WO2001004828A1 - Detection automatique d'objets dans un echantillon biologique - Google Patents

Detection automatique d'objets dans un echantillon biologique Download PDF

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Publication number
WO2001004828A1
WO2001004828A1 PCT/US2000/019046 US0019046W WO0104828A1 WO 2001004828 A1 WO2001004828 A1 WO 2001004828A1 US 0019046 W US0019046 W US 0019046W WO 0104828 A1 WO0104828 A1 WO 0104828A1
Authority
WO
WIPO (PCT)
Prior art keywords
interest
slide
image
candidate object
stage
Prior art date
Application number
PCT/US2000/019046
Other languages
English (en)
Inventor
Gina Mclaren
Bob Ellis
Original Assignee
Chromavision Medical Systems, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Chromavision Medical Systems, Inc. filed Critical Chromavision Medical Systems, Inc.
Priority to EP00947299A priority Critical patent/EP1203343A4/fr
Priority to JP2001510159A priority patent/JP2003504627A/ja
Priority to AU60934/00A priority patent/AU6093400A/en
Publication of WO2001004828A1 publication Critical patent/WO2001004828A1/fr

Links

Classifications

    • 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
    • G01N1/31—Apparatus therefor
    • G01N1/312—Apparatus therefor for samples mounted on planar substrates
    • G—PHYSICS
    • G06—COMPUTING; CALCULATING OR COUNTING
    • G06V—IMAGE OR VIDEO RECOGNITION OR UNDERSTANDING
    • G06V20/00—Scenes; Scene-specific elements
    • G06V20/60—Type of objects
    • G06V20/69—Microscopic objects, e.g. biological cells or cellular parts

