Encoded microcapsules and microarray fabricated therefrom

Inventors

Kwon, Sunghoon • Song, Younghoon • KWON, Taehong • Lee, Daewon • Kim, Junhoi

Assignees

Quantamatrix Inc

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Publication Number

US-10274504-B2

Patent

Publication Date

2019-04-30

Expiration Date


Abstract

Disclosed is a microcapsule encoded depending on the kind of a target substance included therein. The encoded microcapsule has a hydrophilic liquid core including the target substance and a hydrophobic shell surrounding the liquid core. The encoded microcapsule includes graphical codes introduced on the surface of the shell.

Core Innovation

The disclosed technology provides encoded microcapsules in which each microcapsule is encoded depending on the kind of a target substance present in a hydrophilic liquid core. The microcapsule includes a hydrophobic shell surrounding the liquid core, and the hydrophobic shell comprises a photoinitiator whose chromophore is capable of emitting fluorescence after decomposition of the photoinitiator. Graphical codes are engraved on a surface of the hydrophobic shell to distinguish among microcapsules based on the target substance.

The encoded graphical codes are configured so that each graphical code emits fluorescent light at a higher intensity than the rest of the surface of the hydrophobic shell. The technology also provides a method of producing encoded microcapsules by preparing double emulsion droplets with a hydrophilic liquid core containing the target substance and a hydrophobic shell containing a photocurable polymer and the photoinitiator, then curing the photocurable polymer with an external energy source to form core-shell structured microcapsules.

Graphical codes are engraved by irradiating patterned energy on the cured core-shell structured microcapsules, where individual microcapsules are distinguished by fluorescence emitted from the chromophore in the engraved region. The document further describes a microarray comprising a substrate having microwells with the encoded microcapsules introduced into the substrate, where core liquids having the target substances are released when the microcapsules are broken.

The microwell substrate configuration is described as creating independent reaction spaces using immiscible liquid layers and micropillars for microcapsule breaking, enabling drug screening including an apoptosis assay example.

Claims Coverage

The independent claims cover three inventive features: encoded microcapsules, a producing method for such microcapsules, and a microarray using them. The claims recite fluorescence-emitting photoinitiator chromophores, engraved graphical codes with higher-intensity fluorescence, core-shell microcapsule structures, patterned-energy engraving, double emulsion droplets, and a microwell microarray enabling target-substance release.

Encoded microcapsules with fluorescence graphical codes

Microcapsules encoded depending on a kind of a target substance present therein, comprising a hydrophilic liquid core comprising the target substance; a hydrophobic shell surrounding the liquid core, the hydrophobic shell comprising a photoinitiator; wherein the photoinitiator has a chromophore capable of emitting fluorescence after decomposition of the photoinitiator; and graphical codes engraved on a surface of the hydrophobic shell so that the microcapsules are encoded in order to distinguish from each other depending on the kind of the target substance being included in the hydrophilic liquid core; wherein each of the graphical codes emits florescent light at a higher intensity than the rest of the surface of the hydrophobic shell.

Producing encoded microcapsules with double emulsion and patterned-energy engraving

A method of producing encoded microcapsules, the method comprising preparing double emulsion droplets, each of which has a hydrophilic liquid core comprising a target substance and a hydrophobic shell surrounding the liquid core, wherein the hydrophobic shell contains a photocurable polymer and a photoinitiator having a chromophore; by an external energy source, curing the photocurable polymer to form core-shell structured microcapsules; and engraving graphical codes on a surface of the hydrophobic shell by irradiating patterned energy on the cured core shell microcapsules and distinguishing among individual microcapsules by fluorescence emitted from the chromophore of the photoinitiator in the engraved region of the surface; wherein the photoinitiator includes a moiety capable of being decomposed by an external energy source and the chromophore is capable of emitting the fluorescence after decomposition of the photoinitiator.

Microarray with encoded microcapsules in microwells and released core liquids

A microarray, comprising microcapsules encoded to be distinguished from each other depending on a kind of target substances; a substrate having microwells, wherein said microcapsules are introduced in the substrate; and core liquids having the target substances being released when the microcapsules are broken; wherein each of the microcapsules comprises a hydrophilic liquid core comprising the target substances; a hydrophobic shell surrounding the liquid core, the hydrophobic shell comprising a photoinitiator; wherein the photoinitiator has a chromophore capable of emitting fluorescence after decomposition of the photoinitiator; and graphical codes engraved on a surface of the hydrophobic shell so that the microcapsules are encoded in order to distinguish from each other depending on the kind of the target substance being included in the hydrophilic liquid core; wherein each of the graphical codes emits florescent light at a higher intensity than the rest of the surface of the hydrophobic shell.

Collectively, the independent claims require core-shell microcapsules with a hydrophilic liquid core holding a target substance and a hydrophobic shell containing a photoinitiator whose chromophore emits fluorescence after decomposition. Engraved graphical codes on the shell distinguish microcapsules by producing higher-intensity fluorescence in the code regions. A producing method uses double emulsion droplets, curing of a photocurable polymer, and engraving by irradiating patterned energy, and a microarray places such encoded microcapsules in a microwell substrate for target-substance core-liquid release upon microcapsule breaking.

Stated Advantages

Increased code capacity without fluorescent dyes or quantum dots.

Reduced equipment and cost compared with printer-based spot arrays.

Parallel screening with reduced reagent consumption.

Code durability is reported as fluorescence maintained for 20 days or more.

Documented Applications

Drug screening using encoded microcapsules and microarrays.

An apoptosis assay example using CPT, PKF, and PTX with fluorescence imaging and image processing to evaluate drug- and concentration-dependent viability.

Microarray assembly in a microwell substrate using independent reaction spaces created by immiscible liquid layers and micropillar-based microcapsule breaking.

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