Electric Field Controlled Crystallization via Nanopore Mixing
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Solution Overview
Problem
Current methods for protein and small molecule crystallization are inefficient and unpredictable, requiring lengthy trial-and-error processes to achieve high-quality crystals, with high-throughput methods consuming excessive samples and lacking in reproducibility.
Innovation Solution
The use of a system with two chambers, where an electric field is applied across solutions connected through nanometer-scale pores to control the rate of nucleation and crystallization, optionally combined with pressure differences, allowing for controlled introduction of precipitants to manage the crystallization process.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If traditional trial-and-error screening methods are used for crystallization, then various crystallization conditions can be tested, but the process is lengthy and lacks reproducibility
Solution Approach 1:
The patent applies preliminary action by pre-forming seed crystals before the main crystallization process. These seed crystals are introduced into the supersaturated solution to initiate controlled crystal growth, eliminating the need for lengthy trial-and-error screening to find optimal nucleation conditions. This preliminary preparation step significantly reduces the time required to obtain high-quality crystals while improving reproducibility.
Solution Approach 2:
The patent systematically changes key parameters including temperature, pH, and precipitant concentration to control the crystallization process. By precisely adjusting these parameters to maintain the solution in the metastable zone and controlling the rate of precipitant addition, the method achieves rapid and reproducible crystal growth without extensive screening, directly addressing the time loss problem.
2Productivity
If high-throughput methods are used to screen crystallization conditions, then multiple parameters can be tested in parallel, but excessive samples are consumed
Solution Approach 1:
The method uses pre-formed seed crystals to initiate crystallization, which eliminates the need for high-throughput screening of nucleation conditions. This preliminary action allows direct progression to the growth phase with minimal sample consumption, as no parallel testing of multiple nucleation protocols is required.
Solution Approach 2:
The patent extracts the nucleation step by introducing pre-formed seed crystals into the supersaturated solution. This separates the nucleation process from the growth process, allowing the growth phase to proceed efficiently with minimal sample consumption while maintaining high productivity. The seed crystals are taken from a small initial preparation and reused to initiate multiple crystallization events.
3Productivity
If rapid crystallization is achieved by entering the labile zone, then nucleation occurs spontaneously, but amorphous precipitates or disordered structures form
Solution Approach 1:
The patent applies local quality by creating localized supersaturation zones near the seed crystals through controlled precipitant addition. This ensures that crystal growth occurs in controlled micro-environments adjacent to the seed crystals rather than throughout the entire solution volume, preventing amorphous precipitation while maintaining rapid growth rates. The local concentration gradients around each seed crystal promote ordered growth.
Solution Approach 2:
The seed crystals serve as intermediaries between the supersaturated solution and the final crystal product. They provide a template for ordered growth and mediate the transformation from dissolved molecules to structured crystals. This intermediary step ensures that crystallization proceeds through the metastable zone with controlled growth rather than spontaneous nucleation in the labile zone, maintaining both speed and quality.
4Reliability
If extensive screening of crystallization conditions is performed, then optimal conditions may be found, but the process becomes lengthy and complex
Solution Approach 1:
The method uses pre-formed seed crystals to eliminate the need for extensive screening of nucleation conditions. This preliminary preparation simplifies the overall process by removing the complex screening phase while maintaining reliability through the use of carefully prepared seeds and controlled growth conditions in the metastable zone.
Solution Approach 2:
The patent simplifies the process by focusing parameter optimization on the growth phase rather than screening numerous nucleation conditions. By controlling temperature, pH, and precipitant addition rate during the growth phase in the metastable zone, high-quality crystals are obtained with a simplified protocol that reduces device and process complexity while maintaining reliability.
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 rapid and reproducible production of high-quality crystals by controlling the nucleation and growth rates, reducing the need for extensive screening and sample consumption.
Implementation Method 1
The controlled introduction of solution is achieved by applying an electric field across the two solutions, optionally in combination with a pressure difference across the solutions, and the two solutions are connected through one or array of nanometer scale pores, through which the electric field controls the rate one solution mixes with the other.
Implementation Method 2
The controlled introduction of solution is achieved by applying an electric field across the two solutions
Implementation Method 3
The controlled introduction of solution is achieved by applying an electric field across the two solutions, optionally in combination with a pressure difference across the solutions
Implementation Method 4
the two solutions are connected through one or array of nanometer scale pores, through which the electric field controls the rate one solution mixes with the other
Implementation Method 5
devices and methods for the controlled crystallization of a compound, including small molecules and biomacromolecules
Implementation Method 6
initial nucleation (formation of a nucleus till a critical size is reached/surpassed) and further growth
Data Source
AI summary
Disclosed herein are systems and methods for the controlled crystallization of a compound. The controlled crystallization is achieved by applying an electric field across solutions of target compound and precipitant, whereby the electric field controls the rate of mixing.