Rare earth spatial/spectral microparticle barcodes for labeling of objects and tissues

Patent metadata

Field	Value
Publication number	US-9528144-B2
Application number	US-201414214528-A
Country	US
Kind code	B2
Filing date	Mar 14, 2014
Priority date	Mar 15, 2013
Publication date	Dec 27, 2016
Grant date	Dec 27, 2016

Abstract

Polymer microparticles spatially and spectrally encoded using upconversion nanocrystals (UCN) are described for labeling of articles and tissues. UCN having spectrally distinguishable emission spectra are disposed in different portions of an encoding region of each microparticle.

First claim

What is claimed:

1. A microparticle for labeling, the microparticle comprising:
a body comprising a polymer material and including an encoded region;
a first plurality of upconversion nanocrystals disposed in a first portion of the encoded region, the first plurality of upconversion nanocrystals having a first spectral signature; and
a second plurality of upconversion nanocrystals disposed in a second portion of the encoded region spatially separated from the first portion of the encoded region, the second plurality of upconversion nanocrystals having a second spectral signature.

2. The microparticle of claim 1 , wherein the second spectral signature is different from the first spectral signature.

3. The microparticle of claim 1 , wherein the first plurality of upconversion nanocrystals includes a first material doped with one or more rare earth elements and the second plurality of upconversion nanocrystals includes a second material doped with one or more rare earth elements.

4. The microparticle of claim 1 , wherein the first plurality of upconversion nanocrystals are covalently bound to the polymer material.

5. The microparticle of claim 1 , wherein the first plurality of upconversion nanocrystals are bound to the polymer material at the time of particle synthesis through an acrylate group.

6. The microparticle of claim 1 , wherein the first plurality of upconversion nanocrystals are distributed throughout the bulk of the first portion.

7. The microparticle of claim 1 , wherein for each portion of the encoded region, the upconversion nanocrystals are dispersed without aggregation.

8. The microparticle of claim 1 , further comprising a third plurality of upconversion nanocrystals disposed in a third portion of the encoded region spatially separated from the first portion of the encoded region and spatially separated from the second portion of the encoded region, the third plurality of upconversion nanocrystals having a third spectral signature.

9. The microparticle of claim 8 , further comprising a fourth plurality of upconversion nanocrystals disposed in a fourth portion of the encoded region spatially separated from the first portion of the encoded region, spatially separated from the second portion of the encoded region, and spatially separated from the third portion of the coded region, the fourth plurality of upconversion nanocrystals having a fourth spectral signature.

10. The microparticle of claim 9 , wherein the encoded region includes at least six different portions.

11. The microparticle of claim 1 , wherein at least one portion of the encoded region does not include nanocrystals.

12. The microparticle of claim 1 , wherein each spectral signature includes luminescence in multiple distinct bands within a range of 400-800 nm.

13. The microparticle of claim 1 , wherein the polymer material comprises polyurethane acrylate (PUA).

14. The microparticle of claim 1 , wherein the polymer material is biocompatible.

15. The microparticle of claim 1 , wherein the polymer material comprises polyethylene glycol diacrylate (PEG-DA).

16. The microparticle of claim 1 , wherein the upconversion nanocrystals are paramagnetic.

17. The microparticle of claim 1 , wherein at least some of the upconversion nanocrystals comprise gadolinium.

18. A method of making a microparticle for labeling, the method comprising:
providing a first encoded region source material including a polymer and a first plurality of upconversion nanocrystals having a first spectral signature;
providing a second encoded region source material including a polymer and a second plurality of upconversion nanocrystals having a second spectral signature different from the first spectral signature; and
forming a contiguous microparticle by cross-linking with the first encoded region source material forming a first portion of an encoded region of the microparticle, and with the second encoded region source material forming a second portion of the encoded region.

19. The method of claim 18 , wherein the process further includes the step of co-flowing the first encoded region source material and the second encoded region source material to an area for cross-linking.

20. The method of claim 18 , wherein each of the first plurality of upconversion nanocrystals and each of the second plurality of upconversion nanocrystals has a hydrophilic surface.

21. The method of claim 18 , wherein each of the first plurality of upconversion nanocrystals and each of the second plurality of upconversion nanocrystals has a hydrophilic ligand.

22. The method of claim 18 , wherein each of the first plurality of upconversion nanocrystals and each of the second plurality of upconversion nanocrystals has a hydrophobic surface.

23. The method of claim 18 , wherein each of the first plurality of upconversion nanocrystals and each of the second plurality of upconversion nanocrystals has a hydrophobic ligand.

24. The method of claim 18 , wherein the first plurality of upconversion nanocrystals is distributed throughout the bulk of first portion of the encoded region of the microparticle and wherein the second plurality of upconversion nanocrystals is distributed throughout the bulk of the second portion of the encoded region.

25. The method of claim 18 , wherein the method further comprises providing a third encoded region source material including a hydrogel and a third plurality of upconversion nanocrystals having a third spectral signature different than the first spectral signature and wherein the third encoded region source material forms a third portion of the encoded region of the microparticle.

26. The method of claim 18 , wherein the method further comprises providing a fourth encoded region source material including a hydrogel and a fourth plurality of upconversion nanocrystals having a fourth spectral signature different than the first spectral signature and wherein the fourth encoded region source material forms a fourth portion of the encoded region of the microparticle.

27. The method of claim 18 , further comprising selecting the first plurality of upconversion nanocrystals and the second plurality of upconversion nanocrystals by comparing a predicted first spectral response signature with a predicted second spectral response signature, wherein the predicted first spectral response signature is a convolution of the first spectral signature and the spectral response of an image sensor, and wherein the predicted second spectral response signature is a convolution of the second spectral signature and the spectral response of the image sensor.

28. The method of claim 18 , wherein providing the first encoded region source material comprises forming the first plurality of upconversion nanocrystals.

29. The method of claim 18 , wherein providing the first encoded region source material comprises modifying a surface of each of the first plurality of upconversion nanocrystals.

30. The method of claim 18 , wherein the upconversion nanocrystals are paramagnetic.

Assignees

• Massachusetts Inst Technology

Inventors

• Bisso Paul
• Swiston Albert
• Lee Jiseok
• Doyle Patrick S

Classifications

• C12Q1/6825 Primary

  Nucleic acid detection involving sensors · CPC title

• C09K11/7773 Primary

  with alkali or alkaline earth metal · CPC title

• G07D7/0043

  using barcodes · CPC title

• G01N2021/6439

  with indicators, stains, dyes, tags, labels, marks · CPC title

• G07D7/2033

  Matching unique patterns, i.e. patterns that are unique to each individual paper · CPC title