 is a schematic diagram showing another configuration example of a back-illuminated image pickup element including a multilayer film reflection filter according to the present invention. Figure 9 1 is a schematic diagram showing another configuration example of a back-illuminated image pickup element including a multilayer film reflection filter according to the present invention. Figure 10 : is a schematic diagram showing another configuration example of the back-illuminated image pickup element according to the present invention. Figure 11 is a schematic cross-sectional view of another configuration example of the back-side illumination type image pickup element according to the present invention. Figure 12 is a schematic cross-sectional view of another configuration example of the back-side illumination type image pickup element according to the present invention. Figure 13 is a schematic cross-sectional view of another configuration example of the back-side illumination type image pickup element according to the present invention. Figure 14 is a schematic cross-sectional view of another configuration example of the back-side illumination type image pickup element according to the present invention. Figure 15 is a schematic cross-sectional view of another configuration example of the back-side illumination type image pickup element according to the present invention. Figure 16 is a schematic cross-sectional view of another configuration example of the back-side illumination type image pickup element according to the present invention. Figure 17 is a schematic cross-sectional view of another configuration example of the back-side illumination type image pickup element according to the present invention. Figure 18 is a schematic cross-sectional view of another configuration example of the back-side illumination type image pickup element according to the present invention. Figure 19 is a schematic cross-sectional view of another configuration example of the back-side illumination type image pickup element according to the present invention. Figure 20is a schematic cross-sectional view of another configuration example of the back-side illumination type image pickup element according to the present invention. Figure 21 is a schematic cross-sectional view of another configuration example of the back-side illumination type image pickup element according to the present invention. Figure 22 is a schematic cross-sectional view of another configuration example of the back-side illumination type image pickup element according to the present invention. Figure 23 is a schematic cross-sectional view of another configuration example of the back-side illumination type image pickup element according to the present invention. Figure 24 is a schematic cross-sectional view of another configuration example of the back-side illumination type image pickup element according to the present invention. Figure 25 is a schematic cross-sectional view of another configuration example of the back-side illumination type image pickup element according to the present invention. Figure 26 is a schematic cross-sectional view of another configuration example of the back-side illumination type image pickup element according to the present invention. Figure 27 is a schematic cross-sectional view of another configuration example of the back-side illumination type image pickup element according to the present invention. Figure 28 is a schematic cross-sectional view of another configuration example of the back-side illumination type image pickup element according to the present invention. Figure 29 is a schematic cross-sectional view of another configuration example of the back-side illumination type image pickup element according to the present invention. Figure 30 is a schematic cross-sectional view of another configuration example of the back-side illumination type image pickup element according to the present invention. Figure 31 is a schematic cross-sectional view of another configuration example of the back-side illumination type image pickup element according to the present invention. Figure 32 is a schematic cross-sectional view of another configuration example of the back-side illumination type image pickup element according to the present invention. Figure 33A is a schematic cross-sectional view of another configuration example of the back-side illumination type image pickup element according to the present invention. Figure 33B is a schematic cross-sectional view of another configuration example of the back-side illumination type image pickup element according to the present invention. Figure 34A is a schematic cross-sectional view of another configuration example of the back-side illumination type image pickup element according to the present invention. Figure 34B is a schematic cross-sectional view of another configuration example of the back-side illumination type image pickup element according to the present invention. Figure 35 is a diagram showing a configuration example of a groove. Figure 36A : is a schematic diagram showing another configuration example of the back-illuminated image pickup element according to the present invention. Figure 36B : is a schematic diagram showing another configuration example of the back-illuminated image pickup element according to the present invention. Figure 36C : is a schematic diagram showing another configuration example of the back-illuminated image pickup element according to the present invention. Figure 37 is a diagram showing an example of a pattern of a polarizer. Figure 38 : is a schematic diagram showing another configuration example of the back-illuminated image pickup element according to the present invention. Figure 39 : is a schematic diagram showing another configuration example of the back-illuminated image pickup element according to the present invention. Figure 40 : is a schematic diagram showing another configuration example of the back-illuminated image pickup element according to the present invention. Figure 41 : is a schematic diagram showing another configuration example of the back-illuminated image pickup element according to the present invention. Figure 42 : is a schematic diagram showing another configuration example of the back-illuminated image pickup element according to the present invention. Figure 43 is a diagram showing an example of a film having an FP structure. Figure 44 : is a schematic diagram showing another configuration example of the back-illuminated image pickup element according to the present invention. Figure 45 : is a schematic diagram showing another configuration example of the back-illuminated image pickup element according to the present invention. Figure 46 : is a schematic diagram showing another configuration example of the back-illuminated image pickup element according to the present invention. Figure 47 : is a schematic diagram showing another configuration example of the back-illuminated image pickup element according to the present invention. Figure 48 is a diagram showing the results of sensitivity verification. Figure 49 is a diagram showing another result of the sensitivity verification. Figure 50A It is a schematic diagram for explaining the method of manufacturing a back-illuminated image sensor according to the present invention. Figure 50B This is another schematic diagram for explaining the method for manufacturing a back-illuminated image sensor according to the present invention. Figure 50CThis is another schematic diagram for explaining the method for manufacturing a back-illuminated image sensor according to the present invention. Figure 51A This is a schematic diagram for explaining another method of manufacturing a back-illuminated image sensor according to the present invention. Figure 51B This is a schematic diagram for explaining another method of manufacturing a back-illuminated image sensor according to the present invention. Figure 51C This is another schematic diagram for explaining another method of manufacturing a back-illuminated image sensor according to the present invention. Figure 51D This is another schematic diagram for explaining another method of manufacturing a back-illuminated image sensor according to the present invention. Figure 52A This is a schematic diagram for explaining another method of manufacturing a back-illuminated image sensor according to the present invention. Figure 52B This is another schematic diagram for explaining another method of manufacturing a back-illuminated image sensor according to the present invention. Figure 52C This is a schematic diagram for explaining another method of manufacturing a back-illuminated image sensor according to the present invention. Figure 52D This is a schematic diagram for explaining another method of manufacturing a back-illuminated image sensor according to the present invention. Figure 53 is a schematic diagram showing a configuration example of a flow path unit according to the present invention. Figure 54 is a block diagram showing a configuration example of a biological sample analysis system according to the present invention. Figure 55A Schematic diagram showing how light passes through a multilayer film reflection filter. Figure 55B This is a schematic diagram for explaining the calculation method of the transmittance T. Figure 55C This is another schematic diagram for explaining the calculation method of the transmittance T. Figure 55D This is another schematic diagram for explaining the calculation method of the transmittance T. DETAILED DESCRIPTION

[0010] Hereinafter, the preferred mode for carrying out the present invention will be described. Note that the embodiments described below are representative embodiments of the present invention, and the scope of the present invention is not limited to these embodiments. Note that the present invention will be described in the following order. 1. First Embodiment (Back-illuminated Image Sensor) 1.1 Example of PD Well Structure 1.2 Example of the structure related to the excitation light blocking unit 1.3 Configuration Example of an Excitation Light Blocking Section Including a Polarizer 1.4 Construction Examples Related to PD Vertical Stacking Structure 2. Second Embodiment (Flow Path Unit for Biological Sample Analysis) 3. Third Implementation (Biological Sample Analysis System)

[0011] 1. First Embodiment (Back-illuminated Image Sensor) The inventors have found that an imaging element with a specific structure is useful for improving the accuracy of fluorescence detection. That is, the present invention provides an imaging element of a specific type including a plurality of pixel units with a specific structure. In one embodiment, the pixel unit includes at least: an analyte holding portion, which is configured to hold an analyte; and a fluorescence detection portion, which detects fluorescence generated by irradiating the analyte with excitation light, and the imaging element is a back-illuminated type. Including an analyte holding portion and a fluorescence detection portion in each pixel and the imaging element being a back-illuminated type contribute to improving the accuracy of fluorescence detection. For example, since each pixel includes an analyte holding portion and a fluorescence detection portion, it is possible to accurately detect fluorescence originating from tiny biomolecules. Furthermore, for example, in front-illuminated imaging elements, the wiring layer is located directly above the photodiode. Consequently, fluorescence is scattered by the wiring layer and does not strike the photodiode, leading to signal loss. Since the imaging element of the present invention is constructed as a back-illuminated type, fluorescence scattering due to the wiring layer can be prevented.

[0012] In the following 1.1 to 1.4, four main construction examples will be described. The techniques of these construction examples can be used independently or in combination in the present invention. In one embodiment, the construction in 1.3 or 1.4 below can be combined with the construction example described in 1.1 below. In another implementation, the construction in 1.3 or 1.4 below can be combined with the construction example described in 1.2 below.

[0013] 1.1 Example of PD Well Structure

[0014] 1.1.1 Example 1-1 (Basic Construction Example) In one embodiment, the analyte holding portion may have a well shape, and the detection portion may be provided in a manner covering the bottom of the well as the side surfaces of the well. Figure 1 An example of the configuration of a back-illuminated image pickup element according to this embodiment will be described. This figure is a schematic diagram of the configuration of a back-illuminated image pickup element according to the present invention. (d) on the left side of the figure is a schematic diagram of a cross section of the image sensor pixel unit 101. The cross section is a cross section of a plane perpendicular to the light receiving surface of the image sensor. (a) to (c) on the right side of the figure are schematic diagrams showing a part of the light receiving surface of the image pickup element 100 in which pixel units 101 are arranged in a grid pattern, more specifically, schematic diagrams of the following cross section. (a) on the right side of the figure is a schematic diagram of a cross section at the position of the dotted line AA' in (d) of the figure, and this schematic diagram shows a state where multiple pixel units are arranged in a grid pattern. In addition, this cross section is a cross section of a plane parallel to the light receiving surface of the imaging element. (b) on the right side of the figure is a schematic diagram of a cross section at the position of the dotted line BB' in (d) of the figure, and this schematic diagram shows a state in which multiple pixel units are arranged in a grid pattern. In addition, this cross section is a cross section of a plane parallel to the light receiving surface of the imaging element. (c) on the right side of the figure is a schematic diagram of a cross section at the position of the dotted line CC' in (d) of the figure, and this schematic diagram shows a state where multiple pixel units are arranged in a grid pattern. In addition, this cross section is a cross section of a plane parallel to the light receiving surface of the imaging element.

[0015] The pixel unit 101 includes a well 103. As shown in the figure, the well 103 may be covered by an insulating film 102. In FIG. 1A , the opening shape of the well 103 (particularly, the shape in a plane parallel to the light receiving surface) is rectangular, but may be other polygonal shapes, or may be circular, elliptical, etc. as an alternative. The well 103 (and the insulating film 102 covering the well) may be configured to retain the analyte, ie, correspond to an analyte retaining portion.

[0016] Will refer to Figure 2A The sizes of the well 103 and the pixel unit 101 are described. As shown in the figure, the opening size D1 of the well 103 can be, for example, more than 50 nm, preferably more than 100 nm, more than 200 nm or more than 300 nm. For example, the size D1 can be less than 200 μm, preferably less than 150 μm, less than 120 μm, or less than 100 μm. The size D1 can be appropriately set by those skilled in the art according to, for example, the size of the analyte. For example, in the case where the analyte is a cell (a size of the order of tens of μm), the size D1 can be, for example, from 1 μm to 200 μm, in particular from 10 μm to 100 μm. In the case where the analyte is a cellular component such as a nucleic acid or protein, the size D1 can be, for example, from 50 nm to 1000 nm, in particular from 100 nm to 900 nm. For example, when the opening shape of the well is a square, the dimension D1 may refer to the length of one side; when the opening shape is a rectangle, the dimension D1 may refer to the length of the long side; when the opening shape is other rectangles, the dimension D1 may refer to the length of the longest side; when the opening shape is a polygon with more than five sides, the dimension D1 may refer to the longest diagonal distance; when the opening shape is a circle, the dimension D1 may refer to the diameter; and when the opening shape is an ellipse, the dimension D1 may refer to the length of the long axis. The dimension D2 of the bottom of the well 103 can be, for example, 50 nm or more, preferably 100 nm or more, 200 nm or more, or 300 nm or more. For example, the dimension D2 can be 200 μm or less, preferably 150 μm or less, 120 μm or less, or 100 μm or less. The dimension D2 can be appropriately set by a person skilled in the art according to, for example, the size of the analyte. For example, in the case where the analyte is a cell, the dimension D2 can be, for example, from 1 μm to 200 μm, particularly from 10 μm to 100 μm. In the case where the analyte is a cellular component such as a nucleic acid or protein, the dimension D2 can be, for example, from 50 nm to 1000 nm, particularly from 100 nm to 900 nm. For example, if the bottom shape of the well is square, dimension D2 may refer to the length of one side; if the bottom shape is rectangular, dimension D2 may refer to the length of the long side; if the bottom shape of the well is other rectangular, dimension D2 may refer to the length of the longest side; if the bottom shape of the well is a polygon with five or more sides, dimension D2 may refer to the longest diagonal distance; if the bottom shape is circular, dimension D2 may refer to the diameter; and if the bottom shape of the well is elliptical, dimension D2 may refer to the length of the major axis. Dimension D2 may be different from or the same as dimension D1. In the case where dimension D2 is different from dimension D1, dimension D1 of the opening may preferably be larger than dimension D2 of the bottom, as shown in the figure, but as an alternative, dimension D1 may also be smaller than dimension D2. The depth dimension D3 of the well 103 can be, for example, more than 50 nm, preferably more than 100 nm, more than 200 nm, or more than 300 nm. The dimension D3 can be, for example, less than 200 μm, preferably less than 150 μm, less than 120 μm, or less than 100 μm. The dimension D3 can be appropriately set by a person skilled in the art according to, for example, the size of the analyte. For example, in the case where the analyte is a cell, the dimension D3 can be, for example, from 1 μm to 200 μm, in particular from 10 μm to 100 μm. In the case where the analyte is a cellular component such as a nucleic acid or protein, the dimension D3 can be, for example, from 50 nm to 1000 nm, in particular from 100 nm to 900 nm. The dimension D3 can refer to the distance between the opening and the bottom. In addition, the size D4 (also referred to as the cell size) of the pixel unit 101 can be larger than the size D1 of the well, and can be, for example, more than 100 nm, preferably more than 200 nm, more than 300 nm, or more than 400 nm. The size D4 can be, for example, less than 300 μm, preferably less than 200 μm, less than 150 μm, or less than 100 μm. The size D4 can be appropriately set by those skilled in the art according to, for example, the size of the analyte. For example, in the case where the analyte is a cell, the size D4 can be, for example, from 2 μm to 400 μm, in particular from 10 μm to 200 μm. In the case where the analyte is a cellular component such as a nucleic acid or protein, the size D4 can be, for example, from 100 nm to 5000 nm, in particular from 200 nm to 3000 nm. When the shape of the pixel unit is a square, the dimension D4 may refer to the length of one side; when the shape of the pixel unit is a rectangle, the dimension D4 may refer to the length of the long side; when the shape of the pixel unit is other rectangles, the dimension D4 may refer to the length of the longest side; and when the shape of the pixel unit is a polygon with more than five sides, the dimension D4 may refer to the longest diagonal distance.

[0017] The well 103 can be configured to retain the analyte. For example, a compound for retaining the analyte can be fixed on the surface (particularly, the bottom surface) of the well 103. Those skilled in the art can appropriately select the compound according to the type of analyte. The compound is, for example, a nucleic acid, but is not limited thereto, and can be, for example, other compounds such as proteins, peptides, sugars, or lipids. In the case where the analyte is a nucleic acid such as DNA or RNA, the compound may also be a nucleic acid such as DNA or RNA, but is not limited thereto, and may be, for example, a protein, a peptide, a sugar, or a lipid. The analyte may be a compound other than a nucleic acid or a biological particle (eg, a cell or endoplasmic reticulum). In this case, the compound may be, but is not limited to, a nucleic acid, a protein, a peptide, a sugar, or a lipid. The compound to be immobilized may be, for example, a compound for capturing a bioreceptor in a well (particularly the bottom surface of the well), and may be, for example, a SAM reagent, a divalent reagent, an activation reagent (e.g., a carboxylic acid activation reagent), or a biotinylation reagent.

[0018] Pixel unit 101 includes a photodiode 104. The photodiode can be a photodiode for detecting fluorescence. The photodiode can be, for example, a Si photodiode and can have, for example, an Si N region 104N and a Si P region 104P. As shown in the figure, the N region 104N can be surrounded by the P region 104P.

[0019] The photodiode 104 is provided so as to cover not only the bottom of the well but also the side surfaces of the well. Figure 2B The dotted region denoted by reference numeral W1 (particularly, the regions 104P and 104N) in the figure indicates the photodiode covering the bottom surface of the well. The dotted region denoted by reference numeral W2 in the figure (particularly, the regions 104P and 104N) indicates the photodiode 104. As described above, the photodiode 104 also has a well shape and is configured to form the sidewall portion W1 and the bottom portion W2 of the well. In the present invention, as described above, the photodiode can be configured to cover both the bottom and side surfaces of the well, i.e., the photodiode also has a well shape. Therefore, in the fluorescence generated by irradiating sample S1 with excitation light L1, in addition to the fluorescence traveling toward the bottom surface of the well, the fluorescence traveling toward the side surfaces of the well is also detected. This improves the accuracy of fluorescence detection.

[0020] The pixel unit 101 includes a gate electrode portion 105 (also referred to as TG). The gate electrode portion may include, for example, polysilicon (Poly-Si). Alternatively, the gate electrode portion may be configured as a vertical transfer gate (VG), as will be described later. The pixel unit 101 also includes a floating diffusion portion FD, to which electrons accumulated in the photodiode are transferred, and a contact portion CS connected to the floating diffusion portion. As shown in the figure, the photodiode 104 may have a buried photodiode structure. The gate electrode portion 105 may be connected to the photodiode 104 having such a structure. Electrons accumulated in the photodiode 104 are transferred from the gate electrode portion 105 to the floating diffusion portion FD and then read from the contact portion CS. In the present invention, the component used to read electrons from a photodiode is also referred to as an electron reader. As described above, the electron reader can include the gate electrode 105 (TG), the floating diffusion FD, and the contact CS. In the figure, the floating diffusion is provided in each pixel unit, meaning the electron reader has a so-called FD-free structure. In the present invention, the electron reader may have a structure in which a plurality of pixel units share a floating diffusion, that is, a so-called FD sharing structure. The number of pixel units sharing one FD may be four, for example. Figure 2C A configuration example of an FD non-common electronic reading portion and a configuration example of an FD common electronic reading portion are shown. (a) in the figure shows a schematic configuration example (part surrounded by a dotted line) of an example of the FD common type electronic reading unit 251. Figure 2A The construction example in is the same. Figure 2C (b) and Figure 2C (c) shows an example of the construction of an FD non-shared electron reading portion (the portion surrounded by the dotted line). Similar to the electron reading portion 250 shown in (a), the electron reading portion 251 shown in (b) includes a gate electrode portion TG, a floating diffusion portion FD, and a contact portion CS, but the FD and CS are arranged at a position where the FD and CS are shared with adjacent pixel units. FD and CS can be shared by four pixel units, for example. In addition, as in the electron reading portion 252 shown in (c), a Poly-Si contact portion can be used in the FD shared electron reading portion. Note that in the present invention, the shapes, sizes, and arrangements of the photodiodes and the electronic reading portion can be appropriately changed by those skilled in the art, and are not limited to those illustrated in these drawings.

[0021] The pixel unit 101 is separated from other unit pixels by a partition 106. The partition 106 may also be called a trench. As described above, in the back-illuminated image sensor of the present invention, trenches may be provided between the pixel units. Each separator 106 is provided between a unit pixel and other unit pixels. Separators 106 may include an insulator or a metal. Separators 106 prevent excitation light L1 that has entered unit pixel 101 and fluorescence generated by analyte S1 within unit pixel 101 from entering other unit pixels. Separators 106 also prevent electrons in photodiode 104 from entering the photodiodes of other unit pixels.

[0022] The image sensor 100 is of a back-illuminated type, that is, a wiring layer is provided on the side of the photodiode opposite to the side on which fluorescence is incident. Well 103 is provided on one side of photodiode 104, and a wiring layer is provided on the opposite side of photodiode 104. In other words, pixel unit 101 has a multilayer structure in which a wiring layer, a detection unit (photodiode), and an analyte holding unit (well) are arranged in this order. This configuration allows the imaging element of the present invention to obtain a larger fluorescence signal, which helps improve fluorescence detection accuracy.

[0023] like Figure 1 As shown, the imaging element 100 may have a structure in which a plurality of pixel units 101 are arranged in a grid pattern. A person skilled in the art may appropriately select the number of pixel units 101 (i.e., the number of pixels) included in an imaging element 100, for example, based on factors such as the size of the imaging element or the imaging target. The number of pixels may be, for example, 500 pixels or more, and may specifically be 1,000 pixels or more, 5,000 pixels or more, 10,000 pixels or more, 50,000 pixels or more, or 100,000 pixels or more. The upper limit value of the number of pixels of the imaging element does not necessarily need to be specified, but may be, for example, 10 million pixels or less, and specifically, may be 8 million pixels or less, 6 million pixels or less, 4 million pixels or less, or 2 million pixels or less. The lower limit value of the size of the imaging element 100 may be, for example, 3 mm or more, and in particular, may be 5 mm or more, 7 mm or more, or 10 mm or more. The upper limit value of the size may be, for example, 80 mm or less, in particular, 70 mm or less, or 60 mm or less. In one embodiment, the size of the imaging element may be, for example, 3 mm to 80 mm (the size of one side of the rectangle) × 3 mm to 80 mm (the size of the other side of the rectangle), and in particular, the size may be 10 mm to 60 mm × 10 mm to 60 mm. The size of the imaging element may refer to the size of the light receiving surface on which the pixel units are arranged. The shape of the imaging element may be, for example, rectangular, and more specifically, a rectangular or square. If the shape of the light receiving surface of the imaging element is rectangular, the size of the imaging element may refer to the long side of the light receiving surface (the short side may be shorter than this size). If the shape of the light receiving surface of the imaging element is square, the size of the imaging element may refer to one side of the light receiving surface. When an imaging element is incorporated into a biological sample analysis system, only one imaging element may be incorporated, or two or more imaging elements may be incorporated. For example, when two or more imaging elements are used, these imaging elements may be arranged in a tile pattern. For example, a biological sample analysis system may include multiple imaging elements according to the present invention, and the multiple imaging elements may be connected together by tiling. The connected multiple imaging elements may function as a single sensor and, in particular, may form a single imaging surface. The multiple imaging elements may include imaging elements of a single type, or may include imaging elements of two or more types.

