A novel impermeable sterile pouch is developed to allow the forced convective heating mechanism for improving the sterilization cycle. The heating process is parametrically investigated to obtain an optimized condition in which a sterilization load is heated from 20 to 45 °C within 2 min, and the forced convection is experimentally and numerically analyzed to find that the convection coefficient is dramatically increased to 450 W/m2 K when compared with the conventional natural convection coefficient of 80 W/m2 K. The optimized heating process is applied to a sterilization cycle using the impermeable pouch, and the overall sterilization cycle is found to be completed within 7.5 min whose performance is validated by using a process challenge device.
The need for appropriate disinfection is emphasized by various occurrences resulting from improperly decontaminated patient-care items. Various sterilization methods are used in hospitals and clinics, which are normally categorized into physical and chemical sterilization. The physical sterilization is considered the most reliable sterilization method for the items that can withstand heat, and this sterilization method is applicable to both moisture-sensitive and moisture-resistance products, for which dry (160–180 °C) and moist (121–134 °C) heat sterilizers are, respectively, used in hospitals and clinics. The low-temperature chemical sterilizer was developed for reusing heat sensitive medical devices where the sterilization cycles are processed by utilizing chemicals, such as ethylene oxide (EO) and hydrogen peroxide.1–8
The EO gas has been used as a sterilant of the low-temperature (37–63 °C) chemical sterilizer since the 1950s, and it was considered as a representative of chemical sterilization method. Although the EO gas sterilization produces the effective decontamination for various medical devices at low temperature, the hospitals and clinics are gradually reducing the use of this kind of the toxic sterilization method. The toxic sterilant requires long purification process after its sterilization cycle, and overall sterilization cycle normally takes about 10 h. Tyvek® is a sterile medical packaging material with high-gas permeation, serving as an excellent microbial barrier against micro-organisms, which is generally used for chemical sterilization. The porous barrier materials of Tyvek limit sterilization efficiency in order to secure the microbial barrier system, and the flow inside the conventional pouch cannot be controlled independently.9–13
In this work, a novel sterile pouch is presented, which utilizes an impermeable pouch that improves the sterilization efficiency of hydrogen peroxide sterilization. Hydrogen peroxide low-temperature sterilization was developed and commercialized in the 1990s, in which the sterilant of hydrogen peroxide gas provides a robust antimicrobial activity in a wide range of micro-organisms, such as bacteria, yeasts, viruses, and bacteria spores. The sterilant of hydrogen peroxide is not toxic and does not leave significant residues on the sterilized devices, which can be handled safely either for immediate use or storage without long purification process. The hydrogen peroxide is vaporized at a temperature of about 150 °C under atmospheric pressure, but the temperature can be reduced to about 45 °C by processing under vacuum condition (less than 50 Torr for the hydrogen peroxide sterilizer). It is noteworthy that these temperature and pressure conditions are critical for the sterilant to be in the gas phase, which secures the sterilization performance of the hydrogen peroxide sterilizer.
Sterilization loads are required to be heated up to 45 °C during the heating process prior to the sterilization process. When the heating process is not properly performed, the vaporized hydrogen peroxide is condensed on surfaces of the sterilization load. This condensation may be exposed to its user to cause irritation to eyes, mucous membranes, and the skin; its sterilization cycle may not be successfully completed, and the condensed sterilant is also considered as sterilant loss for properly performing a sterilization process. The heating process is, therefore, fundamentally important to secure user safety and sterilization performance. It is important to emphasize that the heating process is not efficient especially under a vacuum condition in which the hydrogen peroxide sterilization is operated, and the overall sterilization cycles normally take about 1 h.14–17
The heat transfer mechanism is investigated in its wide application areas. Thermal convection is a mode of energy transport through the combined action of conduction, energy accumulation, and movement of the medium, and this convective heat transfer mechanism is studied to improve and control heat transfer phenomena inside a thermal system.18–28 In this work, a novel low-temperature sterilization system using an impermeable pouch is presented, which allows forced convective heating to complete an overall sterilization cycle within 7.5 min. The heating mechanism is investigated experimentally and numerically, and the overall sterilization cycles are also validated by using a process challenge device (PCD).
II. EXPERIMENTAL SETUP
A conventional sterile packaging pouch is normally composed of the permeable film (Tyvek), and a sterilant of vaporized hydrogen peroxide is delivered to the sterilization load in the pouch through the permeable film. A novel impermeable pouch (STERPACK®) is presented, which is composed of the impermeable film and nozzle, as depicted in Fig. 1. The film includes polypropylene (PP) and nylon (NY) films whose thickness is 60 and 25 μm, respectively.
