DESCRIPTION

Technical Field

The technical field of the invention is films and surfaces that can be disinfected by heating. The invention refers to a new self-disinfecting, thin and flexible or semi-flexible film that has built-in heating elements that allow it to heat up and return to room temperature in a very short time with the immediate effect of reducing Community Acquired Infections (CAIs) and Healthcare Acquired Infections (HAIs), caused by direct contact with contaminated surfaces.

This is achieved by applying a rapid, thermal shock to the pathogens sitting on the film, killing them. This invention describes the integration of the novel film to high-touch surfaces (by film placement/mounting/embedding) such as door handles and knobs, furniture, medical instruments, carts and equipment, hospital equipment or even masks protection that are susceptible to contamination. The rapid return of the temperature to the ambient temperature allows use without the risk of bums.

Prior Art

Community- Acquired Infections (CAIs) - such as COVID-19 - are infections acquired by the general population in a non-medical setting. CAIs pose a major global risk since they are not limited to a health care setting and can easily spread to congested places through direct (person-to-person) or indirect (via contaminated surfaces or objects) transmission. The recent experience of COVID-19 has revealed the magnitude of the problem and forced governments to take extreme hygiene measures. Surface disinfection has become an undeniable requirement not only in healthcare settings but also in high-traffic areas, including supermarkets, restaurants, public transport, gyms and communal areas. In addition to CAIs, Hospital Acquired Infections (HAIs), are infections that affect patients and health care personnel in hospitals and other health care facilities that are not present on admission [Haque et al., 2018]. HAIs are an ongoing threat as they are responsible for millions of deaths worldwide each year. The prevalence of HAIs is extraordinary: of every 100 hospitalized patients, 7 patients in developed and 10 patients in developing countries will acquire at least one healthcare-associated infection (WHO, fact sheet on HAIs). The prevalence of HAIs in Greek hospitals is ~9% (Gikas et al. 2002), one of the highest rates in the European Union (Cassini et al., 2018). Slightly lower rates exist in the USA and other developed countries (Klevens et al., 2007) (Martone W. et al., 1992). According to the European Center for Disease Prevention and Control, more than 4 million episodes of HAIs are reported each year in Europe (World Health Organization, 2011), corresponding to ~40,000 deaths. In addition to morbidity and mortality, CAIs and HAIs cause a prolonged medical stay and a marked increase in the annual cost of medical care.

The spread of CAIs and HAIs through indirect transmission is caused by viruses, bacteria, and oother microorganisms that are transferred from a contaminated surface to a person. In a health care facility, the presence of contaminated surfaces (e.g. door handle, medical instruments, etc.) is very common. These pathogens can survive for a long time on surfaces and even colonize temporarily on workers' hands (Weber D. et al., 2010). The risk of developing such an infection is higher in low- and middle-income countries mainly due to poor sanitation (WHO, 2011).

Two main criteria are used to assess the microbiological status of contaminated surfaces (Dancer SJ, 2004): (i) the presence of a specific pathogenic marker and (ii) the total number of colonies in Colony Forming Units per cm ² of surface area (CFU/cm ² ). Scientific trials have established a limit of less than 5 CFU/cm ² on all hand contact surfaces in order to minimize HAIs (Dancer S.J., 2004). Chemical methods of decontamination with liquid disinfectants and foams - such as hand washing and frequent surface cleaning - is the gold standard. In fact, most organisms can persist for a long time on surfaces - from a few days to a few months (Kramer A. et al., 2006) - and it is impractical to perform frequent cleaning to keep surfaces disinfected. According to studies in many healthcare facilities, more than half of the surfaces examined were found to be insufficiently clean.

