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Numéro de publicationCN2559986 Y
Type de publicationOctroi
Numéro de demandeCN 02247727
Date de publication9 juil. 2003
Date de dépôt23 août 2002
Date de priorité23 août 2002
Numéro de publication02247727.6, CN 02247727, CN 2559986 Y, CN 2559986Y, CN-Y-2559986, CN02247727, CN02247727.6, CN2559986 Y, CN2559986Y
Inventeurs温龙平, 唐飞, 连崑
Déposant上海博昇微晶科技有限公司
Exporter la citationBiBTeX, EndNote, RefMan
Liens externes:  SIPO, Espacenet
Integrated microfluid and microchip of microarray probe
CN 2559986 Y
Résumé
The utility model relates to the microchip of an integration microfluid and a micro array probe, which is characterized in that the microchip comprises a sample cell, a reagent cell, a detection cell, and a microfluid pipe, and each sample cell, reagent cell, and detection cell are connected through each microfluid pipe. The micro array probe is arranged at the bottom of the detection cell. The microchip also comprises a waste liquid cell which is connected with the detection cell through another microfluid pipe. The utility model has excellent parallel detection ability and can realize large amount sample detection at one time, and the utility model also has the function of fast pre-processing and separating sample, thus greatly enhancing the ability of the chip. The utility model is a chip with high integration capacity and strong parallel detection ability, which can reduce the complexity of detection cost and operation. The utility model is applicable to gene, biochemical, and pharmaceutical industries.
Revendications(2)  Langue du texte original : Chinois
1.一种集成微流体和微阵列探针的微芯片,其特征是:在所述的微芯片上具有试剂池和微流体管道,各试剂池通过各微流体管道相连;在所述各试剂池中,一个或几个试剂池的底部上具有阵列探针。 An integrated microfluidic and microchip microarray probes, characterized in that: a reagent reservoir and the microfluidic conduit on the microchip, each reagent reservoir is connected through the micro fluid conduit; in the respective reagent having an array of probes on the bottom of the pool, the pool of one or several reagents.
2.根据权利要求1所述的集成微流体和微阵列探针的微芯片,其特征是:所述试剂池还包括样品池、废液池。 2. The integrated microfluidic 1, wherein the probe and microarray microchip claim, characterized in that: said reagent reservoir further comprises a sample cell, the waste reservoir.
Description  Langue du texte original : Chinois
集成微流体和微阵列探针的微芯片 Integrated microfluidic and microarray probes microchip

本实用新型属于生物芯片领域,是一种集成微流体和微阵列探针的微芯片。 The utility model belongs to the field of bio-chip is a microarray probes and microfluidic integrated microchips.

背景技术 BACKGROUND

当前的生物芯片(有人称微芯片)按作用原理分,包括两类。 Current biochips (have called microchip) by action principle points, including two categories.

一类是微流体芯片。 One is a microfluidic chip. 微流体芯片通过控制液体在芯片上的流动达到对各种生物组分的检测,也称为LAB-ON-CHIP,即在一个芯片上完成实验室的各项功能。 Microfluidic chip by controlling the liquid flow on the chip reaches the detection of various biological components, also referred to as LAB-ON-CHIP, complete laboratory functions on a single chip. 微流体芯片上液体的控制和各种处理步骤是通过在芯片中制作微过滤器、微阀、微泵、微管道、微反应腔等各种精细微结构来实现的。 Microfluidic chip control and various processing steps of the liquid through the filter in the production of micro-chip, all kinds of fine microstructure micro valves, micro-pumps, micro-pipes, and other micro-reaction chamber to achieve. 本文中所述的微流体芯片就是指上述定义的芯片。 Herein refers to a microfluidic chip of the chip as defined above. 微流体芯片的特点是微型化和集成性优异。 Microfluidic chip features miniaturization and integration is excellent. 所谓的微型化是指生化检测可以在大大缩小的空间及体积中进行,从而大幅度减小试剂和样品的用量,降低检测成本;所谓的集成性是指在单一芯片上实现检测所需的所有或大部分步骤(如:样品的处理、分离、反应和检测)。 Refers to the so-called miniaturized biochemical detection can be greatly reduced and the volume of space is carried out, thus substantially reducing the amount of reagents and samples, reducing testing costs; the so-called integration means to achieve the desired detection on a single chip all or most of the steps (eg: sample handling, separation, reaction and detection). 集成性高可以使检测自动化、标准化和统一化,使检测过程容易操作。 High integration enables detection of automation, standardization and unification, the detection process is easy to operate. 微流体芯片在这两个方面具有优异的性能。 Microfluidic chip has excellent performance in these two areas. 但是,微流体芯片的一个缺点就是平行性较差,也就是说不能方便地实现在单个芯片上实现较多数量的样品检测。 However, a disadvantage of parallel micro-fluidic chip is poor, that is not easily achieve a greater number of samples to achieve the detection on a single chip. 微流体芯片的这个缺点限制了它的检测能力和检测通量。 The micro-fluidic chip disadvantage limits its ability to detect and testing throughput.

