IP Library › Granted Patent US 12,702,963
Granted Patent B2
US 12,702,963 · App. 18/000,884 · Granted Aug 11, 2026

Methods and compositions related to lanthanide-encoded microbeads

Inventors: Yinnian Feng (Stanford, CA); Adam K. White (Stanford, CA); Jamin B. Hein (Stanford, CA); Polly M. Fordyce (Stanford, CA)
Assignees: CZ Biohub SF, LLC; The Board of Trustees of the Leland Stanford Junior University; University of Copenhagen
B01J13/18B01L3/502784G01N33/582B01L2200/0673
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Quick Facts
Patent No.
US 12,702,963
App. No.
18/000,884
Filed
Dec 6, 2022
Granted
Aug 11, 2026
Kind
B2
Art Unit
1797
USPC
436/171
Abstract

The present disclosure provides methods, devices, systems and kits for producing polymeric microbeads, including lanthanide-encoded microbeads. Among others, the present disclosure provides methods, systems and kits for producing functionalized microbeads that include on their surfaces amphipathic moieties with free reactive groups that remain free and can be used for covalently coupling molecules or moieties of inters to the microbeads.

Claims (24)

1 . A method for producing polymeric microbeads comprising lanthanide nanoparticles, comprising:

i) providing a first fluid comprising a microbead matrix component and lanthanide nanoparticles, and a second fluid, wherein the first fluid and the second fluid are immiscible;

ii) contacting the first fluid with the second fluid in a microfluidic device, thereby forming droplets of the first fluid;

iii) removing the formed droplets from the microfluidic device; and

iv) solidifying the microbead matrix component of the formed droplets after the formed droplets are removed from the microfluidic device, thereby forming the polymeric microbeads comprising lanthanide nanoparticles outside of the microfluidic device.

2 . The method of claim 1 , wherein step (i) comprises mixing components of the first fluid outside of the microfluidic device before introducing the first fluid into the microfluidic device.

3 . The method of claim 1 , wherein step (ii) comprises contacting the first fluid with the second fluid at one or more intersections of channels of the microfluidic device.

4 . The method of claim 1 , wherein step (iv) comprises exposing the formed droplets to a temperature or to a compound inducing solidification of the microbead matrix component.

5 . The method of claim 1 , wherein the microbead matrix component is a polymerizable component, and step (iv) comprises polymerizing the polymerizable component.

6 . The method of claim 5 , wherein the first fluid comprises a photoinitiator, and step (iv) comprises irradiating the formed droplets removed from the microfluidic device with UV radiation to polymerize the polymerizable component.

7 . The method of claim 6 , wherein in step (iv) the formed droplets are simultaneously irradiated as a batch.

8 . The method of claim 1 , wherein the first fluid is hydrophobic, and the second fluid is hydrophilic, or the first fluid is hydrophilic, and the second fluid is hydrophobic.

9 . The method of claim 8 , wherein the first fluid is aqueous, and the second fluid is hydrophobic.

10 . The method of claim 8 , wherein the first fluid is hydrophilic, and the second fluid is hydrophobic, and the microbead matrix component comprises one or more polymerizable hydrophilic monomers and/or polymers.

11 . The method of claim 10 , wherein the one or more hydrophilic monomers and/or polymers comprise one or more polyethylene glycol derivatives, one or more acrylamide derivatives, one or more methacrylamide derivatives, or combinations of two or more thereof.

12 . The method of claim 8 , wherein the first fluid is hydrophilic, and the second fluid is hydrophobic, and the hydrophobic fluid comprises an oil, a hydrocarbon, a fatty acid, a siloxane, a fluorocarbon, or a combination of two or more thereof.

13 . The method of claim 1 , wherein the lanthanide nanoparticles comprise a predetermined ratio of at least two types of lanthanide nanoparticles.

14 . The method of claim 1 , wherein step (ii) comprises flow focusing of the first fluid.

15 . The method of claim 1 , wherein the second fluid comprises an amphipathic compound capable of covalently bonding with the microbead matrix component during step (iv), thereby attaching the amphipathic compound to a surface of the polymeric microbeads.

16 . The method of claim 15 , wherein the amphipathic compound comprises a reactive group that remains free upon covalent bonding of the amphipathic compound to the surface of the polymeric microbeads, and the reactive group comprises a carboxyl group, an amino group, an azide group, a hydroxyl group, a hydrazide group or a chloromethyl group.

17 . The method of claim 16 , wherein the reactive group comprises a carboxyl group, and the method further comprises covalently coupling an amino-functionalized oligonucleotide to the surface of the polymeric microbeads.

18 . The method of claim 16 , wherein the reactive group comprises an amino group, and the method further comprises covalently coupling an amino acid, a peptide or a protein to the surface of the polymeric microbeads.

19 . The method of claim 16 , wherein the reactive group comprises an amino group, and the method further comprises performing solid-phase peptide synthesis on a surface of the polymeric microbeads.

20 . The method of claim 1 , wherein the first fluid further comprises ferric nanoparticles.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 27, 2023
From: THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY
To: CZ BIOHUB SF, LLC; THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY
Reel/Frame 065054/0929 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 8, 2022
From: FENG, YINNIAN; WHITE, ADAM K.; FORDYCE, POLLY M.
To: THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY
Reel/Frame 062032/0863 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 8, 2022
From: HEIN, JAMIN B.
To: THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY; UNIVERSITY OF COPENHAGEN
Reel/Frame 062033/0001 →
Continuity (2)
Provisional Application 63037804 · Jun 11, 2020
Related Publication 20230211307A1 · Jul 6, 2023
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