WO2001046671A1 - Appareil et procede pour le controle et la garantie de la qualite d'analyse d'images - Google Patents

Appareil et procede pour le controle et la garantie de la qualite d'analyse d'images Download PDF

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Publication number
WO2001046671A1
WO2001046671A1 PCT/CA2000/001563 CA0001563W WO0146671A1 WO 2001046671 A1 WO2001046671 A1 WO 2001046671A1 CA 0001563 W CA0001563 W CA 0001563W WO 0146671 A1 WO0146671 A1 WO 0146671A1
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Prior art keywords
analysis system
slide
automated analysis
test
test slide
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PCT/CA2000/001563
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English (en)
Inventor
Paul A. Presta
Daniel S. Maclean
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Veracel Inc.
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Priority to AU23365/01A priority Critical patent/AU2336501A/en
Publication of WO2001046671A1 publication Critical patent/WO2001046671A1/fr

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/30—Staining; Impregnating ; Fixation; Dehydration; Multistep processes for preparing samples of tissue, cell or nucleic acid material and the like for analysis
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N2001/2893—Preparing calibration standards

Definitions

  • TITLE APPARATUS AND METHOD FOR IMAGE ANALYSIS QUALITY CONTROL AND ASSURANCE
  • the present invention relates to medical and biological specimen analysis, and more particularly to an apparatus and method for image analysis quality control and assurance.
  • tissue of cellular specimens is an important part of medical and biological diagnostic systems. When collected as exfoliated cells, this process falls under the category of cytology. If the specimen is collected and processed as intact tissue, for example in a biopsy, then the process is within the field of histology. Cells gathered from the bloodstream generally form part of a hematological analysis.
  • the Pap test is a well known procedure under the category of cytological specimen and analysis.
  • the Pap test is based on the Papanicolaou staining protocol.
  • the first step in a Pap test involves scraping the cells from the uterine ectocervix for precancerous lesions of the uterine cervix, and comprises the specimen collection phase.
  • the Pap test cells gathered from the ectocervix are 'smeared' onto a microscope slide and then fixed.
  • the fixation procedure kills and preserves the cells in such a way as to render them inert and representative of their appearance in life and results in a Pap smear for the specimen.
  • the Pap smear is then sent to a laboratory where the preparation and analysis of the specimen is completed.
  • the preparation steps in the laboratory include the staining of the cells and covering the stained cells with a cover slip for protection.
  • the nuclei are stained dark blue while the cytoplasm is stained anything from a blue-green to an orange-pink.
  • the Papanicolaou stain is a combination of several stains or dyes together with a specific protocol designed to emphasize and delineate cellular structures of importance for pathological analysis.
  • the stains or dyes included in the Papanicolaou St ⁇ in are Haematoxylin, Orange G and Eosin Azure (a mixture of two acid dyes, Eosin Y and Light Green SF Yellowish, together with Bismark Brown). Each stain component is sensitive to or binds selectively to a particular cell structure or material. Haematoxylin binds to the nuclear material colouring it dark blue. Orange G is an indicator of keratin protein content. Eosin Y stains nucleoli, red blood cells and mature squamous epithelial cells. Light Green SF yellowish acid stains metabolically active epithelial cells. Bismark Brown stains vegetable material and cellulose. The purpose of the staining procedure is to render the cells visible under magnification and to allow differentiation of various intra-cellular components or compounds.
  • the typical Pap smear prepared according to this procedure comprises a complex arrangement of cells, debris, blood, leukocytes, bacteria, fungus, and other components, as depicted in Fig. 1 (a).
  • Fig. 1 (a) The typical Pap smear prepared according to this procedure comprises a complex arrangement of cells, debris, blood, leukocytes, bacteria, fungus, and other components, as depicted in Fig. 1 (a).
  • conventional Pap smears are highly effective for screening for cervical cancer and other malignant cell forms. While there are great advantages and efficiencies to be achieved through the utilization of automated image analysis, the complex arrangement of cells in a conventional Pap smear complicate the application of automated image analysis.
