Biomaterial detection chip, biomaterial detection device, and biomaterial detection system

By setting a partition wall made of conductor on the biomaterial detection chip and applying voltage, the problem of reduced light detection accuracy caused by high-order structures in biomaterial detection is solved, and high-precision detection of nucleic acids and cells is achieved.

CN115087857BActive Publication Date: 2025-09-26SONY SEMICON SOLUTIONS CORP
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Patent Information

Application Number
CN202180014551.1
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Priority Date
2020-02-19
Filing Date
2021-01-29
Publication Date
2025-09-26
Estimated Expiration
2041-01-29

AI Technical Summary

Technical Problem

When biological substances such as DNA and cells are suspended or fixed in a sample solution, the accuracy of light detection decreases due to their high-order structures, and existing technologies are difficult to solve this problem.

Method used

A biomaterial detection chip is used, in which a voltage is applied on a holding surface, a photoelectric conversion unit is arranged below the holding surface, and a partition wall made of a conductor is arranged between pixels on the holding surface, and a voltage is applied on the holding surface.

Benefits of technology

The accuracy of biological material detection is improved, especially the detection effect of nucleic acids and cells.

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Abstract

A biomaterial detection chip with high detection accuracy is provided. This technology provides a biomaterial detection chip comprising at least: a holding surface composed of a plurality of pixels, each of which holds biomaterial; and a photoelectric conversion unit disposed below the holding surface and on a semiconductor substrate. Conductive partitions are provided between the pixels on the holding surface. Also provided are a biomaterial detection device and a biomaterial detection system using this biomaterial detection chip.
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Description

Technical Field

[0001] This technology relates to a biomaterial detection chip, a biomaterial detection device, and a biomaterial detection system. Background Art

[0002] In recent years, research on technologies for gene analysis, protein analysis, cell analysis, and the like has progressed in various fields such as medicine, drug discovery, clinical testing, food, agriculture, and engineering. Specifically, recent progress has led to the development and practical application of detection technologies for chips, such as lab-on-a-chips, where various reactions, such as the detection and analysis of biological substances such as nucleic acids, proteins, cells, and microorganisms, are performed within microscale channels and wells provided within the chip. These are attracting attention as methods for easily measuring biological substances, etc.

[0003] For example, PTL 1 discloses an optical detection device comprising at least a first substrate, a second substrate, a third substrate, and a fourth substrate. Multiple wells are formed in the first substrate, a heating unit is provided in contact with the wells in the second substrate, multiple light-emitting units are positioned in the third substrate to correspond to the positions of the wells, and multiple light-detecting units are positioned in the fourth substrate to correspond to the positions of the wells. This optical detection device can measure various reactions occurring in the wells.

[0004] Furthermore, for example, PTL 2 discloses a chemical sensor comprising a substrate having a light detection unit formed therein and a plasmon absorption layer laminated on the substrate and having a metal nanostructure that induces plasmon absorption. This chemical sensor can detect emission of light caused by the binding between a probe material fixed to the sensor and a target material.

[0005] [Citation List]

[0006] [Patent Document]

[0007] [PTL 1]

[0008] JP 2010-284152A

[0009] [PTL 2]

[0010] WO 2013 / 080473 Summary of the Invention

[0011] [Technical Issues]

[0012] Even if proteins, such as DNA and antibodies, and biological substances, such as cells, are suspended in a sample liquid or immobilized, they may shrink due to their higher-order structures, which may affect light detection.

[0013] Therefore, the main purpose of this technology is to provide a biomaterial detection chip with high detection accuracy.

[0014] [Solution to the problem]

[0015] Specifically, first, the present technology provides a biological material detection chip, which is composed of multiple pixels, wherein the pixels include at least a holding surface for holding biological material and a photoelectric conversion unit arranged below the holding surface and arranged on a semiconductor substrate, wherein a partition wall made of a conductor is arranged between pixels on the holding surface.

[0016] In the bio-substance detection chip according to the present technology, the partition wall may be designed to apply a voltage when the bio-substance is detected.

[0017] In this case, a positive voltage or a negative voltage may be applied to all the partition walls, and as for the partition walls, a positive voltage or a negative voltage may be applied to the corresponding partition walls.

[0018] Furthermore, the magnitude of the voltage applied to the partition walls may be changed for each partition wall.

[0019] In the bio-substance detection chip according to the present technology, some or all of the partition walls capable of conducting electricity on the holding surface may be covered with a protective film.

[0020] As biological substances detectable by the biological substance detection chip according to the present technology, one or more biological substances selected from nucleic acids, proteins, cells, microorganisms, chromosomes, ribosomes, mitochondria, organelles (cell organelles), and complexes thereof can be exemplified.