[0024] When the imaging element 100 is used to analyze biological samples, a space may be formed so that the analyte can reach and be retained in a well. The space may be a flow path for the analyte to flow. For example, a liquid sample containing the analyte may flow through the space and the analyte may be captured at the bottom surface of the well. At least a portion of the space may be formed into a well shape. Figure 1 As shown, another portion of the space can be formed by a transparent substrate 108. Since the transparent substrate 108 is transparent, the excitation light can reach the interior of the well. The material of the transparent substrate 108 can be glass, but can also be a resin (e.g., acrylic resin, polycarbonate resin, etc.). Therefore, the imaging element 100 may have a space for allowing the analyte to reach the inside of the well, and may further include a transparent substrate 108 forming the space.

[0025] 1.1.2 Example 1-2 (well with column structure) The imaging element 100 described in Example 1-1 above is used so that the excitation light L1 enters the light receiving surface of the imaging element vertically. In the present invention, the excitation light traveling in a direction parallel to the light receiving surface can be applied to the analyte held in the well. For illumination, two or more wells can be connected to each other in a manner forming a columnar structure. Figure 3 An example of an image pickup element irradiated with excitation light will be described. This figure is a schematic diagram showing the structure of a back-illuminated image pickup element according to the present invention. (d) on the left side of the figure is a schematic diagram of a cross section of the image sensor pixel unit 111. This cross section is a cross section of a plane perpendicular to the light receiving surface of the image sensor. (a) to (c) on the right side of the figure are schematic diagrams showing a part of the light receiving surface of the image pickup element 110 in which pixel units 111 are arranged in a grid pattern, and more specifically, are schematic diagrams of the following cross section. (a) on the right side of the figure is a schematic diagram of a cross section at the position of the dotted line AA' in (d) of the figure, and this schematic diagram shows a state where multiple pixel units are arranged in a grid pattern. In addition, this cross section is a cross section of a plane parallel to the light receiving surface of the imaging element. (b) on the right side of the figure is a schematic diagram of a cross section at the position of the dotted line BB' in (d) of the figure, and this schematic diagram shows a state where multiple pixel units are arranged in a grid pattern. In addition, this cross section is a cross section of a plane parallel to the light receiving surface of the imaging element. (c) on the right side of the figure is a schematic diagram of a cross section at the position of the dotted line CC' in (d) of the figure, and this schematic diagram shows a state where multiple pixel units are arranged in a grid pattern. In addition, this cross section is a cross section of a plane parallel to the light receiving surface of the imaging element. (e) on the left side of the figure is a schematic diagram of a cross section of the pixel unit 111 of the imaging element. This cross section is a cross section of a plane perpendicular to the light receiving surface of the imaging element and parallel to the direction in which the excitation light L1 travels. The dotted line D-D' in (e) corresponds to the dotted line D-D' in (a) on the right side of the figure. The dotted line E-E' in (e) corresponds to the dotted line E-E' in (a) on the right side of the figure. The dotted line F-F' in (e) corresponds to the dotted line F-F' in (a) on the right side of the figure.

[0026] The pixel unit 111 includes a well 113. As shown in the figure, the well 113 may be covered by an insulating film 112. The well 113 of the pixel unit 111 has a column shape. The well 113 forms a column together with the wells of two adjacent pixel units. The excitation light L1 is irradiated so as to travel along the direction of the column. The well 113 (and the insulating film 112 covering the well) may be configured to retain the analyte, ie, correspond to an analyte retaining portion.

[0027] Since the wells of the plurality of pixel units form a column in this manner, the excitation light L1 can travel in parallel with the column, thereby preventing the excitation light L1 from entering the photodiode 114 and reducing the noise caused by the excitation light L1.

[0028] The sizes of the well 113 and the pixel unit 111 may be similar to those in the above-described Example 1-1, and the description also applies to this example. Note that the width of the columns in the opening of the well 113 corresponds to the dimension D1 of the opening of the well 103. In addition, the width of the columns on the bottom surface of the well 113 corresponds to the dimension D2 of the bottom of the well 103.

[0029] Like well 103 described in Example 1-1 above, well 113 can be configured to retain an analyte. That is, the surface of well 113 can be configured similarly to the surface of well 103.

[0030] The pixel unit 111 includes a photodiode 114. The photodiode may be, for example, a Si photodiode and may have an N region 114N and a P region 115P, for example, of Si. As shown in the figure, the N region 114N may be surrounded by the P region 115P.

[0031] Like the photodiode 104 described above in Example 1-1, the photodiode 114 is disposed in a manner that covers the bottom of the well and also covers the sides of the well. In the present invention, as described above, the photodiode can be configured to cover both the bottom and side surfaces of the well. That is, the photodiode also has a well shape. Therefore, in the fluorescence generated by irradiating sample S1 with excitation light L1, in addition to the fluorescence traveling toward the bottom surface of the well, the fluorescence traveling toward the side surfaces of the well is also detected. This improves the accuracy of fluorescence detection.

[0032] Pixel unit 111 includes polysilicon (Poly-Si) 115 (also referred to as TG). Polysilicon serves as a gate electrode. Pixel unit 111 also includes a floating diffusion FD to which electrons accumulated in the photodiode are transferred, and a contact CS connected to the floating diffusion. As described in Example 1-1 above, these TG, FD, and CS are also referred to as electron reading units. The electron reading unit and TG, FD, and CS are as described in Example 1-1 above, and the description also applies to this example.

[0033] The pixel unit 111 is separated from other unit pixels by a partition 116. The partition 116 may also be referred to as a trench. The partition 116 may be constructed in the same manner as the partition 106 described in Example 1-1 above.

[0034] The imaging element 110 is of a back-illuminated type, that is, a wiring layer is provided on the side of the photodiode opposite to the side on which fluorescence is incident. Well 113 is provided on one side of photodiode 114, and a wiring layer is provided on the opposite side of photodiode 114. In other words, pixel unit 111 has a multilayer structure in which a wiring layer, a detection unit (photodiode), and an analyte holding unit (well) are arranged in this order. This configuration allows the imaging element of the present invention to obtain a larger fluorescence signal, which helps improve fluorescence detection accuracy.

[0035] The number of pixel units included in the image pickup element 110 and the size of the image pickup element 110 may be as described above for the image pickup element 100 of Example 1, and the description also applies to this example.

[0036] When the imaging element 110 is used to analyze a biological sample, a space may be formed so that the analyte reaches and is held in a well. At least a portion of the space may be formed in a well shape. Figure 3 As shown, another portion of the space can be formed by a transparent substrate 118. Since the transparent substrate 118 is transparent, the excitation light can reach the interior of the well. The material of the transparent substrate 118 can be glass, but can also be a resin (e.g., acrylic resin, polycarbonate resin, etc.). Therefore, the imaging element 110 may have a space for allowing the analyte to reach the inside of the well, and may further include a transparent substrate 118 forming the space.

[0037] 1.1.3 Example 1-3 (Electrode Control of Analyte Position) The imaging element according to the present invention may be provided with an electrode pair to control the position of the analyte in the columnar structure described in Examples 1-2 above. The electrode pair may be a pair of first and second electrodes. Each of the first and second electrodes constituting the electrode pair may preferably be a transparent electrode layer, or may be a metal electrode layer. The first electrode and / or the second electrode may preferably be a transparent electrode layer. The transparent electrode layer can prevent the reduction of light (excitation light and / or fluorescence). In one embodiment, an insulating film can be stacked on a transparent electrode layer or a metal electrode layer. In this embodiment, the electrode layer and the insulating film can be configured to transmit an electric field to the analyte via capacitive coupling. Thus, the location of the analyte (bio-derived material) can be controlled. Will refer to Figures 4A to 4C An example configuration of an imaging element equipped with an electrode pair is described. The imaging elements shown in these figures have the same configuration as the imaging elements described in Examples 1-2 above, except that an electrode pair for retaining the analyte at a predetermined position is added. Therefore, the following description will primarily focus on the configuration of the electrode pair.

[0038] Figure 4A A configuration example is shown in which both the first electrode and the second electrode constituting the electrode pair are provided on the well. (d) on the left side of the figure is a schematic diagram of a cross section of the image sensor pixel unit 121. This cross section is a cross section of a plane perpendicular to the light receiving surface of the image sensor. (a) to (c) on the right side of the figure are schematic diagrams showing a part of the light receiving surface of the image pickup element 120 in which pixel units 121 are arranged in a grid pattern, and more specifically, are schematic diagrams of the following cross section. (a) on the right side of the figure is a schematic diagram of a cross section at the position of the dotted line AA' in (d) of the figure, and this schematic diagram shows a state where multiple pixel units are arranged in a grid pattern. In addition, this cross section is a cross section of a plane parallel to the light receiving surface of the imaging element. (b) on the right side of the figure is a schematic diagram of a cross section at the position of the dotted line BB' in (d) of the figure, and this schematic diagram shows a state where multiple pixel units are arranged in a grid pattern. In addition, this cross section is a cross section of a plane parallel to the light receiving surface of the imaging element. (c) on the right side of the figure is a schematic diagram of a cross section at the position of the dotted line CC' in (d) of the figure, and this schematic diagram shows a state where multiple pixel units are arranged in a grid pattern. In addition, this cross section is a cross section of a plane parallel to the light receiving surface of the imaging element. (e) on the left side of the figure is a schematic diagram of a cross section of the pixel unit 121 of the imaging element. This cross section is a cross section of a plane perpendicular to the light receiving surface of the imaging element and parallel to the direction in which the excitation light L1 travels. The dotted line D-D' in (e) corresponds to the dotted line D-D' in (a) on the right side of the figure. The dotted line E-E' in (e) corresponds to the dotted line E-E' in (b) on the right side of the figure. The dotted line F-F' in (e) corresponds to the dotted line F-F' in (c) on the right side of the figure. (f) on the left side of the figure is a schematic diagram of a cross section of the pixel unit 121 of the imaging element. This cross section is a cross section of a plane perpendicular to the light receiving surface of the imaging element and parallel to the direction in which the excitation light L1 travels. The dotted line G-G' in (f) corresponds to the dotted line G-G' in (a) on the right side of the figure. The dotted line H-H' in (f) corresponds to the dotted line H-H' in (b) on the right side of the figure. The dotted line I-I' in (f) corresponds to the dotted line I-I' in (c) on the right side of the figure.

[0039] The pixel unit 121 includes a first electrode 12EP and a second electrode 12EN. The first electrode 12EP and the second electrode 12EN form a complementary electrode pair. The first electrode 12EP exists directly below the position where the analyte S1 is to be retained, that is, is provided in a manner passing through the center of the pixel unit. The first electrode 12EP may be provided in a manner transverse to the column-like structure. The second electrode 12EN is provided so as to pass between pixels, and in particular, is provided so as to cross the boundary between pixel units.

[0040] Here, for example, assume that first electrode 12EP is a positive electrode, second electrode 12EN is a negative electrode, and the analyte is DNA. Since DNA has a negative charge, applying a voltage between these two electrodes exerts a force on the DNA, causing it to approach first electrode 12EP and separate from second electrode EN. Consequently, the DNA is held at the center of the pixel. Note that, as an alternative, the first electrode 12EP may be a negative electrode, and the second electrode 12EN may be a positive electrode. The polarity of these electrodes may be appropriately changed according to the type of analyte or the control method. In addition, the voltage may be a DC voltage or an AC voltage.

[0041] Figure 4B A configuration example is shown in which a first electrode constituting an electrode pair is provided on a well, and two second electrodes are provided on the well and a transparent substrate. The imaging element 130 and pixel unit 131 shown in the figure are the same as those in the reference numerals except that the second electrode 12EN2 is stacked on the transparent substrate 128. Figure 4A The imaging element 120 and the pixel unit 121 are the same.

[0042] As reference Figure 4A As described above, it is assumed that the first electrode 12EP is a positive electrode, the second electrodes 12EN and 12EN2 are negative electrodes, and the analyte is DNA. Since DNA has a negative charge, by applying a voltage between the first electrode 12EP and the second electrode 12EN, a force acts on the DNA, causing the DNA to approach the first electrode 12EP and separate from the second electrode EN. As a result, the DNA is held at the center of the pixel unit. Furthermore, by applying a voltage between the first electrode 12EP and the second electrode 12EN2, a force acts on the DNA, causing the DNA to approach the first electrode 12EP and separate from the second electrode EN2. Thus, the DNA is held pressed against the bottom surface of the well. As described above, since the force for maintaining the DNA at the center of the pixel unit and the force for pressing the DNA against the bottom surface of the well act on the DNA, the DNA is more reliably maintained at a desired position. In one embodiment, the second electrode 12EN may be omitted, that is, the imaging element 130 may be configured to include the first electrode 12EP and the second electrode 12EN2 instead of the second electrode 12EN. In addition, although the second electrode 12EN is a negative electrode in the above configuration example, the second electrode 12EN may also be configured as a positive electrode. That is, the imaging element 130 may include two first electrodes 12EP and 12EN (also referred to as 12EP2) as positive electrodes and one second electrode 12EN as a negative electrode. As described above, in the present invention, the first electrode and the second electrode can be configured to control the position of the analyte by applying a voltage (DC voltage or AC voltage). The number of electrodes included in the first electrode can be one or two or more. In addition, the number of electrodes included in the second electrode can be one or two or more. Those skilled in the art can appropriately change the quantity, shape and position of the first electrode and the second electrode.

[0043] Figure 4C A configuration example is shown in which a first electrode constituting an electrode pair is provided on a well and two second electrodes are provided on a transparent substrate. The imaging element 140 and pixel unit 141 shown in the figure are the same as those in the reference numeral 120 except that the second electrode 12EN2 is stacked on the transparent substrate 128 and the second electrode is not provided on the well. Figure 4B The imaging element 130 and the pixel unit 131 are the same.

[0044] As reference Figure 4B As described above, it is assumed that the first electrode 12EP is a positive electrode, 12EN2 is a negative electrode, and the analyte is DNA. DNA has a negative charge. Therefore, by applying a voltage between first electrode 12EP and second electrode 12EN2, a force acts on the DNA, causing it to approach first electrode 12EP and separate from second electrode EN2. Consequently, the DNA is held pressed against the bottom surface of the well. Consequently, the DNA is held without separating from the bottom surface of the well.

[0045] 1.1.4 Example 1-4 (Structure without grooves) In the components of the imaging element described in Example 1-1 above, the partition can be omitted. Figure 5 A configuration example in which the partition is omitted will be described.

[0046] (d) on the left side of the figure is a schematic diagram of a cross section of a pixel unit 151 of the image sensor 150. This cross section is a cross section of a plane perpendicular to the light receiving surface of the image sensor. (a) on the right side of the figure is a schematic diagram of a cross section at the position of the dotted line AA' in (d) of the figure, and this schematic diagram shows a state where multiple pixel units are arranged in a grid pattern. In addition, this cross section is a cross section of a plane parallel to the light receiving surface of the imaging element. (b) on the right side of the figure is a schematic diagram of a cross section at the position of the dotted line BB' in (d) of the figure, and this schematic diagram shows a state where multiple pixel units are arranged in a grid pattern. In addition, this cross section is a cross section of a plane parallel to the light receiving surface of the imaging element. (c) on the right side of the figure is a schematic diagram of a cross section at the position of the dotted line CC' in (d) of the figure, and this schematic diagram shows a state where multiple pixel units are arranged in a grid pattern. In addition, this cross section is a cross section of a plane parallel to the light receiving surface of the imaging element.

[0047] The pixel unit 151 is the same as the pixel unit 101 except that the partition 106 is not provided. That is, the insulating film 152, well 153, photodiode 154 (154N and 154P), gate electrode portion 155 (TG), floating diffusion portion FD and contact portion CS that constitute the pixel unit 151 can be similar to the insulating film 102, well 103, photodiode 104 (104N and 104P), gate electrode portion 105, floating diffusion portion FD and contact portion CS described in Example 1-1 above, and the description of these also applies to this example.

[0048] Compared to the imaging element 100 described in Example 1-1 above, the imaging element 150 without a partition can reduce manufacturing costs. In addition, when the fluorescent signal is too weak, the fluorescent signals of adjacent pixels can be added.

[0049] 1.1.5 Example 1-5 (Use of Multilayer Film Reflection Filter) The well surface of the imaging element described in Example 1-1 above can be formed by a multilayer film reflection filter. Figure 6 A configuration example of an image pickup element including a multilayer film reflection filter will be described.

[0050] (d) on the left side of the figure is a schematic diagram of a cross section of a pixel unit 161 of the imaging element 160. This cross section is a cross section of a plane perpendicular to the light receiving surface of the imaging element. (a) on the right side of the figure is a schematic diagram of a cross section at the position of the dotted line AA' in (d) of the figure, and this schematic diagram shows a state in which multiple pixel units are arranged in a grid pattern. In addition, this cross section is a cross section of a plane parallel to the light receiving surface of the imaging element. (b) on the right side of the figure is a schematic diagram of a cross section at the position of the dotted line BB' in (d) of the figure, and this schematic diagram shows a state where multiple pixel units are arranged in a grid pattern. In addition, this cross section is a cross section of a plane parallel to the light receiving surface of the imaging element. (c) on the right side of the figure is a schematic diagram of a cross section at the position of the dotted line CC' in (d) of the figure, and this schematic diagram shows a state where multiple pixel units are arranged in a grid pattern. In addition, this cross section is a cross section of a plane parallel to the light receiving surface of the imaging element.

[0051] The pixel unit 161 is the same as the pixel unit 101 except that a multilayer film reflection filter 162 is used instead of the well 103 and the insulating film 102 . That is, the photodiode 164 (164N and 164P), gate electrode portion 165 (TG), floating diffusion portion FD, contact portion CS and transparent substrate 168 that constitute the pixel unit 161 can be similar to the photodiode 104 (104N and 104P), gate electrode portion 105 (TG), floating diffusion portion FD, contact portion CS and transparent substrate 108 described in Example 1-1 above, and the description of these also applies to this example.

[0052] Since the well surface is formed by the multilayer film reflection filter 162, it is possible to prevent the excitation light L1 from entering the photodiode 164. Therefore, it is possible to reduce noise caused by the excitation light L1 and improve fluorescence detection accuracy.

[0053] Will refer to Figure 7A and Figure 7B An example of the structure of a multilayer film reflection filter will be described.

[0054] Figure 7AThis is a schematic diagram of the filter's multilayer structure. As shown, the multilayer film reflection filter has a multilayer structure in which layers H composed of a high-refractive-index material (hereinafter also referred to as "high-refractive-index layer H") and layers L composed of a low-refractive-index material (hereinafter also referred to as "low-refractive-index layer H") are alternately stacked. As shown in the figure, the two outermost layers of the multilayer film reflection filter can be, for example, of thickness t H As shown in the figure, the two layers can be alternately stacked with a thickness of 2t L The low refractive index material layer L and the thickness is 2t H The high refractive index material layer H. The thickness of each layer can be in the nm level.

[0055] The difference ΔT between the "average transmittance within the wavelength range of excitation light expected to be blocked by the multilayer film reflection filter" and the "average transmittance within the wavelength range of fluorescence expected to pass through the multilayer film reflection filter" is expressed by the following expression (I). In the present invention, the multilayer dielectric film can be constructed so that, for example, the difference ΔT is 99% or greater, and in particular, it can be constructed so as to maximize the difference ΔT. The transmittance T in expression (I) can be calculated using methods known in the art, and the calculation method will be described later. [Mathematical formula 1]

[0056] The assumptions of the above expression (I) are as follows. Excitation light: X nm (consider the range: X - X' < λ < X - X') (The range considered corresponds to the wavelength range of the excitation light that is desired to be blocked.) Fluorescence: Y nm (consider the range: Y - Y' < λ < Y + Y”) (The range considered corresponds to the wavelength range of the fluorescent light that is desired to be transmitted.) High refractive index material: refractive index NH, film thickness t H Low refractive index material: refractive index NL, film thickness t L Number of repetitions: N (N is an integer greater than 1) The total number of layers included in the multilayer film reflection filter: L = 2N + 1 layer (L is an integer greater than 3) The total thickness of the multilayer film reflection filter: 2N (t H + t L ) nm

[0057] Based on e.g. Figure 7BA transmittance versus wavelength diagram illustrates maximizing ΔT. As shown, the multilayer film reflection filter is constructed to maximize the difference ΔT between the average transmittance Ave[T(λ)|Y - Y' < λ < Y + Y"] within the wavelength range λ from Y - Y' to Y + Y", and the average transmittance Ave[T(λ)|X - X' < λ < X + X"] within the wavelength range λ from X - X' to X + X".