  • Fig. 1 (b) One approach followed in the development of automated cytological image analysis systems is the utilization of controlled specimen preparations such as a monolayer specimen and a liquid-based preparation (LBP) as shown in Fig. 1 (b).
  • the advantage of the monolayer specimen preparation technique is the ability to exert control over the physical arrangement of the cells on the microscope slide. By effectively narrowing the tolerances on the physical arrangement of the cellular components, the accuracy and reproducibility of the automated analysis systems is greatly enhanced.
  • One problem that remains with the application of automated analysis systems is the variations which arise as a result of the staining of these cells. Cytological staining remains more of an art than a science. There are many reasons for this. In some cases it is because the stains themselves are poorly manufactured. In other cases it is the technique that is to blame since there is a wide range of parameters to control and few ways of ensuring that all are within acceptable levels.
  • Automated cytological image analysis systems rely on the precise measurement of various features associated with intra-cellular components, such as the nucleus, and these may easily be skewed by poor stain control. For example, overstaining the nucleus of a cell alters the appearance of its chromatin texture, which is one the most important analytical features. Similarly, understaining can compromise the segmentation of the nucleus and thereby affect morphological measures such as its area and perimeter. Thus, the measurement and control of stain variations in cytological, and also histological and hematological, specimens is a crucial issue in the application of automated image analysis for medicine and biology.
  • the present invention provides an apparatus and method for image analysis quality control and assurance suitable for use with automated cytology analysis systems such as the those from the common assignee of the subject invention.
  • the present invention provides a previously stained specimen comprising an encapsulated protein which is deemed to be an optimally stained specimen.
  • the encapsulated protein is placed on a microscope slide, stained and its appearance, and other characteristics, are characterized using the automated analysis system.
  • the slides previously deemed 'optimally stained' provide a benchmark for the analysis of the stain quality in terms of segmentation results or features extracted by the automated analysis system.
  • the present invention provides an apparatus for assessing stain quality of a biological specimen in an automated analysis system, the apparatus comprises: (a) a slide carrier; (b) a layer applied to a surface of the slide carrier, the layer forming a micro-porous surface; (c) a stain- reactive element, the stain-reactive element being deposited in at least some of the micro-pores in the layer on the surface of the slide carrier.
  • the present invention provides a method for verifying the operation of an automated analysis system, the method comprises the steps of: (a) providing a test slide for the automated analysis system, the test slide comprising: (i) a slide carrier; (ii) a layer applied to a surface of the slide carrier, the layer forming a micro-porous surface; (iii) a stain-reactive element, the stain- reactive element being deposited in at least some of the micro-pores in the layer on the surface of the slide carrier; (b) applying the test slide to the automated analysis system and operating the automated analysis system to perform selected processing procedures on the test slide to produce one or more test results for the test slide; (c) recording the test results for the test slide so that the stain-reactive element provides a predictable response for the operation of the automated analysis system.
  • Fig. 1 (a) shows a conventional smear of the type prepared in gynaecologic cytology
  • Fig. 1 (b) shows a conventional liquid-based smear of the type prepared gynaecologic cytology
  • Fig. 2 shows typical cell type variations present in the conventional liquid- based smear of Fig. 1 (b);
  • Figs. 3(a) to 3(d) shows an apparatus and processing steps for synthetic encapsulation of a protein according to one embodiment of the present invention
  • Fig. 4 shows a test slide with encapsulated proteins and staining according to the present invention
  • Figs. 5(a) to 5(b) shows an apparatus and processing steps for synthetic encapsulation of a protein according to another embodiment of the present invention.
  • Fig. 6 shows a natural encapsulation protein mechanism according to another embodiment of the invention
  • Fig. 7 shows in di grammatic form an automated image analysis system of the type suitable for use with the apparatus and method of the present invention.
  • Fig. 2 shows cell type variations in the liquid- based preparation for a typical Pap smear (i.e. prepared according to the Papanicolaou Staining protocol) specimen denoted generally by reference 10, i.e. the gynaecologic cytology specimen of Fig. 1 (b).