The World Health Organization (WHO) indicates that effective hand hygiene is the most important practice to prevent HAIs (Pittet D. et al., 2016). While current practices focus on improving hygiene protocols and specifically hand hygiene, several research efforts have been made to develop and implement new disinfection technologies (Humphreys H., 2014). Ultraviolet (UV) light has been proposed to disinfect contaminated surfaces (Casini B. et al., 2019) (Chang J. et al., 1985). Ultraviolet light has been shown to contribute to the radical reduction of the survival of microorganisms and bacteria. This technology requires the use of powerful UV lamps that must be installed in hospital rooms. A major disadvantage of UV light is its reduced effectiveness in disinfecting shaded surfaces, which has led to the limited practical use of this technology (Andersen B. et al., 2006). In addition, UV exposure cannot be used in high traffic areas or in public areas, e.g. corridors and waiting rooms, as staff and patients cannot be exposed to UV light. An improved variation of the above technology is the use of surface coatings with UV light (Foster HA et al., 2011) (Hwang et al,, 2020). These coatings produce cytotoxic substances and cause a marked decrease in the survival of microbial colonies. However, they do not sufficiently affect all different types of pathogens and are difficult to apply in a clinical setting as they require a constant source of photoactivation.

Coatings impregnated with metals, such as silver or copper, have also been studied as selfdisinfecting surfaces and have been shown to be effective for up to several hours (Schmidt M. et al., 2012). However, these metal surfaces must be coated with corrosion inhibitors that reduce the effectiveness of their antimicrobial action. A similar approach based on coatings containing quaternary ammonium silyloxide and titanyloxide moieties was shown to effectively reduce the number of CFU/cm ² for weeks (Tamini A. et al., 2014).This claim remains highly questionable as the validation process was combined with normal cleaning procedures and even in the second week of use, some of these coatings were found to fall short of the critical threshold of less than 5 CFU/cm ² . More recently, surfaces with geometric micropattems have been proposed as a potential solution to prevent microbial attachment (Xu et al., 2017). Several geometries consisting of micropillars or microchannels have been developed (Mann E. et al., 2014) but no clinical validation of this technology nor has pathogen reduction rate been reported.

Other convectional technologies, such as the 'PullClean' technology (Altitude Medical Incorporated) targeted specifically door handles. PullClean a low-tech handle that incorporates a hand sanitizer — contained in a refillable container — into a doorknob. The downside of this product is that it relies on the individual's willingness to use it, making it difficult to predict its effectiveness. Moreover, it is difficult to imagine how such a handle can be integrated into every surface of a hospital or public space. The application of UV radiation to doorknobs has also been reported but without commercial success due several factors: the radiation must not come into contact with the user, the cost of installation and operation (energy-consuming) is high and the requirement for a special configuration of the surrounding area.

Heating technologies have been implemented to disinfect surfaces using metal heating resistors below or integrated with the surface. The main problems of this application are the high thickness of the film that contains the heating elements, the lack of flexibility of the film, the high current consumption that makes it prohibitive on large surfaces and the significant time required for the surface to return to room temperature that makes heating practically unsuitable for high-touch surfaces. Heating systems for use in the disinfection of medical instruments (patents CN104622542B, CN204484251) have been reported for the purpose of transmitting heat to other media to sterilize them. Heating elements have been used in door handles (CN 108543103 A, CN111852182), but they do not solve the problem of rapid heating and cooling to prevent bums since the whole handle is heated, while the user is forced to wait for a long time until it cools down.

Description of the Invention

The invention consists of a thin and flexible or semi-flexible film (Figure 1) which has micro/nano heaters integrated in its body or on its surface which can instantly heat the surface, and which is then cooled within seconds at ambient temperature and results in the reduction of CAIs and HAIs by applying a rapid, thermal shock to the pathogens on its surface, killing them. The film consists of a thin layer (layer 1) of non- conductive material that provides mechanical support and thermal insulation and a second layer (layer 2) that incorporates the micro/nano heaters and touch microsensors that provide direct heating of the surface by applying the appropriate voltage. Optionally, the film consists of an additional layer of non-electrically conductive material, with high thermal conductivity, which provides protection for the skin when touched. The film has electrodes that are connected to the micro/nano heaters. By applying an appropriate electrical voltage, the film is heated by activating the micro/nano heaters (Figure 2) and thus the pathogens on the surface of layer 2 or 3 are killed as soon as the micro-heaters are activated. The small thickness of the film allows its temperature to quickly change from a temperature that kills pathogens to ambient temperature in a few seconds so that it can be used in applications that require periodic contact with users. In certain applications, this film is placed / embedded on high touch surfaces such as door handles and knobs, touch screens, furniture, medical carts and equipment or even protective masks.