另一类芯片是微阵列芯片。 Another type of chip is a microarray. 微阵列芯片是将二维的芯片表面或者三维的颗粒表面分成许多相同的区域,每个区域产生一种探针用于特异性检测一种靶分子。 Microarray chip surface is two-dimensional or three-dimensional surface of the particles into a plurality of the same regions, each producing a probe for specifically detecting a target molecule. 这里所谓的微阵列是指相同的探针或者不同的探针按照预先设计的图形在芯片上进行分布。 Here refers to the so-called microarray same probe or probe in accordance with different pre-designed pattern is distributed on the chip. 如图3所示,这种阵列可以是相同或者不同探针6的点陈式阵列,也可以是相同或者不同探针6A-6F成块状(图4)、条形(图5)或者探针6G、6H、6J成任意其它形状的分布(图6),本文中所述的微阵列芯片以及微阵列就是指上述定义的概念。 3, such an array may be the same or different probe spots Chen array 6, and may be the same or different probes 6A-6F into blocks (Fig. 4), the strip (FIG. 5) or Probe needle 6G, 6H, 6J into any other shape of the distribution (Fig. 6), and microarray Microarray herein refers to the concept of the above-defined.

微阵列芯片的探针的制作有点样和原地合成等方法。 Microarray probes produced little sampling and in situ synthesis methods. 具体的过程就是将生物分子(寡聚核苷酸、cDNA、基因组DNA、多肽、抗原、抗体等)固定于硅片、玻璃片等固相介质上形成生物分子点阵。 A specific process is to biomolecules (oligonucleotides, cDNA, genomic DNA, polypeptides, antigens, antibodies, etc.) forming lattice biomolecules fixed on a silicon wafer, glass and other solid media. 在待分析样品中的生物分子与生物芯片的探针分子发生杂交或相互作用后,利用扫描仪对杂交信号进行检测和分析。 Probe biomolecule and a biochip of the sample to be analyzed after the occurrence of hybridization or interaction, the use of a scanner to detect and analyze the hybridization signal. 目前应用最广泛的微阵列芯片是基因芯片,它采用OLIGO或DNA片断为探针,检测DNA或mRNA。 At present, the most widely used is microarray gene chip, which uses OLIGO or DNA fragment as a probe to detect DNA or mRNA. 微阵列芯片具有微型化的优点。 Microarray chip has the advantage of miniaturization. 它的另一个很重要的优点就是平行性优异,也就是说它可以在单一的芯片上同时实现很多个靶分子或者样品的检测,因而可以实现高通量检测。 It is another very important advantage is excellent in parallel, which means that it can achieve detection of the target molecule or a number of samples on a single chip, it is possible to achieve high-throughput assay. 例如Affymetrix公司研制的基因表达谱芯片的点阵数可以达到400,000个点。 For example, the number of lattice Affymetrix microarray developed by the company can reach 400,000 points. 但是微阵列芯片很难将样品的预处理等分析前的工作步骤集成到一个芯片上来完成,而只能依靠人工或者专门的仪器来实现这些步骤,也就是说它的集成性不好,因而浪费了大量的人力和物力,而且系统自动化程度不高,不容易标准化。 However, it is difficult to analyze microarray work steps before the pretreatment of the sample, etc. into a single chip in order to complete, and can only rely on manual or specialized equipment to implement these steps, which means that it is not good integration, thereby wasting a lot of manpower and material resources, but also a high degree of automation system does not easily standardized. 如果将微阵列芯片和微流体芯片在同一芯片上实现,就可以兼顾两种芯片的特点,实现优势互补,在保证微型化的基础上,同时达到巨大的平行性和优异的集成性。 If the microarray and microfluidic chip on the same chip, you can take into account the characteristics of two chips, complementary advantages, in ensuring the basis of miniaturization, while achieving great parallel resistance and excellent integration. 可是目前未见这种集成芯片的报道。 However, currently no reports of such an integrated chip.

本实用新型的内容针对目前生物芯片开发的现状和上述分析,本实用新型的目的就是将微流体芯片和微阵列芯片的功能集成在一起,实现一种既具有微流体芯片的高度集成性,又具有微阵列芯片强大的并行检测能力的特点的新型芯片和方法。 The utility model of content development for the current status of the biochip and the above analysis, the utility model is aimed microfluidic chip and microarray functional integration together to achieve both a highly integrated microfluidic chip, but also The new method has a powerful chip and microarray detection capability of parallel features.

