WO2023000638A1 - 一种新型的集成式微阵列生物芯片 - Google Patents

一种新型的集成式微阵列生物芯片 Download PDF

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WO2023000638A1
WO2023000638A1 PCT/CN2022/073753 CN2022073753W WO2023000638A1 WO 2023000638 A1 WO2023000638 A1 WO 2023000638A1 CN 2022073753 W CN2022073753 W CN 2022073753W WO 2023000638 A1 WO2023000638 A1 WO 2023000638A1
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chip
resin
microarray biochip
integrated microarray
novel integrated
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French (fr)
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邱培
朱宇
张珉翔
徐丛
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创芯国际生物科技(广州)有限公司
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    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00—Apparatus for enzymology or microbiology
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    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00—Apparatus for enzymology or microbiology
    • C12M1/16—Apparatus for enzymology or microbiology containing, or adapted to contain, solid media
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    • C12M3/00—Tissue, human, animal or plant cell, or virus culture apparatus

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  • the utility model relates to a biological chip, in particular to a novel integrated microarray biological chip.
  • Rapid, low reagent consumption, and low-cost high-throughput screening of large numbers of compounds is a research goal in the drug screening development process.
  • the rapid and efficient high-throughput screening technology has been widely developed and applied, and has become one of the main technical means of drug screening.
  • it has some limitations, such as the large amount of reagents consumed by multi-well plates (usually 6-96 well plates), the difficulty of sample distribution and operation, and expensive equipment.
  • microfluidic chip technology based on microprocessing technology has high production costs, complex supporting equipment, and it is difficult to ensure high repeatability of test results, making it difficult to be widely used.
  • the utility model provides a novel integrated microarray biochip with fast analysis speed, low reagent consumption and high throughput.
  • the technical scheme of the utility model is:
  • a novel integrated microarray biochip comprising: at least one chip, and a carrier for fixing and loading the chip; the chip includes a chip body and a bottom plate mounted on the bottom of the chip body, and the chip body A plurality of micropores and a water tank are provided, and the water tank surrounds all the micropores.
  • a fixing post is installed on the carrier, and the fixing post is used to fix the chip on the carrier.
  • microholes are arranged in a matrix on the chip body.
  • micropore is in the shape of a cylindrical tube, an inverted mesa tube, a U-shaped tube or an inverted tapered tube at the bottom.
  • the inner wall of the micropore is provided with a hydrophilic coating or a hydrophobic coating.
  • the chip body is also provided with an information code pasting area.
  • the chip also includes an upper cover for covering the microholes, the upper cover includes a cover plate and a side plate in an integrated structure, and the two sides of the chip body are respectively provided with Mating slots.
  • the chip material is selected from at least one of the following: polypropylene resin, polyethylene resin, ethylene-propylene copolymer, polystyrene resin, acrylonitrile-butadiene-styrene resin, polycarbonate resin , polyethylene terephthalate resin, polymethyl methacrylate resin, vinyl chloride resin, polybutylene terephthalate resin, polyarylate resin, polysulfone resin, polyethersulfone resin, poly Ether ether ketone resin, polyetherimide resin, polytetrafluoroethylene, polymethylpentene resin, polyacrylonitrile resin.
  • the chip material is polystyrene resin.
  • the integrated microarray biochip of the utility model has many advantages such as fast analysis speed, less reagent consumption, easy integration and high-throughput analysis, and can overcome the limitation of high-throughput drug screening.
  • Microplates such as 1536-well plates are suitable for a wide range of routine testing equipment, with low barriers to entry.
  • the microarray biochip can be applied to different scenarios by forming 2D cells or 3D organoids with different aggregation densities, providing a multi-dimensional research platform for cell-based high-throughput drug screening, tissue engineering and biosensors.
  • Fig. 1 is a structural schematic diagram of a novel integrated microarray biochip of the present invention.
  • FIG. 2 is a side view of FIG. 1 .