Description of Figures

Figure 1. (A) Implementation of the film on a door handle. The film (1) is placed on top of a door handle (2) and is connected by a cable (3) to a source of electricity. (B) Cross sectional view of the film, consisting of 3 layers (1, 2, 3). Layer 1 is <500 pm thick and is made of low thermal conductivity material. Layer 2 is 0.1-5 pm thick and is electrically conductive. Layer 3 is 1-100 pm thick. An array of micro/nano heaters (III) provides localized, ultra-fast heating. The film also incorporates touch sensors (I) and grooves (II). (C) The film (1) placed on a high touch surface (2) which must be kept disinfected. Figure 2. (A) Top view of the film in one potential embodiment, showing the architecture of the micro/nano heater array consisting of 6X3 units. In this embodiment, each unit of the array is ~2 mm x 2 mm. The design is flexible as it can easily be scaled in size to cover areas of different size. Symbols indicate: I: Terminal, II: Micro/nano heater array, III: Grooves. (B) The film is connected to a power source (I) and to a microcontroller (II) to precisely control its activation. The schematics do not show the touch sensors that can be used in some implementations.

Figure 3. In some embodiments, the film fabrication process consists of 4 steps: (I) Deposition of Layer 2, (II) Pattern transfer to Layer 2, (III) Deposition of Layer 3, (IV) Selective removal of material from layer 1. In this specific embodiment, the membrane consists of 3 layers as indicated by the different coloring. In this particular embodiment, step IV is used to make the grooves in the substrate (Layer 1) that allow the film to be attached to non-flat surfaces as well as to minimize heat loss (by minimizing the contact area with the high-touch surface).

Figure 4. (A) The 2D heat transfer model used to simulate the thermal behavior of the film composed of 4 materials: I: LAYER 1 (silicon), II: LAYER 2 (silicon dioxide), III: Air, IV: High touch surface (at ambient temperature). (B) The time-dependent temperature profile of the top layer (layer 2) for different substrate (layer 1) thicknesses (100-500 pm) when a 1 s electrical pulse is applied. The arrow shows the duration of heating/disinfection.

Figure 5. (A) A heating film, 120 mm long and 15 mm wide, fabricated by Printed Circuit Board (PCB) processes. The microheaters are made from Cu (12 microns thick) and the substrate is made from FR4 (500 microns thick). (B) The time-dependent temperature profile of the microheater layer for two applied voltages. A PID controller was used to control the duty cycle of the electric power.

Detailed Description And Examples

The function of the film is based on the application of voltage so that the built-in micro/nano heaters rapidly increase their temperature up to 50-150°C killing pathogenic organisms on its surface. Due to the small thickness of micro/nano heater layer (layer 2) (in some embodiments the microheaters are less than 200 run thick), heat is localized and temperature rises extremely fast (in ms).

In one embodiment, the film consists of a thin layer (layer 1) of non-conductive material that provides mechanical support and thermal insulation and of a second layer (layer 2) that incorporates the micro/nano heaters and provides direct heating of the surface by applying an appropriate voltage. In some embodiments, layer 1 is less than 500 microns thick while in some embodiments it is a polymer or silicon or glass or ceramic. In some embodiments, Layer 2 is 0.1 to 5 microns thick and is made of a metal or a semiconductor or a conductive polymer. Layer 2 can have a thickness of up to 50 microns if it is produced by standard PCB manufacturing processes, but a higher electric energy/power will be needed to activate it In some embodiments, layer 2 also incorporates touch sensors. In some embodiments the film consists of an additional layer of non-electrically conductive material, such as glass, ceramic or polymer which provides protection for Layer 2 and for the skin upon contact.