[0021] Next, the present technology provides a biological material detection device, including: a biological material detection chip, which is composed of a plurality of pixels, wherein the pixels include at least a holding surface for holding biological material and a photoelectric conversion unit arranged below the holding surface, and wherein a partition wall made of a conductor is arranged between the pixels on the holding surface; and an analysis unit that analyzes electrical information acquired by the biological material detection chip.

[0022] The present technology also provides a biological substance detection system, including a biological substance detection chip composed of a plurality of pixels, wherein the pixels include at least a holding surface for holding biological substances and a photoelectric conversion unit arranged below the holding surface, and wherein a partition wall made of a conductor is arranged between the pixels on the holding surface; and an analysis device that analyzes electrical information acquired by the biological substance detection chip.

[0023] In the present technology, "biological matter" broadly includes nucleic acids, proteins, cells, microorganisms, chromosomes, ribosomes, mitochondria, organelles (cell organelles), and complexes thereof. Cells include animal cells (e.g., blood cell lineage cells) and plant cells. Microorganisms include bacteria such as Escherichia coli, viruses such as tobacco mosaic virus, and fungi such as yeast. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 1 is a schematic conceptual diagram schematically illustrating the interaction between biosubstances S detectable by the biosubstance detection chip 1 , the biosubstance detection device 2 , and the biosubstance detection system 3 according to the present technology.

[0025] Figure 2 1 is a schematic conceptual diagram schematically illustrating the interaction between biosubstances S detectable by the biosubstance detection chip 1 , the biosubstance detection device 2 , and the biosubstance detection system 3 according to the present technology.

[0026] Figure 3 1 is a schematic conceptual diagram schematically illustrating the interaction between biosubstances S detectable by the biosubstance detection chip 1 , the biosubstance detection device 2 , and the biosubstance detection system 3 according to the present technology.

[0027] Figure 4 Schematic conceptual diagram schematically illustrating screening of other substances that can be performed by the biomaterial detection chip 1 , the biomaterial detection apparatus 2 , and the biomaterial detection system 3 according to the present technology.

[0028] Figure 5 Schematic conceptual diagram schematically illustrating screening of other substances that can be performed by the biomaterial detection chip 1 , the biomaterial detection apparatus 2 , and the biomaterial detection system 3 according to the present technology.

[0029] Figure 6 Schematic conceptual diagram schematically illustrating screening of other substances that can be performed by the biomaterial detection chip 1 , the biomaterial detection apparatus 2 , and the biomaterial detection system 3 according to the present technology.

[0030] Figure 7 1 is a schematic plan view schematically showing a first embodiment of a biological substance detection chip 1 according to the present technology, viewed from above.

[0031] Figure 8 is a schematic end view taken along line AA, schematically illustrating a first embodiment of a biomaterial detection chip 1 according to the present technology.

[0032] Figure 91 is a schematic end view schematically showing a modification of the first embodiment of the biological substance detection chip 1 according to the present technology.

[0033] Figure 10 1 is a schematic plan view schematically showing a second embodiment of the biological substance detection chip 1 according to the present technology, viewed from above.

[0034] Figure 11 1 is a schematic plan view schematically showing a first modification of the second embodiment of the biological material detection chip 1 according to the present technology, viewed from above.

[0035] Figure 12 1 is a schematic plan view schematically showing a second modification of the second embodiment of the biological material detection chip 1 according to the present technology, viewed from above.

[0036] Figure 13 1 is a schematic plan view schematically showing a third modified example of the second embodiment of the biological material detection chip 1 according to the present technology, viewed from above.

[0037] Figure 14 1 is a schematic plan view schematically showing a third embodiment of the biological substance detection chip 1 according to the present technology, viewed from above.

[0038] Figure 15 1 is a schematic plan view schematically showing a first modified example of the third embodiment of the biological material detection chip 1 according to the present technology, viewed from above.

[0039] Figure 16 1 is a schematic plan view schematically showing a second modified example of the third embodiment of the biological material detection chip 1 according to the present technology, viewed from above.

[0040] Figure 17 1 is a schematic plan view schematically showing a third modification of the third embodiment of the biological material detection chip 1 according to the present technology, viewed from above.

[0041] Figure 18 1 is a schematic plan view schematically showing a fourth embodiment of the biological substance detection chip 1 according to the present technology, viewed from above.

[0042] Figure 19 1 is a schematic plan view schematically showing a modification of the fourth embodiment of the biological material detection chip 1 according to the present technology, viewed from above.

[0043] Figure 20 is a schematic end view taken along line BB, schematically illustrating a first embodiment of a bio-substance detection chip 1 according to the present technology.

[0044] Figure 21 is a schematic end view taken along line CC, schematically illustrating a third embodiment of the bio-substance detection chip 1 according to the present technology.

[0045] Figure 22 : is a block diagram showing the concept of the biological material detection device 2 according to the present technology.

