The patent badge is an abbreviated version of the USPTO patent document. The patent badge does contain a link to the full patent document.

The patent badge is an abbreviated version of the USPTO patent document. The patent badge covers the following: Patent number, Date patent was issued, Date patent was filed, Title of the patent, Applicant, Inventor, Assignee, Attorney firm, Primary examiner, Assistant examiner, CPCs, and Abstract. The patent badge does contain a link to the full patent document (in Adobe Acrobat format, aka pdf). To download or print any patent click here.

Date of Patent:
Apr. 02, 2019

Filed:

Sep. 29, 2015
Applicant:

Howard Hughes Medical Institute, Ashburn, VA (US);

Inventors:

Robert E. Betzig, Ashburn, VA (US);

Dong Li, Ashburn, VA (US);

Assignee:
Attorney:
Primary Examiner:
Int. Cl.
CPC ...
G01N 21/64 (2006.01); G02B 21/16 (2006.01); G02B 21/06 (2006.01); G02B 21/36 (2006.01);
U.S. Cl.
CPC ...
G01N 21/6458 (2013.01); G01N 21/6428 (2013.01); G02B 21/06 (2013.01); G02B 21/16 (2013.01); G02B 21/367 (2013.01); G01N 2021/6439 (2013.01);
Abstract

A method includes: (a) providing spatially-patterned activation radiation to a sample that includes phototransformable labels, where an optical parameter of the spatially-patterned activation radiation varies periodically in space; (b) providing spatially-patterned excitation radiation to the sample, where an optical parameter of the spatially-patterned excitation radiation varies periodically in space, where (a) and (b) create a non-linear fluorescence emission pattern within the sample, the pattern including H modulation harmonics, with H>1. The method includes (c) detecting radiation emitted from the activated and excited labels, (d) storing detected radiation data, and (e) spatially shifting one or both of the spatially-patterned excitation radiation and the spatially-patterned activation radiation with respect to the sample to spatially shift the non-linear fluorescence emission pattern within the sample, and (f) repeating (a)-(e) at least N times, with N>2. Then, a sub-diffraction-limited final image of the sample is generated based on the stored data for the N positions of the non-linear fluorescence emission pattern within the sample.


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