Continuous Flow Nanoparticle Synthesis with Dynamic Parameter Control

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Solution Overview

Problem

Current methods for synthesizing nanoparticles, such as batch-type and continuous-type reactors, face challenges in producing nanoparticles with uniform size distribution, particularly for biologically active molecules, as they require pre-treatment, are energy-intensive, and struggle with controlling reaction parameters, limiting their application in drug development and industrial use.

Innovation Solution

A continuous flow device with adjustable temperature (10-350 °C) and pressure (1-250 bar) that allows for real-time monitoring and modification of nanoparticle synthesis parameters using Dynamic Light Scattering analysis, enabling the production of nanoparticles with precise size control and customizable structures, including core-shell types, using high-pressure and temperature conditions to broaden solvent applicability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If batch-type reactors are used for nanoparticle synthesis, then economic efficiency improves for bigger batch sizes, but particle size distribution uniformity deteriorates

Engineering Contradiction:
Improvebatch sizeVSAvoidparticle size distribution uniformity
Core Design Contradiction:
ProductivityVSManufacturing precision

Solution Approach 1:

The batch process is segmented into continuous flow stages with multiple reactor units (first reactor unit, second reactor unit) connected in series. This segmentation allows independent control of each reaction stage, enabling uniform particle size distribution while maintaining continuous production efficiency.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The system employs dynamic parameter control where temperature, pressure, and flow rates are continuously adjusted during the synthesis process. The reactor units operate at different temperatures (10-350°C) and pressures (1-250 bar) to optimize each stage, achieving both high productivity and uniform particle size distribution.

Inventive Principle:
Principle #15Dynamics

2Productivity

If top-down technologies (high-pressure homogenization, milling) are used, then nanoparticle production is achieved, but energy consumption increases and requires large material amounts

Engineering Contradiction:
Improvenanoparticle production capabilityVSAvoidenergy consumption
Core Design Contradiction:
ProductivityVSUse of energy by moving object

Solution Approach 1:

Instead of using top-down approaches that break down larger particles (which require high energy), the invention employs bottom-up synthesis where nanoparticles are built from molecular precursors in controlled flow reactions. This inversion of the synthesis strategy dramatically reduces energy consumption while enabling continuous production with minimal material amounts.

Inventive Principle:
Principle #13The other way round (Inversion)

Solution Approach 2:

The system utilizes precise parameter control (temperature 10-350°C, pressure 1-250 bar, flow rates) to optimize reaction conditions for nanoparticle formation. By changing physical parameters continuously along the flow path, the system achieves efficient nanoparticle synthesis without the high energy input required by mechanical methods.

Inventive Principle:
Principle #35Parameter changes

3Productivity

If known continuous reactors working at atmospheric pressure are used, then production of single-metal nanoparticles is achieved, but solvent applicability is narrowed by boiling point limitations

Engineering Contradiction:
Improvecontinuous production capabilityVSAvoidsolvent applicability
Core Design Contradiction:
ProductivityVSAdaptability or versatility

Solution Approach 1:

The system dynamically adjusts pressure (1-250 bar) and temperature (10-350°C) parameters along the continuous flow path. By elevating pressure above atmospheric levels, the boiling points of solvents are increased, allowing continuous production with diverse solvents including water, alcohols, and organic solvents that would otherwise vaporize at atmospheric pressure.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The system exploits phase transition control by maintaining pressure above atmospheric levels to prevent solvent vaporization during high-temperature reactions. This allows the reaction mixture to remain in liquid phase at temperatures that would cause boiling at atmospheric pressure, expanding solvent choices and reaction temperature ranges.

Inventive Principle:
Principle #36Phase transitions

4Manufacturing precision

If milling is used for nanoparticle production, then particles are reduced to nanometer size, but crystal structure can change due to heat-effect

Engineering Contradiction:
Improveparticle size controlVSAvoidcrystal structure stability
Core Design Contradiction:
Manufacturing precisionVSStability of the object's composition

Solution Approach 1:

Instead of mechanically reducing particle size through milling (which generates heat and alters crystal structure), the invention uses bottom-up synthesis where nanoparticles crystallize directly from solution in controlled flow reactions. This approach produces nanoparticles with well-defined crystal structures without the damaging thermal effects of mechanical reduction.

Inventive Principle:
Principle #13The other way round (Inversion)

Solution Approach 2:

The system precisely controls temperature, pressure, and residence time parameters during nanoparticle formation to maintain crystal structure stability. By optimizing reaction conditions in each reactor unit, the system achieves desired particle sizes while preserving the intended crystal phase without the structural changes caused by milling heat.

Inventive Principle:
Principle #35Parameter changes

5Device complexity

If batch-type reactors are used, then synthesis is performed with simpler equipment, but optimization of reaction parameters is difficult and time-consuming

Engineering Contradiction:
Improveequipment simplicityVSAvoidparameter optimization time
Core Design Contradiction:
Device complexityVSLoss of time

Solution Approach 1:

The continuous flow system enables dynamic parameter optimization where temperature, pressure, and flow rates can be independently adjusted in each reactor unit. This dynamic control allows rapid screening and optimization of reaction conditions without the time-consuming batch-to-batch adjustments required by traditional reactors, significantly reducing optimization time.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The segmented reactor design allows independent optimization of each reaction stage. Parameters can be tuned in the first reactor unit for nucleation, then adjusted in the second unit for growth and stabilization, enabling systematic parameter optimization that is much faster than trial-and-error batch processing.

Inventive Principle:
Principle #1Segmentation

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

This approach enables the efficient synthesis of nanoparticles with narrow size distribution and customizable properties, reducing material consumption, minimizing structural rearrangement, and allowing for safe handling, thus overcoming limitations of existing technologies in pharmaceutical and industrial applications.

Implementation Method 1

Real-time monitoring and modification of nanoparticle synthesis parameters using Dynamic Light Scattering analysis

Methodology Applied
Scientific EffectDynamic Light Scattering: Scattering

Implementation Method 2

adjustable temperature (10-350 °C) and pressure (1-250 bar) that allows for real-time monitoring and modification of nanoparticle synthesis parameters

Methodology Applied
Scientific EffectHigh-pressure and temperature conditions: Pressurisation

Data Source

PatentEP2288439B1Instrument and process for nanoparticles production in continuous flow mode
Publication Date: 2019.08.28 DARKHOLDING VADONKEZELE KFT
  • EP2288439B1 patent drawingFigure 1
  • EP2288439B1 patent drawingFigure 2a~2b
  • EP2288439B1 patent drawingFigure 2c~2d

AI summary

The subject of the invention is the (50) continuous flow system for the synthesis of nanoparticles which consist of the (1a) feeding unit connected to the flow path, at least one (2) first reactor unit possessing the (13) heatable reactor-zone, the (3) second reactor unit which follows (2) in the same cascade; the (5) mixing unit and the (1b) second feeding unit between (2) and (3) reactor units, the (9) and (10) feeding pumps connected to the raw material source and/or (22) control unit which is capable of controlling at least one (18) pressure controller and/or controlling the temperature of at least one (13) heatable reactor-zone; each (13) heatable reactor-zone is followed by (14) cooling unit in the cascade. In addition, the subject of this invention is a process for the synthesis of nanoparticles, preferably metal-containing nanoparticles, and nanoparticles of biologically active organic molecules wherein the process is accomplished in the device according to figure 1.