[0046] Figure 23 : is a block diagram showing the concept of a biological substance detection system 3 according to the present technology. DETAILED DESCRIPTION

[0047] Hereinafter, preferred embodiments for implementing the present technology will be described with reference to the accompanying drawings. The embodiments described below illustrate examples of representative embodiments of the present technology, but the scope of the present technology should not be narrowly understood based on the embodiments. Here, the description will be made in the following order.

[0048] 1. Overview of biological material detection using this technology

[0049] (1) Detection of biological substance S itself

[0050] (2) Detection of interactions with biological substances S

[0051] (3) Screening of other substances

[0052] 2. Biomaterial detection chip 1

[0053] (1) First embodiment

[0054] (2) Second embodiment

[0055] (3) Third embodiment

[0056] (4) Fourth embodiment

[0057] (5) Other examples

[0058] (6) Method of applying voltage

[0059] 3. Biological material detection device 2

[0060] 4. Biological material detection system 3

[0061] 1. Overview of biological substance detection performed by this technology

[0062] The following will describe an overview of the detection of a biological substance S performed by the biological substance detection chip 1, the biological substance detection device 2, and the biological substance detection system 3 according to the present technology. The biological substance detection chip 1, the biological substance detection device 2, and the biological substance detection system 3 according to the present technology can be used for (1) detection of the biological substance S itself, (2) detection of interactions of the biological substances S, (3) screening for other substances (e.g., pharmaceutical ingredients) using the biological substance S, and the like. Here, each detection is performed on the holding surface 111 of the biological substance detection chip 1 to be described below.

[0063] (1) Detection of biological substance S itself

[0064] For example, this technology can be used to detect biological substances such as red blood cells, white blood cells, platelets, cytokines, hormones, carbohydrates, lipids, and proteins contained in body fluids such as blood, urine, feces, and saliva; microorganisms such as bacteria, fungi, and viruses contained in body fluids and water; and genes in cells and microorganisms. For example, after staining with a dye specifically targeting the target substance or non-target substance, the presence of the target substance can be detected based on the presence of the desired light. The test results can be used for disease diagnosis, internal environment diagnosis, water quality inspection, and other purposes.

[0065] (2) Detection of interactions with biological substances S

[0066] For example, this technology can be used to detect interactions such as protein interactions, nucleic acid hybridization, and the binding of cytokines and hormones to receptors. Figures 1 to 3 Describe a specific detection example.

[0067] For example, Figure 1 As shown in A to D in FIG, a biological substance S1 such as a protein or a receptor (or a replica of a receptor) is immobilized on a holding surface 111 (refer to FIG. Figure 1 A in FIG), and fixed dyes such as fluorescent dyes F1 to F3 are added to biological substances S2 to S4 to examine their interactions (ref. Figure 1 Then, the biological substances S3 and S4 that do not interact with the biological substance S1 are washed away (refer to Figure 1 C), and the interaction between the biological substance S1 and the biological substance S2 can be detected by detecting the fluorescent dye F1 from the holding surface 111 (refer to Figure 1 D) in.

[0068] For example, Figure 1 As shown in E to H in FIG, biological substances S1 such as cells are immobilized on the holding surface 111, and the trapped light source F1 can be detected by a transporter protein t of the biological substance S1 (eg, a transporter protein in the cell membrane).

[0069] For example, Figure 2 As shown in A to D in FIG, a probe S5 composed of DNA, RNA, etc. is fixed to the holding surface 111 (reference Figure 2 A in ), and adding a sample containing targetable DNA S6 and S7, and intercalator I (reference Figure 2 Then, when DNA S6 having a sequence complementary to probe S5 is contained in the sample, a hybridization reaction occurs. Unhybridized DNA S7 is washed away (refer to Figure 2 C), the hybridization between the probe S5 and the target DNA S6 can be detected by detecting the light from the intercalator I holding the surface 111 (refer to Figure 2 D) in.

[0070] For example, Figure 3 As shown in A to D in FIG. 1 , the biological substance S8 is fixed on the holding surface 111 (refer to FIG. Figure 3 A in ), and adding biological substance S9 that interacts with biological substance S8 to form new substance S10 (reference Figure 3 Next, a dye such as a fluorescent dye F4 that specifically binds to the substance S10 is added (refer to Figure 3 C in FIG), and detecting the fluorescent dye F4 from the holding surface 111 (reference Figure 3 D) in the figure, and thus the interaction between the biological substance S8 and the biological substance S9 can be detected.

[0071] (3) Screening of other substances

[0072] For example, this technology can be used to screen substances that can be agonists or antagonists of various receptors, as well as to screen agents for inhibiting the production of various microorganisms, antibacterial agents, fungicides, etc. Figures 4 to 6 Describe a specific detection example.

