Encoded polymeric microparticles

Inventors

Kwon, Sunghoon • KIM, MiRa • Jang, Jisung • Bae, Hyungjong • Kim, Nari

Assignees

Quantamatrix Inc

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Publication Number

US-10557846-B2

Patent

Publication Date

2020-02-11

Expiration Date


Abstract

Provided are encoded polymeric microparticles and a multiplexed bioassay using the encoded polymeric microparticles. Each of the encoded polymeric microparticles includes an encoded polymeric microparticle core and a silica shell surrounding the microparticle core. Further provided is a method for producing encoded polymeric microparticles. The method includes: mixing a photocurable material with a linker having a functional group polymerizable with the photocurable material and an alkoxysilyl group; applying patterned energy to cure the mixture, followed by encoding to obtain encoded polymeric microparticle cores; and treating the encoded polymeric microparticle cores with a silica precursor to form a silica shell on each encoded polymeric microparticle core.

Core Innovation

The invention provides encoded polymeric microparticles that include an encoded polymeric microparticle core and a silica shell surrounding the core. The core comprises a photocurable polymer and a linker, and the silica shell is formed by treating the encoded cores with a silica precursor to enable strong core-shell bonding between the linker and silica shell.

The encoded polymeric microparticle core is cured by light or electron beam, and the photocurable polymer is patterned by optical lithography to encode the particles. The linker comprises a photocurable functional group chemically bonded with the photocurable polymer and a functional group chemically bonded with the silica shell. The linker/silica chemistry enables strong bonding and supports robust core-shell formation.

The silica shell provides chemical and physical stability and supports surface functionalization for immobilizing biomaterials such as antigens, antibodies, DNAs, RNAs, and oligonucleotides. The document further discloses multiplexed DNA hybridization and 10-plex HPV genotyping on silica-coated encoded particles, and optional incorporation of magnetic materials for magnetic separation and solution exchange in bioassays.

Claims Coverage

The independent claim covers encoded polymeric microparticles having an encoded photocurable polymer core with a silica-shell-forming linker, where the core is cured by light or electron beam and patterned by optical lithography, together with magnetic materials. The independent claim and its dependent claims refine the spatial arrangement of magnetic materials, the nature of the core-silica interface bond, and the types of biomaterials or encoding attributes on the silica shell and core.

Encoded photocurable core with silica-shell linker

Encoded polymeric microparticles comprising an encoded polymeric microparticle core including a photocurable polymer and a linker, wherein the linker comprises a photocurable functional group chemically bonded with the photocurable polymer and a functional group chemically bonded with the silica shell, the linker being represented by Formula 1.

Light or electron-beam curing and optical lithography patterning

The encoded polymeric microparticle core is cured by light or electron beam, and the photocurable polymer is patterned by optical lithography.

Silica shell surrounding the encoded core

A silica shell surrounding the microparticle core, formed via the functional group chemistry of the linker to establish the core-shell relationship.

Magnetic materials in the encoded microparticles

The encoded polymeric microparticles further comprise magnetic materials.

Interposed magnetic nanoparticle layer

Magnetic materials are provided as a layer of magnetic nanoparticles positioned between a microparticle core and a silica shell.

Specific core-to-shell interfacial bond

The microparticle core is connected to the silica shell by —Si—O—Si— bonds.

Biomaterials on the silica shell

The silica shell includes a biomaterial selected from antigens, antibodies, DNAs, RNAs, and oligonucleotides introduced on the shell surface.

Encoding by color or by shape

The encoded polymeric microparticle core is encoded by color or by shape.

Core size threshold

The encoded polymeric microparticle core has a size larger than several micrometers.

Overall, the claims cover encoded polymeric microparticles in which a photocurable polymer core with an optically lithographically patterned, light/electron-beam-cured photocurable linker is coupled to a surrounding silica shell, with magnetic materials integrated and refined by specific bond type, biomaterial presentation on the silica shell, and encoding attributes such as color or shape, as well as a core size threshold.

Stated Advantages

Strong core-shell bonding (—Si—O—Si—) enabled by linker/silica chemistry.

Improved chemical and physical stability.

Reduced nonspecific absorption into the polymer core.

Stable surface functionalization to immobilize biomaterials on the silica shell.

Documented Applications

Multiplexed DNA hybridization on silica-coated encoded particles.

10-plex HPV genotyping on silica-coated encoded particles.

Magnetic separation and solution exchange in bioassays using magnetic materials.

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