  • Fig. 3 is a schematic diagram of various optional styles of the microwells of the integrated microarray biochip of the present invention, wherein Fig. 3-1 is a cylindrical tubular shape, Fig. 3-2 is an inverted tubular shape, and Fig. 3-3 is a U-shaped Tubular, Fig. 3-4 shows a bottom with an inverted tapered tubular structure.
  • FIG. 4 is a schematic structural view of the upper cover of the integrated microarray biochip of the present invention.
  • Fig. 5 is a micropore size comparison between the chip of the present invention and a conventional cell culture well plate.
  • a specific embodiment of the present invention provides a novel integrated microarray biochip, including: at least one chip, and a carrier 1 for fixing and loading the chip.
  • the size of the carrier 1 and the number of chips can be customized according to experimental requirements.
  • a set of microarray biochips generally has 1 to 10 chips.
  • Fixing posts 11 are installed on the carrier 1 , and the fixing posts 11 are used to fix the chips on the carrier 1 .
  • the fixing column can adopt structures such as elastic sheets, buckles (fixed or rotating), clips, etc., as long as the chips can be fixed on the carrier 1, they can be used in the present invention.
  • the chip includes a chip body 2 and a bottom plate 25 mounted on the bottom of the chip body 2, the chip body 2 is provided with microholes 22 and water tanks 21 arranged in a matrix, the chip body 2
  • the water tank 21 surrounds all the micropores 22, and the cross section of the water tank 1 is rectangular.
  • the setting of the water tank 21 surrounding the microholes 22 can maintain a humid environment during the cell culture process, and at the same time greatly reduce the optical error of the outer ring microholes during the detection process.
  • the microwells 22 can be configured in a columnar tube, an inverted tube, a U-shaped tube or an inverted tapered tube at the bottom.
  • a hydrophilic coating or a hydrophobic coating can be coated on the inner wall of the microwell.
  • the chip body 2 is also provided with an information code pasting area, where the information code 24 recorded with the sample information under test can be pasted on this area, and then placed on the corresponding part of the testing device. detected in the adapter.
  • the chip further includes an upper cover 23 for covering the microwell 22 .
  • the upper cover 23 includes a cover plate 231 and a side plate 232 in an integral structure, and the two sides of the chip main body 2 are respectively provided with slots matching the side plate 232 (not clearly shown in FIGS. 1 and 2 ). , when the upper cover 23 is covered on the chip main body 2, the upper cover 23 can completely cover the microhole 22 and the water tank 21.
  • the chip material is selected from at least one of the following: polyolefin resins such as polypropylene resin, polyethylene resin, ethylene-propylene copolymer, or cyclic polyolefin resins, polystyrene, acrylonitrile - Polystyrene resins such as butadiene-styrene resins, polycarbonate resins, polyethylene terephthalate resins, methacrylic resins such as polymethyl methacrylate resins, vinyl chloride resins, Polybutylene terephthalate resin, polyarylate resin, polysulfone resin, polyethersulfone resin, polyetheretherketone resin, polyetherimide resin, polytetrafluoroethylene and other fluororesins, polymethyl Any one or more of acrylic resins such as pentene resins and polyacrylonitriles, and cellulosic resins such as propionate resins. Among them, polystyrene resins are preferable from the viewpoint of
  • the utility model has the advantages of: firstly, according to different use requirements, different shapes of micropores are provided, and different shearing forces are generated by selecting micropores of different shapes and structures to form microarray chips including 2D and 3D organoids with different compactness. Multi-dimensional analysis and research; second, compared with traditional cell plate, its detection system is smaller, it has the advantages of fast analysis speed, less reagent consumption, easy integration, high-throughput analysis, etc., and can save a lot of consumables for small samples; Third, compared with the microfluidic chip, as shown in Figure 5, the chip specification of the utility model matches the standard 384-well plate, 1536-well plate and other micro-hole plates to adapt to a wide range of conventional testing equipment, and the entry threshold Fourthly, the outer ring of the micropores of the chip is equipped with a water tank, which can maintain a humid environment during the cell culture process, and at the same time greatly reduce the optical error of the outer ring micropores during the detection process.