[0073] For example, Figure 4 As shown in A to D in FIG, the receptor R1 (or a replica of the receptor R1) is fixed on the holding surface 111 (reference Figure 4 A in ), and fixed dyes such as fluorescent dyes F5 to F7 are added to substances d1 to d3 to check the operability of the receptor R1 (refer to Figure 4 B in ). Then, substances d2 and d3 that do not bind to receptor R1 are washed away (refer to Figure 4 C), and screening of substances d1 that may be agonists of receptor R1 can be performed by detecting fluorescent dye F5 from the holding surface 111 (refer to Figure 3 D) in.

[0074] For example, Figure 5As shown in A to E in FIG, the receptor R2 (or a replica of the receptor R2) is fixed on the holding surface 111 (see Figure 5 A), and the substance d4 for examining the antagonistic effect of the receptor R2 was added (see Figure 5 Next, a ligand L1 is added that binds to the receptor R2 and to which a dye such as a fluorescent dye F8 is fixed (refer to Figure 5 In this case, if substance d4 can be an antagonist of receptor R2, ligand L1 cannot bind to receptor R2 because receptor R2 and substance d4 are already bound to each other (refer to Figure 5 In this state, the ligand L1 that does not bind to the receptor R2 is washed away (refer to Figure 5 Even if an attempt is made to detect the fluorescent dye F8 from the holding surface 111 after washing, the fluorescent dye F8 is no longer present on the holding surface 111, and no light can be detected (refer to FIG. Figure 5 E).

[0075] On the other hand, for example, Figure 6 As shown in A to E in FIG, the receptor R3 (or a replica of the receptor R3) is fixed on the holding surface 111 (reference Figure 6 A), and added substance d5 (reference Figure 6 Next, a ligand L2 that binds to the receptor R3 is added, and a dye, such as a fluorescent dye F9 (refer to Figure 6 In this case, when substance d5 is not an antagonist of receptor R3, ligand L2 binds to receptor R3 (refer to Figure 6 In this state, when the substance d5 that does not bind to the receptor R3 is washed away (refer to Figure 6 D), the fluorescent dye F9 is detected from the holding surface 111 (ref. Figure 6 E).

[0076] In this way, as Figure 5 and Figure 6 As shown, based on whether the fluorescent dye F8 or the fluorescent dye F9 is detected from the holding surface 111 , screening of the substance d4 can be performed, and the substance d4 may be an antagonist of the receptor R3.

[0077] 2. Biomaterial Detection Chip 1

[0078] The biomaterial detection chip 1 according to the present technology is composed of a plurality of pixels 11, and each pixel 11 includes at least a holding surface 111 on which the biomaterial S is held, and a photoelectric conversion unit 112 disposed below the holding surface 111 and on a semiconductor substrate 12. Here, a partition wall 13 made of a conductor is provided between the pixels 11 on the holding surface 111. Hereinafter, this will be described with reference to an embodiment.

[0079] Examples of the conductor constituting the partition wall 13 include metals, and as for the metal, for example, tungsten (W), aluminum (Al), copper (Cu), titanium (Ti), or the like can be used.

[0080] (1) First embodiment

[0081] Figure 7 is a schematic plan view schematically showing a first embodiment of a biomaterial detection chip 1 according to the present technology, viewed from above, and Figure 8 1 is a schematic end view taken along line AA schematically showing a first embodiment of a biological material detection chip 1 according to the present technology. The biological material detection chip 1 according to the first embodiment has an effective pixel area 11E, in which a plurality of pixels 11 are arranged two-dimensionally in a matrix form. Each pixel 11 includes at least a holding surface 111 and a photoelectric conversion unit 112, and the biological material S is held on the holding surface 111. In the photoelectric conversion unit 112, for example, a photoelectric conversion element such as a photodiode can be freely used. In addition, although not shown, each pixel 11 may include a pixel circuit composed of a charge storage unit, a plurality of transistors, a capacitor element, etc. Although not shown, optical black pixels, wiring areas, etc. may be provided outside the effective pixel area 11E (invalid pixel area O).

[0082] Retention surface 111 is not particularly limited, as long as it has a structure capable of retaining biological material S, and surface treatments can be freely applied. For example, retention surface 111 can be formed by applying a photosensitive silane coupling agent modified to be hydrophilic by ultraviolet radiation, and selectively emitting ultraviolet light toward the area where biological material S is desired to be retained. Furthermore, for example, if retention surface 111 is treated with avidin, biological material S, such as nucleic acid with one end biotinylated, can be retained via an avidin-biotin bond. Furthermore, depending on the configuration capable of retaining a liquid on retention surface 111, biological material S can also be retained in a liquid.

