Miniature Serial Microtome for Block-Face Imaging


A microtome device is used in a variety of microcopy techniques to remove very thin (e.g., in the tens of nanometers range) portions from the top of a sample between successive images. This technology discloses a design for a microtome device that offers several unique features and advantages over commercially available microtomes. A prototype of the microtome has been built and demonstrated to work with a serial block-face scanning electron microscopy in order to serially collect ultrathin sections from plastic embedded biological tissues, specifically from brain tissues. This microtome design allows for a sample to be cut at a location removed from the electron beam axis, thus reducing interference from debris and allowing imaging at a greater range of working distances. This microtome device is lightweight and easy to install utilizing the built-in stage of existing microscopes such that a sample's position and orientation can be controlled along three-axes of rectilinear translation and two axes of rotation. This microtome design utilizes a diamond blade coupled to both the base plate and an actuator to control the movement of the blade in a direction perpendicular to the exposed surface of the pedestal, while producing an output signal that indicates the blade location with respect to the base plate. Advantageously, this allows for a stage coupled pedestal to be moved accurately from an imaging location on the beam axis to a cutting location off the beam axis.

Potential Commercial Applications: Competitive Advantages:

Can be used in a variety of microscopy techniques:
  • scanning electron microscopy
  • light-based (optical, fluorescence) microscopy
  • cathodoluminescence microscopy
Can be used to study any of various types of sample materials:
  • tissue microscopy
  • brain research
  • tissue sectioning
  • imaging
 
  • is compatible with multiple microscopy systems
  • incorporates a feedback sensor to monitor and optimize cutting thickness/forces
  • can cut reproducible sections as thin as 25 nanometers
  • performs cutting off-axis to prevent contamination
  • mounts rapidly onto an existing SEM stage and does not require a custom vacuum chamber door
  • uses the full range of an existing SEM stage for positioning samples
  • incorporates a stage translation that is rectilinear
  • utilizes a pivot flexure bearing for frictionless rotation during cutting
  • cleans knife edge after each cut


Development Stage:
  • In vitro data available
  • Prototype


Inventors:

Kevin Briggman (NINDS)  ➽ more inventions...


Intellectual Property:
U.S. Pat: 9,933,339 issued 2018-04-03
US Application No. 61/991,929
PCT Application No. PCT/US2015/030359
Various international patents pending

Collaboration Opportunity:

The National Institute of Neurological Disorders and Stroke is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize the microtome device. For collaboration opportunities, please contact Smita Sharma at smita.sharma@nih.gov or 301-435-7761.


Licensing Contact:
Smita Sharma, Ph.D., J.D.
Email: smita.sharma@nih.gov
Phone: 301-435-7761

OTT Reference No: E-121-2014-0
Updated: May 14, 2018