[0058] (Calculation Method of Transmittance T in Expression (1)) Figure 55A Schematic diagram showing the case where light passes through the multilayer film reflection filter. As shown in the figure, in this case, light incident from air (air, refractive index n0 = 1) perpendicular to the plane of the multilayer film 162 passes through the L layer of the multilayer film (complex refractive index of the jth layer: N j = n j + ik j ), and emits to the photodiode 164 (Si, complex refractive index: N m = n m +ik m ). In addition to the interface I(0) between the multilayer film 162 and the air and the interface I(L) of the photodiode 164 between the multilayer film 162 and the air, there are interfaces I(1) to I(L-1) between the layers constituting the multilayer film 162. When the material (i.e., complex refractive index) of the multilayer film is determined, the Fresnel reflection coefficient at each interface, the Fresnel transmission coefficient at each interface, and the phase change and wave attenuation in each layer are determined. The transmittance T can be determined using these values determined based on the material of the multilayer film according to the calculation method described on pages 99 to 103 of the document "Fundamental Theory of Optical Thin Films: Supplementary Revised Edition" (Optronics Co., Ltd., published on February 25, 2011). More specifically, the transmittance T is obtained using the following expression (II) in the calculation method. [Mathematical formula 2] The above expression (II) is described on page 103 of the document (particularly, expression (4-50)). The elements in the above expression (II) are as follows. Re(N m ) is the real part of the complex refractive index of Si as described above (= n m ). n0 is the refractive index of air (= 1) as described above. τ0' is a Fresnel transmission coefficient at a virtual interface I(0)' described later, and is described as Expression (4-48) on page 101 of the document. A method for calculating τ0' is described on pages 99 to 103 of the document. In this calculation method, if Figure 55B As shown, the Fresnel coefficient of the virtual interface I(L - 1) 'is obtained according to the Fresnel coefficient of the interface I(L) and the interface I(L - 1), as shown in Figure 55C As shown, the Fresnel coefficient of the virtual interface I(L-1)' is obtained according to the Fresnel coefficient of the virtual interface I(L-2)' and the Fresnel coefficient of the interface I(L-2), and as shown Figure 55D As shown, by repeating similar calculations of the Fresnel coefficients of the virtual interface, the Fresnel coefficients of the virtual interface I(0)' are obtained.

[0059] 1.1.6 Example 1-6 (Multilayer Film Reflective Filter and Grooves Extending into the Filter) The well surface of the imaging element described in Example 6 above is formed by a multilayer film reflection filter. In the present invention, the multilayer film reflection filter can be divided into partitions for each pixel. That is, the partition defining the pixel unit can extend not only to the photodiode but also to the multilayer film reflection filter. Figure 8 This structure will be described.

[0060] (d) on the left side of the figure is a schematic diagram of a cross section of a pixel unit 171 of the image sensor 170. This cross section is a cross section of a plane perpendicular to the light receiving surface of the image sensor. (a) on the right side of the figure is a schematic diagram of a cross section at the position of the dotted line AA' in (d) of the figure, and this schematic diagram shows a state where multiple pixel units are arranged in a grid pattern. In addition, this cross section is a cross section of a plane parallel to the light receiving surface of the imaging element. (b) on the right side of the figure is a schematic diagram of a cross section at the position of the dotted line BB' in (d) of the figure, which shows a state where multiple pixel units are arranged in a grid pattern. In addition, this cross section is a cross section of a plane parallel to the light receiving surface of the imaging element. (c) on the right side of the figure is a schematic diagram of a cross section at the position of the dotted line CC' in (d) of the figure, and this schematic diagram shows a state where multiple pixel units are arranged in a grid pattern. In addition, this cross section is a cross section of a plane parallel to the light receiving surface of the imaging element.

[0061] In pixel unit 161 described in Example 5 above, partition 166 extends to the position of photodiode 164. However, in pixel unit 171 of this example, partition plate 176 extends to multilayer film reflection filter 172. Forming partition plate 176 in this manner prevents excitation light L1 from entering other pixels, which helps reduce noise caused by the excitation light. Consequently, fluorescence detection accuracy can be further improved.

[0062] 1.1.7 Example 1-7 (Multilayer Film Reflection Filter and Groove Variation) In the imaging element described in Example 6 above, the partition extends to the multilayer film reflection filter over the entire periphery of the pixel unit (all four sides of the rectangle defining the pixel unit). In the present invention, the partition may extend to the multilayer film reflection filter in a portion of the periphery of the pixel unit, and the partition does not need to extend to the multilayer film reflection filter in the remaining portion of the periphery of the pixel unit, and may exist up to the photodiode for detecting fluorescence. Figure 9 This structure will be described.

[0063] (d) on the left side of the figure is a schematic diagram of a cross section of a pixel unit 181 of the imaging element 180. This cross section is a cross section of a plane perpendicular to the light receiving surface of the imaging element. (a) on the right side of the figure is a schematic diagram of a cross section at the position of the dotted line AA' in (d) of the figure, and this schematic diagram shows a state where multiple pixel units are arranged in a grid pattern. In addition, this cross section is a cross section of a plane parallel to the light receiving surface of the imaging element. (b) on the right side of the figure is a schematic diagram of a cross section at the position of the dotted line BB' in (d) of the figure, and this schematic diagram shows a state where multiple pixel units are arranged in a grid pattern. In addition, this cross section is a cross section of a plane parallel to the light receiving surface of the imaging element. (c) on the right side of the figure is a schematic diagram of a cross section at the position of the dotted line CC' in (d) of the figure, and this schematic diagram shows a state where multiple pixel units are arranged in a grid pattern. In addition, this cross section is a cross section of a plane parallel to the light receiving surface of the imaging element. (e) on the left side of the figure is a schematic diagram of a cross section taken along the dotted lines DD', EE', and FF' in (a), (b), and (c). This cross section is a cross section of a plane perpendicular to the light-receiving surface of the imaging element.

[0064] In the cross section shown in FIG. 5( d ), the partition 186 extends from the photodiode 184 to the multilayer film reflection filter 182 . On the other hand, in the cross-section shown in FIG. (e), the partition 186 is provided to the photodiode 184 but is not provided on the multilayer film reflection filter 182. Therefore, the excitation light L1 in FIG. (a), (b), and (c) can be emitted so as to travel in the direction of the arrow. When the excitation light L1 is emitted in this direction, it is possible to prevent the excitation light from traveling to the photodiode 184, and the noise caused by the excitation light can be reduced. This helps improve the accuracy of fluorescence detection.

[0065] In addition, as shown in the figure, an N region 183 for detecting the excitation light L1 may be provided in the sidewall portion of the well. This enables reading the signal of the excitation light. In addition, as shown in the figure, the N region 183 can be connected to the trench 186. Therefore, carriers (electrons or holes) can be read. In this embodiment, in addition to the fluorescent signal, the excitation light signal is also read. Therefore, the pixel unit 181 may include two sets of electronic reading parts, one set reading the fluorescent signal and the other set reading the excitation light signal. As shown in the figure, the pixel unit 181 includes the gate electrode portion 105 (TG), the floating diffusion portion FD, and the contact portion CS, and they constitute an electronic reading portion for reading a fluorescent signal. This is as described in Example 1-1 above, and the description also applies to this embodiment. In addition, as shown in the figure, the pixel unit 181 may also include a gate electrode portion TG2, a floating diffusion portion FD2, and a contact portion CS2. These constitute an electronic reading portion that reads the excitation light signal. This is also as described in Example 1-1 above, and the description also applies to this embodiment. Note that in the figure, TG2 is not connected to the N region 183, but TG2 can be configured to be connected to the N region 183. In this case, FD2 is not necessary, and CS2 can be connected to TG2.

[0066] 1.1.8 Example 1-8 (Transparent Well) In the present invention, the sidewall portion of the well may be transparent. Specifically, the sidewall portion may be transparent enough to transmit the excitation light. Figure 10 This structure will be described.

[0067] (d) on the left side of the figure is a schematic diagram of a cross section of a pixel unit 191 of the imaging element 190. This cross section is a cross section of a plane perpendicular to the light receiving surface of the imaging element. (a) to (c) on the right side of the figure are schematic diagrams showing a part of the light receiving surface of the image pickup element 190 in which pixel units 191 are arranged in a grid pattern, and more specifically, are schematic diagrams of the following cross section. (a) on the right side of the figure is a schematic diagram of a cross section at the position of the dotted line AA' in (d) of the figure, and this schematic diagram shows a state where multiple pixel units are arranged in a grid pattern. In addition, this cross section is a cross section of a plane parallel to the light receiving surface of the imaging element. (b) on the right side of the figure is a schematic diagram of a cross section at the position of the dotted line BB' in (d) of the figure, and this schematic diagram shows a state where multiple pixel units are arranged in a grid pattern. In addition, this cross section is a cross section of a plane parallel to the light receiving surface of the imaging element. (c) on the right side of the figure is a schematic diagram of a cross section at the position of the dotted line CC' in (d) of the figure, and this schematic diagram shows a state where multiple pixel units are arranged in a grid pattern. In addition, this cross section is a cross section of a plane parallel to the light receiving surface of the imaging element.

[0068] The pixel unit 191 has a well 199 made of a transparent material. As shown in the figure, the upper surface of the well 199 may be covered with a sheet 192 made of an opaque material. The shape and size of well 199 can be as described above in Example 1-1, and the description also applies to this example. In addition, well 199 can be configured to retain the analyte as described above in Example 1-1.

[0069] Pixel unit 191 includes a photodiode 194. The photodiode may be, for example, a Si photodiode and may have, for example, an N region 194N and a P region 195P of Si. As shown in the figure, N region 194N may be surrounded by P region 195P.

[0070] The pixel unit 191 includes a photodiode 194. The photodiode 194 may be provided only on the bottom side of the well. In addition, the pixel unit 101 includes polysilicon (Poly-Si) 195 (TG). Polysilicon serves as a gate electrode. In addition, the pixel unit 101 includes a floating diffusion FD and a contact CS. These are as described in Example 1-1 above.

[0071] The pixel unit 191 is separated from other unit pixels by a partition 196. The partition 196 may also be called a trench. Each partition 196 is provided between a unit pixel and other unit pixels. Partitions 196 can be made of an insulator or metal. Partitions 196 are arranged to cover photodiodes 194 but do not need to extend to well 199. Therefore, excitation light L1 can travel parallel to the light-receiving surface. Furthermore, since excitation light L1 travels parallel to the light-receiving surface, it is prevented from entering photodiodes 194. This helps improve fluorescence detection accuracy.

[0072] The imaging element 190 is of a back-illuminated type, that is, a wiring layer is provided on the side of the photodiode opposite to the side on which fluorescence is incident. Well 193 is provided on one side of photodiode 194, and a wiring layer (not shown) is provided on the opposite side of photodiode 194. In other words, pixel unit 191 has a multilayer structure in which a wiring layer, a detection unit (photodiode), and an analyte holding unit (well) are arranged in this order. This configuration allows the imaging element of the present invention to obtain a larger fluorescence signal, which helps improve fluorescence detection accuracy.

[0073] When the imaging element 190 is used to analyze biological samples, a space can be formed so that the analyte can reach and be retained in the well. The space can be a flow path for the analyte to flow. For example, a liquid sample containing the analyte can flow through the space, and the analyte can be captured on the bottom surface of the well. At least a portion of the space can be formed into a well shape. Figure 10 As shown, another portion of the space can be formed by a transparent substrate 198. Since the transparent substrate 198 is transparent, the excitation light can reach the interior of the well. The material of the transparent substrate 198 can be glass, but can also be a resin (e.g., acrylic resin, polycarbonate resin, etc.). Therefore, the imaging element 190 may have a space for allowing the analyte to reach the inside of the well, and may further include a transparent substrate 198 forming the space.

[0074] 1.1.9 Example 1-9 (Transparent Well and Groove) The well sidewalls of the pixel unit described in Example 8 above are transparent as a whole. In the present invention, a portion of the well sidewall through which the excitation light travels may be transparent, and the other portion may be formed by a photodiode. Figure 11 This structure will be described.

[0075] (d) on the left side of the figure is a schematic diagram of a cross section of a pixel unit 201 of the image sensor 200. This cross section is a cross section of a plane perpendicular to the light receiving surface of the image sensor. (a) to (c) on the right side of the figure are schematic diagrams showing a part of the light receiving surface of the image pickup element 200 in which pixel units 201 are arranged in a grid pattern, and more specifically, are schematic diagrams of the following cross section. (a) on the right side of the figure is a schematic diagram of a cross section at the position of the dotted line AA' in (d) of the figure, and this schematic diagram shows a state where multiple pixel units are arranged in a grid pattern. In addition, this cross section is a cross section of a plane parallel to the light receiving surface of the imaging element. (b) on the right side of the figure is a schematic diagram of a cross section at the position of the dotted line BB' in (d) of the figure, and this schematic diagram shows a state where multiple pixel units are arranged in a grid pattern. In addition, this cross section is a cross section of a plane parallel to the light receiving surface of the imaging element. (c) on the right side of the figure is a schematic diagram of a cross section at the position of the dotted line CC' in (d), which shows a state where multiple pixel units are arranged in a grid pattern. In addition, this cross section is a cross section of a plane parallel to the light receiving surface of the imaging element. (e) on the left side of the figure is a schematic diagram of a cross section taken along the dotted lines DD', EE', and FF' in (a), (b), and (c). This cross section is a cross section of a plane perpendicular to the light-receiving surface of the imaging element.

[0076] As shown in (d) and (e) of the figure, the pixel unit 201 has a well for retaining the analyte. As shown in FIG. 5( e ), the sidewalls of the well through which the excitation light L1 passes (i.e., the sidewalls perpendicular to the direction of travel of the excitation light L1) are transparent so as not to obstruct the travel of the excitation light. The transparent sidewalls do not have photodiodes or partitions. On the other hand, as shown in FIG. 5( d ), among the side walls of the well, the side wall parallel to the traveling direction of the excitation light L1 is formed by a photodiode, and a partition is provided. Therefore, a portion of the well included in the pixel unit of the imaging element of the present invention can be transparent, while the remaining portion does not need to be transparent. The opaque portion can be formed, for example, by a photodiode. This allows the excitation light to travel parallel to the light-receiving surface, and more fluorescence generated by the excitation light can be received. This helps improve the accuracy of fluorescence detection.

[0077] 1.2 Example of the structure related to the excitation light blocking unit

[0078] 1.2.1 Example 2-1 (Basic Construction Example) In some examples of 1.1 above, a structure in which a multilayer film reflection filter is provided on the surface of the well has been described. In these examples, the multilayer film reflection filter is used as a component to prevent the excitation light from traveling to the detection unit (photodiode). That is, the multilayer film reflection filter is used as an excitation light blocking unit, and the excitation light blocking unit is provided on the analyte holding unit (well). That is, each pixel unit can be provided with an excitation light blocking unit that prevents the excitation light from reaching the detection unit. In addition, the excitation light blocking unit can be configured to transmit fluorescence. In the present invention, the excitation light blocking portion may be provided between the analyte holding portion (well) and the detection portion (photodiode). Figure 12This figure illustrates an example configuration of a back-illuminated imaging element according to the present invention, including an excitation light blocking portion configured in this manner. The figure is a schematic diagram of a cross-section of a pixel of a back-illuminated imaging element according to the present invention. This cross-section is taken along a plane perpendicular to the light-receiving surface of the imaging element.

[0079] Pixel unit 301 includes a well 303 and a photodiode 304. Pixel unit 301 also includes an insulating film 302 and a multilayer film reflective filter 307 positioned between well 303 and photodiode 304. Multilayer film reflective filter 307 corresponds to the excitation light blocking portion described above. Thus, pixel unit 301 can have a multilayer structure in which photodiode 304, multilayer film reflective filter 307, insulating film 302, and well 303 are sequentially arranged. The image pickup element according to the present invention may include a plurality of pixel units 301 arranged in a grid pattern as described in Example 1-1 above.

[0080] The well 303 may be configured to retain the analyte, ie, the well 303 corresponds to an analyte retaining portion. The shape of the well 303 on the plane parallel to the light receiving surface can be a rectangle as described in Example 1-1 above, but can also be other polygons, or can be a circle, an ellipse, etc. As described in Example 1-1 above, the well 303 may be configured to retain the analyte, ie, the well 303 corresponds to an analyte retaining portion. The dimensions of the well 303 and the pixel unit 301 may be as described for the well 103 and the pixel unit 101 in Example 1-1 above, and the description is also applicable to this example.

[0081] Well 303 may be configured to retain the analyte. For example, as described in Example 1-1 above, a compound for retaining the analyte may be immobilized on the surface (particularly, the bottom surface) of well 303.

[0082] The photodiode 304 may be, for example, a silicon photodiode and may have, for example, an N region 304N and a P region 304P of silicon. As shown, the N region 304N may be surrounded by the P region 304P. As shown, the photodiode 304 may be provided only on the bottom side of the well.

[0083] The pixel unit 301 includes a gate electrode portion 305. The gate electrode portion 305 can be configured as a vertical transfer gate (VG). Alternatively, the gate electrode portion 305 can be configured as a transfer gate (TG). The gate electrode portion can include, for example, polysilicon (Poly-Si). The signal charge accumulated in the photodiode 304 is read via the gate electrode portion. The pixel unit 301 also includes a floating diffusion portion FD to which the electrons accumulated in the photodiode are transferred, and a contact portion CS connected to the floating diffusion portion. As shown in the figure, the photodiode 304 may have a buried photodiode structure. A gate electrode 305 is connected to the photodiode 304 having this structure, and electrons accumulated in the photodiode 304 are transferred from the gate electrode 305 to the floating diffusion FD and then read from the contact CS. In the present invention, the component provided for reading electrons from the photodiode is also referred to as an electron reading portion. As described above, the electron reading portion may include a gate electrode portion 305 (VG), a floating diffusion portion FD, and a contact portion CS. FD and VG may or may not be in contact with each other, and the presence or absence of contact may vary depending on the on-voltage of the gate electrode portion. In the figure, the floating diffusion portion is provided in each pixel unit, that is, the electron reading portion has a so-called FD non-shared structure, but the electron reading portion may have a FD non-shared structure as described in Example 1-1 above.

[0084] The insulating film 302 may be, for example, a silicon oxide film, a silicon oxide film containing nitrogen, a silicon nitride film, a silicon nitride film containing oxygen, or a metal oxide film. The insulating film may be an insulating film treated with high-density plasma.

[0085] The multilayer film reflection filter 307 can be referred to as above. Figure 7A and Figure 7B The above description also applies to the present example. That is, the multilayer film reflection filter has a multilayer structure in which layers H containing a high refractive index material (hereinafter, also referred to as "high refractive index layer H") and layers L containing a low refractive index material (hereinafter, also referred to as "low refractive index layer H") are alternately stacked. The multilayer film reflection filter can be configured so as to maximize the difference ΔT represented by the above-mentioned expression (I).

[0086] In the present invention, a multilayer reflection filter can be positioned between the well (analyte retention unit) and the photodiode (detection unit). This multilayer reflection filter blocks the excitation light that impinges on the well (and the analyte) while transmitting the fluorescence generated by the analyte. This reduces noise caused by the excitation light, helping to improve fluorescence detection accuracy.

[0087] The thickness T5 of the multilayer film reflection filter 307 may be, for example, 100 nm to 30 μm, preferably 150 nm to 20 μm, and more preferably 200 nm to 15 μm.

[0088] The pixel unit 301 is separated from other unit pixels by a partition 306. The partition 306 may also be called a trench. Each separator 306 is provided between a unit pixel and other unit pixels. Separators 306 may include an insulator or a metal. Separators 306 prevent excitation light that has entered unit pixel 301 and fluorescence generated by analyte S1 in pixel unit 301 from entering other unit pixels. Separators 306 also prevent electrons in photodiode 304 from entering the photodiodes of other unit pixels.

[0089] The imaging element including the plurality of pixel units 301 of the present invention is of a back-illuminated type, that is, a wiring layer is provided on the side of the photodiode opposite to the side where fluorescence is incident. Well 303 is provided on one side of photodiode 304, and a wiring layer is provided on the opposite side of photodiode 304. In other words, pixel unit 201 has a multilayer structure in which a wiring layer, a detection unit (photodiode), and an analyte retention unit (well) are arranged in this order. This configuration allows the imaging element of the present invention to obtain a larger fluorescence signal, which helps improve fluorescence detection accuracy.

[0090] The imaging element of the present invention including a plurality of pixel units 301 can have a configuration in which the plurality of pixel units 301 are arranged in a grid pattern as described in 1.1 above. The number of pixel units 301 included in one imaging element and the size and shape of the imaging element are as described in 1.1 above, and the description also applies to this example.

[0091] When analyzing a biological sample using an imaging element comprising a plurality of pixel units 301 of the present invention, a space can be formed so that the analyte reaches and is retained in a well. The space can be a flow path through which the analyte flows. For example, a liquid sample containing the analyte can flow through the space and the analyte can be captured on the bottom surface of the well. At least a portion of the space can be formed into a well shape. Figure 12 As shown, another portion of the space can be formed by a transparent substrate 308. Since the transparent substrate 308 is transparent, the excitation light can reach the interior of the well. The material of the transparent substrate 308 can be glass, but can also be a resin (e.g., acrylic resin, polycarbonate resin, etc.). Therefore, the imaging element of the present invention may have a space for allowing the analyte to reach the inside of the well, and may further include a transparent substrate 308 forming the space.

[0092] 1.2.2 Example 2-2 (Photodiode with a Two-Layer Structure) A photodiode for detecting excitation light can be further added to the pixel unit described in Example 1-1 above. That is, in the present invention, each pixel unit can further include an excitation light detection unit for detecting excitation light. The back-illuminated imaging element of the present invention can be configured to use the signal obtained by the excitation light detection unit to process the signal obtained by the fluorescence detection unit. In the following we will refer to Figure 13 This figure illustrates an example of a pixel structure in which a photodiode is added. This figure is a schematic diagram of a cross-section of a pixel of a back-illuminated imaging element according to the present invention. This cross-section is a cross-section taken along a plane perpendicular to the light-receiving surface of the imaging element.