[0083] Since the partition wall 13 is made of a conductor, a voltage can be applied. For example, if a voltage is applied to the partition wall 13 when the biological substance S is held on the holding surface 111, the partition wall 13 acts as an electrode for attracting the charged biological substance S and pushing it to a desired position, such as the center of the pixel.

[0084] The specific structure of the partition wall 13 is not particularly limited as long as it is provided between the pixels 11 on the holding surface 111. For example, Figure 8 As shown, each pixel 11 can be completely separated by partition walls 13. In this case, for example, by applying a positive or negative voltage to all partition walls 13, depending on the positive or negative charge of the biological material S held on the holding surface 111, the biological material S can be attracted to the partition walls 13 or collected at the center of the pixel. More specifically, for example, when detecting negatively charged DNA, applying a negative voltage to all partition walls 13 can collect the DNA at the center of the pixel. This improves detection accuracy.

[0085] Here, as schematically shown according to Figure 9 In a schematic cross-sectional view of a modified example of the first embodiment of the biomaterial detection chip 1 of the present technology, the partition wall 13 may have a configuration in which it is embedded in the semiconductor substrate 12. When the partition wall 13 is embedded in the semiconductor substrate 12, light leakage between pixels can be prevented, and detection accuracy can be further improved.

[0086] (2) Second embodiment

[0087] Figure 10 : is a schematic plan view schematically showing a second embodiment of the biomaterial detection chip 1 according to the present technology viewed from above. The biomaterial detection chip 1 according to the second embodiment is an example in which the partition wall 13 does not exist in the vertical direction when viewed from above and the partition wall 13 exists only in the lateral direction. In this case, for example, when viewed from above, when a positive voltage or a negative voltage is alternately applied to the partition wall 13 in the lateral direction viewed from above, the direction of the biomaterial S can be aligned in a desired direction. More specifically, for example, when negatively charged DNA is detected, as in Figure 10 In the second embodiment shown in , if positive voltage or negative voltage is applied alternately to the partition wall 13 in the lateral direction when viewed from above, the direction of the DNA can be aligned. As a result, the detection accuracy can be improved.

[0088] Here, for example, as schematically shown according to Figure 11 As shown in the schematic cross-sectional view of the first modified example of the second embodiment of the biomaterial detection chip 1 of the present technology, for the purpose of pressure division, a partition wall 13a in the vertical direction when viewed from above may be provided with a space between it and a partition wall 13b in the lateral direction when viewed from above. In this case, for example, as schematically shown according to Figure 12As shown in the schematic cross-sectional view of the second modified example of the second embodiment of the biomaterial detection chip 1 of the present technology, the insulator 14 may be provided between the partition wall 13a in the vertical direction when viewed from above and the partition wall 13b in the lateral direction when viewed from above. Figure 13 In the schematic cross-sectional view of the third modified example of the second embodiment of the biological substance detection chip 1 of the present technology, the partition walls made of the insulator 14 may be provided in the vertical direction viewed from above.

[0089] Any insulating material that can be used for the biomaterial detection chip 1 can be used as the insulator 14 as long as it does not impair the effects of the present technology. For example, oxide films such as silicon oxide (SiO2) and nitride films such as silicon nitride (Si3N4) and silicon oxynitride (SiON) can be used.

[0090] (3) Third embodiment

[0091] Figure 14 : is a schematic plan view schematically showing a third embodiment of the biomaterial detection chip 1 according to the present technology viewed from above. The biomaterial detection chip 1 according to the third embodiment is an example in which the partition wall 13 does not exist in the vertical direction when viewed from above and the partition wall 13 exists only in the lateral direction. In addition, this is an example in which a 0V partition wall 13b3 is arranged between the partition wall 13b1 to which a positive voltage is applied and the partition wall 13b2 to which a negative voltage is applied. When the 0V partition wall 13b3 is arranged, the charge can be stabilized and the flow of the biomaterial S can be formed. More specifically, for example, when negatively charged DNA is detected, as in Figure 14 In the third embodiment shown in FIG, when the negative voltage applied partition wall 13b2, the 0V partition wall 13b3, and the positive voltage applied partition wall 13b1 are arranged in this order, DNA can flow from the negative side to the positive side. For example, DNA can be separated because the flow can differ depending on the difference in DNA charge. As a result, detection accuracy can be improved and additional information can be obtained.

[0092] Here, as in the second embodiment, for example, as schematically shown according to Figure 15 As shown in the schematic cross-sectional view of the first modified example of the third embodiment of the biomaterial detection chip 1 of the present technology, for the purpose of voltage division, the partition wall 13a in the vertical direction when viewed from above may be provided with a space between it and the partition walls 13b1 to 3 in the lateral direction when viewed from above. In this case, for example, as schematically shown Figure 16As shown in the schematic cross-sectional view of the second modified example of the third embodiment of the biomaterial detection chip 1 according to the present technology, the insulator 14 may be provided between the partition wall 13a in the vertical direction when viewed from above and the partition walls 13b1 to 3 in the lateral direction when viewed from above. Figure 17 In the schematic cross-sectional view of the third modification of the third embodiment of the biological substance detection chip 1 of the present technology, the partition walls made of the insulator 14 may be provided in the vertical direction viewed from above.

