Control system of cryogenic substances for rapid temperature control and transdermal drug delivery

Abstract

Medical cooling has evolved beyond its conventional role in cryoablation to encompass a broad range of therapeutic applications, including anti-inflammatory treatment, pain relief, neural blockade, cryo- lipolysis, and surface protection during energy-based thermal procedures. As these applications expand, precise control of cooling temperature has become increasingly critical, since inadequate or excessive cooling can result in unintended cellular damage, treatment failure, tissue discoloration, or irreversible functional impairment. Despite their widespread use, existing medical cooling technologies suffer from fundamental limitations. Many rely on mechanically actuated modulation strategies, which inherently constrain system responsiveness and stability. As a result, cooling is often operated under open-loop control schemes, with jet temperature predominantly regulated indirectly through pressure adjustment. These constraints hinder reliable and reproducible temperature control, thereby limiting the safe expansion of cooling-based therapies into emerging clinical domains that demand higher precision and adaptability. In this doctoral dissertation, an enthalpy control–based cooling technology utilizing a carbon dioxide (CO₂) two-phase jet is proposed to achieve both high cooling performance and precise temperature regulation. By directly controlling the thermodynamic state of the cryogen prior to expansion, the proposed system overcomes the limitations of pressure-dependent and mechanically modulated cooling approaches. The cooling mechanism and controllability of the CO₂ two-phase jet are systematically investigated through high-speed imaging and quantitative heat transfer characterization. These analyses elucidate the relationship between pre-expansion enthalpy, two-phase jet composition, and cooling performance, enabling the development of a robust and precise cooling control strategy. Building upon this capability, foundational studies on subcutaneous temperature modulation are conducted to demonstrate the feasibility of extending the proposed control framework toward medical cooling applications requiring spatially and temporally regulated thermal management. Furthermore, leveraging the precise temperature control and supersonic characteristics of the CO₂ jet, a novel transdermal drug delivery approach is explored. Particle dynamics and penetration behavior are analyzed through combined theoretical, in vitro, and in vivo investigations, confirming enhanced delivery trends and therapeutic efficacy. Collectively, this dissertation establishes a unified enthalpy- based CO₂ two-phase jet control framework, providing both the physical understanding and practical control strategies required for next-generation medical cooling and cooling-assisted therapeutic technologies.