Robot-Guided Atomic Force Microscopy for Mechano-Visual Phenotyping of Cancer Specimens.
Atomic force microscopy (AFM) and other forms of scanning probe microscopy have been successfully used to assess biomechanical and bioelectrical characteristics of individual cells. When extending such approaches to heterogeneous tissue, there exists the added challenge of traversing the tissue while directing the probe to the exact location of the targeted biological components under study. Such maneuvers are extremely challenging owing to the relatively small field of view, limited availability of reliable visual cues, and lack of context. In this study we designed a system that leverages the visual topology of the serial tissue sections of interest to help guide robotic control of the AFM stage to provide the requisite navigational support. The process begins by mapping the whole-slide image of a stained specimen with a well-matched, consecutive section of unstained section of tissue in a piecewise fashion. The morphological characteristics and localization of any biomarkers in the stained section can be used to position the AFM probe in the unstained tissue at regions of interest where the AFM measurements are acquired. This general approach can be utilized in various forms of microscopy for navigation assistance in tissue specimens.
1Center for Biomedical Imaging & Informatics,Rutgers Cancer Institute of New Jersey,Rutgers,The State University of New Jersey,195 Little Albany Street,New Brunswick,NJ 08901,USA.
Wenjin
W
Chen
3Department of Mechanical Engineering,Maryland Robotics Center,Institute for Systems Research,University of Maryland,Glenn L. Martin Hall,College Park,MD 20742,USA.
Zachary
Z
Brandes
4Department of Mechanical Engineering,Vanderbilt University,Room 409,2400 Highland Avenue,Nashville,TN 37205,USA.
Rajarshi
R
Roy
1Center for Biomedical Imaging & Informatics,Rutgers Cancer Institute of New Jersey,Rutgers,The State University of New Jersey,195 Little Albany Street,New Brunswick,NJ 08901,USA.
Marina
M
Chekmareva
3Department of Mechanical Engineering,Maryland Robotics Center,Institute for Systems Research,University of Maryland,Glenn L. Martin Hall,College Park,MD 20742,USA.
Hardik J
HJ
Pandya
3Department of Mechanical Engineering,Maryland Robotics Center,Institute for Systems Research,University of Maryland,Glenn L. Martin Hall,College Park,MD 20742,USA.
Jaydev P
JP
Desai
1Center for Biomedical Imaging & Informatics,Rutgers Cancer Institute of New Jersey,Rutgers,The State University of New Jersey,195 Little Albany Street,New Brunswick,NJ 08901,USA.
David J
DJ
Foran
D001943:Breast Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D018625:Microscopy, Atomic Force / Q000379:methods*; D008867:Microtomy; D012371:Robotics / Q000379:methods*; D013194:Staining and Labeling
atomic force microscopy; robotic microscopy; serial sections registration; virtual microscopy; whole-slide imaging