|Publication number||CN1726386 A|
|Application number||CN 200380106536|
|Publication date||25 Jan 2006|
|Filing date||15 Dec 2003|
|Priority date||20 Dec 2002|
|Also published as||CA2507960A1, CA2507960C, CA2508000A1, CA2508001A1, CA2508070A1, CA2508113A1, CA2508323A1, CA2508323C, CA2508370A1, CA2511032A1, CA2974221A1, CN1726275A, CN1955711A, CN100424166C, CN100472197C, EP1572979A1, EP1572979A4, EP1573297A1, EP1573311A2, EP1573311A4, EP1573312A2, EP1573312A4, EP1573408A2, EP1573408A4, EP1576376A2, EP1576376A4, EP1579190A1, EP1579190A4, EP1579194A2, EP1579194A4, US7400983, US7648678, US7758809, US7937228, US7960178, US8216512, US8257968, US8298815, US8386195, US8394635, US8529836, US8663978, US8673642, US8784735, US8788217, US8969086, US9040284, US9229016, US9599630, US9778273, US20040266015, US20050064535, US20060045806, US20060046298, US20060063265, US20060085140, US20060088928, US20060088940, US20060172426, US20080241876, US20100081167, US20110167930, US20110269238, US20120310422, US20130029409, US20130084567, US20130203103, US20130217108, US20130330252, US20140038232, US20140186218, US20140234170, US20140286838, US20140356935, US20160084862, WO2004057307A1, WO2004058404A2, WO2004058404A3, WO2004058950A1, WO2004059284A2, WO2004059284A3, WO2004059287A2, WO2004059287A3, WO2004059288A2, WO2004059288A3, WO2004059297A1, WO2004059441A2, WO2004059441A3|
|Publication number||200380106536.1, CN 1726386 A, CN 1726386A, CN 200380106536, CN-A-1726386, CN1726386 A, CN1726386A, CN200380106536, CN200380106536.1, PCT/2003/877, PCT/DK/2003/000877, PCT/DK/2003/00877, PCT/DK/3/000877, PCT/DK/3/00877, PCT/DK2003/000877, PCT/DK2003/00877, PCT/DK2003000877, PCT/DK200300877, PCT/DK3/000877, PCT/DK3/00877, PCT/DK3000877, PCT/DK300877|
|Inventors||约翰·法武齐, 本诺·古根海默, 杰夫·劳, 马克·基, 鲍勃·莱思罗普, 罗桑奈·伟谢尔|
|Export Citation||BiBTeX, EndNote, RefMan|
|Referenced by (7), Classifications (40), Legal Events (3)|
|External Links: SIPO, Espacenet|
本发明涉及一种通过按照染色规程依次施加预定量的试剂，而对容纳在载体(例如载玻片)上的至少一种生物样品进行自动染色的方法和装置，其中至少一个载体配备在载体轨道组件中。 The present invention relates to a method and apparatus according to the sequentially applied staining procedures predetermined amount of a reagent, and at least one biological sample accommodated in a carrier (e.g. a glass slide) on the automatic staining, wherein the carrier is equipped with at least one carrier rail component.
该申请涉及样品处理系统和生物样品处理方法领域。 This application relates to the field of biological sample processing system and method for processing a sample. 本发明涉及布置在载体(例如显微镜载玻片)上的样品的自动加工、处理、甚至染色，并且在一些实施例中，涉及样品和载体的连续或批处理，以及取样系统的清洗部件。 The present invention relates to a carrier disposed in (e.g. a microscope slide) on the automatic processing of samples, processing, or even dyeing, and in some embodiments, relates to a cleaning member and a carrier of the sample continuous or batch, and the sampling system. 实施例还涉及样品处理以及样品处理的数据收集、数据维护和数据检索的控制系统。 Example also relates to sample handling and sample handling data collection, data maintenance, and data retrieval control system. 本发明特别涉及的应用领域包括免疫组织化学、原位杂交、荧光原位杂交、特异性染色和微阵列，以及潜在的其它化学和生物学应用。 The present invention particularly relates to application areas include immunohistochemistry, in situ hybridization, fluorescence in situ hybridization, specific staining and microarray, and the potential of other chemical and biological applications.
免疫组织化学(IHC)应用和其它化学及生物学分析中的样品处理，要求一个或许多个不同处理次序或规程作为一个或多个样品分析的一部分。 (IHC) applications and other chemical and biological analysis of immunohistochemistry in sample handling, may require more than one part of the sequence of different treatments or procedures as one or more sample analysis. 这些样品处理次序或规程是由要求分析的个体或组织(例如医院的病理学家和组织学家)规定的，并且进一步由待实施的特定分析指令来规定。 These samples were processed by the requirements of the order or regulation is analyzed individual or organization (such as a hospital pathologist and histologist) regulations, and further analysis by specific instructions to be implemented to regulations.
在样品分析的制备中，生物样品可以通过公知的样品获取技术来取得，并且诸如在IHC应用中通常包括组织，甚至在一些应用中可以包括一个或多个分离的细胞，例如在微阵列样品中，所述生物样品可呈现在样品载体(例如显微镜载玻片)上。 In the preparation of samples analyzed, the biological sample can be obtained by known techniques to obtain a sample, and in such applications typically include tissue IHC, and even in some applications may include one or a plurality of isolated cells, such as in microarray samples , the biological sample in the sample carrier may be presented (e.g. a microscope slide) on. 而且，样品可以某种保存形式不同和潜在地呈现在载体上。 Furthermore, some sample can potentially save different forms and presented on a carrier. 作为一个实例，样品(例如皮肤层或切片)可保存在甲醛中并呈现在载体上，而一个或多个石蜡或其它化学层覆盖样品。 As one example, a sample (e.g., the skin layer or slice) can be stored in formaldehyde and presented on a carrier, and one or more paraffin or other chemical layers overlap the sample.