[0093] Pixel unit 311 includes a well 313 and a fluorescence detection photodiode 314. Pixel unit 311 also includes an insulating film 312, a photodiode 319 for detecting excitation light, and a multilayer film reflection filter 317 between well 313 and photodiode 314. Multilayer film reflection filter 317 corresponds to the excitation light blocking portion described above. Thus, pixel unit 311 can have a multilayer structure in which fluorescence detection photodiode 314, multilayer film reflection filter 317, excitation light detection photodiode 319, insulating film 312, and well 313 are arranged in this order. The image pickup element according to the present invention may include a plurality of pixel units 311 arranged in a grid pattern as described in Example 1-1 above.

[0094] The fluorescence detection photodiode 314, the gate electrode portion 315 (VG), the floating diffusion portion FD, the contact portion CS, the multilayer film reflection filter 317, the insulating film 312 and the well 313 can be the same as the photodiode 304, the multilayer film reflection filter 307, the insulating film 302 and the well 303 for detecting fluorescence described in Example 2-1, and the description in 2-1 also applies to this example.

[0095] The excitation light detection photodiode 319 may be, for example, a Si photodiode and may include, for example, an N region 319N and a P region 319P of Si. As shown in the figure, the N region 319N may be surrounded by the P region 319P. As shown in the figure, the excitation light detection photodiode 319 can be arranged between the well 313 and the multilayer film reflection filter 317.

[0096] The excitation light detection photodiode 319 may be provided with a gate electrode portion 320. Signal charges accumulated in the excitation light photodiode 319 are read via the gate electrode portion. The gate electrode portion 320 (VG2) is configured to read electrons from the excitation light detection photodiode 319. The gate electrode portion 320 (VG2) includes a portion for reading electrons and a portion for passing through the multilayer film reflection filter 317 and the fluorescence detection photodiode 314. The former portion may include, for example, polycrystalline silicon (Poly-Si). The latter portion may be, for example, a metal electrode covered with an insulating film, and the metal electrode may be connected to a wiring layer. In addition, the pixel unit 311 may further include: a floating diffusion portion FD to which electrons accumulated in the excitation light detection photodiode are transferred; and a contact portion CS connected to the floating diffusion portion. As shown in the figure, the photodiode 319 may have a buried photodiode structure. A gate electrode portion 320 (VG2) is connected to the photodiode 319 having this structure, and electrons accumulated in the photodiode 319 are transferred from the gate electrode portion 320 to the floating diffusion portion FD and then read from the contact portion CS.

[0097] The excitation light detection photodiode detects the excitation light signal. Based on the excitation light signal, it can reduce or remove the excitation light noise that may be included in the fluorescence signal. This helps improve the accuracy of fluorescence detection.

[0098] 1.2.3 Example 2-3 (Photodiode and Absorption Filter with Two-Layer Structure) In the pixel unit described in Example 1-1 above, a multilayer film reflection filter is provided between two photodiodes. In the present invention, an absorption filter having an optical characteristic of absorbing excitation light may be provided between the two photodiodes instead of a multilayer film reflection filter. The absorption filter has an optical characteristic of transmitting fluorescence. Figure 14 This figure illustrates an example of a pixel unit structure including an absorption filter. This figure is a schematic diagram of a cross section of a pixel unit of a back-illuminated imaging element according to the present invention. This cross section is a cross section taken along a plane perpendicular to the light-receiving surface of the imaging element.

[0099] Pixel unit 321 includes a well 323 and a fluorescence detection photodiode 324. Pixel unit 321 includes an insulating film 322-1 between well 323 and photodiode 324, an excitation light detection photodiode 327, an absorption filter 326, and an insulating film 322-2. Absorption filter 326 corresponds to the excitation light blocking portion described above. Thus, pixel unit 321 may have a multilayer structure in which fluorescence detection photodiode 324, absorption filter 326, excitation light detection photodiode 327, and well 323 are arranged in this order. The image pickup element according to the present invention may include a plurality of pixel units 321 arranged in a grid pattern as described in Example 1-1 above.

[0100] The fluorescence detection photodiode 324, the gate electrode portion 325 (VG), the floating diffusion portion FD, the contact portion CS, the insulating film 322-1, the insulating film 322-2 and the well 323 can be the same as the fluorescence detection photodiode 304, the gate electrode portion 305, the floating diffusion portion DF, the contact portion CS, the insulating film 302 and the well 303 described in the above Example 2-1, and the description in Example 2 also applies to this example. The excitation light detection photodiode 327, gate electrode portion 329, floating diffusion portion FD2 and contact portion CS2 can be the same as the excitation light detection photodiode 319, gate electrode portion 320, floating diffusion portion FD and contact portion CS2 described in Example 2-2 above, and the description in Example 2-2 also applies to this example.

[0101] The absorption filter 326 may be a filter having optical characteristics for selectively transmitting light within a specific wavelength range and absorbing light within other wavelength ranges. The absorption filter 326 may be a filter having optical characteristics for selectively transmitting fluorescence and absorbing at least excitation light. In the present invention, the absorption filter is positioned between the excitation light detection photodiode and the fluorescence detection photodiode. This prevents the excitation light from reaching the fluorescence detection photodiode, which helps improve fluorescence detection accuracy. Furthermore, because the absorption filter is positioned in front of the excitation light detection photodiode in the optical path of the excitation light, it does not adversely affect the detection accuracy of the excitation light detection photodiode.

[0102] In addition, in the present invention, Figure 16 As shown, N region 344N-1 for detecting fluorescence and N region 344N-2 for detecting excitation light can be provided in a single P region 344P. P region 344P and N region 344N-1 function as a fluorescence detection photodiode. Electrons accumulated in the fluorescence detection photodiode are read by an electron reader (gate electrode portion 345-1, floating diffusion portion FD, and contact portion CS). The P region 344P and the N region 344N-2 function as an excitation light detecting photodiode. Electrons accumulated in the excitation light detecting photodiode are read by the electron reading portion (gate electrode portion 345-2, floating diffusion portion FD2, and contact portion CS2). In the present invention, each pixel unit can be constructed to include a photodiode having such a two-layer structure. This construction will be described in more detail later in Example 4-1 and subsequent examples.

[0103] 1.2.4 Example 2-4 (Use of Photoelectric Conversion Film) The pixel unit described in Examples 2-3 above includes an excitation light detecting photodiode. In the present invention, a photoelectric conversion film may be provided instead of the excitation light detecting photodiode. The photoelectric conversion film may be a photoelectric conversion film having wavelength selectivity, and in particular, may be a photoelectric conversion film that selectively performs photoelectric conversion on the excitation light. Therefore, the photoelectric conversion film is capable of detecting the excitation light. Figure 15 This figure illustrates an example of a pixel structure including a photoelectric conversion film. This figure is a schematic diagram of a cross section of a pixel of a back-illuminated imaging element according to the present invention. This cross section is a cross section taken along a plane perpendicular to the light-receiving surface of the imaging element.

[0104] Pixel unit 331 includes a well 333 and a fluorescence detection photodiode 334. Pixel unit 331 includes an insulating film 332-1, a photoelectric conversion film 337, an absorption filter 336, and an insulating film 322-2 between well 333 and photodiode 334. Absorption filter 336 corresponds to the excitation light blocking portion described above. Thus, pixel unit 331 can have a multilayer structure in which fluorescence detection photodiode 334, absorption filter 336, photoelectric conversion film 337, and well 333 are arranged in this order. The image pickup element according to the present invention may include a plurality of pixel units 331 arranged in a grid pattern as described in Example 1-1 above.

[0105] The fluorescence detection photodiode 334, the gate electrode portion 335, the floating diffusion portion FD, the contact portion CS, the insulating film 332-1, the insulating film 332-2 and the well 333 can be the same as the fluorescence detection photodiode 304, the gate electrode unit 305, the floating diffusion portion FD, the contact portion CS, the insulating film 302 and the well 303 described in the above Example 2-1, and the description in Example 2-1 also applies to this example. Absorption filter 336 may be the same as absorption filter 326 described above in Examples 2-3, and the description in Example 2 also applies to this example.

[0106] The photoelectric conversion film 337 may be a photoelectric conversion film having wavelength selectivity, and in particular, may be a photoelectric conversion film that selectively performs photoelectric conversion on the excitation light irradiated on the analyte. The photoelectric conversion film 337 does not need to photoelectrically convert the fluorescence generated by irradiating the analyte with the excitation light. The photoelectric conversion film may include, for example, an inorganic material or an organic material.

[0107] The inorganic material may be, for example, an inorganic semiconductor material. In one embodiment, the inorganic semiconductor material may be a Group III-V semiconductor material, and may be, for example, a gallium arsenide-based semiconductor or an indium phosphide-based semiconductor. More specific examples of such materials include InGaAs, GaAs, InP, and GaN, and in particular, the material may be InGaAs. In another embodiment, the inorganic material may be a two-dimensional semiconductor material, and the material may be MoS2 or WS2. In another embodiment, the inorganic material may be GaO3.

[0108] The organic material may be, for example, an organic semiconductor material. When the photoelectric conversion film includes an organic semiconductor material, the photoelectric conversion film may include one or more selected from, for example, a p-type organic semiconductor layer, an n-type organic semiconductor layer, and a mixed layer of a p-type organic semiconductor and an n-type organic semiconductor. For example, the photoelectric conversion film may have a single-layer structure of a p-type organic semiconductor, a single-layer structure of an n-type organic semiconductor, or a single-layer structure of a mixed layer of a p-type organic semiconductor and an n-type organic semiconductor. In addition, the photoelectric conversion film may have a multilayer structure of a p-type organic semiconductor layer and an n-type organic semiconductor film, that is, a multilayer structure of "p-type organic semiconductor layer / n-type organic semi-semiconductor layer". In addition, the photoelectric conversion film may have a structure in which a p-type organic semiconductor layer and / or an n-type organic semiconductor and a mixed layer are stacked on each other. For example, the photoelectric conversion film may have a multilayer structure of "p-type organic semiconductor layer / mixed layer of p-type organic semiconductor and n-type organic semiconductor / n-type organic semiconductor layer", a multilayer structure of "p-type organic semiconductor layer / mixed layer of p-type organic semi-semiconductor and n-type organic semiconductor", or a multilayer structure of "n-type organic semiconductor layer / mixed layer of p-type organic semiconductor and n-type organic semiconductor".

[0109] Examples of p-type organic semiconductors include naphthalene derivatives, anthracene derivatives, phenanthrene derivatives, pyrene derivatives, perylene derivatives, tetracene derivatives, pentacene derivatives, quinacridone derivatives, thiophene derivatives, thienothiophene derivatives, benzothiophene derivatives, benzothienothiophene derivatives, triallylamine derivatives, carbazole derivatives, perylene derivatives, chrysene derivatives, fluoranthene derivatives, phthalocyanine derivatives, subphthalocyanine derivatives, porphyrylidene derivatives, metal complexes having heterocyclic compounds as ligands, polythiophene derivatives, polybenzothiadiazole derivatives, and polyfluorene derivatives. The p-type organic semiconductor may be one or more of these.

[0110] Examples of n-type organic semiconductors include fullerenes and fullerene derivatives (e.g., fullerenes such as C60, C70, and C74 (higher fullerenes, endohedral fullerenes, etc.) or fullerene derivatives (e.g., fullerene fluorides, PCBM fullerene compounds, fullerene polymers, etc.)), organic semiconductors having higher (deeper) HOMO and LUMO energy levels than p-type organic semiconductors, and transparent inorganic metal oxides. The n-type organic semiconductor may be one or more of these.

[0111] More specifically, examples of n-type organic semiconductors include heterocyclic compounds containing nitrogen, oxygen or sulfur atoms, such as organic molecules incorporating pyridine derivatives, pyrazine derivatives, pyrimidine derivatives, triazine derivatives, quinoline derivatives, quinoxaline derivatives, isoquinoline derivatives, acridine derivatives, phenazine derivatives, o-phenanthroline derivatives, tetrazole derivatives, pyrazole derivatives, imidazole derivatives, thiazole derivatives, oxazole derivatives, imidazole derivatives, benzimidazole derivatives, benzotriazole derivatives, benzoxazole derivatives, benzoxazole derivatives, carbazole derivatives, benzofuran derivatives, dibenzofuran derivatives, tetraazaporphyrin derivatives, polyphenylene vinylene derivatives, polybenzothiadiazole derivatives or polyfluorene derivatives as part of their molecular skeleton, organometallic complexes and subphthalocyanine derivatives.

[0112] Examples of the groups and the like contained in the fullerene derivatives include: a halogen atom, a straight-chain, branched or cyclic alkyl group or phenyl group, a group containing a linear or condensed aromatic compound, a group containing a halide, a perfluoroalkyl group, a perfluoroalkyl group, a silylalkyl group, a silylalkoxy group, an arylsilyl group, an arylsulfanyl group, an alkylsulfanyl group, an arylsulfonyl group, an alkylsulfonyl group, an arylsulfide group, an alkylsulfide group, an amino group, an alkylamino group, an arylamino group, a hydroxyl group, an alkoxy group, an acylamino group, an acyloxy group, a carbonyl group, a carboxyl group, an amide group; a carbonylalkoxy group, an acyl group, a sulfonyl group, a cyano group, a nitro group, a group containing a chalcogen compound; a phosphino group, a phosphonyl group and derivatives of these.

[0113] The thickness of the photoelectric conversion film can be, for example, 1×10 -8 m (meter) to 5×10 -7 m, preferably 2.5×10 -8 mm to 3×10 -7 m, more preferably 2.5×10 -8 m to 2×10 -7 m, and still more preferably 1×10 -7 m to 1.8×10 -7m. Note that although organic semiconductors are generally classified as p-type and n-type, p-type means that holes are easily transported, and n-type means that electrons are easily transported, and organic semiconductors are not limited to the description of having holes or electrons as thermally excited majority carriers like inorganic semiconductors.

[0114] Examples of materials constituting the photoelectric conversion film that photoelectrically converts light having a green wavelength include rhodamine-based dyes, melacyanine-based dyes, quinacridone derivatives, subphthalocyanine-based dyes (subphthalocyanine derivatives), and the like. In addition, examples of materials constituting the photoelectric conversion film for photoelectrically converting blue light include coumaric acid dyes, tris-8-hydroxyquinoline aluminum (Alq3), melamine cyanine dyes, and the like. Furthermore, examples of the material constituting the photoelectric conversion film for photoelectrically converting red light include phthalocyanine-based dyes and subphthalocyanine-based dyes (subphthalocyanine derivatives). Furthermore, as the photoelectric conversion film, a full-color photosensitive organic photoelectric conversion film that is sensitive to substantially all visible light from the ultraviolet region to the red region can be used.

[0115] The signal charge generated by the photoelectric conversion of the photoelectric conversion film 337 can be read by, for example, a gate electrode portion 339 provided in the photoelectric conversion film 337. Furthermore, the photoelectric conversion film 337 can be provided with a floating diffusion portion FD2 and a contact portion CS2. The gate electrode portion 339, the floating diffusion portion FD2, and the contact portion CS2 can be the same as the gate electrode portion 320, the floating diffusion portion FD2, and the contact portion CS2 described in Example 2-2 above, and the description in Example 2-2 also applies to this example. Based on the read signal charge, noise reduction processing can be performed on the fluorescence signal detected by the fluorescence detection photodiode 334. Therefore, the fluorescence detection accuracy can be improved.

[0116] 1.2.5 Example 2-5 (Another Configuration Example of a Photodiode and Absorption Filter Having a Two-Layer Structure) The pixel units described in Examples 2-1 to 2-4 above include fluorescence detection photodiodes. In the present invention, a quantum dot photoelectric conversion film may be used instead of the fluorescence detection photodiode, and for example, a multilayer film in which a plurality of quantum dot photoelectric conversion films are stacked on each other may be used. Figure 17 An example of a pixel unit constructed in this manner is described. This figure is a schematic diagram of a cross section of a pixel unit of a back-illuminated imaging element according to the present invention. This cross section is a cross section of a plane perpendicular to the light receiving surface of the imaging element.

[0117] The pixel unit 351 includes a multilayer film in which quantum dot photoelectric conversion films 354-1 to 354-5 are stacked on each other except for a well 353. An insulating film 352 is provided between the well 353 and the multilayer film.

[0118] Each quantum dot photoelectric conversion film photoelectrically converts light of a specific wavelength. That is, the multilayer film includes multiple quantum dot photoelectric conversion films that photoelectrically convert light (particularly fluorescence) of different wavelengths. This enables the detection of fluorescence of various wavelengths. Furthermore, one or more of the plurality of quantum dot photoelectric conversion films can perform photoelectric conversion on the excitation light, thereby enabling detection of the excitation light. Each quantum dot photoelectric conversion film can be connected to a corresponding one of the electron readers 355-1 to 355-5. The signal from each quantum dot photoelectric conversion film connected to the corresponding electron reader is read from each electron reader. As described above, each electron reader can include a gate electrode (TG or VG). Furthermore, each electron reader can include a floating diffusion FD and / or a contact CS. Note that the pixel unit in the figure includes a multilayer film of five quantum dot photoelectric conversion films stacked one on top of the other, but the number of quantum dot photoelectric conversion films included in the pixel unit is not limited to five. In the present invention, the pixel unit may include one quantum dot photoelectric conversion film, or may include two or more quantum dot photoelectric conversion films. The wavelength of light to be photoelectrically converted varies depending on the particle size of the quantum dots. Therefore, by changing the particle size of the quantum dots, it is possible to cope with various types of fluorescence.

[0119] 1.2.6 Example 2-6 (Stacking Absorption Filters on a Transparent Substrate) As described above, the imaging element of the present invention is used in combination with a transparent substrate to form a flow path. That is, the present invention also provides a flow path unit including the imaging element and the transparent substrate, wherein the imaging element and the transparent substrate form a flow path. In the present invention, the absorption filter can be stacked on the transparent substrate. Figure 18 A configuration example related to a transparent substrate on which an absorption filter is stacked will be described.

[0120] In any of A to D of the figure, a pixel unit 311 is shown. The pixel unit 311 is as described above with reference to Figure 13 The instructions are described in Example 2-2 of the previous section and apply to this example as well.

[0121] In one embodiment, as shown in FIG. A , the absorption filter 361 may be stacked on a surface opposite to the well-side surface among the two main surfaces of the transparent substrate 318 .

[0122] In another embodiment, as shown in FIG. B , the absorption filter 362 may be stacked on a surface opposite to the well-side surface of the two main surfaces of the transparent substrate 318 , and the absorption filter 362 may be partitioned for each pixel by a partition 363 .

[0123] In another embodiment, as shown in FIG. C , two absorption filters 364 and 365 may be stacked on a surface opposite to the well-side surface of the two main surfaces of the transparent substrate 318. The two absorption filters 364 and 365 may be configured to absorb light having different wavelengths. Note that the number of absorption filters stacked on one main surface of the transparent substrate is not limited to one or two, and may be three or more instead.

[0124] In another embodiment, as shown in FIG. 8D , the absorption filter 366 may be stacked on the well-side surface of both main surfaces of the transparent substrate 318 . Note that although one absorption filter is stacked on the surface in D of the figure, two or more absorption filters may be stacked on the surface, and the two or more absorption filters may be configured to absorb light having different wavelengths.

[0125] As described above, by stacking an absorption filter on a transparent substrate, unnecessary light is absorbed, allowing only the necessary excitation light to reach the analyte. Furthermore, this prevents unnecessary light from reaching the fluorescence detection photodiode. This helps improve fluorescence detection accuracy. Furthermore, by using an absorption filter, a biological sample analysis system can be constructed without using an expensive narrow-band light source such as an LED or a laser.

[0126] 1.2.7 Example 2-7 (Modification of the Well) In the present invention, a concavo-convex shape may be provided on the bottom surface of the well (ie, the surface holding the analyte). In addition, in the present invention, a partition may be provided around the well in such a manner as to define pixel units. In the following we will refer to Figure 19 These configuration examples are described.

[0127] The pixel unit 311-1 of the imaging element shown in FIG. A is the same as that of the above-mentioned reference except that a concave-convex shape is provided on the well bottom surface 371 of the well 313. Figure 13 The pixel unit 311 of the image pickup element described in Example 2-2 is the same. In the present invention, as in the pixel unit 311-1 of the imaging element, a concave-convex shape can be provided on the surface of the well bottom. For example, a convex structure having, for example, a conical shape, a cylindrical shape, a cubic shape, a rectangular parallelepiped shape, or a pyramidal shape (e.g., a triangular pyramidal shape, a square pyramidal shape, or a pentagonal pyramidal shape) can be provided regularly or irregularly on the surface. Alternatively, a concave structure having, for example, a conical shape, a cylindrical shape, a cubic shape, a rectangular parallelepiped shape, or a pyramidal shape (e.g., a triangular pyramidal shape, a square pyramidal shape, or a pentagonal pyramidal shape) can be provided regularly or irregularly on the surface. This surface can prevent fluorescence from being reflected by the surface at the bottom of the well. Therefore, this surface can generate more fluorescence, which helps improve the accuracy of fluorescence detection. The size of the convex or concave structure may preferably be smaller than the wavelength of the fluorescence to be detected. Structures with such small size are particularly suitable for preventing fluorescence reflection.