  • the cell type variations in the Pap smear include squamous intermediate type cells denoted generally by reference 11 , polymorphonuclear leukocyte type cells denoted generally by reference 12, squamous metaplastic type cells denoted generally by reference 13, and debris denoted generally by reference 14.
  • the specimen is stained according to the well-known Papanicolaou (i.e. Pap) staining protocol.
  • the cells in the specimen 10 that respond to the stain comprise naturally-derived, encapsulated protein and this is what the stains will generally bind to.
  • the Haematoxylin will bind to DNA or RNA in the cell nucleus
  • the Orange G stain will selectively bind to keratin in the cytoplasm, etc.
  • the present invention provides a previously deemed optimally stained specimen comprising an encapsulated protein.
  • the encapsulated protein is placed on a microscope slide, stained and its appearance, and other characteristics, are characterized using an automated system, for example an automated image analysis system as described below with reference to Fig. 7.
  • the encapsulated protein comprises a synthetic encapsulated protein or a naturally encapsulated protein that has a predictable character as will also be described in more detail below.
  • the test slide 100 comprises a slide 101 , for example a glass slide, with a micro-porous film or layer 102 applied or formed on a surface of the slide 101.
  • the micro- porous film 102 receives proteins indicated by reference 104, which are deposited as described below.
  • the micro-porous film or layer 104 may be formed in a number of ways.
  • the glass for the slide 102 can be made using the sol-gel process which does not involve melting.
  • the sol-gel process can be used to create an inorganic silicate glass slide 101 with a porous matrix which forms the micro- porous film 104.
  • organic compounds such as alcoholates of silicon, sodium or calcium are used. With water, these compounds split into water and alcohol in a process of hydrolysis which also creates a structure where the metallic atoms are bonded to oxygen atoms in an irregular non-crystalline network, thus forming a gel.
  • Low-temperature treatment turns this gel into an inorganic glass slide with a porous matrix of the form shown in Fig. 3(a).
  • the proteins to be encapsulated can then be inserted into the micro-porous layer 102.
  • the next step as shown in Fig. 3(b) involves applying or encapsulating proteins 104 to the micro-porous film 102 on the slide 101.
  • the proteins 104 for encapsulation can be 'painted' or 'printed' on the film 102 using ink-jet technology, for example.
  • the proteins 104 are emitted from an ink-jet nozzle 110 onto the micro-porous surface 102 and the proteins 104 settle into micro-pores in the film 102.
  • the proteins 104 are deposited in groups 106, indicated individually as 106a, 106b and 106c, and preferably arranged in a regular pattern as shown in Fig. 3(c).
  • the encapsulation process may be completed with subsequent processing of the sol-gel glass or by over- coating the micro-porous film 102 with another porous compound as shown in Fig. 3(d).
  • proteins may be used for the slide 100.
  • suitable proteins include synthetic DNA or RNA (stretches of the double helix manufactured by commonly available techniques), keratin, albumin, etc.
  • these different types of proteins 104 are encapsulated on a slide 118 as described above and arranged in specific regions 120 as shown in Fig 4.
  • the test slide 118 is then processed by the laboratory in the usual manner, for example, according to the Papanicolaou (Pap) staining protocol.
  • the slide 118 is applied as a 'test specimen' to an automated analysis system 200 as shown in Fig.
  • the test slide 118 preferably includes a label 122 with a machine readable identifier 124 such as a barcode.
  • the machine readable identifier 124 facilitates the automatic identification of the test slide 118 when it is applied to the automated image analysis system 200.
  • the automated analysis system 200 examines the different regions 120 of the encapsulated proteins and assesses each region 120 of protein against the results stored from previous 'optimally' stained specimens.
  • the slide 1 18 may also be used as a standard resolution test target.
  • Fig. 5(a) shows a variation of a test slide 130 according to the present invention.