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Abstract

本实用新型提供一种新型的集成式微阵列生物芯片，包括：至少一个芯片，以及用于固定及装载所述芯片的载体；所述芯片包括芯片主体和安装在所述芯片主体底部的底板，所述芯片主体上设有多个微孔和水槽，所述水槽将所有所述微孔包围设置。本实用新型的集成式微阵列生物芯片具有分析速度快、试剂消耗少、易于集成和高通量分析等诸多优点，可以克服高通量药物筛选的限制，规格可以设置成与标准的384孔板、1536孔板等微孔板相吻合以适配于广泛的常规检测设备，准入门槛低。且该微阵列生物芯片可通过形成2D细胞或不同凝聚密度的3D类器官以适用于不同场景需求，为基于细胞的高通量药物筛选、组织工程和生物传感器提供多维度的研究平台。

Description

一种新型的集成式微阵列生物芯片 技术领域
本实用新型涉及一种生物芯片，具体涉及一种新型的集成式微阵列生物芯片。
背景技术
对大量化合物进行快速、低试剂消耗和低成本的高通量筛选是药物筛选发展过程的研究目标。近几年来出现地快速、高效的高通量筛选技术被广泛发展和应用，成为药物筛选的主要技术手段之一。但其自身存在一些局限，如多孔板(通常为6-96孔板)消耗的试剂量大、样品的分配和操作难度较大、设备昂贵等。比如：基于微加工技术的微流控芯片技术，制作成本高，配套设备复杂，且较难保证检测结果的高重复性，难以得到广泛应用。
实用新型内容
针对现有技术存在的问题和缺陷，本实用新型提供一种分析速度快、试剂消耗少、高通量的新型的集成式微阵列生物芯片。本实用新型的技术方案为：
一种新型的集成式微阵列生物芯片，包括：至少一个芯片，以及用于固定及装载所述芯片的载体；所述芯片包括芯片主体和安装在所述芯片主体底部的底板，所述芯片主体上设有多个微孔和水槽，所述水槽将所有所述微孔包围设置。
进一步地，所述载体上安装有固定柱，所述固定柱用于将所述芯片固定在所述载体上。
进一步地，所述微孔呈矩阵状排布在所述芯片主体上。
进一步地，所述微孔为柱形管状、倒台形管状、U形管状或者底部呈倒锥形管状结构。
可选地，所述微孔内壁设有亲水性涂层或疏水性涂层。
进一步地，所述芯片主体上还设有信息码粘贴区域。
进一步地，所述芯片还包括用于遮盖所述微孔的上盖，所述上盖包括成一体结构的盖板和侧板，所述芯片主体的两侧分别设有与所述侧板相配合的插槽。
进一步地，所述芯片材质选自以下的至少一种：聚丙烯树脂、聚乙烯树脂、乙烯-丙烯共聚物、聚苯乙烯树脂、丙烯腈-丁二烯-苯乙烯类树脂、聚碳酸酯树脂、聚对苯二甲酸乙二醇酯树脂、聚甲基丙烯酸甲酯树脂、氯乙烯树脂、聚对苯二甲酸丁二醇酯树脂、聚芳酯树脂、聚砜树脂、聚醚砜树脂、聚醚醚酮树脂、聚醚酰亚胺树脂、聚四氟乙烯、聚甲基戊烯树脂、聚丙烯腈树脂。
优选地，所述芯片材质为聚苯乙烯树脂。
与现有技术相比，本实用新型的有益效果是：
本实用新型的集成式微阵列生物芯片具有分析速度快、试剂消耗少、易于集成和高通量分析等诸多优点，可以克服高通量药物筛选的限制，规格可以设置成与标准的384孔板、1536孔板等微孔板相吻合以适配于广泛的常规检测设备，准入门槛低。且该微阵列生物芯片可通过形成2D细胞或不同凝聚密度的3D类器官以适用于不同场景需求，为基于细胞的高通量药物筛选、组织工程和生物传感器提供多维度的研究平台。
附图说明
图1为本实用新型的新型的集成式微阵列生物芯片的结构示意图。
图2为图1的侧视图。
图3为本实用新型的集成式微阵列生物芯片的微孔的多种可选样式结构示意图，其中图3-1为柱形管状，图3-2为倒台形管状，图3-3为U形管状，图3-4为底 部呈倒锥形管状结构。
图4为本实用新型的集成式微阵列生物芯片的上盖的结构示意图。
图5为本实用新型的芯片与常规细胞培养孔板的微孔尺寸对照。