[0128] The pixel unit 311-2 of the imaging element shown in FIG. B is the same as that in the above reference except that the partition 372 is provided so as to surround the well 313. Figure 13 Pixel unit 311 of the imaging element described in Example 2-2 is identical. Specifically, pixel unit 311-2 includes a partition 372 in the portion surrounded by the dashed line, whereas pixel unit 311 lacks a partition in this portion. Partition 372 also separates pixel units within the well. Partition 372 can be made of an insulator or metal. In the present invention, the partition is arranged to surround the well, thereby preventing fluorescence generated by the analyte in the well or excitation light irradiating the well from traveling to the photodiodes of other pixel units. This reduces noise caused by light in other pixel units, which helps improve fluorescence detection accuracy.

[0129] 1.2.8 Example 2-8 (Tilting of the Well) In the present invention, the well may be arranged so that the bottom surface of the well is inclined relative to the stacking surface between the fluorescence detection photodiode and the multilayer film reflection filter. To arrange the well in an inclined manner, for example, the insulating film supporting the well may be inclined. In addition, when the well is provided in an inclined manner, the lens may be provided in the insulating film.The lens may be a lens having an optical characteristic of converging at least a portion of the fluorescence at the fluorescence detection photodiode. Note that the lens may have an optical characteristic that focuses at least a portion of the excitation light on the excitation light detecting photodiode. In the following, reference will be made to Figure 20 An example of the configuration of the inclined well will be described.

[0130] The pixel unit 381-1 of the imaging element shown in FIG. A includes: a fluorescence detection photodiode 384, a gate electrode portion 385 connected to the fluorescence detection photodiode, a floating diffusion portion FD, a contact portion CS, a partition portion 386, a multilayer film reflection filter 387, an excitation light detection photodiode 389, a gate electrode portion 390 connected to the excitation light detection photodiode, a floating diffusion portion FD2, and a contact portion CS2. These are the same as those described above. Figure 13 The fluorescence detection photodiode 314, gate electrode portion 315, floating diffusion portion FD, contact portion CS, partition portion 316, multilayer film reflection filter 317, excitation light detection photodiode 319, gate electrode portion 320, floating diffusion portion FD2, and contact portion CS2 described in Example 2-2 are the same, and the description also applies to this example. In addition, the transparent substrate 388 is also the same as that described above. Figure 13 The transparent substrate 318 described in Example 2-2 is the same.

[0131] The pixel unit 381-1 includes a well 383. This well is arranged so as to be tilted relative to the incident plane (i.e., the stacking plane between the fluorescence detection photodiode 384 and the multilayer film reflection filter 387) through which fluorescence enters the fluorescence detection photodiode 384. In other words, the bottom surface of the well holding the analyte is tilted relative to the incident plane (i.e., the stacking plane).

[0132] In order to tilt the well as described above, the pixel unit 381-1 is configured such that the insulating film 382 provided between the well 383 and the excitation light detection photodiode 389 is tilted. That is, the two main surfaces of the insulating film are arranged not parallel to each other but intersecting each other (i.e., forming an angle greater than 0 degrees). Alternatively, the upper surface of the excitation light photodiode (the surface on which the excitation light is incident) may be inclined, and in this case, the two main surfaces of the insulating film may be parallel to each other.

[0133] When using straight-line light (e.g., laser light) as excitation light, the well (particularly, the bottom surface of the well holding the analyte) is tilted in this manner, thereby reducing the amount of excitation light incident on the fluorescence detection photodiode. This results in a reduction in noise caused by the excitation light and contributes to improved fluorescence detection accuracy.

[0134] The imaging element 381 - 2 shown in FIG. B is the same as the pixel unit 381 - 1 of the imaging element shown in FIG. A , except that a lens 391 is provided in the insulating film 382 . The lens 391 may be configured to focus at least a portion of the fluorescence generated by irradiating the analyte S1 with the excitation light at the fluorescence detection photodiode 384 . Note that the shape of the lens 391 is not limited to the convex lens shown in the figure, and may be a diffraction lens or the like instead.

[0135] By placing a lens, more fluorescence can be incident on the photodiode, which helps improve the accuracy of fluorescence detection.

[0136] 1.2.9 Example 2-9 (Well Offset) The imaging element of the present invention may be constructed so that the position of the well can be shifted relative to the position of the fluorescence detection photodiode. Figure 21 An example of an image pickup element configured in this manner will be described.

[0137] FIG. A shows an image pickup element 400 in which a plurality of pixel units 401a, 401b, and 401c are arranged. These pixel units are the same as those described above with reference to FIG. 4 except that the position of the well 403 is movable relative to the position of the fluorescence detection photodiode and a color filter 404 is provided. Figure 13 The pixel unit 311 described in Insulating Film Example 2-2 is the same. The color filter 404 includes color filter regions 404a, 404b, and 404c. The color filter region 404a provided in the pixel unit 401a, the color filter region 404b provided in the pixel unit 402b, and the color filter region 404c provided in the pixel unit 401c transmit light of different wavelengths. Note that from the perspective of focusing on each pixel unit, by omitting the term "region," the term "color filter region" can be simply referred to as "color filter."

[0138] Figure A shows the state before trap 403 moves. Figure B shows the state midway through the movement of trap 403, and Figure C shows the state after the movement of trap 403. As shown in these figures, trap 403 can move relative to the position of the fluorescence detection photodiode. On the other hand, the excitation light detection photodiode and the multilayer film reflection filter are fixed in a manner that is immovable relative to the position of the fluorescence detection photodiode. In addition, transparent substrate 408 can also be moved in accordance with the movement. The three types of pixel units 401a, 401b, and 401c shown in these figures are provided with color filters 404a, 404b, and 404c, respectively, that transmit light of different wavelengths. Like the excitation light detection photodiode and the multilayer film reflection filter, these color filters can be fixed in a manner that prevents movement relative to the fluorescence detection photodiode. Furthermore, the location of the color filter can be appropriately selected. For example, as shown in the figure, the color filter can be disposed on the insulating film 402, between the insulating film and the excitation light detecting photodiode, between the excitation light detecting light emitting diode and the multilayer film reflective filter, or between the multilayer film reflective filter and the fluorescence detecting photodiode. As shown in Figure A, before well 403 is moved, analyte Sb is held in the well of pixel unit 401b at the center. As shown in Figure C, after well 403 is moved, the well holding analyte Sb and analyte Sb are moved to pixel unit 401c on the right. Here, the wavelength of light transmitted by color filter 404b on pixel unit 401b is different from the wavelength of light transmitted by color filter 404c on pixel unit 401c on the right. Therefore, light generated by analyte Sb does not need to be detected by, for example, pixel unit 401b at the center, but can be detected by pixel unit 401c on the right after the movement. Conversely, light generated by the analyte can be detected by, for example, pixel unit 401b at the center, but does not need to be detected by pixel unit 401c on the right after the movement. Therefore, the wavelength bands of light generated by the analyte can be distinguished. In addition, light detection before and after the movement can be observed for two wavelengths in a single sequence. This improves analysis speed. In the above-described mode, one well moves across two pixels due to the movement. In this case, the color filter can be configured to transmit light of two different wavelengths depending on the position. In addition, the color filter may be configured to transmit light of three or more different wavelengths according to the position of the well, and the light of three or more different wavelengths may be detected in one sequence by controlling the position of the well. Because the well can be offset in this manner, the effect is achieved by being able to detect light generated from the analyte using multiple pixels. Note that in the above-mentioned drawings, the three color filters 404a, 404b, and 404c have optical properties that transmit light of different wavelengths, but the configuration of the color filters is not limited to this. For example, color filter 404a and color filter 404c may transmit light of the same wavelength, and the wavelength of light transmitted by color filter 404b may be different from the wavelength of light transmitted by color filters 404a and 404c. Alternatively, color filter 404a and color filter 404b may transmit light of the same wavelength, and color filter 404c may transmit light of a different wavelength from the wavelength of light transmitted by color filters 404a and 404b. The aforementioned figures illustrate three types of color filter regions 404a, 404b, and 404c that transmit light of different wavelengths, i.e., three types of color filters having different optical properties. In the present invention, the number of types of optical properties of the color filter regions is not limited to three. For example, the color filter may have two or more types of color filter regions that transmit light of different wavelengths, and may have, for example, two to ten types, particularly two, three, or four types of filter regions.

[0139] 1.2.10 Example 2-10 (Use of waveguides, absorption filters, plasmon filters, metamaterials, or polarizers) The imaging element of the present invention may include one or more of a waveguide, an absorption filter, a plasmon filter, a metamaterial, and a polarizer between a fluorescence detection photodiode and a well. Figures 22 to 29 An example of an image pickup element configured in this manner will be described.

[0140] Figure 22 The pixel unit 411-1 shown includes a well 413, a fluorescence detection photodiode 414, a gate electrode portion 415 connected to the fluorescence detection photodiode, a floating diffusion portion FD, a contact portion CS, a partition 416, a multilayer film reflection filter 417, an excitation light detection photodiode 419, a gate electrode portion 420 connected to the excitation light detection photodiode, a floating diffusion portion FD2, and a contact portion CS2. These are the same as those described above. Figure 13 The well 313, fluorescence detection photodiode 314, gate electrode portion 315, floating diffusion portion FD, contact portion CS, partition portion 316, multilayer film reflection filter 317, excitation light detection photodiode 319, gate electrode portion 320, floating diffusion portion FD2, and contact portion CS2 described in Example 2-2 are the same, and the description also applies to this example. In addition, the transparent substrate 418 is also the same as that described above with reference to FIG. Figure 13 The transparent substrate 318 is the same as that described in Example 2-2.

[0141] The pixel unit 411-1 includes an absorption filter 412 and a waveguide 421 between a fluorescence detection photodiode 414 and a well 413. More specifically, the pixel unit 411-1 has a multilayer structure in which the fluorescence detection photodiode 414, a multilayer film reflection filter 417, a waveguide 421, an absorption filter 412, an excitation light detection photodiode 419, and a well 413 are arranged in this order.

[0142] For example, the absorption filter 412 may have an optical property of absorbing excitation light. Alternatively, the absorption filter 412 may have an optical property of transmitting fluorescence. The absorption filter 412 prevents unnecessary light other than fluorescence from reaching the fluorescence detection photodiode 414. This helps improve fluorescence detection accuracy.

[0143] Furthermore, since the waveguide 421 exists between the absorption filter 412 and the multilayer film reflection filter 417, the fluorescence can more reliably reach the fluorescence detection photodiode, which helps improve the accuracy of fluorescence detection.

[0144] Figure 23 Pixel unit 411-2 is shown as including a waveguide. As shown, a lens 422 or a diffraction grating can be provided instead of the waveguide. The lens or diffraction grating can be configured to collect fluorescence, and in particular, can be configured to collect fluorescence using a fluorescence detection photodiode. This improves the accuracy of fluorescence detection.

[0145] Furthermore, a lens or diffraction grating can have wavelength dependence. More specifically, a lens or diffraction grating can be configured to focus light of a specific wavelength at a specific location, and focus light of another specific wavelength at another specific location. In other words, the light collection point can vary depending on the wavelength. In addition, as shown in the figure, two or more N regions can be formed in one P region, that is, two or more photodiodes can be formed. Since the light collection point changes according to the wavelength and two or more photodiodes are formed, light can be dispersed.

[0146] Figure 24 The pixel unit 411-3 shown includes waveguides 424 arranged in an array. In addition to arranging the waveguides in an array, the pixel unit 411-3 is similar to the above-mentioned Figure 22 The pixel unit 411 - 1 shown is the same. Alternatively, a waveguide may be formed in the insulating film 425 .

[0147] Except that the absorption filter 412 is not provided, Figure 25 The pixel unit 411-4 shown is the same as the above-mentioned Figure 24 The pixel unit 411 - 3 shown is the same. Therefore, the image pickup element of the present invention may not have an absorption filter, but may include a waveguide and a multi-layer film reflection filter.

[0148] Except for the different stacking order of the absorption filter 412, the waveguide 424 and the multilayer film reflection filter 417, Figure 26 The pixel unit 411-5 shown is Figure 24 That is, the pixel unit 411-5 has a multilayer structure in which a fluorescence detection photodiode 414, an absorption filter 412, a waveguide 424, a multilayer film reflection filter 417, an excitation light detection photodiode 419, and a well 413 are arranged in this order.

[0149] exist Figure 27 In the illustrated pixel unit 411-6, a lens structure is formed between the multilayer film reflection filter 417 and the excitation light detection photodiode. For example, the lens structure can be configured to function as a lens by adjusting the shape of the absorption filter 426. In the figure, a concave portion is schematically formed in the absorption filter 426, and the concave portion is configured to function as a lens. This concave lens shape can prevent color mixing.

[0150] exist Figure 28In the illustrated pixel unit 411-7, a plasmon filter 427 is formed between the multilayer film reflective filter 417 and the excitation light detection photodiode. A plasmon filter has the optical property of transmitting only light having a specific wavelength. Therefore, the plasmon filter can be configured to transmit only fluorescence, for example. The plasmon filter can contain metal particles (particularly nanoparticles), and can contain, for example, gold (Au) particles. Alternatively, the pixel unit may include a metamaterial instead of the plasmon filter 427. More specifically, the pixel unit may include a layer containing a metamaterial (also referred to as a "metamaterial layer") between the multilayer film reflection filter 417 and the excitation light detection photodiode. The metamaterial layer may have an optical property of transmitting only light having a specific wavelength, and in particular, may be configured to selectively transmit fluorescence detected by the fluorescence detection photodiode.

[0151] exist Figure 29 In the illustrated pixel unit 411-8, a polarizer 428 is formed between the multilayer film reflection filter 417 and the excitation light detection photodiode. When a polarizer is used, the excitation light is preferably polarized light. The polarizer may have optical properties that quench polarized light serving as excitation light and transmit fluorescence. Note that the mode of using a polarizer will be described in more detail later.

[0152] The above-described structure can also improve the accuracy of fluorescence detection.

[0153] 1.2.11 Example 2-11 (Fluorescent Reflective Material Arranged Above the Well) In the present invention, a material that reflects the fluorescence generated by irradiating the analyte with excitation light can be provided above the well. In particular, the material can transmit the excitation light. The material can be, for example, a multilayer film. Figure 30 This structure will be described.

[0154] The pixel unit 431 shown in the figure includes a well 433, a fluorescence detection photodiode 434, a gate electrode portion 435 connected to the fluorescence detection photodiode, a floating diffusion portion FD, a contact portion CS, a partition 436, a multilayer film reflection filter 437, an excitation light detection photodiode 439, a gate electrode portion 440 connected to the excitation light detection light emitting diode, a floating diffusion portion FD2, and a contact portion CS2. These are the same as those mentioned above. Figure 13 The well 313, fluorescence detection photodiode 314, gate electrode portion 315, floating diffusion portion FD, contact portion CS, partition portion 316, multilayer film reflection filter 317, excitation light detection photodiode 319, gate electrode portion 320, floating diffusion portion FD2 and contact portion CS2 described in Example 2-2 are the same, and the description also applies to this example.

[0155] As shown in the figure, the multilayer film 441 is arranged directly above the well (particularly above the analyte). That is, the multilayer film is arranged so as to sandwich the analyte S1 between the multilayer film 441 and the well 433. The multilayer film can be stacked on, for example, the above-mentioned transparent substrate. The stacked film reflects the fluorescence (dashed arrow) generated by irradiating the analyte with excitation light and transmits the excitation light. Irradiation with the excitation light generates fluorescence that travels toward the fluorescence detection photodiode, but may also generate fluorescence that travels toward the opposite side of the fluorescence detection light-emitting diode (i.e., the well opening side). The fluorescence traveling toward the opposite side is reflected by the multilayer film and detected by the fluorescence detection photodiode. This helps improve the accuracy of fluorescence detection.

[0156] 1.2.12 Example 2-12 (Pinhole Structure) In the present invention, a pinhole structure or a MEMS shutter may be provided on the well to reflect the fluorescence generated by irradiating the analyte with the excitation light. Figure 31 This structure will be described.

[0157] The pixel unit 451 shown in the figure includes a well 453, a fluorescence detection photodiode 454, a gate electrode portion 455 connected to the fluorescence detection photodiode, a floating diffusion portion FD, a contact portion CS, a multilayer film reflection filter 457, an excitation light detection photodiode 459, a gate electrode portion 460 connected to the excitation light detection photodiode, a floating diffusion portion FD2, and a contact portion CS2. These are the same as those mentioned above. Figure 13 The well 313, fluorescence detection photodiode 314, gate electrode portion 315, floating diffusion portion FD, contact portion CS, multilayer film reflection filter 317, excitation light detection photodiode 319, gate electrode unit 320, floating diffusion portion FD2 and contact portion CS2 described in Example 2-2 are the same, and the description also applies to this example.

[0158] As shown in the figure, a cover portion 461 having a pinhole H1 is provided in the opening of the well 453 . Since the pinhole H1 is provided in the cover portion 461 , the analyte S1 can be irradiated with the excitation light (solid arrow in the figure). The inner surface (the surface on the well side) of the cover 461 can include, for example, a material that reflects fluorescence (such as a metal such as Al). Therefore, the fluorescence (dashed arrow in the figure) generated by irradiating the analyte S1 with excitation light is reflected by the cover 461 without leaving the well, as shown in the figure, and travels toward the fluorescence detection photodiode 454.

[0159] Furthermore, as shown, the partition 456 extends to reach the cover. For example, the partition 456 can be configured as a light-guiding wall that guides fluorescence to the fluorescence detection photodiode 454. For example, the partition 456 can include a cladding material or metal (easily embedded light-reflecting material such as Cu, W, or Ti) having a low refractive index. Furthermore, in some embodiments, the partition 456 can be an air gap.

[0160] The cover and the partition can increase the amount of fluorescence reaching the fluorescence detection photodiode, which helps improve the accuracy of fluorescence detection.

[0161] Alternatively, the cover 461 may be a MEMS shutter. Figure 32 An example of a case where a MEMS shutter is used is described. As shown in the figure, a pixel unit 371 of an imaging element has a MEMS shutter 372 added thereto. Figure 31 The structure of the cover portion of the pixel unit 361 of the imaging element shown in the figure. The opening and closing of the pinhole are controlled by moving the MEMS shutter 372 in the direction of the arrow D1 in the figure.

[0162] 1.2.13 Example 2-13 (Excitation Light Blocking Section Provided on Si Single-Layer Structure) Refer to above Figures 22 to 27 The pixel unit described in Example 2-11 includes a fluorescence detection photodiode and an excitation light detection photodiode, that is, has a Si two-layer structure, and in addition to the Si two-layer structure, also includes a multilayer film reflection filter and an excitation light blocking part such as an absorption filter or a waveguide. In the present invention, the pixel unit may be constructed to include not an excitation light detection photodiode but a fluorescence detection photodiode and an excitation light blocking portion. Figure 33A and Figure 33B This structure will be described.

[0163] Figure 33A and Figure 33B The pixel units 471-1 to 471-6 are shown with Figures 22 to 27 The illustrated pixel units 411 - 1 to 411 - 6 are similar except that the pixel units do not include an excitation light detecting photodiode and a gate electrode portion connected to the excitation light detecting light emitting diode. Therefore, the pixel unit of the present invention may have a stacked structure of a fluorescence detection photodiode and an excitation light blocking portion (a multilayer film reflection filter and absorption filter, a waveguide, or a lens).

[0164] 1.2.14 Example 2-14 (Excitation Light Blocking Section Provided on a Si Double-Layer Structure) Refer to above Figures 22 to 27The pixel unit described in Example 2-11 includes an excitation light blocking portion between the fluorescence detection photodiode and the excitation light detection photodiode. In the present invention, in the pixel unit, some components of the excitation light blocking portion may be provided between the fluorescence detection photodiode and the excitation light detection photodiode, and other components of the excitation light blocking portion may be provided between the excitation light detection diode and the well. Figure 34A and Figure 34B This structure will be described.

[0165] Figure 34A and Figure 34B The pixel units 481-1 to 481-6 are shown with Figures 22 to 27 Pixel units 411-1 to 411-6 are shown similar except that some components of the excitation light blocking portion are between the well and the excitation light detecting photodiode and other components of the excitation light blocking portion are between the well and the excitation light detecting LED. Pixel units of the present invention may be constructed as described above.

[0166] 1.2.15 Example 2-15 (Groove Shape) In the imaging element in which a plurality of pixel units are arranged as described in the above-mentioned Example 2-1, as Figure 35 As shown in the left area 490 of the figure, the multilayer film reflective filters of two adjacent pixel units are separated from each other by a partition. The groove shape of the partition can be any of the shapes (a) to (c) on the right side of the figure. These shapes will be described below.

[0167] As shown in FIG. (a), the groove shape may be a shape in which a substantially rectangular parallelepiped shape of the high refractive index layer H and a substantially trapezoidal shape of the low refractive index layer L are alternately stacked. That is, in the high refractive index layer H, the multilayer film reflection filter may be vertically dug, and in the low refractive index layer L, the multilayer film reflection filter may be dug in a manner having a tapered angle. Alternatively, the multilayer film reflection filter may be excavated to have a taper angle in both the high refractive index layer H and the boat refractive index layer L. Therefore, the groove shape may be such that the width narrows from the shallow portion toward the deep portion of the multilayer film reflection filter as shown in FIG. (b). Alternatively, the multilayer film reflection filter can be excavated so as to have no taper angle in both the high refractive index layer H and the boat refractive index layer L. Therefore, the groove shape can be a shape having a constant width at any depth in the multilayer film reflection filter as shown in FIG. (c).

[0168] 1.3 Configuration Example of an Excitation Light Blocking Section Including a Polarizer

[0169] 1.3.1 Example 3-1 (Basic Construction Example) The back-illuminated image sensor according to the present invention may include the excitation light blocking portion as described in 1.2 above. In one embodiment, the excitation light blocking portion may include a polarizer. In this case, the excitation light may be polarized light, for example. Hereinafter, a configuration example of a back-illuminated image pickup element including a polarizer of the present invention will be described with reference to the drawings.