  • the proteins 104 are deposited in the micro-porous film 132 and arranged in groups 134, shown individually as 134a, 134b, 134c, 134d, 134e, in varying densities.
  • the proteins 104 may be deposited in the varying amounts 134 as a part of a local stain scale.
  • test slide 140 comprises a slide 141 and a micro-porous layer or film 142. Proteins 144 are encapsulated in the micro-porous layer 142 according to the process as described above. As also described above, an overcoat layer 146 is applied, and according to this aspect of the invention, the overcoat layer 146 is applied in various thicknesses indicated individually as 146a, 146b, 146c, and 146d, in Fig. 5(b). After the encapsulated proteins 144 in the test slide 140 are exposed to the stain protocol, the test slide 140 may used in an automated analysis system (Fig. 7) to not only evaluate the suitability of the stain processing, but also to identify the stain components that are somehow compromised. The test slide 140 may also be used as a standard resolution test target and to supply dynamic range information.
  • naturally encapsulated proteins are utilized in a test slide instead of the synthetic encapsulation process as described above.
  • the naturally encapsulated proteins may comprise cells that are cloned from a single cell to produce a monotype culture of cells, or more simply, the naturally encapsulated proteins may comprise a monotype derived from an immortal cell line such as a cancer.
  • An immortal cell line is MCF-7which derived from a breast cancer as depicted in Fig. 6. All of the cells have identical appearance and structure when harvested correctly using standard, widely understood procedures. In practical terms, the immortal cell line would be cultured and harvested to produce a suspension of the cells in an appropriate preservative solution.
  • a second or third cell type may be cultured and added to the mix. This suspension would be used to make a monolayer specimen on a test slide utilizing known LBP procedures. After being appropriately labelled, the monolayer slide specimen provides the stain 'test' slide.
  • the test slide accompanies the other specimens through the staining procedure used in the laboratory.
  • the unique label identifies the slide as a 'test' specimen and the automated analysis system 200 treats it accordingly.
  • the automated analysis syst m 200 could perform image segmentation and feature extraction on the test slide and then compare these results to those of an optimally-stained slide held somewhere in its memory.
  • the extent and type of deviation from the optimal characteristics allow the automated analysis system 200 to reject slide from a batch that are improperly stained or to alert the laboratory to incipient problems with the stain technique before they become detrimental to the automated analysis.
  • the automated system 200 comprises an automated cell classifier for performing the analysis.
  • the automated system 200 includes a turntable 202 for manipulating slides, i.e. including the test slide 100 with the encapsulated protein, a slide dotter 204 for placing marks on the slide, hardware including a processor and memory storage device 206, a camera 208, and a light source 210.
  • a robotic arm (not shown) places the slide in a predetermined position on the scanning turntable 202, which is motorized for manipulating the position of the slide.
  • the barcode for example 124 on the test slide 118 (Fig.
  • the slide dotter 204 places a physical reference mark on the slide at a predetermined reference position.
  • the automated cell classifier maps out fields of view on the slide and the location of each field of view with respect to the reference position.
  • the light from the illuminated specimen is separated into different predetermined spectral bands by a prism assembly associated with the light source.
  • the camera 208 comprises three cameras and each camera captures images in one of the predetermined spectral bands.
  • a controller controls the light source and cameras and a processor converts the images into data suitable for processing.
  • the system for capturing images of the slide may comprise a system according to certain embodiments disclosed in commonly assigned International Patent Application Nos. WO 98/52016 and WO 98/35262.
  • the automated cell classifier performs an analytical scan of the slide and identifies cells which may be irregular.
  • preferred automated cell classifiers are described in commonly assigned International Patent Application Nos. WO 98/30317; WO 98/22909; WO 97/11350; WO 97/04419; WO 97/04418; WO 97/04348; and WO 97/50003, the disclosures of which are hereby incorporated by reference.
  • Preferred devices are also disclosed in commonly assigned United States Patent Nos. 5,532,874 and 5,708,830, the disclosures of which are hereby incorporated by reference.
