USA as Represented by Secretary of the Navy

The University of Chicago

University System of Maryland

Igor L Medintz

Kimihiro Susumu

Hedi M Mattoussi

James B Delehanty

Philip E Dawson

Michael H Stewart

W Russ Algar

Jeffrey R Deschamps

Alan L Huston

Mario Ancona

Ellen R Goldman

Eunkeu Oh

Glyn Dawson

Juan Bautista Blanco-Canosa

Kelly Boeneman

George P Anderson

J Matthew Mauro

Alexander L Efros

Okhil Nag

Harry Tetsuo Uyeda

Melissa M Massey

Joyce A Breger

Lauren D Field

Niko Hildebrandt

Joseph S Melinger

Sebastian A Diaz

Susan Buckhout-White

Moungi G Bawendi

Mladen Barbic

Christopher M Jewell

Thomas Pons

John J Macklin

Parag Chitnis

Dorothy Farrell

Scott Walper

Ryan Walters

Johanna Scheinost

Krystina Hess

James N Vranish

Nashaat Rasheed

Jesper Brask

John R Cressman

Markus Muttenthaler

Bertalan K Andrasfalvy

Lorenzo Berti

Paolo Facci

A nanoplatelet serves as a substrate for immobilizing enzymes involved in consecutive reactions as a cascade. This results in a significant increase in the rate of catalysis as well as final product yield compared to non-immobilized enzymes or enzymes immobilized to quantum dots.

Self-assembled nanoplatelet-enzyme bioconjugates providing for increased biocatalytic efficiency

Lipase activity can be detected with a biosensor that includes a quantum dot adhered to a construct having a lipase-cleavable ester to attach a fluorophore acceptor configured as a F&#xf6;rster resonance energy transfer (FRET) acceptor to the QD when the construct is bound thereto. Cleavage of the ester by a lipase results in a measurable reduction in FRET. In further embodiments, the cleavable ester can be used to detect esterase activity, or the ester could be replaced with a glycosidic linkage to detect glycoside activity.

Nanoparticle-based lipase biosensor utilizing a custom-synthesized peptidyl-ester substrate

A nanoparticle (for example, quantum dot) serves as a substrate for immobilizing enzymes involved in consecutive reactions as a cascade. This results in a significant increase in the rate of catalysis as well as final product yield compared to non-immobilized enzymes.

Nanoparticle-attached enzyme cascades for accelerated multistep biocatalysis

Time-resolved nucleic acids include a long-lifetime FRET donor with an emission lifetime of at least one millisecond (such as a terbium complex), configured as a donor in a first FRET process, and at least one fluorescent dye with an emission lifetime of less than 100 nanoseconds configured as an acceptor in the FRET process. They can be configured as photonic wires, hybridization probes or beacons, and/or systems for computing logical operations.

Fluorescence-based computation system

Time-resolved nucleic acid hybridization probes

A construct for detecting cellular membrane potential includes a nanoparticle operable as an electron donor; a modular peptide attached to the nanoparticle, the peptide comprising a nanoparticle association domain, a motif configured to mediate peptide insertion into the plasma membrane, and at least one attachment point for an electron acceptor positioned at a controlled distance from the nanoparticle; and an electron acceptor. The nanoparticle can be a quantum dot and the electron acceptor can be Cfullerene. Emission correlates with cellular membrane potential.

Modular, multifunctional nanoparticle-based bioconjugate for realtime visualization of cellular membrane potential

Provided are compositions and methods for promoting tolerance to auto-immune antigens. In general the compositions include quantum dots (QDs) that are in association with auto-immune peptide antigens. It is shown that QDs can be used to generate immunological tolerance by controlling the density of self-antigen on QDs. Peptide-QDs rapidly concentrate in draining lymph nodes, and co-localize with macrophages expressing scavenger receptors involved intolerance. Treatment with peptide-QDs reduces disease incidence 10-fold. The degree of tolerance and the underlying expansion of regulatory T cells correlates with the density of myelin molecules presented on QDs such that higher numbers of tolerogenic particles displaying lower levels of self-peptide are more effective for inducing tolerance than fewer particles each displaying higher densities of peptide. The disclosure is therefore relevant to promoting tolerance to antigens that are involved in a variety of autoimmune disorders.