免疫应用例如需要包括诸如脱蜡、靶挽回(target retrieval)和染色这些步骤的处理次序或规程，特别是对于原位杂交(ISH)技术来说。 Immunization applications such as dewaxing need to include the target restore (target retrieval) and the processing order of these steps or procedures staining, especially for in situ hybridization (ISH) technique is. 以前，在一些应用中，这些步骤由人工来实施，因此潜在地导致这是一个耗时的规程并且需要人员主动参与到样品处理中。 Previously, in some applications, these steps manually implemented, thus potentially leading to it is a time consuming procedure and requires personnel to actively participate in the sample processing. 为了满足对有利样品处理以及几乎不用人工烦琐操作的需求，已经对样品处理的自动化作了一些尝试。 In order to meet the demand for beneficial and almost no manual sample handling cumbersome operation of automated sample processing has made some attempts. 然而，以前的这些努力并没有充分满足对自动样品处理的需求。 However, these previous efforts did not fully meet the demand for automated sample handling. 以前对自动样品处理的努力在一些方面存在缺陷，即阻碍更稳定的自动样品处理，例如：对样品处理缺乏足够的计算机控制和监测；对处理规程和处理状态、特别是对各个样品缺乏信息共享；缺乏诊断能力；以及对多个样品的批处理缺乏实时或适应能力。 Previous efforts for automatic sample handling deficiencies exist in some respects, that impede a more stable automatic sample handling, such as: lack of adequate sample processing computer control and monitoring; procedures for handling and processing status, especially the lack of information sharing for each sample ; lack of diagnostic capacity; and the lack of real-time batch processing of multiple samples or adaptability.
过去在对呈现在载体(例如载玻片)上的样品进行自动样品处理方面的努力(例如US6,352,861和US5,839,091)，都没有提供如本文所表现的多个优点和其它特征组合。 In the past presented in a carrier (e.g. a glass slide) on samples automated sample processing effort (e.g. US6,352,861 and US5,839,091), do not provide a number of advantages such as the performance herein, and other combinations of features.
生物样品(例如组织样品)在染色之前必须进行制备。 Biological sample (e.g., a tissue sample) must be prepared prior to staining. 组织载玻片根据将要对组织实施的染色方法种类接受预处理过程。 Tissue slides were stained according to the method that will be acceptable to the organization and implementation of the type of pre-treatment process. 该预处理包括脱蜡或靶挽回。 The pre-treatment includes dewaxing or target to restore. 载玻片上组织的制备在其装载到自动染色仪内之前经常需要在实验室内人工完成。 Preparation of tissue on the slide before it is loaded into the automatic staining instrument often need to be done manually in the laboratory. 这种预处理包括将载玻片于缓冲液或其它类型的处理液体中浸渍一预定量的时间和温度。 Such pretreatment comprises the slides in a buffer solution or other types of treatment liquid immersed a predetermined amount of time and temperature.
然而，人工制备是笨重的并且预处理是不充分的，这是因为为了得到正确的预处理结果，必须非常精确地观察液体的时间和温度，这未免太苛刻了。 However, is bulky and artificially prepared pretreatment is not sufficient, because in order to obtain the correct pre-treatment results, the liquid must be very accurately observe the time and temperature, which would be too harsh.
在该背景下，本发明的一个目的是，在自动染色装置中对载体(例如载玻片)上的生物样品进行自动预处理，从而生物样品的全部处理都可以在一个自动装置中来实施。 In this context, an object of the present invention, in the automatic staining apparatus of the carrier (e.g., a glass slide) on the automated biological sample pretreatment, whereby all of the processing of a biological sample can be implemented in an automatic apparatus.
本发明包括一种在自动染色装置中对容纳在载体上的至少一个生物样品进行处理的方法，所述方法包括以下步骤：在预定的载体部位配置至少一个承载生物样品的载体，所述载体配置在基本上水平的位置上；将所述至少一个载体绕枢轴旋转到基本上垂直的位置；将所述基本上垂直取向的载体在罐内浸渍一段预定的处理时间。 The present invention comprises an automatic staining apparatus for receiving at least one biological sample on a support for processing, said method comprising the steps of: at a predetermined portion of the carrier have at least one biological sample bearing carrier, said carrier configuration in a substantially horizontal position; the at least one carrier is pivoted to a substantially vertical position; said substantially vertically oriented carrier impregnated in the tank for a predetermined processing time. 优选的是，载体部位是载体轨道，其中多个载体配置在载体固定器内，而载体可单独绕枢轴旋转。 Preferably, the carrier portion is a carrier rail, wherein a plurality of carriers arranged in a carrier holder, and the carrier may be separately pivotable.
通过按照染色规程依次施加预定量的试剂，而用对容纳在载体上的至少一个生物样品进行自动染色的装置来实现该目的，其中至少一个载体配置在载体轨道组件中，而载体轨道组件包括在载体配置到载体轨道组件中之后用于预处理载体上的生物样品的装置，所述生物样品预处理装置包括配置在载体轨道组件中的罐；载体固定器；以及用于将配置在载体固定器中的载体绕枢轴旋转到垂直位置的装置和将垂直载体浸渍到罐内的装置。 Sequentially applied staining procedures by following a predetermined amount of reagent, and this object is achieved by at least one biological sample accommodated on a carrier automatic staining apparatus, wherein at least one carrier arranged on a carrier rail assembly, and the carrier track assembly comprising After the carrier track assembly configured to support the apparatus of biological samples on a support for pretreatment, the biological sample comprises a pre-processing means arranged in the carrier track assembly in a can; anchor carrier; and means for the carrier holder disposed A carrier pivoted to a vertical position and the vertical support means immersed into the tank means.
