CYTOLOGICAL IMAGING SYSTEMS AND METHODS

• US 20080013168A1
• Filed: 09/25/2007
• Published: 01/17/2008
• Est. Priority Date: 10/29/1999
• Status: Active Grant

• Current Assignee: Cytyc Corporation (Hologic Incorporated)
• Original Assignee: Cytyc Corporation (Hologic Incorporated)
• Inventors: Zahniser, David, Knox, William, Maenle, Garrick
• Granted Patent: US 7,446,935 B2
• Time in Patent Office: Days
• US Class Current: 359/383
• CPC Class Codes: G01N 1/30 Staining; Impregnating ; Fixation; Dehydration; Multistep processes for preparing samples of tissue, cell or nucleic acid material and the like for analysis
• CPC Class Codes: G01N 15/1012 Calibrating particle analysers; References therefor
• CPC Class Codes: G01N 15/1433 using image recognition
• CPC Class Codes: G01N 15/1468 with spatial resolution of the texture or inner structure of the particle
• CPC Class Codes: G01N 15/147 the analysis being performed on a sample stream
• CPC Class Codes: G01N 2015/1006 for cytology
• CPC Class Codes: G01N 2015/1472 with colour
• CPC Class Codes: G01N 2015/1488 Methods for deciding
• CPC Class Codes: G01N 21/3151 using two sources of radiation of different wavelengths G01N21/33 - G01N21/39 take precedence
• CPC Class Codes: G02B 21/0016 Technical microscopes, e.g. for inspection or measuring in industrial production processes
• CPC Class Codes: G02B 21/32 Micromanipulators structurally combined with microscopes
• CPC Class Codes: G02B 21/34 Microscope slides, e.g. mounting specimens on microscope slides
• CPC Class Codes: G06T 2207/30024 Cell structures in vitro; Tissue sections in vitro
• CPC Class Codes: G06T 7/0012 Biomedical image inspection
• CPC Class Codes: G06T 7/73 using feature-based methods
• CPC Class Codes: G06V 20/693 Acquisition

Abstract

The present invention relates to the analysis of specimens. Specifically, the invention relates to methods and apparatus for reviewing specimen slides, including apparatus for holding the slides. The invention also relates to an automatic focusing method for an imaging system and methods for accommodating vibration in the imaging system. In particular, the methods and apparatus may be applied to the automated analysis of cytological specimen slides.

Claims

1-101. -101. (canceled)

102. An automatic focusing method for an optical system, comprising:

performing an initial course focus action along a focal axis at a scan position corresponding to a point on a surface of a slide, wherein the slide comprises at least three fiducial points;

determining a global focal plane by determining positions of the at least three fiducial points, and determining a scan axis slope, index axis slope, and focus intersect of the global focal plane based on the positions of the at least three fiducial points; and

respectively performing a plurality of subsequent fine focus actions along a plurality of focal axes at a plurality of scan positions corresponding to different points on the slide surface, wherein the performance of at least one of the fine focus actions comprises estimating an initial coordinate along the respective focal axis as a function of the global focal plane, and obtaining images of the slide at a plurality of coordinates relative to the initial coordinate along the respective focal axis.

103. The method of claim 102, wherein the initial coordinate corresponds to a point on the global focal plane.

104. The method of claim 102, wherein the initial coordinate is an estimated in-focus coordinate along the respective focal axis.

105. The method of claim 102, wherein each of the coordinates is a predetermined distance from the initial coordinate.

106. The method of claim 102, wherein the performance of the course focus action comprises determining an in-focus coordinate along the focal axis.

107. The method of claim 106, wherein the performance of each of the fine focus actions is based on the in-focus coordinate determined in the course focus action.

108. The method of claim 107, wherein the performance of each of the fine focus actions comprises estimating an in-focus coordinate along the respective focal axis as a function of the in-focus coordinate determined in the course focus action and the global focal plane, wherein the initial coordinate is an estimated in-focus coordinate along the respective focal axis.

109. The method of claim 102, wherein the performance of the course focus action comprises repeatedly obtaining images of the slide at different coordinates along the focal axis until an in-focus coordinate is determined.

110. The method of claim 104, wherein the performance of each of the fine focus actions comprises obtaining images of the slide at predetermined coordinates relative to the estimated in-focus coordinate along the respective focal axis.

111. The method of claim 102, wherein the performance of each fine focus action comprises selecting one of the plurality of coordinates as an in-focus coordinate based on an analysis of the obtained images.

112. The method of claim 102, wherein the performance of at least one of the course focus action and each fine focus action comprises:

obtaining images of the slide at a plurality of coordinates along the focal axis;

determining a plurality of focus scores for the respective coordinates; and

selecting one of the coordinates as an in-focus coordinate based on the focus scores.

113. The method of claim 112, wherein the coordinate having a maximum focus score is the coordinate selected as the in-focus coordinate.

114. The method of claim 102, wherein the slide carries a biological specimen.

115. The method of claim 102, wherein the course focus action and fine focus actions are performing during a single image scan.

116. The method of claim 102, wherein the performance of one or both of the course focus action and fine focus actions comprises moving an element of the optical system relative to the slide surface to coordinates along the respective focal axes.

117. The method of claim 102, wherein the performance of the fine focus actions comprises moving an element of the optical system relative to the slide along a scan axis to the respective scan positions.

118. The method of claim 102, wherein the images of the slide are obtained at a plurality of coordinates within a predetermined range along the respective focal axis.