Molecularly imprinted particles
Inventors
Bishop, Barney • RAMANAN, Mrinalini • ZHU, Yaling
Assignees
Publication Number
US-12105092-B2
Publication Date
2024-10-01
Expiration Date
2040-05-12
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Abstract
Molecularly imprinted particles comprising a label are described herein, in particular such particles prepared by RAFT polymerization, as are compositions and kits comprising such particles, and methods for preparing and using such particles.
Core Innovation
The invention provides molecularly imprinted particles that comprise a core formed by a crosslinked polymer network, where the core incorporates a detectable label, particularly a fluorescent label. The invention also describes compositions and kits containing such particles, and methods for their preparation using reversible addition-fragmentation chain transfer (RAFT) polymerization of compositions containing a functional monomer, a crosslinker, and a detectable label. The label can be a fluorophore or other detectable moiety, incorporated directly during polymerization.
The background section explains that prior technologies for labeled microparticles required either multi-step, post-synthesis covalent modifications or covalent attachment of labels during synthesis, primarily focusing on silica or hydrogel-based particles. These methods are noted to have limitations and complexities. The invention addresses the need for new and effective particles with labels, along with versatile methods for preparing them for a variety of uses.
The invention further details the creation of particles by RAFT polymerization in a one-pot process, allowing for the formation of cores with embedded labels. These particles can also incorporate additional functionalities on their outer layer, such as analyte capture or detection elements, and can be surrounded by a polymeric shell for further applications. The label may be reversibly quenchable, such as a fluorescent dye, able to respond to environmental changes like pH. Compositions and kits comprising these labeled particles, as well as methods for using them to detect analytes or environmental changes, are included in the scope of the invention.
Claims Coverage
The independent claim defines one main inventive feature regarding the preparation of particles with crosslinked polymer networks, attractively associated with a fluorescent label using RAFT polymerization.
Preparation of particles with crosslinked polymer networks attractively associated with a fluorescent label via RAFT polymerization
The inventive feature consists of: - Performing a reversible addition-fragmentation chain transfer (RAFT) polymerization of a composition to form a particle core. - The composition comprises a vinyl functional monomer (acrylamide, methacrylamide, acrylate, or methacrylate) and a crosslinker (chosen from diamine acrylamide, diamine methacrylamide, polyamine acrylamide, polyamine methacrylamide, diol acrylate, diol methacrylate, polyol acrylate, and polyol methacrylate). - The polymerization is carried out in the presence of a fluorescent label selected from a defined group of fluorescein derivatives and similar molecules. - The polymer network and label are associated via an attractive association that is electrostatic, hydrophobic, or hydrogen-bonding in nature.
In summary, the independent claim covers the RAFT polymerization-based preparation of crosslinked polymer particles with a fluorescent label attractively associated within the core, specifying the types of monomers, crosslinkers, labels, and associations that define the inventive concept.
Stated Advantages
Provides new and effective particles comprising a label and versatile methods for preparing them.
Allows direct incorporation of a detectable label during the polymerization process, simplifying synthesis compared to multi-step modification approaches.
Particles prepared are stable under formulation and extended storage conditions, with fluorescence intensities preserved for up to 3 to 4 months at 4° C.
The method permits reversible quenching and activation of fluorescence in the labeled microparticles, enabling detection of environmental changes such as pH.
Negligible fluorophore leakage occurs during particle synthesis even under high temperature conditions, ensuring containment of the label.
The method allows for adaptation and introduction of new functionalities via polymeric shell layers or outer layer modification.
Compositions and kits are versatile and suitable for various applications including analyte capture and detection.
Documented Applications
Capturing or detecting an analyte by contacting the analyte with a molecularly imprinted particle comprising a functionality for capture or detection.
Detecting an environmental change, such as a change in pH, by exposing the molecularly imprinted particle to the change and monitoring a reporter functionality.
High throughput screening involving contact with analytes such as drugs.
Use as reporters for environmental changes, including pH shifts.
Fluorescent particle sorting and cost-efficient imaging for visualization and quantification of particles.
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