Expansion Technology

Technology #16900-17875-18127-18129-18384

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Scalable 3D superresolution microscopy of mouse brain tissue. (A) Volume rendering of a portion of hippocampus showing neurons (expressing YFP, shown in green) and synapses [marked with anti-Bassoon (blue) and antibody to Homer1 (red)]. (B) Volume rendering of dendrites in CA1 slm. (C) Volume rendering of dendritic branch in CA1 slm. (D) Mossy fiber bouton in hilus of the dentate gyrus. (i) to (iii), selected z-slices. Scale bars, (A) 100 μm in each dimension; (B) 52.7 μm (x); 42.5 μm (y); and 35.2 μm (z); (C) 13.5 μm (x); 7.3 μm (y); and 2.8 μm (z); (D), (i) to (iii) 1 μm.
Categories
Inventors
Professor Edward Boyden
Program in Media Arts and Sciences, MIT
External Link (www.media.mit.edu)
Fei Chen
Department of Biological Engineering, MIT
Paul Tilliberg
Program in Media Arts and Sciences, MIT
Jae-Byum Chang
Program in Media Arts and Sciences, MIT
Asmamaw Wassie
Department of Biological Engineering, MIT
Shahar Alon
Program in Media Arts and Sciences, MIT
Chih-Chieh Yu
Department of Biological Engineering, MIT
Yongxin Zhao
Program in Media Arts and Sciences
Andrew Beck
Beth Israel Deaconess Medical Center
Octavian Becur
Beth Israel Deaconess Medical Center
Managed By
Ben Rockney
MIT Technology Licensing Officer
Patent Protection

Expansion Microscopy

US Patent Pending 2016-0116384

Expansion Microscopy

PCT Patent Application WO 2015-127183

Iterative Expansion Microscopy

US Patent Pending 2016-0305856

Nanoscale Imaging of Proteins and Nucleic Acids via Expansion Microscopy

US Patent Pending 2017-0067096

Nanoscale Imaging of Proteins and Nucleic Acids via Expansion Microscopy

PCT Patent Application WO 2017-027367

Protein Retention Expansion Microscopy

US Patent Pending US 2017-0089811

Protein Retention Expansion Microscopy

PCT Patent Application WO-2017-027368

Three-Dimensional Nanofabrication by Patterning of Hydrogels

US Patent Pending US 2017-0081489

Three-Dimensional Nanofabrication by Patterning of Hydrogels

PCT Patent Application WO 2017-04981

Methods for Expanding Clinical Tissue Specimens

PCT Patent Application Filed
Publications
Nanoscale Imaging of RNA with Expansion Microscopy
Nature Methods , August 1, 2016, p. 679-684
Expansion Microscopy
Science, January 30, 2015, p. 543-548
Protein-Retention Expansion Microscopy of Cells and Tissues Labeled Using Standard Fluorescent Proteins and Antibodies
Nature Biotechnology , September 1, 2016, p. 987-992

Applications

This invention is an optical imaging method for biological specimens based on physically expanding the specimen. 


Problems Addressed

Microscopy has facilitated the discovery of many biological insights by optically magnifying images of structures in fixed cells and tissues. However, the resolution to a light microscope is limited. The existing super-resolution techniques are limited in three aspects: imaging depth, throughput, and complexity/cost. High resolution in conventional imaging techniques is only achieved in thin layers. Additionally, in super-resolution imaging techniques based on single-molecule imaging, the throughput is not high enough to image a large specimen, such as an entire organ. Lastly, super-resolution imaging techniques generally require relatively expansive and complex optical systems. The Inventors addressed these issues by developing Expansion Microscopy, which physically expands the specimen, resulting in physical magnification. 

Technology

The Inventors have developed a method for optically imaging biological specimens with a resolution better than predicted by the classical diffraction limit, based on physically expanding the specimen. Expansion microscopy involves embedding a tissue into a swellable material that is formed by infusing the tissue with reactive monomers which then undergo polymerization. Expansion microscopy can be performed repeatedly on the same sample, essentially enabling arbitrary magnification. Additionally, proteins can be visualized within the specimen by anchoring fluorophores directly to the expandable gel matrix. Nucleic acid can also be anchored to the gel for both in situ genomic and transcriptomic assessment, as well as to enable nucleic acid barcodes to be used to identify essentially arbitrary numbers of molecules. To adapt the expansion microscopy technology in the clinical setting, the Inventors have designed variants of expansion microscopy that incorporate de-paraffinization, antigen retrieval and aggressive protease digestion into a comprehensive workflow to expand various common clinical specimens. De-paraffinization and antigen retrieval address the recovery of archived clinical samples for immunohistochemistry, while aggressive protease digestion is critical for the success of sample expansion, as most of the human tissues contain abundant hard-to-digest structural proteins. 

Advantages

  • Swollen material with embedded biological specimen can be imaged on any optical microscope
  • Allows for effective imaging of features below the classical diffraction limit
  • Provides a feasible and a robust way to homogenously expand clinical tissue samples