本发明提供了一种通过将载体从水平位置绕枢轴旋转到垂直位置，而在自动染色装置中完成预处理的自动化方法和装置。 The present invention provides a carrier by the pivoted from the horizontal position to the vertical position, and complete automation of the pretreatment method and apparatus in an automatic staining apparatus. 载体的这种绕枢轴旋转确保载体在预处理和染色过程中适当地取向。 Such carrier pivotally ensure carrier suitably oriented in the pretreatment and dyeing processes.
通过本发明，将载体上生物样品的制备集成到自动染色装置中，以便使生物样品一旦容纳在载体上就装载到染色装置内，其中预处理和染色规程都可在装置内自动实施。 By the present invention, the preparation of biological samples on a support integrated into an automated staining apparatus, so that the biological sample is once accommodated in the carrier to be loaded into the dyeing apparatus, wherein the pre-treatment and staining procedures can be automatically implemented in the apparatus.
优选的是，所选择的液体从至少一个供应罐供应到一个罐内。 Preferably, the selected at least one liquid supply from a tank to the supply tank. 填充和排空此罐的步骤由装置的控制系统来控制，从而确保载体根据染色规程中有关这一点的信息接受适当的预处理步骤。 This step of filling and emptying the tank is controlled by means of the control system, to ensure that information on this carrier suitable pre-treatment step according to the staining protocol.
优选的是，液体从供应箱转移到转移罐内并向上到达一个罐内。 Preferably, the liquid transferred from the supply tank to the transfer tank to a tank on arrival. 据此，装置优选地包括气动装置，所述气动装置用于将处理液从供应罐转移到转移罐内、从转移罐转移到该罐内，以及将液体从该罐排到转移罐内、从所述转移罐排到废物收集罐内。 Accordingly, the apparatus preferably comprises a pneumatic device, said pneumatic means for the transfer of treatment liquid from the supply tank to the transfer tank, transferred from the transfer tank to the tank, the tank and the liquid is discharged from the transfer tank, from The transfer tank discharged waste collection tank. 通过用气动系统转移液体而获得的优点是，至少一个转移罐、供应罐和废物罐可位于装置外部，借此可增大容量，因为对罐的尺寸没有限制。 Advantages of using a pneumatic system the transfer liquid is obtained that at least one transfer tank, supply tank and waste tank may be located in an external device, whereby the capacity can be increased, because there is no restriction on the size of the tank. 而且，通过本发明的这个实施例，可使浸渍的载体承受一系列的依次填充及从罐中排出的液体，因为系统容易适合包含几个含有不同液体的供应罐，同样还包含几个废物罐，从而可将废物分类。 Moreover, by this embodiment of the invention, the impregnated support can withstand a series of sequentially filling and discharging the liquid from the tank, because the system is easily adaptable to contain several different supply tank containing a liquid, the same also contains several waste tank , which can waste classification.
优选的是，所述罐配有用于加热罐内含有的处理液的加热部件，并且加热部件能够有利地将罐的内容物加热到至少60℃的升高温度，更优选的是至少90℃，甚至更优选的是至少115℃。 Preferably, the tank is equipped with a heating means for heating the treatment liquid contained in the tank, and the heating member can advantageously be tank contents are heated to elevated temperatures of at least 60 ℃, more preferably at least 90 ℃, even more preferably at least 115 ℃. 借此，罐内的液体温度被加热升高到120℃，甚至有150℃那么高，并且在该温度下保持10-20分钟，而没有沸腾显示。 Thereby, the temperature of the liquid tank is heated raised to 120 ℃, and even as high as 150 ℃, and maintained at this temperature for 10-20 minutes, without boiling display. 在一个实施例中，加热部件适合将液体加热到95℃并保持40分钟，以便实施靶挽回过程。 In one embodiment, the heating member for heating the liquid to 95 ℃ and 40 minutes, in order to implement the target restore process.
按照本发明的一个实施例，通过在至少一个载体绕枢轴旋转到垂直位置之后降低载体固定器并将载体浸渍到罐内，而将至少一个垂直载体浸渍到罐内。 According to one embodiment of the present invention, after at least one carrier by pivoted to a vertical position to reduce the carrier holder and the carrier was immersed into the tank, and at least one vertical carrier impregnated into the tank. 借此，得到紧凑的罐布置和载体固定器布局。 In this way, get a compact arrangement and immobilized tank layout.
组织的处理方法是组织样品的预处理。 Treatment organization is pretreated tissue samples. 然而，通过本发明，意识到，可对垂直位置的载体上的组织样品实施其它类型的处理，例如漂洗载体。 However, by the present invention, to realize, can support the vertical position of the tissue sample on the implementation of other types of processing, e.g., rinsing the carrier. 可以用按照本发明的装置实施的其它方法包括组织样品的脱蜡或靶回收过程。 Other methods may be used in accordance with embodiments of the apparatus of the present invention comprises a process of recovering dewaxing or target tissue sample.
按照本发明，罐是具有上开口槽的加长箱，所述槽使垂直取向的载体插入容器内，以便进行处理。 According to the present invention, the tank having an upper opening groove is elongated box, the vertical orientation of said slot is inserted into the container carrier, for processing. 借此，罐的体积以及由此需要的处理液的量都最小。 Thereby, the volume and the amount of the processing liquid tank are thus required minimum.
优选的是，所述装置包括用于使排出的液体循环以便在载体的随后预处理过程中重新使用的装置。 Preferably, the apparatus includes means for discharging the liquid circulation means for pre-processing vector in subsequent re-use. 借此，用于装置操作(即组织载体的预处理和漂洗)的液体量可最小，从而使废物的处理容易以及成本降低。 In this way, the amount of liquid used in operation of the device (ie, pre-treatment and rinsing organization carrier) can be minimized, so that waste disposal easier and reduce costs.