[0170] In a solid-state imaging device that detects samples such as biologically derived substances, a high excitation light cutoff ratio (high S / N ratio) and miniaturization of pixel size (high throughput) are required. Figure 36A The pixel unit 301 described in Example 1.2 above is shown. The pixel unit includes a multilayer film reflective filter 307 as a component for blocking excitation light. To achieve a high excitation light cutoff ratio, the film thickness of the multilayer film reflective filter needs to be increased. However, as a trade-off, the thickness of the pixel structure increases, and as miniaturization progresses, optical crosstalk is more likely to occur.

[0171] In order to more reliably prevent the transmission of the excitation light, the thickness T1 of the multilayer film reflection filter 307 of the pixel unit 301 is considered to be, for example, about several μm (particularly, about 3 μm to 4 μm). The back-illuminated image pickup element of the present invention including a polarizer instead of a multilayer film reflection filter has, for example, Figure 36B The configuration shown, and the thickness T2 of the polarizer can be, for example, 1 μm or less (particularly, about 0.2 μm to 0.3 μm). As described above, in the present invention, by using a polarizer as an excitation light blocking portion, the height of the pixel can be reduced, which is very advantageous for miniaturization of the pixel. Furthermore, since polarizers have a high excitation light cutoff ratio, using polarizers instead of multilayer reflective filters can improve the S / N ratio, which contributes to improved fluorescence detection accuracy.

[0172] The polarizer transmits polarized light of S-polarized light or P-polarized light incident along the arrangement direction, and quenches the other polarized light. Therefore, in the present invention, the polarized light quenched by the polarizer can be applied to the analyte as excitation light. Fluorescence is generated due to irradiation. The excitation light passing through the analyte holding portion (especially, the nanotrap) is quenched by the polarizer, and only fluorescence passes through the polarizer. The transmitted fluorescence is detected by a fluorescence detection photodiode. Therefore, by using a polarizer, the excitation light can be selectively cut off by polarization, that is, a high excitation light cut-off ratio can be achieved. In addition, since the thickness of the polarizer is significantly smaller than the thickness of the multilayer film reflection filter, the height of the pixel can be reduced. Reducing the height of the pixel is also useful for suppressing optical crosstalk. In addition, the reduction in pixel height makes it possible to form a structure that is conducive to pixel miniaturization.

[0173] In the following we will refer to Figure 36B and Figure 36C A back-illuminated imaging element including a polarizer according to the present invention will be described. The pixel unit 501 shown on the right side of the figure includes a well 503 and a fluorescence detection photodiode 504. Pixel unit 501 includes an insulating film 502-1, a polarizer 507, and an insulating film 502-2 between well 503 and photodiode 504. Polarizer 507 corresponds to the excitation light blocking portion described above. Therefore, pixel unit 501 can be constructed as a multilayer structure having photodiode 504, polarizer 507, and well 503 arranged in this order. The image sensor according to the present invention may include a plurality of pixel units 501 arranged in a grid pattern as described in Example 1-1 above. That is, as shown in the left plan view of the figure, the back-illuminated image sensor 500 may include a plurality of pixel units 501 arranged in a grid pattern.

[0174] In the figure, the well 503, the photodiode 504 (N region 504N and P region 504P), the gate electrode portion 505, the partition portion 506 and the transparent substrate 508 can be the same as the well 303, the photodiode 304 (N region 304N and P region 304P), the gate electrode portion 305, the partition portion 306 and the transparent substrate 308 described in Example 2-1 above, and the description also applies to this example.

[0175] The pixel unit 501 includes a polarizer 507 between the well 503 and the fluorescence detection photodiode 504. The polarizer 507 can be stacked on the well 503 via an insulating film 502-1. Alternatively, the polarizer 507 can be stacked on the fluorescence detection photodiode 504 via an insulating film 502-2. These insulating films can be, for example, SiO2.

[0176] like Figure 36C As shown, analyte S1 is irradiated with excitation light L1 (solid arrow) which is polarized light. A portion of the emitted excitation light passes through the analyte S1, passes through the well 503, and then reaches the polarizer 507. The excitation light L1, which is polarized light, is quenched by the polarizer 507. Therefore, the excitation light L1 does not reach the fluorescence detection photodiode 504. By irradiating the analyte S1 with the excitation light L1, fluorescence L2 (dashed arrow) is generated. The fluorescence L2 passes through the polarizer 507 and reaches the fluorescence detection photodiode 504.

[0177] As mentioned above, the polarizer can selectively allow fluorescence to reach the photodiode, which helps improve the accuracy of fluorescence detection.

[0178] 1.3.2 Example 3-2 (Polarizer Pattern) In the present invention, polarizers are not used to obtain polarization information. Therefore, a single polarizer can be stacked within a single pixel, or it can be stacked within multiple pixel units. In other words, a single polarizer can be positioned to cover the detection units of two or more pixel units. Furthermore, the polarizer can be oriented in any direction relative to the photodiode.

[0179] For example, Figure 37 As shown in (a), for the four photodiodes PD1 to PD4, a polarizer can be arranged along an inclined direction relative to the pixel arrangement direction, or as shown in (b), for the four photodiodes PD1 to PD4, a polarizer can be arranged along a horizontal direction or a vertical direction relative to the pixel arrangement direction. Furthermore, as shown in (c) and (d) of the figure, for each photodiode, one polarizer may be arranged in an oblique direction or in a horizontal or vertical direction relative to the pixel arrangement direction.

[0180] 1.3.3 Example 3-3 (Example using unpolarized light) In the present invention, the light emitted from the light source may be non-polarized light. In this case, a polarizer that uses non-polarized light as polarized light may be provided on the optical path from the light source to the analysis unit. Figure 38 A construction example illustrating this case.

[0181] In one embodiment, a polarizer can be stacked on a transparent substrate. For example, as shown in the figure, a polarizer 509 can be disposed between transparent substrates 508-1 and 508-2, i.e., a multilayer structure of a transparent substrate, a polarizer, and a transparent substrate can be formed. Unpolarized light L10 is emitted from a conventional light source and reaches the multilayer structure. Light L11, which is the unpolarized light L10 that passes through the multilayer structure, is polarized light. Polarized light L11 is applied to the analyte. Note that polarizers can be stacked on a transparent substrate.

[0182] The pixel unit 511 shown in the figure is the same as the pixel unit 501 described in Example 3-1 above. The polarizer 507 stacked on the photodiode 504 of the pixel unit 501 has the optical property of quenching the polarized light L11. Therefore, the excitation light can be blocked as described in Example 3-1.

[0183] For example, a polarizer is mounted on a cover glass substrate, which serves as a transparent substrate. The polarizer stacked on the photodiode is configured so that the transmission / quenching characteristics are opposite to those of the polarizer on the cover glass for polarized light. In other words, the polarized light transmitted by the polarizer on the cover glass is quenched by the polarizer stacked on the photodiode.

[0184] As described above, a light source emitting unpolarized light can be used by providing a polarizer that transmits light of a specific polarization on the optical path between the light source and the well, and providing a polarizer that quenches light of a specific polarization on the optical path between the well and the fluorescence detection photodiode.

[0185] 1.3.4 Example 3-4 (Combination of Polarizer and Excitation Light Absorption Filter) In addition to the polarizer, the pixel unit of the imaging element of the present invention may also include an excitation light absorption filter. These combinations can more reliably block the excitation light. Figure 39 An example of the configuration of a pixel unit of an image pickup element having such a combination will be described.

[0186] The pixel unit 521 of the imaging element shown in A of the figure includes a well 523 and a fluorescence detection photodiode 524 . The pixel unit 521 includes an insulating film 522-1, an absorption filter (e.g., a multilayer film reflection filter) 529, a polarizer 527, and an insulating film 522-2 between the well 523 and the photodiode 524. The absorption filter 529 and the polarizer 527 correspond to the excitation light blocking portion described above. Therefore, the pixel unit 521 can be constructed as a multilayer structure having the photodiode 523, the polarizer 527, the absorption filter 529, and the well 523 arranged in this order.

[0187] In the figure, the well 523, the photodiode 524 (N region 524N and P region 524P), the gate electrode portion 525, the partition portion 526 and the transparent substrate 528 can be the same as the well 303, the photodiode 304 (N region 304N and P region 304P), the gate electrode portion 305, the partition portion 306 and the transparent substrate 308 described in Example 2-1 above, and the description also applies to this example.

[0188] The pixel unit 521 includes an absorption filter 529 in addition to the polarizer 527. Therefore, the excitation light cutoff ratio can be further improved.

[0189] In addition, the position of the polarizer 527 and the position of the absorption filter 529 only need to be between the well 523 and the fluorescence detection photodiode 524 (particularly, on the optical path of the excitation light between the well 523 and the fluorescence detection photodiode 524), and can be changed appropriately. For example, as in the image pickup element 531 shown in B of the figure, the pixel unit 521 may have a multilayer structure in which a photodiode 523, an absorption filter 529, a polarizer 527, and a well 523 are arranged in this order.

[0190] 1.3.5 Example 3-5 (Materials for Analyte Retention Unit) The pixel unit of the imaging element of the present invention includes an analyte holding portion as described above, in particular a well for holding an analyte. The analyte holding portion can be stacked on the excitation light blocking portion and stacked, for example, with an insulating film between them. The material of the analyte holding portion and the insulating film can be any material that does not adversely affect the light to be analyzed, and can be appropriately selected by those skilled in the art. Preferably, these materials are materials that do not interfere with polarization and are weather-resistant to the reagent.

[0191] For example, Figure 36B The well 503 shown may include a material such as SiO 2 , SiN, or a resin material. In addition, if Figure 40 In the pixel unit 541 shown in FIG. 1A , the material of the bottom surface 543 - 2 of the well may be different from the material of the sidewall 543 - 1 of the well. For example, the material of the bottom surface 543 - 2 of the well may be SiN or glass. In addition, as shown in the figure, the bottom surface 543 - 2 can be stacked on the polarizer 547 (or absorption filter). That is, the bottom surface 543 - 2 can be used as an interlayer film between the well 543 (especially, the well sidewall) and the modulator 547.

[0192] Note that the photodiode 544 (N region 544N and P region 544P), gate electrode portion 545, partition portion 546 and transparent substrate 548 can be the same as the photodiode 304 (N region 304N and P region 304P), gate electrode portion 305, partition portion 306 and transparent substrate 308 described in Example 2-1 above, and the description also applies to this example.

[0193] In addition, as shown in the pixel unit 551 in FIG. B , the entire well 553 may include SiN or glass. Note that the components of the pixel unit 551 other than the well shown in FIG. 5B are the same as those in FIG. 5A .

[0194] 1.3.6 Example 3-6 (Plasma Filter) The pixel unit of the imaging element of the present invention may include a plasma filter as an excitation light blocking portion. In the present invention, the wavelength selectivity of the plasma filter can be used to selectively block the excitation light and allow the fluorescence to reach the photodiode. Figure 41 A configuration example using a plasma filter will be described.

[0195] The pixel unit 561 of the imaging element shown in A of the figure includes a well 563 and a fluorescence detection photodiode 564 . The pixel unit 561 includes an insulating film 562-1, a plasmon filter 567, and insulating films 562-2 to 562-4 between the well 563 and the photodiode 564. The plasmon filter 567 corresponds to the excitation light blocking portion described above. Therefore, the pixel unit 561 can be configured to have a multilayer structure in which the photodiode 564, the plasmon filter 567, and the well 563 are arranged in this order.

[0196] In the figure, the well 563, the photodiode 564 (N region 564N and P region 564P), the gate electrode portion 565, the partition portion 566 and the transparent substrate 568 can be the same as the well 303, the photodiode 304 (N region 304N and P region 304P), the gate electrode portion 305, the partition portion 306 and the transparent substrate 308 described in Example 2-1 above, and the description also applies to this example.

[0197] Plasmon filter 567 is a filter that selectively blocks excitation light and transmits fluorescence through the surface plasmon resonance effect. The filter may include, for example, a metal, such as Al or Cu, but is not limited thereto. As shown in the schematic cross-sectional view of FIG. B, the filter may have holes arranged in an array (also referred to as a hole array). By adjusting the spacing and / or diameter of the holes, the wavelength of light to be blocked can be adjusted. The spacing and diameter can have the dimensions shown in Figure B. The spacing refers to the interval between the holes in the unit structure. As a result of these adjustments, for example, the transmission characteristics of light in the wavelength range from visible light to near-infrared light can be adjusted.

[0198] Those skilled in the art can appropriately select the material of the insulating films 562 - 1 to 562 - 4 . Although there are three insulating films between the well and the plasma filter in the figure, the number of insulating films does not need to be 3. The number of insulating films provided therebetween may be one or more, and may be one, two, three, four, or five, for example. Although there is one insulating film between the photodiode and the plasma filter in the figure, the number of insulating films does not need to be 1. The number of insulating films provided therebetween may be one or more, and may be one, two, three, four, or five, for example. As described above, the insulating films may be made of, for example, silicon oxide, nitrogen-containing silicon oxide, silicon nitride, oxygen-containing silicon nitride, or metal oxide. They may be made of a high-density plasma-treated insulating film.

[0199] 1.3.7 Example 3-7 (Fabry-Perot Resonator Spectroscopy) The pixel unit of the imaging element of the present invention may include a film having a Fabry-Perot structure (also referred to herein as an FP structure) as an excitation light blocking portion. In the present invention, the wavelength selectivity of the film having the FP structure can be used to selectively block the excitation light and allow the fluorescence to reach the photodiode. Figure 42 A configuration example using a film having an FP structure will be described.

[0200] The imaging element 571 shown in the figure includes a well 573 and a fluorescence detection photodiode 574 . The pixel unit 571 includes a film 577 having an FP structure between the well 573 and the photodiode 574. The film 577 having the FP structure corresponds to the excitation light blocking portion described above. Therefore, the pixel unit 571 can be configured as a multilayer structure having the photodiode 574, the film 577 having the FP structure, and the well 573 arranged in this order.

[0201] In the figure, the well 573, the photodiode 574 (N region 574N and P region 574P), the gate electrode portion 575, the partition portion 576 and the transparent substrate 578 can be the same as the well 303, the photodiode 304 (N region 304N and P region 304P), the gate electrode portion 305, the partition portion 306 and the transparent substrate 308 described in Example 2-1 above, and the description also applies to this example.

[0202] The film 577 having an FP structure blocks excitation light in a wavelength-selective manner by using Fabry-Perot resonator spectrometry. For example, a film having an FP structure having a multilayer film structure made of a high-refractive material (such as a TiO2 / SiO2-based multilayer film or a PolySi / SiO2-based multilayer film) can be used. The film having an FP structure can block excitation light with a film thickness thinner than that of the multilayer film reflection filter.

[0203] The optical properties of the film having the FP structure can be adjusted by adjusting the thickness and material of each layer constituting the film and the number of layers. Figure 43 Explain this.

[0204] Figure A shows a graph showing the transmittance of a TiO2 / SiO2-based multilayer film at various wavelengths (top) and a schematic cross-sectional view of the multilayer film (bottom). In this figure, the horizontal axis λ (nm) represents the wavelength λ of light incident on the multilayer film, and the vertical axis T represents the ratio of light incident on the multilayer film that passes through the multilayer film (i.e., transmittance T). As shown in the figure, the multilayer film has 18 layers, and the thickness of each layer is shown to the right of each layer. The total thickness of the multilayer film is 1168 nm. The transmittance of light (the percentage of light reaching Si) passing through the film having the multilayer structure in the figure in the direction indicated by the arrow in the figure is plotted in the figure. The transmittance of the multilayer film has a peak near 550 nm, and the half-value width at the peak is about 10 nm. The transmittance of 530 nm excitation light through the multilayer film is 1 / 60 or less relative to the transmittance of 550 nm fluorescence. Assuming that fluorescence with a wavelength of 553 nm is generated by irradiating the analyte with excitation light of a wavelength of 532 nm (half-value width of approximately 30 nm), the multilayer film can selectively transmit the fluorescence generated by irradiating the analyte with the excitation light and selectively block the excitation light.

[0205] FIG. B illustrates a graph showing the transmittance of a polySi / SiO2-based multilayer film at various wavelengths (top) and a schematic cross-sectional view of the multilayer film (bottom). In this figure, the horizontal axis λ (nm) represents the wavelength λ of light incident on the multilayer film, and the vertical axis T represents the ratio of light transmitted through the multilayer film (i.e., transmittance T) of the light incident on the multilayer film. As shown in the figure, the multilayer film has 9 layers, and the thickness of each layer is shown on the right side of each layer. The total thickness of the multilayer film is 650 nm. The transmittance of light (the percentage of light reaching Si) passing through the film having the multilayer structure in the figure in the direction indicated by the arrow in the figure is plotted in the figure. The transmittance of the multilayer film has a peak near 550 nm, and the half-value width at the peak is about 20 nm. The transmittance of 530 nm excitation light through the multilayer film is 1 / 10 or less of the transmittance of 550 nm fluorescence. Assuming that fluorescence with a wavelength of 553 nm is generated by irradiating the analyte with excitation light of a wavelength of 532 nm (half-value width of approximately 30 nm), the multilayer film can selectively transmit the fluorescence generated by irradiating the analyte with the excitation light and selectively block the excitation light.

[0206] As described above, a film having an FP structure can selectively transmit fluorescence and selectively block excitation light. In addition, by adjusting the structure of the film, it is possible to selectively transmit or block light of a desired wavelength.

[0207] 1.4 Construction Examples Related to PD Vertical Stacking Structure

[0208] 1.4.1 Example 4-1 (Basic Construction Example) As described in 1. above, the backside-illuminated imaging element according to the present invention includes a fluorescence detection unit that detects fluorescence generated by irradiating the analyte with excitation light. In one embodiment, the fluorescence detection unit may include two or more photodiodes. The two or more photodiodes may be arranged in a vertically stacked structure between the analyte retaining unit and the wiring layer. Hereinafter, a configuration example of a back-illuminated image pickup element including a fluorescence detection section having two or more photodiodes according to the present invention will be described with reference to the drawings.

[0209] To analyze biological samples, it may be necessary to use two or more fluorescent substances. For example, in DNA sequencing, throughput is higher when using a two-color chemistry using two types of fluorescent substances or a four-color chemistry using four types of fluorescent substances, compared to a single-color chemistry using a single type of fluorescent substance. This is because in the case of a single-color chemistry, in order to use the fluorescent substances, the fluorescent substances and blockers used to specify each base need to be washed away, and more staining and image reading are required, but these times can be reduced in a two-color or four-color method.

[0210] Because the fluorescence detection unit of the back-illuminated imaging element according to the present invention includes two or more photodiodes, it can simultaneously detect light of two or more different wavelengths. This improves the throughput of biological sample analysis using two or more fluorescent substances. For example, the base sequence of nucleic acids (e.g., DNA or RNA) can be determined with fewer staining cycles, thereby increasing the throughput of base sequencing.

[0211] Two or more photodiodes are preferably arranged in a manner that forms a vertical stacking structure between the analyte holding portion and the wiring layer. For example, this is particularly applicable to nucleic acid sequencing. In nucleic acid sequencing, due to the extension of the DNA at a specific position fixed in the plane by fluorescence detection, when the photodiodes are vertically stacked at the same position of the light receiving surface (when the photodiodes are stacked in the depth direction), it is easy to obtain fluorescence information indicating DNA extension. In addition, the size of the pixel unit on the light receiving surface can be reduced by the vertical stacking structure.

[0212] In the following we will refer to Figure 44 Description of a Backside Illumination Type Image Pickup Element This figure is a schematic cross-sectional view of an example of a backside illumination type image pickup element.

[0213] The pixel unit 701 includes a well 703. As shown in the figure, the well 703 may be covered by an insulating film 702. In the figure, the shape of the well 703 is rectangular, but it can also be other polygonal shapes, or it can be circular or elliptical, etc. The well 703 (and the insulating film 702 covering the well) may be configured to retain the analyte, ie, correspond to an analyte retaining portion. The description of the well 103 and the insulating film 102 described above in 1.1 also applies to the well 703 and the insulating film 702 .

[0214] The pixel unit 701 includes two photodiodes 704-1 and 704-2. The photodiodes may be silicon photodiodes, for example. The photodiode 704 - 1 includes an N region 704N1 and a P region 704P. The photodiode 704 - 2 includes an N region 704N2 and a P region 704P. In this figure, the N region 704N1 of the photodiode 704-1 and the N region 704N2 of the photodiode 704-2 are in contact with each other, but these regions may be separated from each other. In the latter case, the two N regions may be separated by a P region. As shown, N regions 704N1 and 704N2 may be surrounded by P region 704P.

[0215] In the present invention, since the pixel unit includes two photodiodes in this manner, two light beams having different wavelengths can be detected in one pixel unit. As described later, in the present invention, the number of photodiodes included in one pixel unit is not limited to two, and may be three or more instead.

[0216] As shown, the two photodiodes 704-1 and 704-2 are arranged in a direction perpendicular to the light receiving surface, ie, vertically stacked on each other. For example, as described above, the vertical stacking structure is particularly suitable for DNA sequencing.

[0217] The pixel unit 701 may include an insulating film 707 . The well 703 and the photodiode 704 may be stacked via the insulating film 707 .

[0218] Although not shown in the figure, the pixel unit can be separated from other unit pixels by a partition. The description of the partition 106 described in 1.1 above also applies to the partition of this example.

[0219] Although not shown in the figure, the pixel unit includes a gate electrode portion connected to the photodiodes 704-1 and 704-2, respectively. The gate electrode portion can be polysilicon as described in 1.1 above. An example of the configuration of the gate electrode portion will be described later in 4.2.

