A New Method for Blotless TEM Imaging (Case 2066)

Principal Investigator:


Anubhav Tripathi, PhD, Professor

School of Engineering

Brown University

Providence, RI


Brief Description:


Transmission electron microscopy (TEM) is a useful imaging technique whereby a beam of electrons creates an image as it transmits through an ultra-thin specimen. The benefit of this imaging technique is that TEM system is capable of imaging at a significantly higher resolution than traditional light microscopes due to the small wavelength of the electron beams. This enables researchers to examine fine details of the sample, such as a single column of atoms, which is tens of thousands times smaller than the smallest resolvable object in a light microscope. Because of its obvious advantages, TEM forms a major analysis method in a range of scientific fields, in both physical and biological sciences. However, current use of TEM system has been limited due to a few significant problems associated with the specimen preparation process. TEM specimens must be prepared and placed into gridded specimen holders to allow for the imaging process to start. The principal difficulty is that this preparation process can be a complex and arduous procedure. TEM specimens are required to be at most hundreds of nanometers thick because the electron beam interacts readily with the sample. Although materials that have dimensions small enough to be electron transparent can be quickly prepared by the deposition of a dilute sample containing the specimen onto support grids or films, the deposition of these solutions will generally result in the creation of a droplet that is too large and thick for sampling requiring that the sample to be blotted. Currently, people have been using filter paper to overcome this problem. However, this procedure usually introduces high shear to the specimen that can deform the structure of the molecule being imaged and is done at the expense of a great deal of time, both of which limit the ability to examine certain specimens and the formation of certain natural structures over time.


In order to overcome these problems associated with current specimen preparation process, the novel invention introduces an advanced system that automatically places and controls the size of a sample droplet formed in a TEM sample while eliminating the need for a blotting step in a manner that accelerates the preparation process thereby allowing previously unobserved structures to be viewed. As compared to a conventional machine, where the blotting procedure can deform the structure of the molecule of interest, the present invention utilizes a very slow shear rate for removal of the excess sample fluid. By eliminating the blotting step and controlling flow rates and residence times in the micro channels, the system of the present invention can facilitate the rapid and direct visualization of aggregates that are formed within the ten to hundred millisecond time scales. All of the operation described here will be controlled by a computer, which will allow researchers to gain very accurate knowledge of microstructure age at the time of freezing. This invention thus represents a unique window for the examination of the temporal evolution of aggregate morphologies.


By introducing the new system that can automatically prepare TEM samples for examination by depositing extremely small samples onto a grid without the need for a blotting step, the novel invention represents a significant advance in artifact-free imaging capability for nanoscale systems.




Continuation-in-Part patent application 13/439,296 is pending


Patent Information:
For Information, Contact:
Margaret Shabashevich,
Manager of Operations
Office of Industry Engagement & Commercial Venturing
Brown University
401-863-7499 iecv@brown.edu
Anubhav Tripathi
Jinkee Lee
Arijit Bose
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