Biocompatible Magnetic Nanocrystals with Reactive Ester Surface

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Solution Overview

Problem

Current methods for producing biocompatible magnetic nanocrystals face challenges with chemical stability, colloidal stability, and biocompatibility in physiological conditions, limiting their applications in biological and biomedical fields, particularly in terms of solubility and surface functionality for conjugation with biomolecules.

Innovation Solution

A one-pot reaction technique using non-polar or weak-polar solvents and biocompatible macromolecules to produce magnetic nanocrystals with surface reactive N-hydroxysuccinimide ester moieties, enabling high solubility, colloidal stability, and long-term storage, as well as easy conjugation with biomolecules.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If thermal decomposition method is used to prepare magnetic nanocrystals, then crystallinity degree and magnetic responsivity are improved, but the surface becomes hydrophobic requiring complicated ligand-exchange procedures

Engineering Contradiction:
Improvecrystallinity degreeVSAvoidsurface functionality
Core Design Contradiction:
Stability of the object's compositionVSEase of manufacture

Solution Approach 1:

The patent applies preliminary action by incorporating biocompatible macromolecules (such as PEG derivatives with carboxyl or amino groups) into the thermal decomposition reaction system before nanocrystal formation. These macromolecules adsorb onto the nanocrystal surface during synthesis, pre-functionalizing the surface with hydrophilic and biocompatible groups. This eliminates the need for subsequent ligand-exchange procedures while maintaining high crystallinity achieved through thermal decomposition.

Inventive Principle:
Principle #10Preliminary action

2Stability of the object's composition

If hydrophobic surface modification is applied to magnetic nanocrystals, then colloidal stability in organic solvents is improved, but solubility and biocompatibility in physiological buffers deteriorate

Engineering Contradiction:
Improvecolloidal stabilityVSAvoidbiocompatibility
Core Design Contradiction:
Stability of the object's compositionVSAdaptability or versatility

Solution Approach 1:

The patent applies parameter changes by systematically varying the molecular weight, chain length, and functional group composition of biocompatible macromolecules used as surface modifiers. By optimizing these parameters, the nanocrystals achieve both hydrophilic character for physiological buffer compatibility and sufficient steric stabilization for colloidal stability. The macromolecules are selected with specific molecular weights (typically 200-20000 Da) and functional group densities to balance these competing requirements.

Inventive Principle:
Principle #35Parameter changes

3Adaptability or versatility

If complex ligand-exchange procedures are used to transfer nanocrystals to aqueous solution, then biocompatibility is improved, but preparation complexity and time increase

Engineering Contradiction:
ImprovebiocompatibilityVSAvoidpreparation complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent applies merging by combining the surface functionalization step with the nanocrystal synthesis step into a single integrated process. Biocompatible macromolecules are introduced into the reaction mixture before or during thermal decomposition, allowing simultaneous nanocrystal formation and surface functionalization. This one-pot approach merges two separate procedures (synthesis followed by ligand exchange) into one operation, dramatically reducing preparation complexity and time while ensuring uniform surface coverage.

Inventive Principle:
Principle #5Merging (Combining)

4Manufacturing precision

If uniform particle size distribution is achieved through size-selection processes, then manufacturing precision is improved, but production efficiency decreases

Engineering Contradiction:
Improveparticle size distributionVSAvoidproduction efficiency
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

The patent applies parameter changes by systematically optimizing reaction parameters including temperature, time, precursor ratios, and macromolecule concentrations to directly control nanocrystal nucleation and growth. By adjusting these parameters, the process produces nanocrystals with narrow size distributions (typically <10% standard deviation) without requiring post-synthesis size selection. The biocompatible macromolecules also act as size-controlling agents during growth, enabling precise size control through their molecular characteristics.

Inventive Principle:
Principle #35Parameter changes

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 resulting biocompatible magnetic nanocrystals exhibit enhanced solubility and colloidal stability in physiological buffers, allowing for stable storage and efficient conjugation with biomolecules, expanding their applications in biological and biomedical uses.

Implementation Method 1

thermal decomposition method developed recently has successfully overcome the above-mentioned problems. As higher reaction temperature are usually adopted in the thermal decomposition method, the nucleation process, growth process and the crystallinity degree of the resultant nanocrystals can better be controlled

Methodology Applied
Scientific EffectThermal decomposition: Pyrolysis

Implementation Method 2

the surface of the magnetic nanocrystal is bonded with a biocompatible macromolecule... the biocompatible magnetic nanocrystals exhibit enhanced solubility and colloidal stability

Methodology Applied
Scientific EffectAdsorption: Adsorption

Data Source

PatentUS8226844B2Biocompatible magnetic nanocrystal, powder of a biocompatible magnetic nanocrystal bearing a surface reactive group and preparations thereof
Publication Date: 2012.07.24 INST OF CHEM
  • US8226844B2 patent drawing
  • US8226844B2 patent drawing
  • US8226844B2 patent drawing

AI summary

This invention is concerned with biocompatible magnetic nanocrystals highly soluble and dispersible in a physiological buffer, powder of biocompatible magnetic nanocrystals and nanocrystals bearing surface reactive N-hydroxysuccinimide ester moiety, and preparations thereof. The magnetic nanocrystals in powder form are highly soluble in a physiological buffer. The resultant aqueous colloidal solution presents long term stability in ambient conditions. Moreover, the carboxyl group on the surface of the magnetic nanocrystals can be converted to N-hydroxysuccinimide ester moiety in an organic solvent. The resultant powder of the magnetic nanocrystals carrying surface N-hydroxysuccinimide ester moiety is soluble and dispersible in an aqueous solution. Different types of biomolecules bearing amino group can covalently be attached to the magnetic nanocrystal simply by mixing them in aqueous solutions. Moreover, the powder of the magnetic nanocrystals bearing surface N-hydroxysuccinimide ester moiety retain reaction activity with biomolecule after long-term storage.