[0093] (4) Fourth embodiment

[0094] Figure 18 Schematic plan view schematically showing a fourth embodiment of the biomaterial detection chip 1 according to the present technology viewed from above. The biomaterial detection chip 1 according to the fourth embodiment is an example including three regions: a region of a partition wall 13b1 to which a positive voltage is applied, a region of a partition wall 13b2 to which a negative voltage is applied, and a region of a 0V partition wall 13b3. When the region of the 0V partition wall 13b3 is provided, the charge can be stabilized and the flow of the biomaterial S can be formed. More specifically, for example, when negatively charged DNA is detected, as in Figure 18 In the fourth embodiment shown in FIG, when a negative voltage-applied partition wall 13b2, a 0V partition wall 13b3, and a positive voltage-applied partition wall 13b1 are arranged in this order, DNA can flow from the negative side to the positive side. For example, DNA can be separated because the flow can differ depending on the difference in DNA charge. As a result, detection accuracy can be improved and additional information can be obtained.

[0095] Figure 19 1 is a schematic plan view schematically showing a modified example of the fourth embodiment of the biomaterial detection chip 1 according to the present technology, viewed from above. As in this modified example, when the areas of the partition walls 13b2 and 13b1 to which a positive voltage or a negative voltage is applied are inserted between the areas of the 0V partition wall 13b3, the biomaterial S can be collected in the center of the biomaterial detection chip 1. More specifically, for example, when negatively charged DNA is detected, as in Figure 19 In the modification of the fourth embodiment shown in , if the region of the partition wall 13b1 to which a positive voltage is applied is inserted between the regions of the 0 V partition wall 13b3, DNA can be collected at the center of the biomaterial detection chip 1.

[0096] (5) Other examples

[0097] As another example, although not shown, it is possible to adjust the magnitude of the voltage applied to the partition wall 13. For example, by adjusting the magnitude of the voltage applied to the partition wall 13 for each region, the desired biomass S can be collected for each region according to the charge of the biomass S.

[0098] Although not shown, some or all of the partition walls 13 may be covered with a protective film. When the partition walls 13 are covered with the protective film, the thickness and material of the protective film are selected so that the partition walls 13 are electrically conductive on the holding surface 111. When the protective film is provided, weather resistance to heat, light, water, acid, alkali, chemicals, etc. can be improved, and the partition walls 13 can be kept in contact with water, acid, alkali, or chemicals for a long time.

[0099] The material for forming the protective film can be freely selected as long as the effects of the present technology are not impaired. For example, silicon oxide (SiO2), silicon nitride (Si3N4), silicon oxynitride (SiON), etc. can be used.

[0100] (6) Method of applying voltage

[0101] As long as the effect of the present technology is not impaired, the method of applying the voltage to the partition wall 13 can be freely designed. For example, as shown in the end view taken along line BB, it is schematically shown Figure 20 In the first embodiment of the biomaterial detection chip 1 according to the present technology, shown in FIG, a voltage can be applied to the inactive pixel region O by connecting the partition wall 13 to the gate 15 via the semiconductor substrate 12. In this case, the gate 15 can control positive or negative charge. In addition, although not shown, an external voltage can be applied from the upper side of the chip to the partition wall 13 in the inactive pixel region O.

[0102] As long as the effect of the present technology is not impaired, the method of making the partition wall 13 have 0V can be freely designed. For example, as shown in the schematic end view taken along the line CC, Figure 21 According to the third embodiment of the biomaterial detection chip 1 of the present technology shown in FIG, 0 V can also be obtained by connecting the partition wall 13 b 3 to the P-type region 113 .

[0103] 3. Biological Material Detection Device 2

[0104] Figure 22 This is a block diagram illustrating the concept of a biomaterial detection device 2 according to the present technology. The biomaterial detection device 2 according to the present technology includes at least the biomaterial detection chip 1 described above and an analysis unit 21. Furthermore, a light emitting unit 22, a storage unit 23, a display unit 24, a temperature control unit 25, and the like may be provided depending on their purpose. Each of these units will be described below. Since the biomaterial detection chip 1 is already described above, its description will be omitted.

[0105] (1) Analysis Unit 21

[0106] The analysis unit 21 analyzes the optical information acquired by the biomaterial detection chip 1. For example, the optical information acquired by the biomaterial detection chip 1 can be used to detect the presence of biomaterial S, to detect the presence of interaction with biomaterial S, or to screen for medicinal ingredients.