[0220] The pixel units 701 may be arranged in an array to form an imaging element. The imaging element is of a back-illuminated type, that is, a wiring layer (not shown) is provided on the side of the photodiode opposite to the side on which fluorescence is incident. Well 703 is provided on one side of photodiode 704, and a wiring layer is provided on the opposite side of photodiode 704. In other words, pixel unit 701 has a multilayer structure in which a wiring layer, a detection unit (photodiode), and an analyte retention unit (well) are arranged in this order. This configuration allows the imaging element of the present invention to obtain a larger fluorescence signal, which helps improve fluorescence detection accuracy.

[0221] 1.4.2 Example 4-2 (Configuration Example of an Image Pickup Element Including Two Photodiodes) The imaging element described in Example 4-1 above includes gate electrode portions connected to two photodiodes, respectively. In the case where the two photodiodes form a vertically stacked structure, the light-receiving area of the photodiode farther from the well (lower photodiode) is smaller than the light-receiving area of the photodiode closer to the well (upper photodiode). Therefore, it is easy to form gate electrodes respectively assigned to the two photodiodes, and in particular, it is possible to reduce the area of the pixel unit (the area of the surface parallel to the light-receiving surface). In the following, reference will be made to Figure 45 Explain this.

[0222] The upper portion of the figure shows a schematic cross-sectional view of a pixel unit of an image pickup element including two photodiodes. This cross-sectional view is a schematic cross-sectional view taken along a plane perpendicular to the light receiving surface.

[0223] The pixel unit 711 includes a well 713 and insulating films 712 and 717. These are the same as the well 703 and insulating films 702 and 707 described in Example 4-1 above, and the description also applies to this example.

[0224] The pixel unit includes two photodiodes 714-1 and 714-2. These photodiodes may be silicon photodiodes, for example. The photodiode 714 - 1 includes an N region 714N1 and a P region 714P. The photodiode 714 - 2 includes an N region 714N2 and a P region 714P. In the figure, N region 714N1 and N region 714N2 are in contact with each other, but these regions may also be separated from each other. In the latter case, the two N regions may be separated by a P region. As shown, N regions 714N1 and 714N2 may be surrounded by P region 714P.

[0225] As shown, two photodiodes 714-1 (specifically N region 714N1) and 714-2 (specifically N region 714N2) are arranged perpendicular to the light receiving surface, i.e., vertically stacked on each other. For example, as described above, the vertical stacking structure is particularly suitable for DNA sequencing.

[0226] Photodiode 714-1 is connected to gate electrode portion 715-1. Photodiode 714-2 is connected to gate electrode portion 715-2. These gate electrode portions may include polysilicon as described in 1.1 above. These gate electrode portions are connected to the wiring layer. In addition, the imaging element is a back-illuminated type, and the wiring layer is arranged below in the figure. In other words, the imaging element has a multilayer structure in which a well, a photodiode, and a wiring layer are arranged in this order.

[0227] Figures A, B, and C in the lower portion of the figure are schematic diagrams of cross sections taken along lines AA', BB', and CC' in the upper portion of the figure, respectively. These schematic cross-sectional views are of a case where a plurality of pixel units 711 are arranged in an array to form an imaging element.

[0228] As shown in FIG. A, the well 713 appears in a cross-sectional view taken along line AA'. As shown in FIG. 8B , the P region 714P and the N region 714N1 constituting the photodiode 714 - 1 appear in a cross-sectional view taken along line BB′. As shown in FIG. C, in addition to P region 714P and N region 714N2 constituting photodiode 714-2, N region 714N1 also appears in the cross-sectional view taken along line CC'. Furthermore, as shown in FIG. B and FIG. C, the area of N region 714N2 of photodiode 714-2 is smaller than the area of N region 714N1 of photodiode 714-1. This area difference is utilized to arrange gate electrode portion 715-1 connected to photodiode 714-1, thereby preventing an increase in the size of the pixel unit.

[0229] As described above, since the two photodiodes are provided in a manner forming a vertical stack structure, two fluorescent beams having different wavelengths can be detected in one pixel unit. Furthermore, in a vertical stacked structure, by making the light-receiving area of the lower photodiode smaller than that of the upper photodiode, the gate electrode can be arranged without increasing the pixel unit size. This contributes to reducing the size of the imaging element.

[0230] 1.4.3 Example 4-3 (Configuration Example of an Image Pickup Element Including Three Photodiodes) The imaging element described in Examples 4-1 and 4-2 above includes two photodiodes constituting a fluorescence detection unit. The fluorescence detection unit of the pixel unit of the imaging element of the present invention may include three or more photodiodes. Figure 46 A pixel unit of an imaging element including a fluorescence detection unit having three photodiodes will be described.

[0231] The upper portion of the figure shows a schematic cross-sectional view of a pixel unit of an imaging element including three photodiodes. The cross-sectional view is a schematic cross-sectional view taken along a plane perpendicular to the light-receiving surface. Note that while three gate electrode portions are shown in the cross-sectional view, these are shown for convenience to facilitate understanding of this example and do not fully correspond to the cross-sectional view shown in the lower portion of the figure.

[0232] The pixel unit 721 includes a well 723 and insulating films 722 and 727. These are the same as the well 703 and insulating films 702 and 707 described in Example 4-1 above, and the description also applies to this example.

[0233] Each pixel unit includes two photodiodes 724-1, 724-2, and 724-3. These photodiodes may be silicon photodiodes, for example. The photodiode 724 - 1 includes an N region 724N1 and a P region 724P. The photodiode 724 - 2 includes an N region 724N2 and a P region 724P. The photodiode 724 - 3 includes an N region 724N3 and a P region 724P. In the figure, N region 724N1 and N region 724N2 are in contact with each other, or N region 724N2 and N region 724N3 are in contact with each other. In the present invention, these N regions may be separated from each other. In the case where two N regions are separated from each other, the two N regions may be separated by a P region. As shown, N regions 724N1 , 724N2 , and 724N3 may be surrounded by a P region 724P.

[0234] As shown, three photodiodes 724-1 (particularly, N region 724N1), 724-2 (particularly, N region 714N2), and 724-3 (particularly, N region 714N3) are arranged perpendicular to the light receiving surface, i.e., vertically stacked on top of each other. For example, as described above, this vertical stacking structure is particularly suitable for DNA sequencing.

[0235] Photodiode 724-1 is connected to gate electrode portion 725-1. Photodiode 724-2 is connected to gate electrode portion 725-2. Photodiode 724-3 is connected to gate electrode portion 725-3. These gate electrode portions may include polysilicon as described in 1.1 above. These gate electrode portions are connected to the wiring layer. In addition, the imaging element is a back-illuminated type, and the wiring layer is provided below the figure. That is, the imaging element has a multilayer structure in which a well, a photodiode, and a wiring layer are arranged in this order.

[0236] Figures A, B, C, and D in the lower portion of the figure are schematic diagrams of cross sections taken along lines AA', BB', CC', and DD' in the upper portion of the figure, respectively. These schematic cross-sectional views are of a case where a plurality of pixel units 721 are arranged in an array to form an imaging element.

[0237] As shown in FIG. A, the well 723 appears in a cross-sectional view taken along line AA'. As shown in FIG. 8B , the P region 724P and the N region 724N1 constituting the photodiode 724 - 1 appear in a cross-sectional view taken along line BB′. As shown in FIGC, in addition to P region 724P and N region 724N2 constituting photodiode 724-2, N region 724N1 also appears in the cross-sectional view taken along line CC'. As shown in FIGD, in addition to P region 724P and N region 724N3 constituting photodiode 724-3, N region 724N1 and N region 724N2 also appear in the cross-sectional view taken along line D-D'. As can be seen from Figures B, C, and D, the area of N region 724N2 of photodiode 724-2 is smaller than the area of N region 724N1 of photodiode 724-1. Furthermore, the area of N region 724N3 of photodiode 724-3 is smaller than the area of N region 724N2 of photodiode 724-2. This area difference is utilized to arrange gate electrode portions 725-1 and 725-2 without increasing the size of the pixel unit.

[0238] As described above, since the three photodiodes are arranged in a vertical stack structure, three fluorescent beams having different wavelengths can be detected in one pixel unit. Furthermore, in a vertical stacked structure, by making the light-receiving area of the lower photodiode smaller than that of the upper photodiode, the gate electrode can be arranged without increasing the pixel unit size. This contributes to reducing the size of the imaging element.

[0239] 1.4.4 Example 4-4 (Sensitivity Verification with Two Photodiodes) The sensitivity of each photodiode was verified for the pixel unit 711 described in Example 4-2 above. The sensitivity verification was performed based on the integrated value of the light intensity at a silicon depth of 3 μm in the fluorescence wavelength region of common fluorescent substances (red light (668 nm) and green light (545 nm)).

[0240] like Figure 47As shown, the upper end of the upper photodiode PD1 (N region) is defined as PD1s, and the lower end is defined as PD1e. Similarly, the upper end of the lower photodiode PD2 (N region) is defined as PD2s, and the lower end is defined as PD2e.

[0241] exist Figure 48 In Figure 1, the intensity of red and green light is plotted against the depth of the Si layer. The figure also shows the absorption of these light beams. As shown, the intensity of red and green light decreases with increasing depth. Therefore, the absorption of these light beams increases. From the figure, we can obtain the integrated value of the light intensity of PD1 at the position from PD1s to PD1e. Similarly, from the figure, we can obtain the integrated value of the light intensity of PD2 at the position from PD2s to PD2e. In this verification, it is assumed that PD1 is used to detect green light and PD2 is used to detect red light.

[0242] The G / R ratios were calculated when the position of PD1 was fixed and PD2 was moved to various positions. In addition, the G / R ratios were calculated when the position of PD2 was fixed and PD1 was moved to various positions. Figure 49 The calculated G / R ratio is shown. These results show that, with PD1 fixed in position, the deeper the PD2s is positioned, the higher the G / R ratio. Furthermore, with PD2 fixed in position, the shallower the PD1e is positioned, the higher the G / R ratio. Therefore, to improve sensitivity, it is considered necessary to separate the positions of the two PDs in the Si in the depth direction (perpendicular to the light-receiving surface). Additionally, it can be seen that in this case, for 3 μm silicon, the sensitivity ratio is 1.32. In addition, based on these results, in the present invention, the photodiode closer to the wiring layer among the two or more photodiodes can be configured to detect fluorescence of a longer wavelength.

[0243] Manufacturing method

[0244] 1.5.1 Example 1 of Manufacturing Method (Image Pickup Element Including PD Having Well Structure) For example, the image pickup element according to the present invention can be manufactured by applying a well-known technique in the technical field related to image pickup elements. Figure 50A and Figure 50B An example of a method for manufacturing an image pickup element according to the present invention will be described. In this example, an example of a manufacturing process of an image pickup element 1100 having the same structure as the image pickup element 100 described in Example 1-1 above will be described.

[0245] Figure 50A and Figure 50BFIG. 1 is a schematic diagram for explaining a flow chart of a method for manufacturing a back-illuminated image sensor according to the present invention. like Figure 50A As shown in (a), a Si wafer 1104P for forming a photodiode is prepared, and a photoresist PR is applied to the surface S1 of the wafer in a manner of drawing a predetermined pattern. For example, as shown in the figure, the photoresist PR can be applied to the area other than the area where the sidewall of the well is to be formed.

[0246] After coating, as shown in (b) and (c) of the figure, the N region 1104N of the photodiode is embedded by photolithography. The shape of the N region 1104N to be formed can be appropriately designed by those skilled in the art based on, for example, the structure of the well to be formed or the position and shape of the FD or gate electrode portion 1105 to be described later.

[0247] Next, as shown in FIG. ( c ), a hard mask HM is formed on the surface S1 .

[0248] After forming the hard mask HM, as shown in FIG. (d), polysilicon is buried in the region where the partition is to be formed. The burying can be performed by, for example, dry etching.

[0249] Next, after removing the hard mask HM, as shown in FIG. (e), FD is formed in a portion of the P region 1104P. Then, as shown in FIG. (f), a polysilicon layer is formed on the surface S1, and a photoresist PR is stacked on the polysilicon layer. The photoresist PR can be applied in a manner that draws a predetermined pattern. For example, as shown in the figure, the photoresist PR can be stacked in the region other than the gate electrode portion.

[0250] After stacking, only the polysilicon to be the gate electrode portion 1105 is left by photolithography and dry etching, and the rest of the polysilicon layer is removed as shown in FIG. Then, a wiring layer 1109 is provided on the surface S1, and a contact portion CS connected to the FD is also formed.

[0251] Next, if Figure 50B As shown in (h), the wafer is flipped over.

[0252] Next, as shown in FIG. 1( i ), in a portion of the surface S2 of the wafer where a partition is to be formed, tungsten is buried in the polysilicon to form a partition 1106. The burying can be performed by, for example, wet etching.

[0253] After forming the partition 1106, as shown in FIG (j), a photoresist PR is stacked on the surface S2 in a manner of drawing a predetermined pattern. For example, the photoresist may be stacked in a portion other than a portion where a well is to be formed.

[0254] Next, as shown in FIG. (k), dry etching is performed to form a well structure in the P region.

[0255] After the well structure is formed, as shown in FIG. 1 , a color filter (or a multilayer film reflection filter) 1103 is formed to form the well surface, and an insulating film 1102 is further formed on the color filter 1103. Thus, the imaging element 1100 is manufactured.

[0256] As shown in FIG. 1( m ), the imaging element 1100 is combined with various members forming a flow path unit (such as a transparent substrate 1108 ) to form a flow path unit 1110 for analyzing a biological sample.

[0257] Figure 50C A schematic cross-sectional view shows an example of a flow path unit 1110 for analyzing a biological sample. As shown in the figure, the flow path unit 1110 for analyzing a biological sample includes a back-illuminated imaging element 1100 according to the present invention and a transparent substrate 1108, and the imaging element 1100 and the transparent substrate 1108 are arranged to form a flow path C. To form a space for the flow path C, the back-illuminated imaging element 1100 and the transparent substrate 1108 may be connected via a wall 1111.

[0258] Flow path C is the flow path through which a biological sample containing an analyte flows. As the biological sample flows through flow path C, the analyte is captured in the well of imaging element 1100 (specifically, the bottom surface of the well). The analyte is then illuminated with excitation light, and the fluorescence generated by the illumination with the excitation light is detected by imaging element 1100.

[0259] 1.5.2 Manufacturing Method Example 2 (Image Pickup Element Including Multilayer Film Reflective Filter) In the following we will refer to Figures 51A to 51C An example of a method for manufacturing an image pickup element according to the present invention will be described. In this example, an example of a manufacturing flow of an image pickup element including the plurality of pixel elements 311 described in Example 2-2 above will be described. Each pixel unit 311 includes a fluorescence detection photodiode 314 and an excitation light detection photodiode 319. Therefore, in order to form the pixel unit 311, these two photodiodes are manufactured using different Si wafers. After forming the structure of each photodiode, the two photodiodes are stacked. Figure 51A and Figure 51B In FIG, row Si1L shows a flow chart for forming a fluorescence detection photodiode, and row Si2L shows a flow chart for forming an excitation light detection photodiode. Figure 51C , a flow chart after two photodiodes are joined together is shown. The details of these processes will be described below.

[0260] like Figure 51AAs shown in (a), a Si wafer 1314P for forming a fluorescence detection photodiode and a Si wafer 1319P for forming an excitation light detection photodiode are prepared. A photoresist PR is applied to the surface S11 of the Si wafer 1314P in a manner of drawing a predetermined pattern. For example, as shown in the figure, the photoresist PR may be applied to a region other than a region where an N region is to be formed. A photoresist PR is also applied to the surface S21 of the Si wafer 1319P in a manner of drawing a predetermined pattern. For example, as shown in the figure, the photoresist PR may be applied to a region other than the region where the N region is to be formed.

[0261] As shown in FIG. 1( b ), an N region 1314N is embedded in a Si wafer 1314P for forming a fluorescence detection photodiode by photolithography. Similarly, an N region 1319N is embedded in the Si wafer 1319P by photolithography. After the N region is formed, a hard mask layer HM is formed in a predetermined pattern, and the hard mask layer HM is formed to cover the region except the region where the polysilicon is to be buried.

[0262] As shown in FIG. 3( c ), polysilicon is buried in the two wafers. The burying can be performed by, for example, dry etching.

[0263] After embedding, the hard mask is removed, and then, as shown in (d1) of the figure, a photoresist PR for forming FD is formed on the surfaces S11 and S21 of the wafer in a manner of drawing a predetermined pattern. As shown in the figure, the photoresist PR is stacked in an area other than the area where the FD (Si1L row) or FD2 (Si2L row) is to be formed. Next, ion implantation is performed. As shown in (d2) of the figure, FD (Si1L row) is formed in the area of the Si wafer 1314P where the photoresist is not stacked by ion implantation. Similarly, FD2 (Si2L row) is formed on the Si wafer 1319P by ion implantation. Then, the photoresist PR is removed. The photoresist PR is stacked in the region other than the region where the gate electrode portion is to be embedded. Next, as shown in (d2) of the figure, a dry etching process is performed to scrape the region where the gate electrode portion is to be embedded. Then, the photoresist PR is removed.

[0264] Next, as shown in (e1) of the figure, a photoresist PR for forming a gate electrode portion is formed on the surfaces S11 and S21 of the wafer in a manner of drawing a predetermined pattern. As shown in the figure, the photoresist PR is stacked in an area other than the area where the gate electrode portion is to be buried. Next, as shown in (e2) of the figure, a dry etching process is performed to scrape the area where the gate electrode portion is to be buried. Then, the photoresist PR is removed. Then, the photoresist PR is removed, and the entire exposed surface of Si is oxidized during the removal process. As a result of the oxidation, a thermal oxide film is formed in the area where the gate electrode portion is to be buried. Therefore, the inner surface of the trench is covered with the thermal oxide film.

[0265] Next, as shown in FIG. (f), a polysilicon layer is formed on the surface S11 and the surface S21. Therefore, the polysilicon is also buried in the trench. Then, a photoresist is formed on the polysilicon layer of each wafer. The photoresist is formed in a portion where a gate electrode portion is to be formed.

[0266] After forming the photoresist, the polysilicon layer in the region where the photoresist is not formed is removed by photolithography and dry etching processes, and as shown in FIG. 5( g ), gate electrode portions 1315 - 1 and 1320 - 1 are formed.

[0267] Then, if Figure 51B As shown in FIG. 1 (h), a contact portion CS and a wiring layer 1329 are formed on the surface S11 of the wafer of the fluorescence detection photodiode. Thus, the wiring layer 1329 and the gate electrode portion 1315-1 are connected to each other. In addition, an adhesive material for bonding (to be described later) is applied to the surface S21 of the wafer of the excitation light detection photodiode.

[0268] After the wiring layer is formed, as shown in FIG. (i), the wafer of the fluorescence detection photodiode is turned over. Likewise, for the excitation light detection photodiode, the wafer can be flipped over, and bonding to be described later can be performed in this state.

[0269] Next, as shown in FIG. (j), the polysilicon embedded in the wafer is dry-etched to embed tungsten into the photodiode for fluorescence detection and the photodiode for excitation light detection. Thus, a partition 1316 is formed, and a gate electrode portion 1320-2 is also formed in the P region of the fluorescence detection photodiode.

[0270] Then, as shown in FIG. (k), a multilayer film reflection filter 1317 is formed on the surface S12 of the fluorescence detection photodiode (the surface opposite to the surface where the wiring layer is to be formed). To form the multilayer film reflection filter, two insulating films having different refractive indices can be alternately formed.

[0271] After forming the multilayer film reflection filter, as shown in FIG. (1), a hard mask HM is formed on the multilayer film reflection filter. The hard mask HM is formed in an area other than the area where the separator and gate electrode are to be formed. Then, after forming the hard mask, a dry etching process is performed, and then tungsten is buried. Thus, the separator 1316 and the gate electrode 1320-2 are formed in the multilayer film reflection filter. In addition, a contact CS2 is formed, which will be connected to FD2 at a later stage.

[0272] Next, as shown in (m) of the figure, the hard mask HM is removed.

[0273] After removing the hard mask, as shown in FIG (n), the excitation light detection photodiode is stacked on the multilayer film reflection filter by an adhesive. Gate electrode portion 1320-1 and gate electrode portion 1320-2 are connected to each other by stacking. In addition, FD2 is connected to CS2.

[0274] Next, if Figure 51C As shown in (o), an insulating film 1312 is formed on the excitation light detection photodiode.

[0275] Then, as shown in FIG. 13 (p), a material 1313 for forming a well is stacked on the insulating film 1312, and a photoresist is stacked on the material in a manner of drawing a predetermined pattern. The photoresist is stacked in areas other than the area where the well is to be formed.

[0276] Then, as shown in (q) of the figure, the material 1313 is etched by, for example, dry etching to form a well. Thus, an imaging element in which the pixel units 1311 are arranged is manufactured.

[0277] As shown in FIG. 1( r ), the imaging element is combined with various members forming the flow path unit (such as a transparent substrate 1318 ) to form a flow path unit 1300 for analyzing a biological sample.

[0278] Figure 51D A schematic cross-sectional view shows an example of a flow path unit 1300 for analyzing a biological sample. As shown in the figure, the flow path unit 1300 for analyzing a biological sample includes a back-illuminated imaging element 1331 according to the present invention and a transparent substrate 1318. The imaging element 13313 and the transparent substrate 1318 are arranged to form a flow path C. To form the flow path C, the imaging element 13313 and the transparent substrate 1318 may be connected via a well 1332.

[0279] Flow path C is the flow path through which a biological sample containing an analyte flows. As the biological sample flows through flow path C, the analyte is captured in the well of imaging element 1331 (specifically, the bottom surface of the well). The analyte is then illuminated with excitation light, and the fluorescence generated by the illumination with the excitation light is detected by imaging element 1331.