在本发明的优选实施例中，载体轨道组件配置在抽屉(drawer)组件内，其中轨道从装置中缩回，以便装载和卸载载体。 In a preferred embodiment of the present invention, the carrier track assembly is disposed in the drawer (drawer) assembly, wherein the track is retracted from the apparatus, for loading and unloading the carrier. 抽屉组件与装置的抽屉接收部件内的罐配合，所述罐能够同时处理容纳在载体轨道组件中的多个载体固定器内的载体。 Cans with drawers and drawer assembly receiving member within the apparatus, the tank capable of simultaneously processing a plurality of carriers in a carrier accommodated in the carrier track assembly fixture within. 抽屉组件使装置在使用时非常灵活，如载体可以装载到一个抽屉中或从其上卸载下来，而其它抽屉中的载体可独立于其进行处理。 Drawer assembly of the apparatus when using a very flexible, such as a carrier can be loaded into a drawer or unloaded therefrom, and the other drawer carrier may be independent of its processing. 而且，抽屉的使用使得自动染色装置的操作容易。 Moreover, the use of the drawer so that the operator easily automated staining apparatus. 每个抽屉的罐可优选地与有利地布置在装置外部的公共供应罐和废物罐相连。 Each drawer can may preferably with an external device is advantageously arranged in a common supply tank and connected to the waste tank.
附图说明 Brief Description
以下参照附图来描述本发明的优选实施例，其中：图1是按照本发明优选实施例的染色装置的示意性透视图；图2是图1所示染色装置中的工作区的顶视图；图3是在按照本发明的装置中包括滑轨组件和罐的抽屉组件的示意性前视图；图4是闭合位置的抽屉组件的透视图；图5是开放位置的图4的抽屉组件；图6是按照本发明优选实施例的滑轨的顶部透视图；图7是布置在抽屉组件中的滑轨固定器和箱的细节图； The drawings will be described a preferred embodiment of the present invention, with reference, in which: Figure 1 is a schematic perspective view of a dyeing device according to a preferred embodiment of the present invention; FIG. 2 is a top view of the dyeing apparatus shown in Figure 1 workspace; Figure 3 is a device according to the present invention comprises a slide assembly and a schematic of the drawer assembly of the tank front view; Fig. 4 is a perspective view of the closed position of the drawer assembly; Figure 5 is an open position of FIG drawer assembly 4; FIG. 6 is a top perspective view of a rail according to a preferred embodiment of the present invention; FIG. 7 is arranged in the drawer assembly in the rail holder and a detailed view of the box;
图8是按照本发明优选实施例的罐的透视图；图9是图8的罐的前视图；以及图10是罐的处理液的操纵流程图。 8 is a perspective view of a can according to a preferred embodiment of the present invention; FIG. 9 is a front view of the canister of FIG. 8; and FIG. 10 is a flowchart showing the can to manipulate treatment liquid.
具体实施方式 DETAILED DESCRIPTION
图1表示出按照本发明的样品处理系统101的一个示意性实施例。 Figure 1 shows a sample processing system according to the present invention 101 in exemplary embodiments. 内阁(cabinet)部分4形成系统的外部，并用于满足系统的总体结构考虑(顶部的内阁部分没有表示在图1中)。 Cabinet (cabinet) portion 4 is formed outside the system, and to meet the overall structure of the system considered (not shown in the top part of the cabinet in Figure 1). 样品处理系统可包括多个用于操纵和处理样品及样品载体(例如载玻片，潜在地为显微镜载玻片)的抽屉6。 Sample processing system may include a plurality of samples and for manipulating and handling the sample carrier (e.g., a glass slide, potentially as a microscope slide) of the drawer 6. 其它样品载体可与本发明相容地来容纳。 Other sample carrier may be compatible with the present invention to accommodate. 每个抽屉可构造成能够容纳样品载体保留组件，例如载玻片保留组件、载体轨道、模块或盒。 Each drawer may be configured to accommodate a sample carrier retention component, e.g., a glass slide retention assembly, the carrier rails, module or cassette.
样品载体保留组件的一个实施例可包括载玻片保留组件6(如图7所示)。 Sample carrier retention assembly of one embodiment of retention assembly may include a glass slide 6 (as shown in Figure 7). 载玻片保留组件可包括滑轨、模块或盒。 Slides retention assembly may include rails, module or cassette. 载玻片保留组件6被构造成能够将多个载玻片容纳在对应于样品载体保留设备的至少一个结构中。 Slides assembly 6 is configured to retain a plurality of slides can be held in at least one structure corresponding to the sample carrier retention devices. 正如下面进一步描述的，在样品的处理中采用样品载体保留组件。 As described further below, using the components in the sample carrier retained in the processing of the sample. 应该进一步注意，样品载体保留组件是具有抽屉的可去除的构造，并且可堆放或驻留在其它保留组件内。 It should be further noted that the sample carrier retention assembly is constructed having a removable drawer, and can be stacked or reside in other retention components.
