Macromolecular Crystallization Control via Segmented Observation

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Solution Overview

Problem

Current methods for controlling macromolecular crystallization lack universality and effectiveness in industrial production, particularly in observing crystal form, determining the crystal induction period, and ensuring the properties of crystal systems, such as particle size, morphology, and purity, which are crucial for pharmaceutical applications.

Innovation Solution

A high-precision experiment system that integrates environment control, droplet addition, and real-time observation using a closed space with a platform-equipped horizontal moving slot, droplet adding control module, observing module, and experiment condition control module, allowing for accurate positioning, temperature, and humidity control, along with high-speed camera observation for real-time data collection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If a confined space is used to control crystal form, then crystal growth can be accurately controlled, but observation of crystal form and determination of crystal induction period become difficult

Engineering Contradiction:
Improvecrystal form controlVSAvoidcrystal observation
Core Design Contradiction:
Manufacturing precisionVSDifficulty of detecting and measuring

Solution Approach 1:

The system divides the observation function into multiple components: a high-power camera for real-time imaging, a microscope for detailed crystal structure observation, and a computer system for data processing. This segmentation allows simultaneous confined space control and effective observation by distributing detection capabilities across multiple devices rather than relying on a single observation method.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces an intermediary observation system that includes optical instruments (microscope, camera) as mediators between the confined crystallization space and the researcher. These intermediaries capture and transmit crystal growth information without disrupting the confined environment, enabling accurate observation while maintaining crystal form control.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Ease of operation

If traditional experiment systems are used, then simple operation is maintained, but accurate droplet addition and real-time observation capabilities are insufficient

Engineering Contradiction:
Improveoperation simplicityVSAvoiddroplet addition accuracy
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The system employs self-service mechanisms for droplet addition through automated syringe pumps and microfluidic devices that automatically control droplet volume and positioning. The observation system also operates autonomously with automated camera triggering and data collection, reducing manual intervention while maintaining high precision in droplet addition and real-time monitoring.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent replaces manual mechanical droplet addition with automated control systems including syringe pumps, microfluidic channels, and computer-controlled positioning mechanisms. This substitution maintains ease of operation through automated interfaces while significantly improving droplet addition accuracy and enabling precise control of crystallization conditions.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Productivity

If high-throughput crystal production is implemented, then productivity increases, but drug loss and environmental impact increase

Engineering Contradiction:
Improvecrystal production throughputVSAvoiddrug loss
Core Design Contradiction:
ProductivityVSLoss of substance

Solution Approach 1:

The system implements recovery mechanisms for mother liquor and dissolved macromolecules through controlled backwash processes and filtration systems. Instead of discarding all liquid waste, the system recovers valuable components from the crystallization medium, reducing drug loss while maintaining high-throughput production capabilities through automated waste management and resource recovery processes.

Inventive Principle:
Principle #34Discarding and recovering

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 system enables precise control of macromolecular crystallization, increasing crystallization efficiency and success rate, facilitating high-throughput crystal production with minimal drug loss and environmental impact, suitable for large-scale and repeated use.

Implementation Method 1

The crystallization induction period of the target crystal form is determined by the real-time data of the high-power camera

Methodology Applied
Scientific EffectPhotography: Photography

Implementation Method 2

controlling droplet morphology and evaporation rate

Methodology Applied
Scientific EffectEvaporation: Evaporation

Implementation Method 3

controlling temperature and humidity conditions around the microlelement platform

Methodology Applied
Scientific EffectTemperature control: Heating

Implementation Method 4

the accurate position control of a syringe needle, the macromolecular solution can be added into the correct positions

Methodology Applied
Scientific EffectInjection: Injector

Data Source

PatentUS11452948B2Experiment system and method for accurate controlling of macromolecular crystallization process
Publication Date: 2022.09.27 DALIAN UNIV OF TECH
  • US11452948B2 patent drawing
  • US11452948B2 patent drawing

AI summary

An experiment system and method for accurate controlling of macromolecular crystallization process. The system has a platform-equipped horizontal moving slot and channel dedicated backwash module, a droplet adding control module, an observing module, a user observation computer system, and an experimental condition control module. A high-precision movement knob of the x-axis platform and the y-axis platform of the system and the accurate position control of a syringe needle are used to ensure that the macromolecular solution can be added into the correct positions of convex or concave. The crystallization induction period of the target crystal form is determined by the real-time data of the high-speed microcamera, and the crystal cultivation environment is adjusted in real time. This is simple and easy to operate, high in productivity, can be applied to the conventional experimental replication.