[0280] 1.5.3 Manufacturing Method Example 3 (Image Pickup Element Including Multilayer Film Reflective Filter) In the following we will refer to Figures 52A to 52C An example of a method for manufacturing an imaging element according to the present invention will be described. In this example, an example of a manufacturing process for an imaging element 1341 including the plurality of pixel elements 301 described in Example 2-1 above will be described. Details of these processes will be described below.

[0281] like Figure 52A As shown in (a), a Si wafer 1304P for forming a fluorescence detection photodiode is prepared. A photoresist PR is applied to the surface S1 of the Si wafer 1304P in a manner of drawing a predetermined pattern. For example, as shown in the figure, the photoresist PR may be applied to a region other than a region where an N region is to be formed.

[0282] As shown in FIG. 1( b ), an N region 1314N is embedded in a Si wafer 1314P for forming a fluorescence detection photodiode by photolithography. After the N region is formed, a hard mask layer HM is formed in a predetermined pattern so as to cover the region except for the region where the polysilicon is to be buried.

[0283] As shown in FIG. 3( c ), polysilicon is embedded in both wafers. The embedding can be performed by, for example, dry etching.

[0284] After embedding, the hard mask is removed. Then, as shown in (d1) of the figure, a photoresist PR for forming an FD is formed on the surface S11 of the wafer in a predetermined pattern. As shown in the figure, the photoresist PR is stacked in areas other than the area where the FD is to be formed. Next, ion implantation is performed. As shown in (d2) of the figure, an FD is formed in the area of the Si wafer 1304P where the photoresist is not stacked. The photoresist PR is then removed.

[0285] Next, as shown in (e1) of the figure, a photoresist PR for forming a gate electrode portion is formed on the surface S1 of the wafer in a manner of drawing a predetermined pattern. As shown in the figure, the photoresist PR is stacked in an area other than the area where the gate electrode portion is to be buried. Next, as shown in (e2) of the figure, a dry etching process is performed to scrape the area where the gate electrode portion is to be buried. Then, the photoresist PR is removed, and the entire exposed surface of Si is oxidized during the removal process. As a result of the oxidation, a thermal oxide film is formed in the area where the gate electrode portion is to be buried. Therefore, the inner surface of the trench is covered with the thermal oxide film.

[0286] Next, as shown in FIG. (f), a polysilicon layer is formed on the surface S1, so that the polysilicon is also buried in the trench. Then, a photoresist is formed on the polysilicon layer in a portion where a gate electrode portion is to be formed.

[0287] After forming the photoresist, the polysilicon layer in the region where the photoresist is not formed is removed by photolithography and dry etching, and as shown in FIG. 5( g ), the gate electrode portion 1305 is formed.

[0288] Then, if Figure 51B As shown in (h) of FIG. 1 , a wiring layer 1339 is formed on the surface S1 of the wafer of the fluorescence detection photodiode. Thus, the wiring layer 1339 is formed, and the contact portion CS connected to the FD is also formed.

[0289] After the wiring layer is formed, as shown in FIG. (i), the wafer of the fluorescence detection photodiode is turned over.

[0290] Next, as shown in FIG. 5( j ), the polysilicon embedded in the wafer is dry-etched to embed tungsten in both the photodiode for fluorescence detection and the photodiode for excitation light detection.

[0291] Then, as shown in FIG. (k), a multilayer film reflection filter 1307 is formed on the surface S2 of the fluorescence detection photodiode (the surface opposite to the surface where the wiring layer is to be formed). To form the multilayer film reflection filter, two insulating films having different refractive indices can be alternately formed.

[0292] After forming the multilayer film reflection filter, a hard mask HM is formed on the multilayer film reflection filter, as shown in FIG. (1). The hard mask HM is formed in the area other than the area where the partition is to be formed. After forming the hard mask, dry etching is performed, and then tungsten is embedded. Thus, partitions 1306 are formed in the multilayer film reflection filter.

[0293] Next, as shown in (m) of the figure, the hard mask HM is removed.

[0294] After removing the hard mask, as Figure 52C As shown in (n), an insulating film 1302 is formed on the multilayer film reflection filter.

[0295] Then, as shown in (o) of the figure, a material 1303 for forming a well is stacked on the insulating film 1302, and a photoresist is further stacked on the material in a manner of drawing a predetermined pattern. The photoresist is stacked in the region except the region where the well is to be formed.

[0296] Then, as shown in FIG. 1( p ), the material 1303 is etched by, for example, dry etching to form a well. Thus, an imaging element in which the pixel unit 1301 is arranged is manufactured.

[0297] As shown in (q) of the figure, the imaging element is combined with various members forming the flow path unit (such as the transparent substrate 1308 ) to form a flow path unit 1400 for analyzing a biological sample.

[0298] Figure 52D A schematic cross-sectional view shows an example of a flow path unit 1400 for analyzing a biological sample. As shown in the figure, the flow path unit 1400 for analyzing a biological sample includes a back-illuminated imaging element 1341 and a transparent substrate 1308 according to the present invention, and the imaging element 1341 and the transparent substrate 1304 are arranged to form a flow path C. To form the flow path C, the back-illuminated imaging element 1341 and the transparent substrate 1308 may be connected via a well 1342.

[0299] Flow path C is the flow path through which a biological sample containing an analyte flows. As the biological sample flows through flow path C, the analyte is captured in the well of imaging element 1341 (specifically, the bottom surface of the well). The analyte is then illuminated with excitation light, and the fluorescence generated by the excitation light is detected by imaging element 1341.

[0300] 2. Second Embodiment (Flow Path Unit for Biological Sample Analysis)

[0301] The present invention provides a flow path unit including a back-illuminated imaging element according to the present invention. For example, the flow path unit can be used for analyzing biological samples, but can also be used for other purposes.

[0302] The biological sample may be a sample containing an analyte. The analyte may produce fluorescence due to the above-mentioned excitation light. The analyte may be, for example, a nucleic acid, more specifically, DNA or RNA. That is, the flow path unit of the present invention may be a flow path unit for analyzing nucleic acids.

[0303] Nucleic acid analysis can be nucleic acid sequence analysis. That is, the flow path unit of the present invention can be a flow path unit for analyzing nucleic acids. The flow path unit is particularly suitable for determining the base sequence of nucleic acids.

[0304] The analyte may be a biological substance other than nucleic acid, and may be, for example, a protein, a lipid, a peptide, or a sugar. The analyte may be an antibody or an antigen.

[0305] The analyte can be a biological particle, i.e., a cell or a non-cellular biological particle. The cell can be, for example, a blood cell, but can also be other cells. Alternatively, the non-cellular biological particle can be an extracellular vesicle, particularly an exosome or a microvesicle. The analyte can be bacteria or viruses.

[0306] Will refer to Figure 53 An example configuration of a flow path unit according to the present invention will be described. The flow path unit 2000 shown in the figure includes a back-illuminated imaging element 100 according to the present invention, a sample supply flow path unit 2001 that supplies a sample (specifically, a liquid sample) to the imaging element 100, and a sample discharge flow path unit 2002 that discharges the sample from the imaging element. These three elements are fluidically connected to form a flow path C.

[0307] For example, the sample supply flow path unit 2001 may be fluidically connected to a container storing a sample to be analyzed. The sample discharge flow path unit 2002 can be fluidically connected to, for example, a container for collecting waste fluid.

[0308] The sample flows in the flow channel C, and an analyte (for example, nucleic acid) contained in the sample is captured in the well of the imaging element 100 .

[0309] In the well, a chemical or biological reaction using the analyte can occur. For example, a nucleic acid extension reaction can occur in the well. The nucleic acid extension reaction can be a reaction for nucleotide sequencing. Sequencing can be Sanger sequencing or next generation sequencing. Next generation sequencing can be pyrophosphate sequencing, synthesis sequencing or ligation sequencing.

[0310] The flow path C is designed to facilitate the flow of the biological sample S. The flow path C can be formed into a flow path structure such as a microchip (a chip including a micrometer-scale flow path) or a flow cell. The width of the flow path C can be, for example, 1 mm or less, and can specifically be 10 μm or more and 1 mm or less, for example 20 μm or more and 500 μm or less. The flow path C and the flow path structure including the flow path C can be made of materials such as plastic or glass. In order to illuminate the analyte in the well of the imaging element with excitation light, at least a portion of the flow path may be transparent. In particular, the portion of the flow path through which L1 passes in the figure may be transparent. As described above, in the flow path unit and imaging element according to the present invention, the portion through which excitation light and fluorescence pass may be transparent.

[0311] 3. Third Implementation (Biological Sample Analysis System)

[0312] The present invention also provides a biological sample analysis system including a backside-illuminated imaging element or a flow path unit according to the present invention. In this system, the backside-illuminated imaging element or the flow path unit according to the present invention can be interchangeably incorporated into the system. In other words, the backside-illuminated imaging element or the flow path unit according to the present invention can be used as a disposable component in the system.

[0313] Will refer to Figure 54 The following describes an example of a system configuration. The biological sample analysis system 3000 shown in the figure includes, in addition to the flow path unit 2000 according to the present invention (or the back-illuminated imaging element according to the present invention), an information processing unit 3100, a process control system 3200, an optical system control system 3300, a fluid control system 3300, and a fluid storage system 3400.

[0314] The flow path unit 2000 according to the present invention and the imaging element included therein are as described above in 1. and 2.

[0315] The information processing unit 3100 includes, for example, a processing unit that processes various types of data (e.g., fluorescence data) and a storage unit that stores the various types of data. The processing unit can perform analysis based on the fluorescence data obtained by the imaging element of the flow path unit. This analysis can be, for example, for determining the base sequence, but other types of processing are also possible.

[0316] The information processing unit 3100 can be configured to output various types of data (e.g., optical data and images). For example, the information processing unit 3100 can output various types of data generated based on fluorescence data (e.g., base sequence data, identification data about analytes, etc.). In addition, the information processing unit 3100 can be configured to accept input of various types of data, and for example, accept analysis instruction data from a user. The information processing unit 3100 can include an output unit (e.g., a display, etc.) or an input unit (e.g., a keyboard, etc.) for performing output or input.

[0317] The information processing unit 3100 can be configured as a general-purpose computer, or as an information processing device including, for example, a CPU (or GPU), RAM, and ROM. The information processing unit 3100 can be included in a housing provided with one or more of the process control system 3200, the optical system control system 3300, the fluid control system 3400, and the fluid storage system 3500, or can be external to the housing. In addition, various processes or functions to be performed by the information processing unit 3100 can be implemented by a server computer or cloud connected via a network.

[0318] The process control system 3200 may be a system for controlling a process (particularly a biological or chemical process) performed in a flow cell. This system may control, for example, the temperature of the flow cell and / or the supply or discharge of samples or reagents to or from the flow cell. To perform control, the process control system 3200 may include a temperature adjustment system. Furthermore, the process control system 3200 may control other elements 3300, 3400, or 3500 to perform control.

[0319] The optical system control system 3300 can be configured to control the irradiation of the analyte with excitation light and the acquisition of fluorescence data generated by the irradiation of the excitation light. The optical system control system 3300 may include, for example, a light irradiation unit. The light irradiation unit may include a light source unit that emits light and a light guiding optical system that guides the light to the irradiation position (for example, the analyte in the well set in the imaging element). The light source unit includes one or more light sources. For example, the light source type is a laser light source or an LED. The light source unit emits excitation light. In addition, the light source unit can emit non-polarized light or can emit polarized light. The wavelength of the light emitted from each light source can be appropriately selected in a manner to produce the desired fluorescence. The light can have a wavelength of any one of ultraviolet light, visible light and infrared light, for example. The light guiding optical system includes optical elements such as a beam splitter, a reflector or an optical fiber. In addition, the light guiding optical system may also include a lens for focusing light, for example, including an objective lens.

[0320] The fluid control system 3400 controls the supply of fluid to the flow path unit 2000 and / or the discharge of fluid from the flow path unit 2000. The fluid control system 3400 may include, for example, one or more pump units. The fluid control system 3400 may include a pump unit that controls the supply of fluid to the flow path unit 2000 and / or a pump unit that controls the discharge of fluid from the flow path unit 2000.

[0321] The fluid storage system 3500 may include a container for holding a sample, a container for holding a reagent, and a container for holding a waste liquid, and may be configured to control these containers. For example, a temperature control device may be included to detect and / or control the temperature in these containers.

[0322] (Testing Department) The detection unit 6102 includes at least one light detector that detects light generated by irradiating light onto biological particles. The light to be detected can be, for example, fluorescence or scattered light (for example, one or more of forward scattered light, backscattered light, and side scattered light). Each light detector includes one or more light receiving elements and includes, for example, an array of light receiving elements. Each light detector can include one or more photomultiplier tubes (PMTs) and / or photodiodes such as APDs and MPPCs as light receiving elements. Each light detector includes, for example, a PMT array in which a plurality of PMTs are arranged in a one-dimensional direction. In addition, the detection unit 6102 can include an imaging element such as a CCD or a CMOS. Using the imaging element, the detection unit 6102 can obtain an image of the biological particles (for example, a bright field image, a dark field image, or a fluorescent image).

[0323] The detection unit 6102 includes a detection optical system that allows light of a predetermined detection wavelength to reach corresponding photodetectors. The detection optical system includes a spectroscopic unit such as a prism or diffraction grating, or a wavelength separation unit such as a dichroic mirror or filter. The detection optical system is configured to disperse light, for example, generated by irradiating biological particles with light, and detect the dispersed light using a greater number of photodetectors than the number of fluorescent dyes used to label the biological particles. A flow cytometer incorporating such a detection optical system is called a spectral flow cytometer. Furthermore, the detection optical system is configured to separate light corresponding to the fluorescence wavelength range of a specific fluorescent dye from light generated, for example, by irradiating biological particles with light, and to cause corresponding photodetectors to detect the separated light.

[0324] In addition, the detection unit 6102 may include a signal processing unit that converts the electrical signal obtained by the light detector into a digital signal. The signal processing unit may include an A / D converter as a device for performing the conversion. The digital signal obtained as a result of the conversion performed by the signal processing unit may be sent to the information processing unit 6103. The information processing unit 6103 may process the digital signal as data related to light (hereinafter also referred to as "light data"). The light data may be, for example, light data including fluorescence data. More specifically, the light data may be light intensity data, and the light intensity may be light intensity data about light including fluorescence (which may include features such as area, height, and width).

[0325] Note that the present invention may also have the following configurations. [1] A back-illuminated imaging element comprising: A plurality of pixel units, each of the pixel units comprising at least: an analyte retaining portion configured to retain an analyte; and A fluorescence detection section detects fluorescence generated by irradiating the analyte with excitation light. [2] The back-illuminated imaging element according to [1], wherein The analyte holding portion has a well shape, and The detection portion is provided so as to cover not only the bottom of the well but also the side surfaces of the well. [3] The back-illuminated image pickup element according to [1] or [2], wherein grooves are provided between the pixel units. [4] The back-illuminated image sensor according to any one of [1] to [3], wherein two or more of the wells are connected to each other to form a columnar structure. [5] The back-illuminated image sensor according to any one of [1] to [4], wherein an electrode pair is provided for each pixel unit, and a voltage is applied to the electrode pair in such a manner as to adjust the position of the analyte. [6] The back-illuminated image pickup element according to any one of [1] to [5], wherein each of the pixel units is provided with an excitation light blocking portion that prevents the excitation light from reaching the detection portion. [7] According to the back-illuminated imaging element described in [6], The excitation light blocking portion includes a multilayer film reflection filter. [8] The back-illuminated imaging element according to [7], wherein the multilayer reflection filter is provided between the analyte retaining portion and the detection portion. [9] The back-illuminated image pickup element according to any one of [1] to [8], wherein each of the pixel units further includes an excitation light detection unit for detecting the excitation light.

[10] The back-illuminated image pickup element according to [9] is configured to process the signal obtained by the fluorescence detection section using the signal obtained by the excitation light detection section.

[11] The back-illuminated imaging element according to any one of [6] to

[10] , wherein: The excitation light blocking portion includes a polarizer, a plasma filter, a metamaterial, or a multilayer film having a Fabry-Perot structure.

[12] The back-illuminated image pickup element according to any one of [6] to

[11] , wherein the excitation light blocking portion is configured to transmit the fluorescent light.

[13] The back-illuminated imaging element according to any one of [6] to

[12] , wherein: The excitation light blocking portion includes a polarizer, and The excitation light is polarized light.

[14] The back-illuminated imaging element according to any one of [6] to

[12] , wherein: The excitation light blocking portion includes a polarizer, and One polarizer is provided so as to cover two or more of the pixel-based detection sections.

[15] The back-illuminated image sensor according to any one of [1] to

[14] , wherein the fluorescence detection section includes two or more photodiodes.

[16] The back-illuminated imaging element according to

[15] , wherein the two or more photodiodes are arranged to form a vertical stacked structure between the analyte holding portion and the wiring layer.

[17] The back-illuminated imaging element according to

[15] or

[16] , wherein the photodiode closer to the wiring layer among the two or more photodiodes is configured to detect fluorescence of a longer wavelength.

[18] The back-illuminated image pickup element according to any one of

[15] to

[17] , wherein the two or more photodiodes form a two-layer structure or a three-layer structure.

[19] A flow path unit for biological sample analysis, comprising: A back-illuminated imaging element comprising a plurality of pixel units, each of the pixel units comprising at least: an analyte holding portion configured to hold an analyte; and a fluorescence detecting portion detecting fluorescence generated by irradiating the analyte with excitation light; and A flow channel supplies the biological sample to the analyte holding portion.

[20] A biological sample analysis system uses a flow path unit for biological sample analysis to analyze a biological sample, the flow path unit comprising: A back-illuminated imaging element comprising a plurality of pixel units, each of the pixel units comprising at least: an analyte holding portion configured to hold an analyte; and a fluorescence detecting portion detecting fluorescence generated by irradiating the analyte with excitation light; and A flow channel supplies the biological sample to the analyte holding portion. Reference Signs List

[0326] 100 camera components 101 pixel units 102 insulating film Well 103 104 photodiode 105 gate electrode portion 106 partition 108 transparent substrate

Claims

1. A back-illuminated imaging element comprising: A plurality of pixel units, each of the pixel units comprising at least: an analyte retaining portion configured to retain an analyte; and A fluorescence detection section detects fluorescence generated by irradiating the analyte with excitation light.

2. The back-illuminated image sensor according to claim 1, wherein The analyte holding portion has a well shape, and The detection portion is provided so as to cover not only the bottom of the well but also the side surfaces of the well.

3. The back-illuminated image sensor according to claim 2, wherein: In the back-illuminated image sensor, grooves are provided between the pixel units.

4. The back-illuminated image sensor according to claim 2, wherein: Two or more of the wells are connected to each other in a manner of forming a column structure.

5. The back-illuminated image sensor according to claim 2, wherein: Each pixel unit is provided with an electrode pair, and a voltage is applied to the electrode pair in such a manner as to adjust the position of the analyte.

6. The back-illuminated image sensor according to claim 1, wherein Each pixel unit is provided with an excitation light blocking portion, which prevents the excitation light from reaching the detection portion.

7. The back-illuminated image sensor according to claim 6, wherein: The excitation light blocking portion includes a multilayer film reflection filter.

8. The back-illuminated image sensor according to claim 7, wherein The multilayer film reflection filter is provided between the analyte retaining portion and the detection portion.

9. The back-illuminated image sensor according to claim 1, wherein Each of the pixel units further includes an excitation light detection unit for detecting the excitation light.

10. The back-illuminated image sensor according to claim 9, wherein The back-illuminated image pickup element is configured to process a signal obtained by the fluorescence detection section using a signal obtained by the excitation light detection section.

11. The back-illuminated image sensor according to claim 6, wherein The excitation light blocking portion includes a polarizer, a plasma filter, a metamaterial, or a multilayer film having a Fabry-Perot structure. 12 . The back-illuminated image pickup element according to claim 11 , wherein the excitation light blocking portion is configured to transmit the fluorescent light.

13. The back-illuminated image sensor according to claim 6, wherein The excitation light blocking portion includes a polarizer, and The excitation light is polarized light.

14. The back-illuminated image sensor according to claim 6, wherein The excitation light blocking portion includes a polarizer, and One polarizer is provided so as to cover two or more of the pixel-based detection sections. 15 . The back-illuminated image sensor according to claim 1 , wherein the fluorescence detection section includes two or more photodiodes.

16. The back-illuminated image sensor according to claim 15, wherein: The two or more photodiodes are arranged to form a vertical stack structure between the analyte holding portion and the wiring layer.

17. The back-illuminated image sensor according to claim 16, wherein: The photodiode closer to the wiring layer among the two or more photodiodes is configured to detect fluorescence of a longer wavelength.

18. The back-illuminated image sensor according to claim 15, wherein The two or more photodiodes form a two-layer structure or a three-layer structure.

19. A flow path unit for biological sample analysis, the flow path unit comprising: A back-illuminated imaging element comprising a plurality of pixel units, each of the pixel units comprising at least: an analyte holding portion configured to hold an analyte; and a fluorescence detecting portion detecting fluorescence generated by irradiating the analyte with excitation light; and A flow channel supplies the biological sample to the analyte holding portion.

20. A biological sample analysis system, which uses a flow path unit for biological sample analysis to analyze a biological sample, the flow path unit comprising: A back-illuminated imaging element comprising a plurality of pixel units, each of the pixel units comprising at least: an analyte holding portion configured to hold an analyte; and a fluorescence detecting portion detecting fluorescence generated by irradiating the analyte with excitation light; and A flow channel supplies the biological sample to the analyte holding portion.

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