As shown in Fig. 2, the pouch is designed to be operated by using a designated sterilizer (STERLINK®), and the needle of the sterilizer moves upward to connect the pouch when a sterilization cycle is initiated. The sterilant of the vaporized hydrogen peroxide is provided directly into the pouch through the nozzle by which the pouch is connected to the sterilizer, and the sterilant is diffused inside the pouch. The nozzle contains a sealing pad made of an elastic material such as silicone rubber, and the needle can pass through the nozzle without creating vacuum leakage. It is also noteworthy that the sterilant and residual gas are pumped out after the sterilization cycle, the needle is removed from the nozzle, and the pouch is automatically sealed to constitute a sterile barrier system (SBS) under vacuum condition.
The heat transfer process is classified into thermal conduction, radiation, and convection, as demonstrated in Fig. 2. The thermal boundary condition is characterized by the sterilization vacuum chamber whose temperature is set to be 55 °C. The initial condition for the sterilization load is experimentally and numerically set to be 20 °C, and the load temperature is required to increase up to 45 °C for obtaining a successful sterilization cycle. It is noteworthy that the initial temperature of the pouch and ambient condition are experimentally controlled to have the same condition for the load of 20 °C. A remote temperature sensor (HiTemp140, MadgeTech, Inc.) is used as a sterilization load to monitor the temperature and to investigate the heating mechanism of the pouch in which the sensor utilizes a resistance temperature detector (RTD). The sensor is dependent on pressure change, and the experiments are performed under the fixed pressure conditions as shown in Fig. 3. The sterilization process parameters of the pressure and temperature are also independently monitored by the sensors of the sterilizer.
The optimized heating process for the impermeable pouch is experimentally found and applied for its sterilization cycle. The sterilization performance is validated by using the half-cycle overkill method to demonstrate the sterility assurance level (SAL) of 10−6 in which the PCD is used as a single stainless-steel lumen with an inside diameter of 0.7 mm and a length of 500 mm. The SAL of 10−6 is validated by using self-contained biological indicator (SCBI; BT96) containing more than 1.0 × 106 Geobacillus stearothermophilus (ATCC 7953) spores. The PCD including the SCBI is placed at the hardiest position inside the impermeable pouch to be exposed to the half cycle, and the performance was validated with three consecutive half sterilization cycles according to the international standard of ISO 14937. It is important noting that the insufficient heating may result in the sterilant condensation inside the PCD and failure of the sterilization cycle.
III. RESULTS AND DISCUSSION
The heat transfer mechanism is experimentally and numerically investigated. The red circles and blue squares shown in Fig. 3 are the experimental results obtained under the vacuum and atmospheric pressure conditions, respectively. The temperature profiles are obtained by using the remote temperature sensor, which is positioned at the center of the sterilization vacuum chamber. It is important to emphasize that the convective heating is negligible under vacuum condition, and the difference between the red and blue curves comes from the convection heating. It is also noteworthy that the two curves are obtained under the same conditions for the conduction and radiation heat transfer mechanisms.
The conduction is the transfer of internal energy by microscopic collisions between particles in matter, and the rate of energy transfer between the two bodies depends on the temperature difference and the properties of the thermal conductive interface. The conduction heat transfer is basically described by Fourier’s law in which the rate of conduction heat through a material is proportional to the negative gradient in the temperature and to the area. The differential form of the heat conduction law is given as
where Qs is the conductive heat flux per unit surface area, k is the thermal conductivity, and −∇T is the negative temperature gradient. Based on the experimental results, the contact fraction is numerically fitted to be 1% of the total area of the sterilization load.
The thermal radiation is electromagnetic radiation generated by the thermal motion of particles in matter, and it is due to the conversion of thermal energy into electromagnetic energy. The thermal radiation is characterized by surface properties, such as surface temperature and its spectral emissivity, which is expressed by Kirchhoff’s law, and the effective emissivity for the sterilization load is numerically fitted to 0.8. The radiation transfer heat is directly proportional to the emissivity and the fourth power of temperature by the Stefan–Boltzmann law as
where QR is the radiated heat flux per unit surface area, ɛ is the emissivity, σ is the Stefan–Boltzmann constant, and TC and TL are temperature of the sterilization chamber and load, respectively.