本实用新型的目的是通过以下技术方案实现的,本实用新型一种集成微流体和微阵列探针的微芯片,其特征是:在所述的微芯片上具有试剂池和微流体管道,各试剂池通过各微流体管道相连。 The utility model aims to achieve the following technical solutions, the utility model and an integrated microfluidic microarray probes microchip, which is characterized by: a reagent tank and piping on the microfluidic microchip, each reagent reservoir is connected through the microfluidic channels. 为了表达方便,将存放试剂、样品或混合液的腔体统称为试剂池。 To facilitate expression, the storage agent, or a mixture of the sample chamber are collectively called the reagent reservoir. 在所述的各试剂池中,一个或几个试剂池的底部上具有微阵列探针。 In each of the reagent according to the pool, or on the bottom of a pool of several reagents having microarray probes. 上述带微阵列探针的试剂池又称为检测池。 Reagents pool above with microarray probes, also known as the detector cell. 所述试剂池还可包括样品池以及废液池,所述废液池可经另一微流体管道与检测池相连。 The pool also includes a sample cell reagents and waste reservoir, the waste reservoir can be connected via the pipeline and another microfluidic flow cell. 本实用新型当用于检测应用时,其检测步骤举例如下:样品首先被注入样品池中,然后由样品池流入检测池。 The utility model is used to detect when the application, its detection step for example as follows: First, the sample is injected into the sample cell, and then flows into the sample cell detection cell. 在检测池中,样品与检测池底部的微阵列探针发生反应,反应完成后,废液流入废液池;然后,各种试剂分别从各自的试剂池中顺序流入检测池,对反应物进行清洗或反应。 In the detector cell, bottom cell sample with the detection microarray probe reaction, after the completion of the reaction, the waste into the waste tank; then, a variety of reagents, and flows into the detection cell pool from the respective order of reagent addition, the reaction was carried out cleaning or reaction. 每种试剂在充分清洗或反应后被排入废液池。 Each reagent fully discharged after cleaning or reaction waste reservoir. 之后,用光学或其它检测装置对检测池中的反应物进行检测。 Thereafter, optical or other detection apparatus for detecting an object in the pool of the reaction is detected. 整个过程只需要注入样品(可能也包括试剂),剩下的全部操作都在芯片上自动完成。 The whole process only need to inject the sample (which may include reagent), and the rest all operations are done automatically on the chip. 目前的微阵列芯片的样品需要先进行外部预处理,然后才能用微阵列芯片进行检测,而且各种预处理过程全部是靠手工或者其它专门仪器来完成。 Samples of microarray chips need for external preprocessing before using microarray detection, and various pre-process all by hand, or other specialized equipment to complete. 在本实用新型芯片中,则不需要这些外部预处理步骤,原来的外部预处理步骤现在完全或者大部分可以在本实用新型芯片上进行。 In this practical new chip, you do not need these external preprocessing step, the original external preprocessing step can be carried out now entirely or mostly on the utility model chips. 在现有的微流体芯片中,检测池中一般只有一种探针或反应物,也只能检测一种样品或者一种成分,而在本实用新型芯片中,由于在检测池的底部制作了微探针的阵列,所以可以同时检测多种样品或者样品的多种成分。 In the conventional micro-fluidic chip, the detection cell is generally only one probe or the reactants, can only be detected in a sample or a component, and in the utility model chip, since the cell at the bottom of the detection made microprobe array, it is possible to simultaneously detect multiple components of the sample or multiple samples. 因而本实用新型芯片的功能更为全面。 Thus the utility model chip functions more comprehensive.

综上所述,本实用新型的优点主要有:1.与目前微流体芯片相比:由于检测腔中制作了微阵列探针,本实用新型芯片具有更优异的并行检测能力,比现有的微流体芯片检测范围更为强大,一次可以实现大数目样品的检测;2.与现有的微阵列芯片相比:由于集成了具有快速样品前处理和分离功能的微流体芯片的能力,本实用新型芯片不需要额外的、复杂的、耗费人力和物力的样品前处理和分离工作,大大提高了芯片的功能、降低了检测的成本和操作的复杂性,因而系统的自动化程度更高,更易于标准化。 In summary, this has the advantages are: 1, compared with the current microfluidic chip: Since the detection chamber produced a microarray probes, the utility model has superior chip parallel detection capability than the existing microfluidic chip detection range more powerful, one can achieve a large number of samples detected; 2 compared with the conventional microarrays: By integrating ability before fast sample handling and separation function of the micro-fluidic chip, the utility The new chip does not require an additional, complex, labor-consuming sample preparation and material handling and separation work, greatly improving the functionality of the chip, reducing the cost and complexity of testing operations, and thus a higher degree of automation systems, easier standardization.

