Cryogenic cooling apparatus, methods, and applications
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Solution Overview
Problem
Existing cryogenic cooling methods for small biological samples, such as those used in X-ray crystallography, suffer from irreproducibility, sample damage, and slow cooling rates, leading to incomplete data collection and structural variability due to ice nucleation and conformational changes during cooling.
Innovation Solution
A cryogenic cooling manifold and method that controls the gas layer above a liquid cryogen to achieve variable and rapid cooling rates, minimizing ice formation and sample damage by using a specially designed manifold with channels and heating elements to manage the temperature transition and gas flow.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Temperature
If manual plunge cooling into liquid nitrogen is used, then cooling is achieved, but cooling rate is slow and ice nucleation occurs
Solution Approach 1:
The patent introduces a controlled gas layer as an intermediary medium between the sample and liquid nitrogen. This gas layer mediates heat transfer, enabling rapid cooling while preventing direct contact that would cause ice nucleation. The gas layer acts as a buffer that controls the cooling process and eliminates harmful ice formation.
Solution Approach 2:
The patent changes the physical parameters of the cooling environment by controlling gas flow rate, gas temperature, and gas layer thickness. By adjusting these parameters, the system achieves optimal cooling rates while maintaining conditions that prevent ice nucleation, transforming the cooling process from a harmful direct plunge to a controlled parametric process.
2Object-affected harmful factors
If fast cooling is applied, then ice formation is reduced, but sample damage increases due to thermal stress
Solution Approach 1:
The patent applies local quality control by creating a non-uniform temperature distribution in the gas layer. The gas temperature and flow characteristics are optimized locally at different positions around the sample, allowing rapid heat removal from critical regions while maintaining gentler conditions elsewhere, thus preventing both ice formation and thermal shock damage.
Solution Approach 2:
The system dynamically adjusts gas flow rate and gas layer thickness during the cooling process. By making the cooling conditions time-dependent and adaptive, the system can achieve fast initial cooling to prevent ice nucleation, then gradually reduce cooling intensity to minimize thermal stress on the sample structure.
3Temperature
If gas flow is increased to remove cold gas layer, then cooling rate increases, but energy consumption increases
Solution Approach 1:
The patent applies partial action by using just enough gas flow to achieve the necessary cold gas layer removal and optimal cooling rate, rather than excessive gas flow. The system identifies and maintains the minimum required gas flow conditions that still achieve rapid cooling, thereby reducing energy consumption while preserving cooling effectiveness.
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
Enables cooling rates up to 100,000 K/s for small samples, ensuring reproducible and optimal cryopreservation with minimal ice formation and sample contamination, improving data collection efficiency in X-ray crystallography and other biotechnological applications.
Implementation Method 1
A cryogenic cooling manifold and method that controls the gas layer above a liquid cryogen to achieve variable and rapid cooling rates, minimizing ice formation and sample damage by using a specially designed manifold with channels and heating elements to manage the temperature transition and gas flow
Implementation Method 2
Cooling rates up to 100,000 K/s for small samples, ensuring reproducible and optimal cryopreservation with minimal ice formation and sample contamination
Data Source
AI summary
A cryogenic cooling manifold and methods incorporating a cryogenic cooling manifold for managing the gas layer(s) above a liquid cryogen to control cooling temperature-time profiles and ice formation for microliter and smaller samples that are plunged through the gas and into the liquid cryogen.