[0107] Here, the analysis unit 21 can be implemented in a personal computer or CPU, or can be stored as a program in hardware resources including a recording medium (e.g., a nonvolatile memory (USB memory), HDD, or CD), etc., and can function through the personal computer or CPU.

[0108] (2) Light-emitting unit 22

[0109] The biomaterial detection device 2 according to the present technology may include, for example, a light emitting unit 22 for emitting excitation light. The light emitting unit 22 emits light toward the biomaterial S held on the holding surface 111 of the biomaterial detection chip 1. Here, in the biomaterial detection device 2 according to the present technology, the light emitting unit 22 is not essential, and an external light emitting device or the like may be used to emit light toward the biomaterial S.

[0110] The type of light emitted from the light emitting unit 22 is not particularly limited, but in order to reliably generate fluorescence or scattered light from the microparticles, it is desirable to have a constant light direction, wavelength, and light intensity. As examples, a laser, an LED, etc. can be exemplified. When a laser is used, its type is not particularly limited, and an argon ion (Ar) laser, a helium-neon (He-Ne) laser, a dye laser, a krypton (Cr) laser, a semiconductor laser, and a solid laser in which a semiconductor laser and a wavelength conversion optical element are combined can be used alone, or two or more thereof can be used in free combination.

[0111] A plurality of light-emitting units 22 may be provided depending on their purpose. For example, one light-emitting unit 22 may be provided for each pixel 11 of the biological substance detection chip 1. Furthermore, when a substrate on which light-emitting elements such as LEDs are arranged at positions corresponding to the pixels 11 of the biological substance detection chip 1 is laminated on the biological substance detection chip 1, light can be emitted to the biological substance S.

[0112] (3) Storage unit 23

[0113] The biomaterial detection device 2 according to the present technology may include a storage unit 23 in which various types of information are stored. The storage unit 23 may store all items related to detection, such as optical data acquired by the biomaterial detection chip 1, analysis data generated by the analysis unit 21, and optical data emitted by the light emitting unit 22.

[0114] In the biological material detection apparatus 2 according to the present technology, the storage unit 23 is not essential, and an external storage device can be connected. For example, a hard disk or the like can be used as the storage unit 23 .

[0115] (4) Display unit 24

[0116] The biomaterial detection device 2 according to the present technology may include a display unit 24 that displays various types of information. The display unit 24 can display all items related to detection, such as optical data acquired by the biomaterial detection chip 1, analysis data generated by the analysis unit 21, optical data emitted by the light emitting unit 22, and data stored in the storage unit 23.

[0117] In the biological substance detection apparatus 2 according to the present technology, the display unit 24 is not essential, and an external display device can be connected. As the display unit 24, for example, a display, a printer, etc. can be used.

[0118] (5) Temperature control unit 25

[0119] The biological substance detection device 2 according to the present technology can include a temperature control unit 25 that maintains the biological substance S held on the holding surface 111 of the biological substance detection chip 1 at a predetermined temperature and heats or cools it to a predetermined temperature. For example, when the biological substance S is an enzyme, the temperature control unit 25 can control the temperature so as to maintain an optimal temperature. In addition, when the biological substance S is a nucleic acid and the presence of hybridization is detected using the present technology, the temperature control unit 25 can perform control so as to maintain a temperature range within which hybridization is possible. As the temperature control unit 25, a thermoelectric element such as a Peltier element can be used.

[0120] A plurality of temperature control units 25 may be provided depending on their purpose. For example, one temperature control unit 25 may be provided for each pixel 11 of the biological substance detection chip 1. Furthermore, when a substrate on which thermoelectric elements are arranged at positions corresponding to the pixels 11 of the biological substance detection chip 1 is laminated on the biological substance detection chip 1, the temperature of the biological substance S can be controlled.

[0121] Here, in the biological substance detecting apparatus 2 according to the present technology, the temperature control unit 25 is not necessary, and the temperature of the biological substance S may be controlled using an external temperature control device or the like.

[0122] 4. Biological Material Detection System 3

[0123] Figure 23 This is a block diagram illustrating the concept of a biomaterial detection system 3 according to the present technology. This biomaterial detection system 3 according to the present technology includes at least the biomaterial detection chip 1 according to the present technology described above and an analysis device 31. Furthermore, a light emitting device 32, a storage device 33, a display device 34, a temperature control device 35, and the like may be provided, depending on their purpose.

[0124] The biomaterial detection chip 1 and each device can be connected via a wired or wireless network. Here, since the details of each device are the same as those of the biomaterial detection device 2 of the present technology described above, their description will be omitted here.

[0125] Here, in the present technology, the following configuration can be used.

