Portable diffraction-based imaging and diagnostic systems and methods

Patent metadata

Field	Value
Publication number	US-11525778-B2
Application number	US-202016940077-A
Country	US
Kind code	B2
Filing date	Jul 27, 2020
Priority date	Aug 16, 2013
Publication date	Dec 13, 2022
Grant date	Dec 13, 2022

Abstract

The disclosure features systems and methods for measuring and diagnosing target constituents bound to labeling particles in a sample. The systems include a radiation source, a sample holder, a detector configured to obtain one or more diffraction patterns of the sample each including information corresponding to optical properties of sample constituents, and an electronic processor configured to, for each of the one or more diffraction patterns: (a) analyze the diffraction pattern to obtain amplitude information and phase information corresponding to the sample constituents; (b) identify one or more particle-bound target sample constituents based on at least one of the amplitude information and the phase information; and (c) determine an amount of at least one of the particle-bound target sample constituents in the sample based on at least one of the amplitude information and the phase information.

First claim

What is claimed is:

1. A diagnostic system, comprising:
a reagent composition comprising:
a plurality of beads, wherein each bead comprises at least one target binding moiety conjugated to the bead and comprising a moiety that binds to a viral nucleic acid, and a label binding moiety; and
a plurality of metallic nanoparticles, wherein each nanoparticle of at least some of the plurality of nanoparticles comprises a moiety conjugated to the nanoparticle that binds to the label binding moiety;

a detector configured to obtain one or more diffraction patterns of a sample, wherein each of the diffraction patterns comprises information corresponding to optical properties of sample constituents; and
an electronic processor configured to, for each of the one or more diffraction patterns:
(a) analyze the diffraction pattern to obtain amplitude information and phase information corresponding to the sample constituents;
(b) identify one or more particle-bound target sample constituents based on at least one of the amplitude information and the phase information; and
(c) determine an amount of at least one of the particle-bound target sample constituents in the sample based on at least one of the amplitude information and the phase information.

2. A method for detecting a viral nucleic acid, the method comprising:
exposing the viral nucleic acid to a bead conjugated to a target binding moiety and to a label binding moiety, wherein the target binding moiety binds to the viral nucleic acid;
labeling the bead with a metallic nanoparticle;
after labeling the bead with the metallic nanoparticle, forming a coating over at least a portion of the bead and at least a portion of the metallic nanoparticle;
obtaining a diffraction image of the at least partially coated bead; and
identifying the viral nucleic acid based on at least one of amplitude information and phase information from the diffraction image.

3. The method of claim 2 , wherein the bead is formed of silica.

4. The method of claim 2 , wherein the metallic nanoparticle is a gold nanoparticle.

5. The method of claim 2 , wherein the metallic nanoparticle comprises a binding moiety that binds to the label binding moiety of the bead.

6. The method of claim 5 , wherein the binding moiety of the metallic nanoparticle comprises biotin, and wherein the label binding moiety of the bead comprises streptavidin.

7. The method of claim 2 , wherein the coating comprises a metallic coating.

8. The method of claim 7 , wherein the metallic coating comprises at least one member of the group consisting of gold and silver.

9. The method of claim 2 , wherein the coating comprises at least one member of the group consisting of Pt, Al, Cu, Ni, Fe, Cd, Se, Ge, Pd, Sn, Ti, and Si.

10. The method of claim 2 , wherein identifying the viral nucleic acid comprises determining spatial amplitude information and spatial phase information for the at least partially coated bead from the diffraction image, and determining whether the at least partially coated bead is bound to the viral nucleic acid based on at least one of the spatial amplitude information and the spatial phase information.

11. The method of claim 2 , further comprising illuminating the at least partially coated bead with partially coherent radiation prior to obtaining the diffraction image.

12. The method of claim 11 , further comprising obtaining the image by detecting illumination radiation that is transmitted through the at least partially coated bead.

13. The method of claim 2 , further comprising:
labeling the bead with a plurality of metallic nanoparticles; and
forming the coating over at least a portion of the bead and one or more of the plurality of metallic nanoparticles.

14. The method of claim 2 , wherein the target binding moiety comprises an oligonucleotide.

15. The method of claim 2 , wherein the target binding moiety comprises an aptamer.

16. The method of claim 2 , wherein the viral nucleic acid comprises RNA.

17. The method of claim 2 , wherein the viral nucleic acid comprises DNA.

Assignees

• Massachusetts Gen Hospital

Inventors

• Weissleder Ralph
• Lee Hakho
• Im Hyungsoon
• Castro Cesar

Classifications

• G01N33/57557

  of other specific parts of the body, e.g. brain · CPC title

• G01N33/5755

  of the uterine cervix, uterine corpus or endometrium · CPC title

• G03H1/0443

  Digital holography, i.e. recording holograms with digital recording means (holobject computation G03H1/0866) · CPC title

• G03H2001/0447

  In-line recording arrangement · CPC title

• G01N21/4788 Primary

  Diffraction (for sizing particles G01N15/0205) · CPC title