在优选实施例中，载玻片可如预处理和染色过程所要求的那样构造在垂直及水平位置(如图3和图6所示)。 In a preferred embodiment, the slides can be configured as required for pretreatment and dyeing processes in the vertical and horizontal position (shown in FIG. 3 and FIG. 6). 这允许用多种方式对载玻片进行自动预处理和染色，包括如传统的人工实验室方法中所接受的预处理和染色。 This allows a variety of ways on the slides automatically pretreatment and dyeing, including such traditional manual methods accepted laboratory pretreatment and dyeing. 载玻片最初装载到水平位置的载体保留组件(例如滑轨)和抽屉内。 Slides initially loaded into the carrier to retain the component's horizontal position within (such as rails) and drawers. 载玻片由可调节的载体支持体(如图7所示)水平支撑着。 Slides by an adjustable carrier support (Figure 7) horizontally supported. 如果需要预处理(例如脱蜡)，系统就将载玻片旋转到垂直位置并将这些样品下降到浸渍处理罐内(下面进一步描述)，然后用所需的液体进行填充。 If desired pre-treatment (e.g. dewaxing), the system will rotate to a vertical position and slides these samples decreased to an immersion treatment tank (further described below), and then filled with the desired liquid. 在一些实施例中，滑轨降低，从而影响载玻片的下降(参见图3和图7)。 In some embodiments, the rails decreases, thus affecting the slides decreased (see FIG. 3 and FIG. 7). 为了在载玻片上实施染色过程，如以下所述，系统将载玻片旋转到水平位置，而注射器或探头将液体施加到样品上。 In order to implement the process of dyeing on a slide, as described below, the system is rotated to the horizontal position of the slides, and a syringe or probe is applied to the liquid sample. 每个载玻片能够单独旋转，因此可对具有不同要求的不同样品进行单独处理。 Each slide can be rotated individually, and therefore may have different requirements of the different samples were treated separately.
样品处理系统通过预处理过程(例如脱蜡)可使样品的处理步骤或载玻片上呈现的细胞制备自动化。 Automated sample handling system allows the preparation of the sample processing steps or slides presented on cells through the pretreatment process (e.g. dewaxing). 系统提供广泛的载玻片预处理。 The system provides a wide range of glass slides pretreated. 通常实施的两种类型的预处理实例是(但不限于)，脱蜡和靶挽回。 Examples of two types of pre-treatment is usually performed (but are not limited to), and the target restore dewaxing. 在一些实施例中，这些过程必须用垂直取向、浸渍在多种液体罐内的载玻片来实施。 In some embodiments, these processes must be oriented vertically, immersed in a variety of liquid tank slides implemented. 脱蜡包括将载玻片在一系列液体中浸渍短时间(潜在地为约5-10分钟)。 The slides were immersed dewaxing comprises a series of liquid in a short time (potentially for about 5-10 minutes). 此过程预计首先从样品上去除已经固定或呈现在其中的石蜡，其次去除石蜡溶剂，然后缓慢地使样品再水合。 This process is expected to be removed from the first sample which has been fixed or presented in paraffin, followed by removal of the paraffin solvent, the sample is then slowly rehydrated. 靶挽回，在一些实施例中为抗原决定簇脱模，包括将载玻片浸渍在热缓冲液处理罐内，并且在一些实施例中，浸渍约20分钟，然后将载玻片冷却约20分钟。 Target restore, in some embodiments of epitopes release, including the slides are immersed in the heat treatment buffer tank, and in some embodiments, immersed for about 20 minutes, and then the slides were cooled for about 20 minutes . 在优选实施例中温度维持在约95℃。 Example In a preferred embodiment the temperature is maintained at about 95 ℃. 在靶挽回中，标志或其它标示用来标记感兴趣的样品部分，例如其细胞或结构。 In the restore target, a logo or other mark used to mark the sample portion of interest, e.g., the cell or structure.
为了实施这些相同的预处理过程，系统在一些实施例中模仿或对应于人工使用的供应源的过程和物理属性。 To implement this, the same pretreatment process, system mimic or correspond to a supply of human use and the physical properties of the process in some embodiments. 据此，可配备处理罐101(如图3、7和8所最佳示出的)。 Accordingly, can be equipped with the processing tank 101 (FIG. 3, 7 and 8 best shown). 在一些实施例中，每个处理罐101的元件，如图4和5所示，构造在抽屉100内。 In some embodiments, each processing element tank 101, as shown in Figures 4 and 5, constructed in a drawer 100. 在一些优选实施例中，维持实施预处理过程所需的液体体积，而无需每个彼此面对面的载玻片取向(在常规系统中，它们是面对面的)，尽管处理罐甚至贯穿载玻片表面来分布液体。 In some preferred embodiments, the pretreatment process to maintain the volume of liquid required to implement, without the orientation of each slide face each other (in conventional systems, they are face to face), even in spite of the processing tank throughout the surface of the slide to distribute the liquid.
在一些实施例中，处理罐能够加热载玻片。 In some embodiments, the processing tank can be heated glass slide. 此热量通过热电耦甚至贯穿每个个体载玻片的表面。 This heat through the thermocouple even through the surface of each individual slides. 热量的精确和物理施加导致处理步骤的标准化和重复性。 Heat is applied to cause the precise processing steps and physical standardization and repeatability. 填充和加热任务由计算机控制的调度程序来执行(如下面进一步描述的)。 Filling and heating task scheduler by a computer-controlled to perform (as further described below). 考虑到任何数目的载玻片的存在和缺失，可调节液体的体积。 Taking into account the presence and absence of any number of slides, adjustable volume of the liquid.
按照本发明的染色装置1的优选实施例在图1和2中示出。 Dyeing apparatus according to the present invention is preferably one of the embodiment of Figures 1 and 2 are shown. 染色装置1包括围绕试剂站2的矩形框架4，以及第一和第二载玻片部分5，试剂站2包括试剂瓶室，其中每个室内放置有试剂瓶3，许多分离的轨道组件6放置在第一和第二载玻片部分5上，每个轨道组件6容纳许多一个挨一个地安装在轨道组件6内的显微镜载玻片7。 Dyeing apparatus 1 comprises a rectangular frame surrounding the reagent station 2 of 4, and first and second slide glass part 5, the reagent station 2 comprises a reagent bottle chamber, wherein each reagent bottle 3 is placed indoors, many tracks separate component 6 is placed on the first and second slide glass portion 5, each accommodating a plurality of track assembly 6 mounted side by side in the microscope slide rail assembly 6 7. 在图示的实施例中，每个轨道可容纳8个载玻片，但是轨道可设计成能够容纳任何适当数目的载玻片。 In the illustrated embodiment, each track can hold eight slides, but the track may be designed to accommodate any suitable number of slides. 由于一个挨一个地布置有8个轨道，因此图示实施例可容纳高达64个载玻片7，每个在载玻片的上面都固定有样品例如组织，因此试剂可从上方施加到每个载玻片上的样品中。 Since there are arranged side by side eight tracks, and therefore the illustrated embodiment can accommodate up to 64 slides 7, each of which is fixed in the above sample, such as tissue slides, and thus the reagent can be applied from above to each of the sample on the slide.