  • Other preferred devices are disclosed in commonly assigned U.S. Patent Application of Ryan S. Raz and louri Lappa, entitled “Database Element Retrieval By Example", Serial No. 09/115,608, filed July 15, 1998, the disclosure of which is hereby incorporated by reference.
  • the automated cell classifier 200 digitizes the images captured by the camera 208 and the images are manipulated using known techniques.
  • the techniques used are techniques disclosed in certain embodiments of the publications incorporated by reference above, such as, for example, International Patent Application Nos. WO 98/22909 and WO 97/1 1350, the disclosures of which are hereby incorporated by reference.
  • the images captured by the camera 208 comprise data concerning cells and background material in each of the fields of view.
  • each cell comprises nuclear and cytoplasmic material.
  • the data is analyzed to determine which portions of the images represent background material, cytoplasmic material, or nuclear material. Segmentation is performed by the automated cell classifier 200 to distinguish the background, nucleus and cytoplasm within each image.
  • the automated cell classifier 200 performs feature extraction, in which each nucleus identified during segmentation is analyzed separately.
  • the automated cell classifier 200 uses neural networks and algorithms to reach a classification forthe nuclei identified during segmentation.
  • the classification may be performed utilizing a neural network or elliptical basis function, as known by those of ordinary skill in the art.
  • the classifications preferably comprise a score, such as, for example, a score on a scale of 0 to 1 , where 0 identifies nuclei of benign cells and 1 identifies nuclei of abnormal cells.
  • the classifications developed by the automated cell classifier comprise a score representing the likelihood that the nucleus is abnormal or benign.
  • test slides according to the present invention find particular application for (1 ) specimen preparation quality control/assurance and for (2) automated analysis system integrity assurance.
  • the preparation of a monolayer specimen, including its staining characteristics, is evaluated, verified and quantified using a test slide with a naturally encapsulated protein set, for example, the breast cancer cell line, MCF-7, as described above.
  • a naturally encapsulated protein set for example, the breast cancer cell line, MCF-7, as described above.
  • the immortal cell line derived from MCF-7 breast cancer cells can be commercially obtained from the American Type Culture Collection (ATCC). These cells are raised and harvested using standardized techniques in a typical biological laboratory. The harvesting of the cells, for example using the enzyme trypsin, produces many hundreds of thousands of identical cancer cells. The harvested cells are placed in suspension using an appropriate preservative solution and vial that is compatible with the LBP technique used by the laboratory. The suspension of a monotype of cancer cells is then used by the laboratory to create one or more test slides (as described above) according to the present invention in the form of monolayer specimens. The test slides are labelled and included in the batch staining procedure used for the actual medical specimens on a regular basis. The use of these test slides on a regular basis allows the laboratory to create a time-series so that the quality of the specimen preparation procedure may be tracked over time.
  • ATCC American Type Culture Collection
  • the first quality assurance procedure may comprise quantifying the density of the cells on the test slide.
  • the quantification step can be done quickly by any image analysis system and comprises using a gross calculation of the area covered by the cells. By dividing this area by the known area of a single cancer cell, the total number of cells on the test slide can be determined. This information provides an important indicator of the quality of the specimen deposition technique and can alert the laboratory to problems with that technique that might jeopardize the diagnostic value of the preparation.
  • the second quality assurance procedure applied to the test slide by the automated analysis system comprises estimating the success of the cell segmentation, i.e., the accurate separation of the cell nucleus from its cytoplasm.
  • the monotype (or multiple monotypes) nature of the specimen on the test slide facilitates this analysis. This is because the area of the cell occupied by the nucleus, and the perimeter of the nucleus, are known in advance to great precision.
  • the total area occupied by the nucleus, for any one cell type may be compared to the expected results. This may, for example, indicate whether or not the cells are over or understained. Further analysis of the variations in cell nucleus area, perimeter, shape, etc.
  • the type and extent of the stain variations may allow the automated analysis system to 'adjust' its analysis accordingly so as to accommodate these variations found in the 'true' medical specimens providing that the variations are not so extreme as to render the results completely inaccurate.
