Gold Colloid Production via Segmented Citrate-Ascorbate Reduction

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Solution Overview

Problem

Existing methods for producing gold colloid fail to achieve uniform particle size and perfect spherical shape, which are crucial for enhancing the sensitivity and reliability of in-vitro diagnostic agents.

Innovation Solution

A multi-step method involving a nucleation step with citrate as the first reducing agent and a growth step with ascorbate as the second reducing agent, where the addition of ascorbate is simultaneous with the second gold salt, to control the particle size and shape of gold colloid particles.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If a citrate alone is used as a reducing agent, then the production process is simple, but gold colloid having a uniform particle size distribution and spherical shape cannot be obtained

Engineering Contradiction:
Improvesimplicity of production processVSAvoiduniformity of particle size distribution and spherical shape
Core Design Contradiction:
Ease of manufactureVSManufacturing precision

Solution Approach 1:

The reduction process is divided into two distinct steps: a nucleation step using citrate as reducing agent to form initial particles, and a growth step using ascorbate as reducing agent to control particle size and shape. This segmentation allows each step to be optimized independently, achieving both uniform particle size distribution and spherical shape while maintaining process simplicity

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The nucleation step is performed first to pre-form uniform nuclear colloidal particles with citrate before the growth step. This preliminary action establishes a uniform particle foundation that enables precise control of final particle size and shape in the subsequent growth step, resolving the contradiction between process simplicity and manufacturing precision

Inventive Principle:
Principle #10Preliminary action

2Device complexity

If a citrate or ascorbate alone is used as reducing agent, then the production process is straightforward, but gold colloid having a sharp particle size distribution cannot be obtained

Engineering Contradiction:
Improvecomplexity of reduction processVSAvoidsharpness of particle size distribution
Core Design Contradiction:
Device complexityVSManufacturing precision

Solution Approach 1:

The reduction process is segmented into nucleation (citrate) and growth (ascorbate) steps, where each reducing agent performs a specific function. Citrate controls nucleation to establish uniform particle numbers, while ascorbate controls growth to sharpen particle size distribution, achieving precise control without excessive process complexity

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Different reducing agents (citrate and ascorbate) with distinct chemical properties are used in sequence to change the reduction parameters. Citrate provides initial reduction for nucleation, while ascorbate provides controlled reduction for growth, enabling sharp particle size distribution through parameter optimization

Inventive Principle:
Principle #35Parameter changes

3Adaptability or versatility

If gold colloid has different aspect ratios, then various diagnostic uses can be accommodated, but the chroma saturation decreases and sensitivity is reduced

Engineering Contradiction:
Improverange of diagnostic usesVSAvoidchroma saturation and diagnostic sensitivity
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The growth step using ascorbate as reducing agent specifically promotes spherical particle formation by controlling anisotropic growth. This spheroidality ensures uniform aspect ratios across all particles, maintaining high chroma saturation and diagnostic sensitivity while still allowing size variation for different diagnostic applications

Inventive Principle:
Principle #14Spheroidality (Curvature)

4Productivity

If the particle size of gold colloid is not uniform, then production flexibility is maintained, but the sensitivity and reliability of in-vitro diagnostic agents cannot be improved

Engineering Contradiction:
Improveproduction flexibilityVSAvoidsensitivity and reliability of diagnostic agents
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The two-step reduction process segments particle formation into controlled nucleation and growth phases. This segmentation enables precise control of particle size uniformity through optimized parameters in each step, achieving both production flexibility and high diagnostic sensitivity/reliability

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The sequential addition of reducing agents with different properties provides inherent feedback control. Citrate establishes initial particle uniformity, and ascorbate refines size distribution based on the nucleated particles, creating a self-regulating system that ensures uniform particle size for high diagnostic performance

Inventive Principle:
Principle #23Feedback

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 method produces gold colloid with a targeted particle size of 17 nm or more and a uniform, perfect spherical shape, achieving a sharp particle size distribution and high chroma saturation, making it suitable for in-vitro diagnostic agents with a standard deviation of less than 10%.

Implementation Method 1

a nucleation step of forming nuclear colloidal particles by adding a first reducing agent to a first gold salt solution... a citrate is used as the first reducing agent

Methodology Applied
Scientific EffectReduction: Reduction

Implementation Method 2

a growth step of growing nuclear colloid particles by adding a second gold salt and a second reducing agent... an ascorbate is used as the second reducing agent

Methodology Applied
Scientific EffectReduction: Reduction

Data Source

PatentEP2027956B1Process for production of colloidal gold
Publication Date: 2017.07.05 TANAKA KIKINZOKU KOGYO KK
  • EP2027956B1 patent drawingFigure 1~3
  • EP2027956B1 patent drawing
  • EP2027956B1 patent drawing

AI summary

It is an object of the present invention to provide a method for producing gold colloid having a targeted particle size, a sharp particle size distribution and a uniform and perfect spherical shape. The present invention relates to a method for producing gold colloid including a nucleation step of forming nuclear colloidal particles by adding a first reducing agent to a first gold salt solution; and a growth step of growing nuclear colloid by adding a second gold salt and a second reducing agent to the solution of the nuclear colloidal particles, characterized in that the growth step is performed at least once; a citrate is used as the first reducing agent and an ascorbate is used as the second reducing agent; and the addition of the ascorbate in the growth step is performed simultaneously with addition of the second gold salt. According to the method for producing gold colloid of the present invention, gold colloid having a sharp particle size distribution and a uniform and perfect spherical shape can be obtained.