Biocompatible Upconversion Nanoparticles with Epitaxial CaF2 Shell

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Solution Overview

Problem

Current upconversion nanoparticles (UCNPs) face challenges due to potential toxicity of lanthanides and complex, unreliable synthesis protocols that are not suitable for large-scale production, and the CaF2 shell synthesis methods result in explosive boiling and non-uniform products, limiting their biocompatibility and reproducibility.

Innovation Solution

Development of biocompatible UCNPs with a core of cubic α-NaYbF4 and an epitaxial CaF2 shell, optimized with a specific molar ratio of Tm/(Y+Yb+Tm) and Yb/(Y+Yb+Tm), synthesized in a single reactor vessel using a method that involves heating a solvent mixture and injecting core and shell precursor solutions, enabling efficient NIR-to-UV upconversion for imaging and photoactivation applications.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional UCNP synthesis protocols are used, then upconversion nanoparticles can be produced, but the synthesis is complex and unreliable, leading to poor reproducibility and unsuitability for large-scale production

Engineering Contradiction:
ImprovescalabilityVSAvoidsynthesis protocol complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent combines the core formation and shell growth steps into a single one-pot synthesis reaction. The core UCNP precursors and shell precursors are mixed together in one reaction vessel and heated simultaneously, eliminating the need for separate synthesis steps and intermediate handling. This merging of steps simplifies the overall protocol and enables scalable production.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The synthesis protocol is segmented into distinct precursor solutions (core precursors and shell precursors) that are prepared separately but combined in a controlled one-pot reaction. This allows for independent optimization of each component while maintaining overall process simplicity and reproducibility.

Inventive Principle:
Principle #1Segmentation

2Manufacturing precision

If CaF2 shell synthesis is performed using conventional methods, then shell formation occurs, but explosive boiling occurs and products are non-uniform, limiting biocompatibility and reproducibility

Engineering Contradiction:
Improveproduct uniformityVSAvoidexplosive boiling
Core Design Contradiction:
Manufacturing precisionVSObject-affected harmful factors

Solution Approach 1:

The patent modifies the synthesis parameters by using a one-pot reaction at controlled temperatures (300-350°C) with specific precursor ratios and concentrations. The use of organic acid solvents and controlled heating rates prevents explosive boiling while maintaining uniform shell formation. The reaction parameters are optimized to ensure gradual and controlled shell growth.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses organic acid solvents and ligands as intermediaries to mediate the shell formation process. These intermediaries control the precipitation and growth of CaF2 shells, preventing explosive reactions and ensuring uniform coating on the core particles. The ligands act as buffering agents that regulate the reaction kinetics.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If lanthanide-containing UCNPs are used, then upconversion imaging is achieved, but potential toxicity of lanthanides limits biocompatibility

Engineering Contradiction:
Improveimaging performanceVSAvoidtoxicity
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent employs a core-shell structure where the toxic lanthanide-containing core is nested within a biocompatible CaF2 shell. This nested architecture provides physical isolation of the toxic components from the biological environment while preserving the upconversion imaging function of the core. The shell acts as a protective barrier that eliminates direct contact between lanthanides and biological systems.

Inventive Principle:
Principle #7Nested doll (Nesting)

Solution Approach 2:

The patent creates a composite nanoparticle structure combining lanthanide-doped core material with biocompatible CaF2 shell material. This composite structure integrates the optical functionality of lanthanides with the biocompatibility of calcium fluoride, achieving both imaging performance and safety for in vivo applications.

Inventive Principle:
Principle #40Composite materials

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The novel UCNPs exhibit enhanced biocompatibility, improved upconversion efficiency, and stability, allowing for high-contrast in vivo imaging and effective photoactivation with minimal toxicity and improved scalability, as demonstrated by their ability to penetrate deep tissues and activate light-sensitive molecules with low-power NIR lasers.

Implementation Method 1

Upconverting luminescence refers to an anti-Stokes type process in which the sequential absorption of two or more photons leads to the emission of light at shorter wavelength (e.g., ultraviolet, visible, and near-infrared) than the excitation wavelength.

Methodology Applied
Scientific EffectUpconversion luminescence: Photoluminescence

Implementation Method 2

Utilizing long-lived, ladder-like energy levels of Ln3+, the intensity of anti-Stokes luminescence of UCNPs is orders of magnitude more potent compared with those of conventional synthetic dyes or quantum dots (QDs).

Methodology Applied
Scientific EffectEnergy transfer:

Implementation Method 3

exciting the UCNP with a laser having a wavelength from about 900 nm to about 1064 nm; causing the UCNP to emit a luminescence at a wavelength of from about 340 nm to about 380 nm

Methodology Applied
Scientific EffectUpconversion: Photoluminescence

Data Source

PatentUS10179177B2Coated up-conversion nanoparticles
Publication Date: 2019.01.15 UNIV OF MASSACHUSETTS
  • US10179177B2 patent drawing
  • US10179177B2 patent drawing
  • US10179177B2 patent drawing

AI summary

The invention provides novel biocompatible upconversion nanoparticle (UCNP) that comprises a core of cubic nanocrystals (e.g., comprising α-Na Lna, Lnb Lnc F4) and an epitaxial shell (e.g., formed from CaF2; wherein Lnb is Yb), and related methods of preparation and uses thereof.