US 12,405,193 B2
Iterative direct expansion microscopy
Deblina Sarkar, Cambridge, MA (US); Edward Stuart Boyden, Chestnut Hill, MA (US); Asmamaw T. Wassie, Boston, MA (US); and Jinyoung Kang, Cambridge, MA (US)
Assigned to Massachusetts Institute of Technology, Cambridge, MA (US)
Filed by Massachusetts Institute of Technology, Cambridge, MA (US)
Filed on Feb. 19, 2020, as Appl. No. 16/794,849.
Claims priority of provisional application 62/809,062, filed on Feb. 22, 2019.
Prior Publication US 2020/0271556 A1, Aug. 27, 2020
This patent is subject to a terminal disclaimer.
Int. Cl. G01N 1/36 (2006.01); G01N 1/28 (2006.01)
CPC G01N 1/36 (2013.01) [G01N 1/28 (2013.01); G01N 1/286 (2013.01); G01N 2001/2873 (2013.01)] 34 Claims
OG exemplary drawing
 
1. A method for iteratively enlarging a sample of interest comprising biomolecules for microscopy, the method comprising the steps of:
a) contacting the sample with a biomolecule anchoring agent (BAA), wherein the BAA comprises a biomolecule binding moiety and an anchor;
b) embedding the sample in a first swellable material, wherein the biomolecules in the sample anchor to the first swellable material;
c) subjecting the sample to a disruption of the endogenous physical structure of the sample;
d) swelling the first swellable material resulting in an enlargement of the sample;
e) re-embedding the enlarged sample in a non-swellable material to form an enlarged sample hybrid;
f) embedding the enlarged sample hybrid in a second swellable material, wherein the second swellable material is the same as the first swellable material; and
g) swelling the second swellable material to further enlarge the sample,
wherein the biomolecules in the sample remain anchored to the first swellable material.