  • the full range of extracted features may be used to further analyze the specimen on the test slide and to decide whether the stain variations are within the allowable band of variations or if they cannot be accommodated by the automated image analysis system.
  • test slide 100 with the synthetic encapsulated protein set as described above with reference to Figs. 3 and 5 is utilized.
  • the test slide 100 can serve the dual purpose of both verifying the stain quality and verifying the image resolution and positioning accuracy for the automated analysis system.
  • the objective is to create the test slide 100 with a set of encapsulated proteins whose density and overcoating can provide a scale for stain uptake.
  • the proteins are physically arranged on the microscope slide to create a set of optical resolution targets to determine the quality of the optics of the automated image analysis system.
  • the encapsulated proteins may co-exist with an optical target created by standard technique (i.e. metal- evaporation, etc.)
  • test slide 100 with the encapsulated protein set is then handled in precisely the same manner as a standard medical or biological specimen, i.e. the test slide 100 and encapsulated protein set is stained and cover-slipped in the usual fashion and submitted to the automated analysis system for review.
  • the test slide 100 is submitted to the automated analysis system and the bar code encounters the test specimen, the machine readable bar code 124 (Fig. 4) on the slide 100 alerts the automated image analysis system to the purpose of the test slide 100.
  • the automated analysis system then executes a pre-determined range of analytical procedures to gauge the stain uptake in each of the different protein groups 120 (Fig. 4) used on the test slide 100.
  • the automated analysis system is configured to move to the region of interest and begins its analysis.
  • the groups 120 of encapsulated proteins may be deposited in a series of increasing concentrations following some type of scale (linear, logarithmic, etc.).
  • the automated analysis system may make a high-resolution determination of the stain uptake for that protein.
  • the automated analysis system can determine whether that stain batch is suitable for medical or biological analysis and also which, if any, of the stains is beginning to fail.
  • the automated analysis system may make a simultaneous evaluation of its optical integrity by comparing this target to previously-evaluated targets.
  • the test slide 100 could simply hold a standard resolution test target along with the encapsulated proteins.
  • test slide with encapsulated protein test specimen provides a number of advantages including the following.
  • the synthetically encapsulated proteins can be manufactured in a variety of ways, with high tolerances, to arrive at test specimens that supply predictable and quantifiable results when stained. The ability to be able to predict these results under a variety of conditions allows the automated image analysis system to perform both self-checks and preparation checks to ensure the integrity of its performance.
  • the naturally encapsulated proteins can supply a similarly predictable test specimen if some type of cellular monotype is used and harvested correctly, as described above.
  • Standard format the use of microscope slides (or equivalent) in order to create test specimens allows their introduction into the chain of specimen preparation and analysis without interrupting the analysis chain or unduly affecting the outcomes.
  • Increased dynamic range In the case of a synthetically encapsulated protein set, the use of a variety of protein densities and/or over-coating procedures permits the creation of a test specimen slide 100 whose sensitivity to stain variations is much greater than that of a typical cytological or histological specimen. This allows better resolution of subtle distinctions between staining results in the test slide specimen 100 and is used to both establish the suitability of the staining procedure and estimate its time to failure.
  • test slide 100 with encapsulated protein provides a vehicle or mechanism that fits into the natural workflow of an automated system, for example, an automated image analysis system as described above.

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Abstract

L'invention concerne un appareil de lame test permettant d'évaluer la qualité de la coloration d'un spécimen biologique dans un système d'analyse automatisé. La lame test comprend un porteur de lame, une couche microporeuse appliquée à la surface dudit porteur, un élément réagissant à la coloration déposé sur la surface microporeuse. Les éléments réagissant à la coloration peuvent comprendre au moins une protéine encapsulée et de l'ADN synthétique, de l'ARN synthétique, de la kératine ou de l'albumine ou une protéine encapsulée naturellement obtenue auprès d'une culture de souche cellulaire immortelle, telle que les cellules MCF-7.