The red and blue curves shown in Fig. 3 are obtained under the same conditions for the conduction and radiation heating whose fractional contribution is found to be 10% and 90%, respectively, in which each contribution is calculated by averaging each heat flux during the heating process of 100 s. The blue curve of the figure is obtained with the natural convection whose heat transfer coefficient is numerically fitted to be 80 W/m2 K. The conductive, radiative, and natural convective heat transfer mechanism is analyzed, and each contribution is calculated to be 4%, 35%, and 61%, respectively. It is also noteworthy that the convective heat transfer mechanism is most effective, and it is found that the heating process for the low-temperature sterilizer can be improved by controlling its operation pressure.
Thermal convection can be classified into natural and forced convection depending on how the fluid motion is initiated. In natural convection, any fluid motion is caused by natural means with low heat transfer efficiency (the blue curve in Fig. 3), and heat transfer can be enhanced by the fluid motion in the forced convection (the black curve in Fig. 3). The rate of convection heat transfer is expressed by Newton’s law of cooling as follows:
where QC is the convective heat flux per unit surface area, Hc is the convective heat transfer coefficient, and TA is the temperature of the gas inside the pouch. The convective heat transfer coefficient is strongly dependent on the fluid properties and type of fluid flow, i.e., laminar or turbulent. The laminar and turbulent flow regimes can be characterized by the Reynolds number defined as
where ρ, u, L, μ, and ν are the density of the fluid, flow speed, characteristic linear dimension, dynamic viscosity, and kinematic viscosity of the fluid, respectively. As demonstrated in Fig. 2, the pressure of the pouch and sterilization chamber can be independently controlled by the sterilizer, and the air flow of the pouch can be controlled together with the shape of the pouch.
The pouch is operated to be swelled and shrunk periodically to generate turbulent flow inside the pouch, which increases the heat transfer coefficient, and the period is parametrically investigated in a range from 0.3 to 5.0 s to find an optimized condition for the forced convection. The black triangles plotted in Fig. 3 represent the temperature profile obtained for the optimized condition whose oscillation period is 0.5 s, and the overall heating efficiency was significantly increased to obtain the heating of the sterilization load from 20 to 45 °C to be completed within 100 s. It is fitted by using the numerical modeling to find that the convective heat transfer coefficient is 450 W/m2 K (black line), which is about 5.6 times higher than the nature convection whose coefficient is 80 W/m2 K (blue line). The Reynolds number for each case is calculated to be 17 400 and 568, which are corresponding to the Nusselt number of 80.2 and 14.2, where the flow velocity for each case has been found to be 68.5 and 2.15 m/s, respectively.29 A larger Nusselt number indicates more active convection with turbulent flow, and it is found that the turbulent flow inside the pouch can dramatically increase the rate of convection heat transfer even under vacuum condition.
Shown in Fig. 4 are profiles of the operational parameters of temperature and pressure monitored by using the remote sensors positioned in the impermeable pouch during the overall sterilization cycle. It is found that overall sterilization cycle can be completed only in 7.5 min in which the heating (2 min), vacuuming (1 min), sterilization (4 min), and purification (0.5 min) processes are included. As depicted in the figure, the sterilization process consists of two consecutive identical sterilization phases in which the critical process parameters of the phases are same. The sterilization performance is also successfully validated by using the PCD with three consecutive half sterilization cycles according to the international standard of ISO 14937. It is noteworthy that the overall cycle time for the conventional hydrogen peroxide sterilization is about 1 h including the heating time of about 20 min, and the novel impermeable pouch enables an extremely fast sterilization cycle.
The key feature of the impermeable pouch is that the pressure and the pouch and chamber can be controlled independently during a sterilization cycle. It is noteworthy that the sterilization process is rapidly completed, which is experimentally found to be related with the pouch compression, which is a pressure peak in each sterilization phase, as depicted in Fig. 4. The pressure peak is resulted by increasing pressure of the chamber while the pouch is isolated, and the compression pressure is parametrically investigated to obtain the optimized condition for enhancing sterilization efficiency. Further investigation will be performed to understand its underlying physics, and the results will be reported elsewhere.
A novel sterile pouch using an impermeable film is presented to improve the heating process, and the experimental and numerical investigations are performed to find that the convective heat transfer coefficient for the forced convective heating is increased more than five times when compared to the natural convective heating. By virtue of the impermeability, the sterilization process is also improved to obtain an overall sterilization cycle completed within 7.5 min, and it is interpreted in terms of the pouch compression.
This study was supported by the National R&D Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (Grant No. 2019-0082624). Additional support for this study was provided by the KAIST NEW DEAL PROJECT funded by the Ministry of Science and ICT, Republic of Korea.
All authors contributed equally to this work.
The data that support the findings of this study are available from the corresponding author upon reasonable request.