Cryogenic Cooling Manifold for Ice-Free Rapid Sample Plunging
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Solution Overview
Problem
Current methods for cooling small biological samples in cryogenic applications, such as X-ray crystallography, result in sample damage and irreproducible results due to rapid cooling rates and ice formation, which hinder the determination of molecular structures and lead to low diffraction quality.
Innovation Solution
A cryogenic cooling manifold system that manages gas layers above a liquid cryogen to control cooling temperature-time profiles and prevent ice formation, enabling variable and high cooling rates for small samples, with features like a vertically oriented plunge bore, supply and exhaust channels, and a heater to maintain optimal temperature gradients.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If rapid cooling is used to achieve high cooling rates, then cooling speed is improved, but sample damage increases due to ice formation
Solution Approach 1:
The invention changes the physical-chemical parameters of the cooling environment by introducing controlled gas flow rates and temperatures. By adjusting gas flow parameters (velocity, temperature, composition), the system achieves rapid cooling while preventing ice crystal formation through modified heat transfer characteristics and vapor pressure control.
Solution Approach 2:
The invention uses an inert gas atmosphere (such as nitrogen or argon) to replace ambient air during the cooling process. This inert environment prevents oxidative damage to the sample while the controlled gas flow enables rapid heat extraction. The inert atmosphere also suppresses unwanted chemical reactions and maintains a stable cooling environment.
2Device complexity
If manual cooling methods are used, then device complexity is reduced, but measurement precision decreases due to irreproducible results
Solution Approach 1:
The invention incorporates feedback control mechanisms that monitor cooling parameters (temperature, gas flow rate, pressure) and automatically adjust them to maintain optimal cooling conditions. Temperature sensors and flow meters provide real-time data to a control system that modulates gas flow and cooling power, ensuring reproducible results across multiple samples while maintaining manageable system complexity.
Solution Approach 2:
The invention uses pneumatic systems to control gas flow through the sample environment. By regulating gas pressure and flow rates through valves and flow controllers, the system achieves precise control over the cooling process. The pneumatic system enables reproducible cooling conditions without requiring complex mechanical moving parts.
3Productivity
If high cooling rates are applied, then productivity is improved, but manufacturing precision deteriorates due to ice crystal formation
Solution Approach 1:
The invention applies preliminary action by pre-cooling the gas stream and preparing the sample environment before the actual rapid cooling begins. The gas flow is pre-conditioned to optimal temperature and velocity, and the sample chamber is pre-stabilized. This preliminary preparation ensures that when rapid cooling commences, the conditions are already optimized to prevent ice formation while achieving high cooling rates.
Solution Approach 2:
The invention employs periodic modulation of gas flow rates and temperature during the cooling process. By alternating between different flow regimes and temperature levels, the system controls the cooling rate dynamically. This periodic action prevents runaway cooling that would cause ice formation while maintaining high average cooling rates for improved productivity.
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 achieves the largest possible cooling rates for small samples, up to 100,000 K/s, while minimizing sample damage and ensuring reproducibility, thereby optimizing cryopreservation and improving the quality of molecular structure determination.
Implementation Method 1
manages the gas layers above a liquid cryogen to control cooling temperature-time profiles
Implementation Method 2
manages the gas layers above a liquid cryogen to control cooling temperature-time profiles
Implementation Method 3
with features like a vertically oriented plunge bore, supply and exhaust channels, and a heater to maintain optimal temperature gradients
Implementation Method 4
This system achieves the largest possible cooling rates for small samples, up to 100,000 K/s
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.