用于沿X和Y(以及Z)方向(如箭头X和Y所示)移动探头10的机器人臂20，布置在染色装置的框架4上方。 (As indicated by arrows X and Y shown) robot arm for moving the probe along the X and Y (and Z) direction 10 of 20, arranged in the frame 4 above the dyeing apparatus. 机器人臂20因此可以将探头10定位在所有试剂瓶3以及所有显微镜载玻片7的上方，并且进一步操纵探头10，以吸取任一瓶3中包含的部分试剂，从而将那部分试剂传送并施加到任一载玻片7上，以便对每个载玻片7上的样品有选择地进行染色或处理。 Robot arm 20 of the probe 10 can be positioned in all the reagent bottles 3, and all the top 7 of the microscope slide, and further manipulation of the probe 10, in order to absorb any portion contained in the reagent bottle 3, so that part of the reagent delivery and applying either on a glass slide 7, so as to selectively dyed or treated sample 7 on each slide. 利用合适的控制装置，例如具有用于此目的的合适软件和输入数据的计算机(未示出)，该染色装置1能够对需要不同染色或处理试剂和过程的样品进行自动染色或处理。 The use of suitable control means, e.g., with a suitable software and the input data for this purpose computer (not shown), the dyeing apparatus 1 is capable of dyeing or require different treatment agents and processes for automatic sample dyed or treated.
如图1，探头10容纳在机器人头22中并由机器人臂20来操纵。 Figure 1, the probe 10 is accommodated in the robot head 22 by the robotic arm 20 to manipulate. 探头10上升到上部位置(在Z方向)，在此处清楚地看到，瓶3在探头10的下面，但是机器人包括机器人头22中用于降低探头10的装置，以便将探头尖浸到所选择的试剂瓶3的内容物中并吸取选定量的用于所选择的染色或处理过程的试剂。 Probe 10 rises to the upper position (in the Z direction), here clearly seen, the bottle 3 below probe 10, but the robot comprising a robot head 22 for reducing device probe 10, so that the probe tip immersed in the the contents of the selected reagent bottle 3 and drawing a selected amount of reagent for the selected staining or treatment process. 机器人头22还配有指向下方的CCD照相机25。 Robot head 22 comes with 25 CCD camera pointing down. 利用照相机确定载玻片和试剂瓶以及装置在工作区域内的其它特性的状态信息，例如阅读配置在试剂容器上的代码，以确定系统内的试剂种类和试剂部位。 Using a camera to determine the slides and reagent bottles and means other characteristics in the work area of the status information, such as reading the reagent container arranged on the code to determine the reagents and reagent site within the system. 照相机还可确定组织样品载体的状态，例如特定载玻片的部位、指示有关呈现在载玻片上的组织样品或待实施的处理方案的信息的信息索引，例如代码。 The camera may also determine the status of a tissue sample carrier, e.g., site specific slides, tissue samples relevant indication presented on a glass slide, or index information of the information processing scheme to be implemented, such as the code.
本发明的染色装置1还包括探头清洗站8和试剂混合器9，机器人臂20还布置成能够将探头运送到清洗站8以及试剂混合器9。 Dyeing device 1 of the invention further comprises a reagent probe wash station 8 and the mixer 9, the robot arm 20 is also arranged to be conveyed to the probe washing station 8 and a reagent mixer 9.
当滑轨组件6在上部位置时(如图3所示)，滑轨组件6中的载玻片7装载和卸载到水平位置。 When the slide assembly 6 is in the upper position, the slide assembly slides 6 7 loading and unloading to a horizontal position (shown in Figure 3). 滑轨组件6布置在载玻片升降机63中，当滑轨6在其上部位置时，载玻片固定器62适合在水平位置和垂直位置7v之间绕枢轴转动载玻片7。 6 is arranged in the slide assembly 63 slides the lift, when the rail 6 is in its upper position, the slide glass holder 62 for rotating the slides 7 between the horizontal and vertical positions 7v pivot. 包括滑轨升降机63的滑轨组件6被布置成抽屉组件100的移动部100a。 Slide assembly 63 includes a lift rail 6 is arranged to move the drawer assembly portion 100a 100 of. 在抽屉组件100的相应静止部100b，配备罐101。 In the drawer assembly of the corresponding stationary portions 100b 100, 101 with the tank.
染色装置优选地包括八个抽屉组件(如图1所示)。 Dyeing apparatus preferably includes eight drawer assembly (as shown in Figure 1). 然而，应该意识到，根据设计性能，还可提供任何其它数目。 However, it should be appreciated that, according to the design performance, and may provide any other number. 每个抽屉组件100包括载玻片、载玻片升降机63、包括温度控制部件64的滑轨组件6、罐101、用于收集染色液体的滴盘65，和包括指示器的控制装置，所述指示器用于不同使用者信息及处理监视目的。 Each assembly 100 includes drawer slides, slides lift 63, comprising a temperature control means 6 of rail assembly 64, tank 101 for collecting liquid dye drip tray 65, and control means including indicator, the Indicators for different user information and treatment monitoring purposes.