Definitions

  • the invention relates generally to light
  • microscopy and, more particularly, to automated light
  • biological specimen such as bone marrow, lymph nodes,
  • peripheral blood cerebrospinal fluid, urine,
  • method of cell specimen preparation is to react a
  • nucleic acid which is reactive with a component of
  • the cells of interest such as tumor cells.
  • reaction may be detected using an enzymatic reaction
  • alkaline phosphatase such as alkaline phosphatase or glucose oxidase or
  • HER2 (neu) is a growth factor receptor and
  • hybridization methods are typically used for HER2/neu
  • rare events e.g., finding one tumor cell in a
  • the present invention provides a method
  • a slide carrier which preferably holds
  • the slide carriers are loaded into an
  • the system automatically locates a scan area for each slide during slide processing.
  • magnification image is acquired and processed to
  • a high magnification image is
  • control slides including positive
  • candidate objects of interest for a slide may be
  • cytotechnologist may view the mosaic or may also
  • the mosaic may be stored on magnetic media for future
  • invention preferably includes the steps of
  • thresholded image to determine the presence of one or
  • the scan area is automatically determined by scanning
  • the derived focal plane enables subsequent
  • the focal plane is determined by
  • a focal plane across the array Preferably, a focal plane
  • acquired image is calculated to form a set of
  • the region of interest is a region of interest
  • n preferably n columns wide, where n is a power of 2.
  • the pixels of this region are then processed using a
  • a slide is mounted onto a
  • the slide carrier is positioned in an input
  • the invention is a HER2/neu expression in tissue.
  • tissue especially breast tissue.
  • FIG. 1 is a perspective view of an apparatus for
  • Fig. 2 is a block diagram of the apparatus shown
  • Fig. 3 is a block diagram of the microscope
  • Fig. 4 is a plan view of the apparatus of Fig. 1
  • Fig. 5 is a side view of a microscope subsystem
  • Fig. 6a is a top view of a slide carrier for use
  • Fig. 6b is a bottom view of the slide carrier of
  • Fig. 7a is a top view of an automated slide
  • Fig. 7b is a partial cross-sectional view of the
  • Fig. 8 is an end view of the input module of the
  • Fig. 9a-9d illustrate the output operation of
  • Fig. 10 is a flow diagram of the procedure for
  • Fig. 11 shows the scan path on a prepared slide
  • Fig. 12 illustrates an image of a field acquired
  • Fig. 13A is a flow diagram of a preferred embodiment
  • Fig. 13B is a flow diagram of a preferred embodiment
  • Fig. 14 is a flow diagram of a procedure for
  • Fig. 15 shows an array of slide positions for
  • Fig. 16 is a flow diagram of a procedure for
  • Fig. 17A is a flow diagram of an overview of the
  • Fig. 17B is a flow diagram of a procedure for
  • Fig. 18 is a flow diagram of a procedure for
  • Fig. 19 is a flow diagram of a procedure for
  • Fig. 20 is a flow diagram of a procedure for
  • Fig. 21 is a flow diagram of a procedure for
  • Fig. 22 illustrates a mosaic of cell images
  • Fig. 23 is a flow diagram of a procedure for
  • Fig. 24 illustrates the apparatus functions
  • the invention provides an automated tissue image
  • proliferative disorder for example those associated with
  • MIB-I Microvessel density analysis, the oncogene
  • nucleoli HIV p24
  • HPV human papiloma virus
  • mitotic index generally any combination
  • ACISTM Cellular Imaging System
  • a worklist is a group of
  • a specimen group consists of
  • H/E staining protocol is compatible with
  • the specimen may
  • third antibody i.e., patient negative
  • This calibration consists of radiometric
  • the output of the worklist is a stained
  • a cellular specimen (a "sample") is split to
  • sample provides two or more subsamples.
  • sample provides two or more subsamples.
  • cellular material derived from a subject includes cellular material derived from a subject.
  • Such samples include but are not limited to hair,
  • tissue refers to a mass of connected cells (e.g.,
  • biological fluid refers to liquid material derived from a
  • sample also includes media containing isolated
  • reaction may be determined by one skilled in the art
  • the HER2/neu method uses an anti-HER2/neu
  • kit like that provided by DAKO (Carpinteria, CA) .
  • slide includes a cover-slip medium to protect the
  • coverslip covers the entire prepared specimen.
  • control slides are run with every worklist. The set
  • H/E hematoxylin/eosin
  • the staining procedure is as follows: (1) Bring
  • the invention also provides automated methods
  • the estrogen and progesterone receptors The estrogen and progesterone receptors,
  • immunohistochemistry system such as that provided by
  • a micrometastases is
  • metastatic recurring disease is similar to
  • micrometastasis but is detected after cancer therapy
  • MIB-1 is an antibody that can be used in
  • the clinical stage at first presentation is related
  • metastasis death from neoplasia, low disease-free
  • Angiogenesis is a complex regional vascular endothelial fibroblast fibroblast fibroblast fibroblast fibroblast fibroblast fibroblast fibroblast fibroblast fibroblast fibroblast fibroblast fibroblast fibroblast fibroblast fibroblast fibroblast fibroblast fibroblast fibroblast fibroblast fibroblast fibroblast fibroblast fibroblast fibroblast fibroblast fibroblast fibroblast fibroblast fibroblast fibroblast fibroblasts, hematoma, hematoma, hematoma, hematoma, hematoma hematoma hematoma hematoma hematoma hematoma hematoma hematoma hematoma hematoma hematoma hematoma hematoma hematoma hematoma hematoma hematoma hematoma hematoma hematoma hematoma hematoma hematoma hematoma hematoma hematoma hematoma hematoma hematoma hem
  • Intratumor microvessel density can be assessed by anti-CD34
  • malignancies including neoplasms of breast, colon,
  • p53 is performed using an anti-p53 antibody, for
  • a nucleoli is an
  • Cervical dysplasia Cervical dysplasia
  • dysplastic cells are of the same kind but of a lesser amount
  • HIV HIV p24 antigen levels
  • the HIV p24 protein test is used for the
  • the test can be used to detect the virus, measure the amount of virus, and
  • HPV Human Papiloma Virus
  • HPV transmitted virus which causes warts .
  • the patient data entry interface is
  • HER2/neu is composed of tissue samples that are
  • One slide is prepared with the HER2/neu
  • worklist is the: (1) worklist name or identifier of protocol (e.g., HER2/neu) ; barcode of the positive
  • Case is the: (4) patient ID; (5) accession number;
  • the input hopper is composed of all the
  • the system reads industry standard barcodes .
  • the barcode relates the type of protocol the
  • the HER2-positive application (1) finds the
  • the HER2-negative application (1) finds the
  • the HER2 application (1) finds the specimen, (2)
  • the Slide Display Interface displays the list of
  • the set of patient slides is a
  • H/E image is
  • pathologist determines whether or not the cancer is
  • This image is displayed. This image can be reduced to
  • the pathologist can have the features available
  • the pathologist has the following capabilities: (1)
  • pathologist has the following capabilities: (1) to
  • a User Interface lists all the patient cases that have already been reviewed and analyzed by
  • the pathologist can choose one or
  • the interface that displays the patient reports
  • Network connectivity is site specific.
  • Site specificity is desired for sending reports via
  • the instrument can have at least two user modes .
  • One user mode is a locked protocol consistent with
  • a second user mode is modifiable by
  • the apparatus 10 comprises a
  • microscope subsystem 32 housed in a housing 12.
  • housing 12 includes a slide carrier input hopper 16
  • the housing 12 secures the microscope subsystem from
  • the computer subsystem further includes a computer
  • peripherals including storage device 21, pointing
  • external power supply 24 is also shown for powering
  • the apparatus 10 further includes a CCD camera 42 for acquiring images through the microscope
  • control of system processor 23 controls a number of
  • controller 31 provides displacement of the microscope
  • microscope subsystem 32 further includes a motorized
  • objective turret 44 for selection of objectives.
  • the purpose of the apparatus 10 is for the
  • tumor cells e.g., tumor cells.
  • the preferred embodiment may be utilized for rare event detection in which
  • biological specimen may be prepared with a reagent to
  • apparatus of the present invention is used to detect
  • a slide carrier 60 is illustrated in
  • Each slide carrier holds up to 4 slides. Up to 25 slide

Abstract

La présente invention concerne un procédé, un système (Fig. 2), et un appareil destinés à la microscopie photonique automatique (Fig. 2, 31) permettant de détecter des protéines associées à des troubles liés à la prolifération cellulaire.
PCT/US2000/019046 1999-07-13 2000-07-12 Detection automatique d'objets dans un echantillon biologique WO2001004828A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP00947299A EP1203343A4 (fr) 1999-07-13 2000-07-12 Detection automatique d'objets dans un echantillon biologique
JP2001510159A JP2003504627A (ja) 1999-07-13 2000-07-12 生物試料中の物体の自動検出
AU60934/00A AU6093400A (en) 1999-07-13 2000-07-12 Automated detection of objects in a biological sample

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US14382399P 1999-07-13 1999-07-13
US60/143,823 1999-07-13

Publications (1)

Publication Number Publication Date
WO2001004828A1 true WO2001004828A1 (fr) 2001-01-18

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2000/019046 WO2001004828A1 (fr) 1999-07-13 2000-07-12 Detection automatique d'objets dans un echantillon biologique

Country Status (4)

Country Link
EP (1) EP1203343A4 (fr)
JP (1) JP2003504627A (fr)
AU (1) AU6093400A (fr)
WO (1) WO2001004828A1 (fr)

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