PCT/CA2000/001563 1999-12-20 2000-12-20 Appareil et procede pour le controle et la garantie de la qualite d'analyse d'images WO2001046671A1 (fr)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006068858A1 (fr) * 2004-12-22 2006-06-29 Cytyc Corporation Caracterisation par coloration pour cytologie automatisee
WO2013090567A3 (fr) * 2011-12-13 2013-10-10 Lab Vision Corporation Dispositifs et procédés de validation immunohistochimique
DE102012216336A1 (de) * 2012-09-13 2014-03-13 Leica Biosystems Nussloch Gmbh Verfahren zum Färben einer histologischen Probe und Färbeautomat
WO2021219702A1 (fr) * 2020-04-28 2021-11-04 Leeds Teaching Hospitals Nhs Trust Lames de test et procédés de production dans l'évaluation de coloration

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4812412A (en) * 1987-02-26 1989-03-14 Health Research Inc. Standard specimen and method of making and using same
EP0352026A2 (fr) * 1988-07-19 1990-01-24 Ruby Pauline Bonderman Lamelle de contrôle ou d'étalonnage munie de plusieurs zones à niveaux ou types différents de composants à détecter et procédé et dispositif pour sa préparation
JPH08151232A (ja) * 1994-11-28 1996-06-11 Central Glass Co Ltd ゾルゲル膜およびその形成法
US5846749A (en) * 1994-10-12 1998-12-08 The Regents Of The University Of California Quantitative measurement of tissue protein identified by immunohistochemistry and standardized protein determination
WO2000061282A1 (fr) * 1999-04-08 2000-10-19 Affymetrix, Inc. Substrats en silice poreux pour la synthese et l'analyse de polymeres

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4812412A (en) * 1987-02-26 1989-03-14 Health Research Inc. Standard specimen and method of making and using same
EP0352026A2 (fr) * 1988-07-19 1990-01-24 Ruby Pauline Bonderman Lamelle de contrôle ou d'étalonnage munie de plusieurs zones à niveaux ou types différents de composants à détecter et procédé et dispositif pour sa préparation
US5846749A (en) * 1994-10-12 1998-12-08 The Regents Of The University Of California Quantitative measurement of tissue protein identified by immunohistochemistry and standardized protein determination
JPH08151232A (ja) * 1994-11-28 1996-06-11 Central Glass Co Ltd ゾルゲル膜およびその形成法
WO2000061282A1 (fr) * 1999-04-08 2000-10-19 Affymetrix, Inc. Substrats en silice poreux pour la synthese et l'analyse de polymeres

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
PATENT ABSTRACTS OF JAPAN vol. 1996, no. 10 31 October 1996 (1996-10-31) *

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006068858A1 (fr) * 2004-12-22 2006-06-29 Cytyc Corporation Caracterisation par coloration pour cytologie automatisee
WO2013090567A3 (fr) * 2011-12-13 2013-10-10 Lab Vision Corporation Dispositifs et procédés de validation immunohistochimique
DE102012216336A1 (de) * 2012-09-13 2014-03-13 Leica Biosystems Nussloch Gmbh Verfahren zum Färben einer histologischen Probe und Färbeautomat
US9464970B2 (en) 2012-09-13 2016-10-11 Leica Biosystems Nussloch Gmbh Method for staining a histological sample, and automated stainer
US9885641B2 (en) 2012-09-13 2018-02-06 Leica Biosystems Nussloch Gmbh Method for staining a histological sample, and automated stainer
DE102012216336B4 (de) * 2012-09-13 2018-12-13 Leica Biosystems Nussloch Gmbh Verfahren zum Färben einer histologischen Probe und Färbeautomat
WO2021219702A1 (fr) * 2020-04-28 2021-11-04 Leeds Teaching Hospitals Nhs Trust Lames de test et procédés de production dans l'évaluation de coloration
GB2609805A (en) * 2020-04-28 2023-02-15 Leeds Teaching Hospitals Nhs Trust Test slides and methods of production in stain assessment

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