滑轨组件6在图6中示出。 Rail assembly 6 is shown in FIG. 6. 滑轨组件6包括滑轨61，后者在各个载玻片接收室68(如图6所示)中优选地具有8个载玻片7的容量。 Rail assembly 6 comprises a rail 61, which slides in the respective receiving chamber 68 (shown in FIG. 6) preferably has a capacity of eight slides 7. 与每个室68相连的是载玻片固定器62。 And each chamber 68 is connected to a slide glass holder 62. 载玻片固定器62包括具有载玻片夹69和启动装置67的绕枢轴旋转装置，所述载波片夹69在水平载玻片位置与垂直载玻片位置之间绕枢轴旋转。 Slide glass holder 62 includes means 67 having a pivoting clip 69 slides and actuating means, said carrier film holder 69 between a horizontal position and a vertical slide glass slides pivot position. 载玻片7，7v在其载玻片固定器62中单独绕枢轴旋转，而载玻片夹69通过按压所配备的两个嵌片67，可绕枢轴旋转，其中一个从水平位置旋转到垂直位置，另一个使载玻片从垂直位置返回到水平位置。 Slides 7,7v in its holder 62 slides separately pivotable clamp 69 and a slide glass by pressing the two panels 67 is equipped with, pivotally, wherein a rotation from the horizontal position to the vertical position and the other slides were returned from the vertical position to a horizontal position.
当抽屉100载有一个或多个载玻片7并且还处于染色过程中时，滑轨在上部位置。 When the drawer 100 contains one or more slides 7 and also in the dyeing process, the rail at the upper position. 当载玻片7装载之后，载玻片7就旋转到垂直位置7v，然后滑轨6用载玻片升降机63降低，以便将垂直设置的载玻片7v浸渍到下面的罐101内。 After loading slides 7, slides 7 rotates to the vertical position 7v, then lifts the glass slide rail 6 with 63 lowered so 7v slides were immersed vertically into the tank 101 below. 抽屉组件也在图4，5和7中示出。 Drawer assembly 4, 5 and 7 are also shown. 载玻片升降机63适合在载玻片7v浸渍在罐的液体中时搅动载玻片7v。 Lifts 63 slides in a slide glass for 7v 7v slides immersed in agitated liquid in the tank.
罐101填充有来自转移罐110(参见图10)的预定量的处理液。 Tank 101 is filled with a predetermined amount of the treatment liquid from the transfer tank 110 (see Fig. 10). 相关的处理液此前已经从供应罐111经气压装置转移到转移罐110。 Related treatment solution had already been transferred from the supply tank 111 pneumatic device to transfer tank 110. 通过采用转移罐110以及用包括真空泵113的气动系统控制液体的转移，可完成泵给，而液体无需与泵给元件接触。 By using the transfer tank 110 and includes a vacuum pump with pneumatic control system 113 transfer liquid pump to be completed, but without the need for components in contact with the liquid pump. 这是有利的，因为液体残留在元件中的危险由此降到最小。 This is advantageous, since the risk of liquid remaining in the element thereby minimized.
优选地配备总共8个抽屉。 Preferably provided with a total of 8 drawers. 据此，这意味着，这8个罐也配备在染色装置中。 Accordingly, this means that 8 is also equipped with tanks in dyeing apparatus. 每个罐101容纳高达8个浸渍的载玻片7v。 Each tank 101 accommodates up to eight slides impregnated 7v. 罐的主要功能是，当载玻片下降到罐内之后，在一定时间内(例如15分钟)将罐内的液体从室温加热到预定温度，并维持预定温度例如高达约120℃，而在预处理时间(例如10-20分钟)没有任何沸腾显示。 The main function of the tank is dropped into the tank when the slide glass after a certain time (e.g. 15 minutes) to the liquid tank is heated from room temperature to a predetermined temperature, and to maintain a predetermined temperature, for example up to about 120 ℃, whereas in the pre- Processing time (e.g. 10-20 minutes) without any boiling display. 优选的温度一般是约40℃-约120℃，正如所需的处理所确定的。 The preferred temperature is generally from about 40 ℃ - about 120 ℃, as determined by the required processing. 非常常见的是，优选温度在80℃-100℃之间，更优选的温度在95℃-98℃之间。 Very commonly, the preferred temperature between 80 ℃ -100 ℃, more preferably at temperatures between 95 ℃ -98 ℃. 对于一些特殊的处理，优选的温度在110℃-130℃之间，甚至高达约150℃。 For some special treatment, preferably at temperatures between 110 ℃ -130 ℃, even up to about 150 ℃.
在处理时间之后，将热源关掉，并通过提升滑轨道组件6、借此将垂直载玻片7v从罐101中提起，来去除载玻片7v。 After processing time, turn off the heat source, and 6, whereby the vertical slides 7v lifted from the tank 101 by raising the slide rail assembly, to remove the slides 7v. 罐101可用于脱蜡、再水合以及热诱导的靶挽回。 Tank 101 can be used for dewaxing, rehydration and heat-induced target to restore. 这些过程是在具有载玻片的染色装置上实施的，所述载玻片在垂直取向、浸渍在填充有不同所需试剂和空的各个罐内。 These processes are stained with the embodiment of the apparatus slides, the slides in a vertical orientation, was immersed in and filled with different reagents needed to empty the respective tank. 对靶挽回过程，罐内的液体水平上升到载玻片上的标记之上。 Target restore process, the liquid level of the tank rises above the mark on the slide. 加热部件适合加热到约95℃，并将该温度维持高达40-60分钟。 Heating means for heating to about 95 ℃, and the temperature is maintained up to 40-60 minutes. 在罐内完成的预处理过程包括将载玻片在一系列液体中浸渍短时间例如5-10分钟。 Pretreatment process is completed in the tank comprises a series of slides were immersed in a liquid in a short time, for example 5-10 minutes. 脱蜡过程预计首先从组织样品上去除固定在其上的石蜡，其次去除石蜡溶剂，然后依次通过一系列的试剂使样品再水合。 Dewaxing process is expected to first remove the paraffin fixed thereon from the tissue sample, followed by removal of the paraffin solvent, followed by a series of reagent samples rehydrated.
