Cryogenic Bubble Interaction: Challenges, Motivation and Potential Benefits in Cryosurgery

Schematic demonstrating the idea of an ultrasound-aided cryosurgical process comprising oscillating bubbles in liquid nitrogen for operating on a tumor. This idea was also discussed in Mondal et al., "Acoustic Cavitation-induced Shear: A Mini- Review," Biophysical Reviews (2021) and Mondal et al., "Numerical Investigation of the Flow-field Due to Oscillating GN2-LN2 Interface in Presence of Ultrasound," Space Cryogenics Workshop (2021). Credit: Indian Institute of Technology Kharagpur, IndiaCryogenic fluid management systems use pumps, turbines, pipes (chilldown lines), valves/orifice, etc., operating at very low temperatures (below 120 K) that are at considerable risk of heat-inleak from ambient surroundings (300 K). This leads to the development of a multiphase environment, consisting of both liquid and vapor, and manifests as several bubbles that undergo intense growth and collapse (commonly known as cavitation). Cavitation damage is a well-known risk to equipment, often causing the failure of the entire cryogenic system. However, bubbles in cryogenic systems need not always be a threat. Our investigation reveals the useful nature of bubble oscillation and its potential for specific applications at liquid nitrogen (LN2) temperature. 

This is possible when we look more closely at the different forms of bubble interaction that ultimately lead to cavitation damage. These include liquid jets, shockwaves, streaming motion, etc. Among these, streaming motion in liquid dominates when the bubble keeps oscillating in the presence of an acoustic perturbation (or soundwave), something quite like that taking place in a turbopump. It has been pointed out by previous authors that bubble interaction depends on certain physical properties of the fluid: compressibility, surface tension and viscosity for example. When compared to fluids at room temperature, these values vary by a significant margin for cryogens, LN2 for example. Hence, the flow features in multiphase LN2 would likely vary from that in water. 

Challenges

But there are many challenges with investigating bubbles in LN2. First and foremost, bubble oscillation generally takes place over a short time (~ microsecond) and spatial scales (~ micrometers). It is very difficult even with modern equipment to isolate and examine nitrogen bubbles at that resolution in LN2. In addition, there are other challenges to running repeatable experiments on such a small entity as a bubble in a controlled environment. The accessory costs (high-speed camera, specially fabricated leakproof vessels with optical windows, etc.) further add to the challenges of operating with LN2. 

Motivation

But these difficulties are much less when weighing the motivation behind applying nitrogen bubbles in creative applications, and one of these is the role of LN2 in cryosurgical operations. Cryosurgery provides a unique method of cancer treatment, wherein the premalignant and malignant tissues are frozen by open spraying of LN2. This is followed by several alternate cycles of freezing and thawing until the frozen part peels off/detaches from the body. This is relatively painless because liquid nitrogen can desensitize nerves around a frozen tissue. Also, LN2 – being non-toxic, inert and non-irritating – can sanitize the skin around a cancerous tissue. However, the multiple freezing and thawing cycles (until the portion peels off) invite problems like osmotic stress, denaturation of macromolecules, the release of lysosomal proteases, membrane disruption and intracellular ice formation. Hence, a less risk-prone cryosurgical process can help improve its effectiveness.

Potential Benefits

Oscillating bubbles in the presence of ultrasound can help improve the efficiency of these cryosurgical processes. This is because bubbles are known to generate several chemical and physical effects during their sustained oscillation or microstreaming. These oscillating bubbles, when introduced into a liquid, are known to inactivate microbes and generate shear forces in the adjacent liquid. However, the mechanism of these sub-processes is not clearly understood. Also, the typical governing parameters for micro streaming are not clearly documented. 

Our Findings

We try to navigate through this complex problem by first understanding the chemical effects of bubbles in controlled environment, with low dissolved gas concentration. Our studies (albeit in water) suggest that under such conditions, bubble collapse, as well as the rate of chemical reaction, is sharply reduced. This indicates that there is a much lesser chance of any untoward chemical reaction under evacuated conditions, irrespective of the solvent liquid.

To understand the physical effects of bubbles, two-dimensional and three-dimensional simulations were then performed to capture the dynamics of a single bubble (assigned properties of nitrogen vapor), located in the middle of a 20 kHz (and low power) acoustic field. Subcooled LN2 is selected as the surrounding liquid to assume minimal effects of heat and mass transfer. A fully developed ultrasound standing wave field is simulated around a bubble at resonant conditions. The liquid was free of any dissolved gases, in conjunction with our earlier experiment. We observed the shape evolution of the bubble with time (for both 2D and 3D simulation), showing a dominant and periodic shape (called shape mode oscillation). Additionally, 3D simulations helped capture the simultaneous formation of flow vortices in the adjacent liquid boundary layer. These vortices help generate shear stresses. The number of these vortices depends indirectly on the dominant shape mode. 

It was observed that the dominant shape could be controlled by indirectly controlling the operating pressure amplitude of the perturbation and the bubble radius. This finding offers confidence in the fact that shear stresses required for cryosurgery can be induced by bubbles and tuned by changing the power amplitude and frequency (to control the bubble size distribution) of the perturbation. Also, a controlled low-pressure environment (using a vacuum pump) would prevent external gas contamination. This may help check any chemical effects.

By combining conventional cryosurgery with simple ultrasonic equipment, one can facilitate an ultrasound-aided cryosurgical process, for efficient removal of cancerous tissue. This can be accomplished by operating a piezoelectric transducer in tandem with the nozzle spraying LN2 under evacuated conditions. The power amplitude and frequency of the transducer would be the operating parameters alongside that of the LN2 spray. 

Overall, cryogenics can help provide a solution to this increasingly widespread problem by updating conventional techniques with inexpensive ultrasound-based techniques, reducing the diagnosis time as well as the associated risks with post-surgery complications, and above all, offering relief to patients using modern treatment. Our preliminary results suggest that cryogenic flow-field can be abrasive and prospective for additional futuristic applications.

Image: Schematic demonstrating the idea of an ultrasound-aided cryosurgical process comprising oscillating bubbles in liquid nitrogen for operating on a tumor. This idea was also discussed in Mondal et al., "Acoustic Cavitation-induced Shear: A Mini-Review," Biophysical Reviews (2021) and Mondal et al., "Numerical Investigation of the Flow-field Due to Oscillating GN2-LN2 Interface in Presence of Ultrasound," Space Cryogenics Workshop (2021). Credit: Indian Institute of Technology Kharagpur, India

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