图1～4中，1、载体，11、固定柱，2、芯片主体，21、水槽，22、微孔，23、上盖，24、信息码，25、底板，221、圆柱形管状，222、倒圆台形管状，223、U形管状，224、底部呈倒圆锥形管状结构，231-盖板，232-侧板。
具体实施方式
下面结合附图和具体的实施例对本实用新型做进一步详细说明，所述是对本实用新型的解释而不是限定。
如图1和2所示，本实用新型具体实施例提供了一种新型的集成式微阵列生物芯片，包括：至少一个芯片，以及用于固定及装载所述芯片的载体1。载体1的尺寸以及芯片的数量可以根据实验要求来定制。一般而言，一套微阵列生物芯片一般设置1～10个芯片。所述载体1上安装有固定柱11，所述固定柱11用于将所述芯片固定在所述载体1上。具体地，所述固定柱可以采用弹片、卡扣(固定式或旋转式)、夹子等结构，只要能将所述芯片固定在所述载体1上都可以用于本实用新型。
如图2和3所示，所述芯片包括芯片主体2和安装在所述芯片主体2底部的底板25，所述芯片主体2上设有呈矩阵排布的微孔22和水槽21，所述水槽21将所有所述微孔22包围设置，水槽1截面为矩形。水槽21包围微孔22设置可使细胞培养过程中保持湿润环境，同时大大减少检测过程中外圈微孔的光学误差。此外，为了形成2D细胞或不同凝聚密度的3D类器官，所述微孔22可以设置为柱形管状、倒台形管状、U形管状或者底部呈倒锥形管状结构。为了提高或降低细胞在微孔内壁的粘附性，可以在微孔内壁上涂覆亲水性涂层或疏水性涂层。
进一步地，为了保证受检样本信息准确无误，所述芯片主体2上还设有信息码粘贴区域，可将录有受检样本信息的信息码24粘贴在该区域，再放置于检测设备对应的适配器中进行检测。
进一步地，如图4所示，为了防止样本收到污染，所述芯片还包括用于遮盖所述微孔22的上盖23。所述上盖23包括成一体结构的盖板231和侧板232，所述芯片主体2的两侧分别设有与所述侧板232相配合的插槽(图1和2中未明显显示)，当将所述上盖23盖在芯片主体2上，所述上盖23可以完全覆盖微孔22和水槽21。
在本实施例中，所述芯片材质选自以下的至少一种：聚丙烯树脂、聚乙烯树脂、乙烯-丙烯共聚物等聚烯烃类树脂或环状聚烯烃类树脂、聚苯乙烯、丙烯腈-丁二烯-苯乙烯类树脂等聚苯乙烯类树脂、聚碳酸酯树脂、聚对苯二甲酸乙二醇酯树脂、聚甲基丙烯酸甲酯树脂等甲基丙烯酸类树脂、氯乙烯树脂、聚对苯二甲酸丁二醇酯树脂、聚芳酯树脂、聚砜树脂、聚醚砜树脂、聚醚醚酮树脂、聚醚酰亚胺树脂、聚四氟乙烯等氟类树脂、聚甲基戊烯树脂、聚丙烯腈等丙烯酸类树脂、丙酸酯树脂等纤维素类树脂任意一种或多种。其中，从培养容器所要求的成形性和灭菌性的方面考虑，优选聚苯乙烯树脂。
综上所述，与现有技术相比，本实用新型的有益效果是：
本实用新型的优点在于：其一，根据不同使用需求提供不同形状微孔选择，通过选用不同形状结构的微孔来产生不同剪切力，形成包括2D及不同紧密程度3D类器官微阵列芯片进行多维度分析研究；其二，相较于传统细胞孔板，其检测体系更小，具有分析速度快、试剂消耗少、易于集成、高通量分析等优点，同时对于小样本可节省大量耗材；其三，与微流控芯片相比，如图5，本实用新型的芯片规格与标准的384孔板、1536孔板等微孔板相吻合以适配于广泛的常规检测设备，准入门槛更低；其四，本芯片微孔外圈设置水槽，可使细胞培养过程中保持湿润环境，同时大大减少检测过程中外圈微孔的光学误差。
以上所述实施例仅表达了本实用新型的几种实施方式，其描述较为具体和详细，但并不能因此而理解为对本实用新型专利范围的限制。应当指出的是，对于本领域的普通技术人员来说，在不脱离本实用新型构思的前提下，还可以做出若干变形和改进，这些都属于本实用新型的保护范围。因此，本实用新型专利的保护范围应以所附权利要求为准。