In addition, in some embodiments, layer 1 has grooves or pillars or holes on the side not in contact with layer 2. The grooves/pillars are optional and have a dual role: they make this layer flexible or semi-flexible and provide thermal insulation as the trapped air inside them is an excellent thermal insulator. Implementations with the three layers are shown in Figure IB.

In some embodiments, the micro/nano heaters are distributed uniformly in the layer 2 to ensure homogeneous heating of layer 2 and/or of layer 3 in the event of their activation. Pathogens on the surface of layer 2 or/and 3 are killed when the micro/nano heaters are activated by applying voltage to their terminals. The heating can be instantaneous due to the small thickness of the film. Its temperature returns to ambient temperature in seconds or in fractions of a second as soon as the voltage is cut off. The activation/disinfection of the film requires a power supply and optionally a microcontroller that determines the time of voltage application and the electric power of the supply (determines the maximum temperature that the film will reach).

In one embodiment, the operation sequence of the film with its electronic accessories is as follows: (i) voltage is applied to the terminals of the micro/nano heaters activating them, (ii) the disinfection temperature is then reached quickly (in msec or sec), (iii) after a short time interval (in some implementations that interval has a range of 300 ms - 30 s the micro/nano heaters are turned off allowing the film surface to reach room temperature in seconds or fractions of a second (in ms).

In another embodiment the heating of the film is activated after the contact of the surface of the film with the skin or with another surface so that the sequence of operation is as follows: (1) the micro/nano heaters are initially deactivated, (2) a person touches the upper surface of film, (3) the film detects this event through the built-in touch sensors and activates the micro/nano heaters immediately after the person stops touching the surface, (4) the disinfection temperature is reached very quickly (in miliseconds or seconds), (3) after a certain time (e.g. 1-30 sec ) the micro/nano heaters are switched off allowing the film to reach ambient temperature in seconds . According to preliminary tests, it is possible to complete this thermal cycle in seconds. The concept of rapid heating and cooling is widely used in the food processing industry (e.g. ultrapasteurization of milk), but has never been applied to surface disinfection. For example, E.coli bacteria become inactive in 0.4 seconds when heated to 72°C (Sorqvist et al., 2003), while hepatitis A viruses are instantly inactivated at 85°C (Bidawid et al., 2000). For a complete list of deactivation times for common bacteria and viruses, see 'BOIL WATER' (Technical Brief from WHO, 2015) while different temperature and time parameters are applied to different pathogens.

Implementation

The design of the film was based on recent advances in flexible, wearable electronics (Kim et al. 2012) and flexible, MicroElectroMechanical Systems (MEMS) sensors (Xu et al., 2003) as various microfabrication processes have been developed to create flexible MEMS micro/nano heaters.

In one embodiment, as shown in Fig. 2, integrated micro/nano heaters (meander type) are used to provide uniform heating throughout the area. This particular design shows an array of 18 microheaters connected in series with the number varying depending on the surface area of the film. In different implementations, the micro/nano heater array is powered by a DC or AC power supply, by a battery or even by an energy recovery mechanism from the environment. An electronic microcontroller can be used to control the duration and electrical power of the actuation. A prototype developed in one embodiment uses standard microfabrication processes to make MEMS micro/nano heaters.

Figure 3 shows the four steps of the process followed. In some implementations, materials established in the MEMS field have been used. For layer 2, in some implementations we used metal and preferably Al, Cr/Au, ITO or polysilicon. For layer 3 in some embodiments, a thermally stable plastic and preferably parylene, or SiO2, or silicon nitride, or titanium nitride were used.

The production process of the film with standard microfabrication processes, used to manufacture MEMS micro/nano heaters, is the following: a layer of conductive material (layer 2) which constitutes the micro/nano heaters is deposited uniformly on an electrically, non-conductive substrate (layer 1), while in some embodiments a coating of a protective electrically, non-conductive material layer is placed on top of layer 2. In some embodiments, grooves or pillars or holes are created in the substrate to allow it to be attached to non-flat surfaces as well as to minimize heat dissipation.