如诸如图8和9所示，罐101是加长的，具有开放槽102，可通过槽102插入载玻片7v。 As such as shown in Figures 8 and 9, the tank 101 is elongated, having an open groove 102, 102 may be inserted through the slot slides 7v. 这使得罐的体积相对小些，从而又可以相当快速地加热罐内的液体和/或使加热并维持罐内流体温度的能耗相当低。 This makes the volume of the tank is relatively small, which in turn can be quite rapidly heated liquid tank and / or energy consumption of the heating and maintaining temperature of the fluid tank is very low. 罐101经液体连接管103填充和排空，且加热部件104优选地位于罐的下部。 Tank 101 through the liquid connection pipe 103 is filled and emptied, and the heating member 104 is preferably located in the lower tank. 罐101在两侧还配有绝缘侧壁部件，用于促进加热，由此缩短加热时间。 Tank 101 is also equipped on both sides of the insulating sidewall member for facilitating heating, thereby shortening the heating time. 罐101还配有用于登记罐内的液体水平的传感器装置(未示出)和用于登记流体温度并将这些数据馈送到装置的控制系统的传感器。 Tank 101 is also equipped with sensor means for registration of the liquid level of the tank (not shown) and for registering the fluid temperature and the data fed to the control system of the apparatus of the sensor.
预处理液或试剂可储存在许多单个容器内，其中一些容器储存用于脱蜡的液体，一些容器用于靶挽回，而一些容器用于储存100％的乙醇、蒸馏水和缓冲液。 Pretreatment or reagents that can be stored in a plurality of individual containers, wherein some of the liquid storage container for dewaxing, some containers used to restore the target, and a container for storing a number of 100% ethanol, distilled water and buffers. 容器有利地具有与装置的预处理过程性能所需的特定液体量对应的不同体积。 Advantageously, the container having a different amount of the specific volume of the liquid with the required pre-processing performance of the device corresponding.
供应容器111与罐101之间的液体转移是经转移罐110(如图10所示)进行的。 Transfer the liquid supply container 111 and the tank 101 through the transfer tank is between 110 (Figure 10) performed. 液体转移通过施加到转移罐110上的正、负气压来实现。 Liquid transfer by applying to the positive transfer tank 110, a negative air pressure to achieve. 优选地配备两个分离的转移罐(未示出)，一个用于含水溶液，第二个用于有机溶液。 Preferably equipped with two separate transfer tank (not shown), one for an aqueous solution, the second for the organic solution. 同样，为了倾空罐，废液经转移罐110转移到废物容器112。 Similarly, in order to pour cans, waste transfer tank 110 via transfer into a waste container 112. 优选地配备废物罐，例如一个用于有毒废液，一个用于无毒废液。 Preferably has a waste tank, for example, a toxic waste, one for non-toxic waste.
流体可以在任何容器与任何罐之间的两个方向上转移。 Fluid can be transferred in both directions between any container of any tank. 流体转移的操作顺序由装置的控制系统来确定。 Sequence of fluid transfer operations by means of the control system is determined. 脱蜡试剂可重新使用并从干净到肮脏周期性地循环。 Dewaxing agents can be re-used from clean to dirty cyclically. 用过的肮脏脱蜡液体和罐的漂洗液被使用者或控制系统当作废物弃掉。 Dewaxing used dirty liquid and rinse tank is discarded as waste user or control system. 靶挽回缓冲液和水在控制系统中被标记为“一次使用(single use)”，并且在使用之后转移到废物中。 Restore target buffer and water in the control system are marked as "single use (single use)", and after use is transferred to waste.
优选地，按照本发明的方法可包括：诸如在完成所需的处理之后将载体上的至少一个生物样品暂时储存在罐内的适当液体中，直到载体上的生物样品去除、用于离机处理为止。 Preferably, the method according to the present invention may include: such as after completion of the required processing at least one biological sample is temporarily stored in a suitable carrier liquid in the tank, until the biological sample carrier is removed from the machine for processing so far. 一般，罐的这种使用在过夜染色方面(例如在半夜完成)是特别有利的。 In general, this tank overnight use in dyeing (e.g., completed at midnight) is particularly advantageous.
以上按照一些优选示范性实施例描述了本发明的装置和方法。 In accordance with some preferred above exemplary embodiment describes apparatus and methods of the invention. 然而，通过本发明意识到，在不脱离如所附权利要求书限定的本发明范围的前提下，可以对所述方法和装置做出许多其它变型和等同。 However, by the present invention is realized, without departing from the appended claims as defined by the scope of the present invention, the premise of the method and apparatus can make many other variations and equivalents.
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|International Classification||B01L3/02, G01N1/10, B32B5/02, G01M1/38, G01N15/06, G05B21/00, G01N35/02, G01N35/00, G01N1/30, G01N1/31|
|Cooperative Classification||G01N1/31, Y10T436/25, Y10T436/2575, Y10T436/114998, Y10T436/114165, Y10T436/11, Y10T436/112499, Y10T436/113332, G01N2035/00039, G01N2035/00089, G01N35/00712, G01N35/00732, G01N2035/00881, G01N2035/00376, G01N2035/00435, G01N2035/00366, G01N2035/00326, G01N2035/00306, G01N35/0092, G01N2035/00891, G01N1/312, G01N35/00871, G01N35/0099, Y10S901/41, Y10S901/02, G01N1/30|
|European Classification||G01N35/00R, G01N35/00G3L, G01N35/00G5, G01N1/31B|
|25 Jan 2006||C06||Publication|
|22 Mar 2006||C10||Entry into substantive examination|
|25 Mar 2009||C14||Grant of patent or utility model|