Claims (9)

  1. 一种新型的集成式微阵列生物芯片，其特征在于：包括：至少一个芯片，以及用于固定及装载所述芯片的载体；所述芯片包括芯片主体和安装在所述芯片主体底部的底板，所述芯片主体上设有多个微孔和水槽，所述水槽将所有所述微孔包围设置。
  2. 根据权利要求1所述的一种新型的集成式微阵列生物芯片，其特征在于：所述载体上安装有固定柱，所述固定柱用于将所述芯片固定在所述载体上。
  3. 根据权利要求1所述的一种新型的集成式微阵列生物芯片，其特征在于：所述微孔呈矩阵状排布在所述芯片主体上。
  4. 根据权利要求3所述的一种新型的集成式微阵列生物芯片，其特征在于：所述微孔为柱形管状、倒台形管状、U形管状或者底部呈倒锥形管状结构。
  5. 根据权利要求4所述的一种新型的集成式微阵列生物芯片，其特征在于：所述微孔内壁设有亲水性涂层或疏水性涂层。
  6. 根据权利要求1所述的一种新型的集成式微阵列生物芯片，其特征在于：所述芯片主体上还设有信息码粘贴区域。
  7. 根据权利要求1所述的一种新型的集成式微阵列生物芯片，其特征在于：所述芯片还包括用于遮盖所述微孔的上盖，所述上盖包括成一体结构的盖板和侧板，所述芯片主体的两侧分别设有与所述侧板相配合的插槽。
  8. 根据权利要求1～7任意一项所述的一种新型的集成式微阵列生物芯片，其特征在于：所述芯片材质选自以下的至少一种：聚丙烯树脂、聚乙烯树脂、乙烯-丙烯共聚物、聚苯乙烯树脂、丙烯腈-丁二烯-苯乙烯类树脂、聚碳酸酯树脂、聚对苯二甲酸乙二醇酯树脂、聚甲基丙烯酸甲酯树脂、氯乙烯树脂、聚对苯二甲酸丁二醇酯树脂、聚芳酯树脂、聚砜树脂、聚醚砜树脂、聚醚醚酮树脂、聚醚酰亚胺树脂、聚四氟乙烯、聚甲基戊烯树脂、聚丙烯腈树脂。
  9. 根据权利要求8所述的一种新型的集成式微阵列生物芯片，其特征在于：所述芯片材质为聚苯乙烯树脂。
PCT/CN2022/073753 2021-07-21 2022-01-25 一种新型的集成式微阵列生物芯片 WO2023000638A1 (zh)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104480010A (zh) * 2014-11-28 2015-04-01 清华大学 生物反应装置及其应用
CN204848893U (zh) * 2015-07-15 2015-12-09 中国科学院广州生物医药与健康研究院 一种单孔黑边并带水槽的细胞培养板
CN210528952U (zh) * 2019-05-21 2020-05-15 甘肃农业大学 一种恒温细胞多功能培养箱

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104480010A (zh) * 2014-11-28 2015-04-01 清华大学 生物反应装置及其应用
CN204848893U (zh) * 2015-07-15 2015-12-09 中国科学院广州生物医药与健康研究院 一种单孔黑边并带水槽的细胞培养板
CN210528952U (zh) * 2019-05-21 2020-05-15 甘肃农业大学 一种恒温细胞多功能培养箱

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