Harnessing quantum dots to study, visualize, and promote immune tolerance

A construct for detecting cellular membrane potential includes a nanoparticle operable as an electron donor; a modular peptide attached to the nanoparticle, the peptide comprising a nanoparticle association domain, a motif configured to mediate peptide insertion into the plasma membrane, and at least one attachment point for an electron acceptor positioned at a controlled distance from the nanoparticle; and an electron acceptor. The nanoparticle can be a quantum dot and the electron acceptor can be Cfullerene. Photoacoustic emission from the construct correlates with cellular membrane potential.

Multifunctional nanoparticle bioconjugates for photoacoustic-based recording of cellular membrane potential

Time-resolved nucleic acid hybridization beacons

The invention relates to a nanoscale antenna including a nucleic acid scaffold having a structure selected from the group consisting of a Holliday junction, a star, and a dendrimer; and a plurality of fluorophores attached to the scaffold and configured as a FRET cascade comprising at least three different types of fluorophores including at least one quantum dot, arranged with (a) a plurality of initial donor fluorophores fixed in exterior positions on the structure, (b) a terminal acceptor fluorophore fixed in a central position on the structure, and (c) a plurality of intermediate fluorophores fixed in positions on the scaffold between the initial acceptor fluorophores and the terminal acceptor fluorophores.

Quantum dots in modular nucleic acid scaffolds operable as nanoscale energy harvesting and focusing arrays

Nanoparticles (and optionally a cargo such as a drug) can be delivered to cells by attaching just a single dendritic peptide to the nanoparticle. The dendritic peptide includes a polyhisitidine motif and a hinge and a spacer connecting the polyhistidine to a lysine-based dendritic wedge displaying at least two copies of a cell-penetrating peptide motif.

Use of single dendritic wedge cell penetrating peptides to facilitate cellular delivery of nanoparticles and nanoparticles carrying cargos

The invention relates to a nanoscale antenna including a nucleic acid scaffold having a structure selected from the group consisting of a Holliday junction, a star, and a dendrimer; and a plurality of fluorophores attached to the scaffold and configured as a FRET cascade comprising at least three different types of fluorophores, arranged with (a) a plurality of initial donor fluorophores fixed in exterior positions on the structure, (b) a terminal acceptor fluorophore fixed in a central position on the structure, and (c) a plurality of intermediate fluorophores fixed in positions on the scaffold between the initial acceptor fluorophores and the terminal acceptor fluorophores.

Use of modular nucleic acid scaffolds to create nanoscale energy harvesting and focusing arrays

A glass pipette such as an electrode for electrophysiological recording is coated with quantum dots. This greatly aids the ability to observe the glass pipette, particular in tissue as the quantum dots provide an excellent performance under two-photon illumination used to visualize objects at depths of hundreds of microns.

Coatings of semiconductor quantum dots for improved visibility of electrodes and pipettes

Described herein is a time-gated, two-step FRET relay effective to provide temporal transference of a prompt FRET pathway, or provide spectro-temporal encoding analytical signals and other information. A FRET relay assembly includes a long lifetime FRET donor (for example, a lanthanide complex), a semiconductor quantum dot (QD) configured as an intermediate acceptor/donor in FRET, and a fluorescent dye configured as a terminal FRET acceptor, wherein the long lifetime FRET donor has an excited state lifetime of at least one microsecond and the QD and fluorescent dye each have excited state lifetimes of less than 100 nanoseconds.

Spectro-temporal optical encoding of information using a time-gated fluorescence resonance energy transfer (FRET)

Growing community of inventors

Springfield, VA, United States of America

Igor L Medintz