附图说明 Brief Description

图1为本实用新型微芯片的示意图,图2为本实用新型的使用情况图,图3-6为各种形状的探针微阵列示意图。 Figure 1 is a schematic diagram of a utility model microchip, Figure 2 is the use of a utility model, Fig. 3-6 is a schematic diagram of the microarray probes of various shapes.

图中代号说明I芯片 II转台1检测池 2废液池 3微管道4试剂池 5样品池 6、6A-6J微阵列探针7、8微管道实施例利用LIGA工艺和微阵列芯片制作工艺相结合的方法,在PMMA上制作微流体和微阵列集成的芯片。 Figure II turntable Code Description I chip a waste reservoir detection cell 2 3 4 reagent micro channel 5 sample cell pool 6,6A-6J microarray probes 7,8 micro channel embodiment utilizes LIGA process and microarray production process phase a combination of methods, in the production of PMMA and microarray integrated microfluidic chip. 该芯片的检测池中制作有微阵列探针,可以同时进行多个样品的检测,芯片的制作采用我们申请的另一项独立专利制作;芯片中液体的驱动原理采用离心力驱动的方法。 Detecting the production of the chip has a micro-cell array probe, multiple samples can be detected simultaneously, the chip produced using another separate patent application of our production; chip driving principle of the liquid using a centrifugal force-driven approach. 关于这种离心力的微流体控制系统,我们申请了另一项独立的发明专利技术;芯片的检测系统也申请了另一项独立的发明专利;芯片I的结构如图1所示。 About this centrifugal microfluidic control system, we applied for another independent patent technology; chip detection system is also applied for another independent patent; chip I structure shown in Figure 1. 如图1,在本实用新型芯片I上具有样品池5、试剂池4、检测池1、废液池2和各微管道3、7、8,各试剂池4通过各微管道3与样品池5相连,样品池5经微管道7与检测池1相连,在检测池1的底部具有微阵列探针6,可同时进行多个样品的检测,在检测池1的一端经微管道8与废液池2相通连。 Figure 1 on the utility model chips I have the sample cell 5, 4 pool reagents, testing pool 1, pool 2 and each micro waste pipes 3,7,8, 4 each reagent reservoir through the micro channel 3 and the sample cell 5 is connected to the sample cell 5 through 7 and detect micro-pipeline connected to a pool at the bottom of the detection cell having a microarray probe 6, multiple samples can be detected simultaneously, through micro-channels 8 at one end and waste detection cell 1 2 communication of liquid pool. 如图2,可将本芯片I放在转台II上,通过转台II绕其中心O的旋转,和调节该芯片I绕自己的轴心O′转动的角度θ,使离心力F大于管道的毛细管阻力,将液体从一个池送到另一个池中。 2, this chip can be placed on the turntable I II, through the rotation center O II around the turntable, and adjust the chip I about its own axis O 'of the rotation angle θ, so that the centrifugal force F is greater than the resistance of the capillary tube the liquid from one pool to another pool.

芯片I的工作过程如下:各种试剂被预先存贮在各自的试剂池4中。 Working process of chip I is as follows: the various reagents are previously stored in the respective reagent reservoir 4.

检测时,首先将待测样品滴入样品池5;在离心力F的作用下,样品经微管道7流入检测池1与检测池底部的微阵列探针6发生反应;反应充分后,通过离心力的控制,样品经微管道8流入废液池2;利用离心力,微流体控制系统通过使不同的试剂从各自的试剂池4顺序进入检测池1对探针进行清洗或反应,清洗或反应充分后,废液经微管道8流入废液池2;在上述预处理过程和反应完成后,利用检测系统对检测池中的微阵列探针6进行检测,定性或定量确定样品的成分。 Detection, the first sample cell sample to be tested was dropped 5; F under the action of centrifugal force, the sample is detected by the micro-pipe 7 into the bottom of pool 1 and pool microarray detection probe 6 react; After the reaction sufficiently, by centrifugal force control samples were micro-conduit 8 into the waste tank 2; use of centrifugal force, the microfluidic control system by different reagents from the respective reagent into the detection cell 4 cell 1 sequence probe cleaning or reaction, or the reaction sufficiently after washing, waste through micro channel 8 into the waste tank 2; pretreatment process and after the above reaction was completed, using the detection system of the microarray pool detecting probe 6, qualitatively or quantitatively determine the components of the sample.

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Classifications
Classification internationaleC12Q1/68, G01N33/68, G01N33/53
Événements juridiques
DateCodeÉvénementDescription
9 juil. 2003C14Granted
11 oct. 2006C19Lapse of patent right due to non-payment of the annual fee