[0126] (1) A biomaterial detection chip, comprising a plurality of pixels, wherein the pixels include at least a holding surface for holding biomaterial and a photoelectric conversion unit disposed below the holding surface and on a semiconductor substrate,

[0127] Partition walls made of a conductor are provided between the pixels on the holding surface.

[0128] (2) The biomaterial detection chip according to (1),

[0129] When the biological substance is detected, a voltage is applied to the partition wall.

[0130] (3) The biomaterial detection chip according to (2),

[0131] A positive voltage or a negative voltage is applied to all the partition walls.

[0132] (4) The biomaterial detection chip according to (2),

[0133] A positive voltage or a negative voltage is applied to the partition wall.

[0134] (5) The biomaterial detection chip according to any one of (2) to (4),

[0135] The magnitude of the voltage applied to the partition walls can be changed for each partition wall.

[0136] (6) The biomaterial detection chip according to any one of (1) to (5),

[0137] Wherein, some or all of the electrically conductive partition walls on the holding surface are covered by a protective film.

[0138] (7) The biomaterial detection chip according to any one of (1) to (6),

[0139] The biological substance is one or more biological substances selected from nucleic acids, proteins, cells, microorganisms, chromosomes, ribosomes, mitochondria, organelles (cell organelles) and complexes thereof.

[0140] (8) A biological substance detection device comprising:

[0141] A biomaterial detection chip composed of a plurality of pixels, wherein the pixels include at least a holding surface for holding biomaterial and a photoelectric conversion unit provided below the holding surface, and wherein a partition wall made of a conductor is provided between pixels on the holding surface; and

[0142] An analyzing unit analyzes the electrical information obtained by the biomaterial detection chip.

[0143] (9) A biological substance detection system comprising:

[0144] A biomaterial detection chip composed of a plurality of pixels, wherein the pixels include at least a holding surface for holding biomaterial and a photoelectric conversion unit provided below the holding surface, and wherein a partition wall made of a conductor is provided between pixels on the holding surface; and

[0145] An analyzing device analyzes the electrical information obtained by the biomaterial detection chip.

[0146] [List of Reference Numbers]

[0147] 1Biological material detection chip

[0148] 11 pixels

[0149] S biological matter

[0150] 111 Keep Surface

[0151] 12Semiconductor substrate

[0152] 112 photoelectric conversion units

[0153] 13 partition wall

[0154] 14 Insulator

[0155] 15 gate

[0156] 113 P-type region

[0157] 21 analysis units

[0158] 22 light-emitting units

[0159] 23 storage units

[0160] 24 display units

[0161] 25 temperature control units

[0162] 31Analysis device

[0163] 32 Lighting Device

[0164] 33 Storage device

[0165] 34 display devices

[0166] 35 temperature control device.

Claims

1. A biomaterial detection chip, consisting of a plurality of pixels, wherein: The pixel includes at least a holding surface for holding biological matter and a photoelectric conversion unit provided below the holding surface and on a semiconductor substrate, wherein a partition wall made of a conductor is provided between the pixels on the holding surface, When the biological substance is detected, a voltage is applied to the partition wall.

2. The biomaterial detection chip according to claim 1, in, A positive voltage or a negative voltage is applied to all of the partition walls.

3. The biomaterial detection chip according to claim 1, in, A positive voltage or a negative voltage is applied to the partition wall.

4. The biomaterial detection chip according to claim 1, in, The magnitude of the voltage applied to the partition walls can be changed for each partition wall.

5. The biomaterial detection chip according to claim 1, in, Some or all of the electrically conductive partition walls on the holding surface are covered by a protective film.

6. The biomaterial detection chip according to claim 1, in, The biological substance is one or more biological substances selected from microorganisms, chromosomes, organelles and complexes thereof.

7. The biomaterial detection chip according to claim 6, wherein: The biological substance is one or more biological substances selected from nucleic acids, proteins, cells, ribosomes, mitochondria and complexes thereof.

8. A biological substance detection device comprising: A biomaterial detection chip composed of a plurality of pixels, wherein the pixels include at least a holding surface for holding biomaterial and a photoelectric conversion unit provided below the holding surface, and wherein a partition wall made of a conductor is provided between the pixels on the holding surface; and an analyzing unit for analyzing the electrical information acquired by the biomaterial detection chip, When the biological substance is detected, a voltage is applied to the partition wall.

9. A biological substance detection system comprising: A biomaterial detection chip composed of a plurality of pixels, wherein the pixels include at least a holding surface for holding biomaterial and a photoelectric conversion unit provided below the holding surface, and wherein a partition wall made of a conductor is provided between the pixels on the holding surface; and an analysis device for analyzing the electrical information obtained by the biomaterial detection chip, When the biological substance is detected, a voltage is applied to the partition wall.

Citation Information

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