To mass produce the film and to reduce costs, we used in some implementations roll-to-roll manufacturing processes where only metals and plastic materials are used. In other implementations, we applied processes used to manufacture Printed Circuits Boards (PCBs) boards in the electronics industry, where copper and FR4 are typically used for layers 2 and 1 respectively. In such implementations, the FR4 layer is typically 500 microns thick or less and the copper layer can be as high as 50 microns. Roll-to-roll processing is a process of manufacturing electronic devices on a flexible roll usually made of plastic or glass. The desired design is transferred to the roll by photolithography or printing techniques. The following two tables (table 1 and table 2) summarize the two methodologies mentioned above (with reference to the respective materials) by which the membrane can be manufactured.

Table 1. Film production steps with microfabrication/MEMS processes applied in different implementations.

Table 2. Roll-to-Roll film production steps implemented in different implementations

* ITO is a transparent metal/oxide. It is suitable for applications where functionality and aesthetics are important (e.g. glass doors, mirrors, touch screens). Validation of working Principle using Simulations

A 2D heat transfer simulation (in COMSOL) was performed to demonstrate the film’s working principle. The aim was to demonstrate theoretically that a simple thermal cycle consisting of a heating phase, a disinfection phase (steady state/temperature) and a cooling phase can be completed in about one second. We aimed for the duration of a single thermal cycle to be 1 s. For practical purposes - the disinfection phase is expected to last few seconds in order to kill the pathogens of interest.

The COMSOL model (COMSOL is a commercially available software for simulating physical processes) (Joyti B. et al. ,2016) consists of a substrate (layer I) of silicon of various thicknesses (100 - 500 jim) and a 5 m thick SiO ₂ (glass) layer (layer II) with embedded micro/nano heaters onto which the pathogens are putatively deposited (Figure 4A). In our simulations, the density of the SiO ₂ film (layer II in Figure 3A) is 2500 [kg/m ³ ], the thermal conductivity is 1.4 [W/mK], and the heat capacity is 750 [J/kgK]. The density of silicon (layer 1) is 2320 [kg/m ³ ], its thermal conductivity is 1.49 [W/mK] and the heat capacity is 678 [J/kgK], The dynamic viscosity, density, thermal conductivity and thermal conductivity of air were taken from the COMSOL database. We assumed that heat is transferred to the air by free convection and that the bottom of the silicon substrate is connected to a high touch surface (layer IV), such as a door handle. Layer IV was assumed to be at ambient temperature. We also assumed that the SiO ₂ layer is heated uniformly. We simulated the time-dependent temperature of the SiO ₂ film when an electrical pulse activates the micro/nano heaters for 1 second. The COMSOL results confirm the following (figure 4B): 70 ms and 400 ms are needed to reach the target temperature of 150°C (from room temperature) for the 100 pm and 500 pm thick silicon substrates respectively. A similar time response was obtained during the cooling phase. The decontamination phase (where the temperature is constant) lasted -800 ms and -200 ms for the 100 pm and 500 pm silicon substrates respectively. Veiy short response times are expected, due to the extremely small thermal masses involved in the micro/nano scale.

Previous studies suggest that such short heat shocks are sufficient to kill any pathogens deposited on contaminated surfaces (Parry JV et al., 1984).

Typical values for the electrical power required to reach the desired temperature was - 10 ⁹ x 10 ¹¹ W per cubic meter of film material (depending on substrate thickness), where higher powers can be used to shorten the time response. That means, for a typical door handle (total area 0.01 m ² ), a standard car-size battery will last thousands of cycles. For high touch surfaces found in high traffic areas (e.g. hospitals), it may be advisable to connect the film to an AC electrical outlet. If the target temperature is lower (e.g. 100°C), then the power consumption will be significantly reduced. It should be mentioned that in the unlikely event that someone touches the film while it is still warm; the temperature of human skin will not rise significantly. This is due to the large heat capacity of human tissue compared to the heat capacity of the film.

The use of the micro/nano heater film is intended to significantly improve hygiene and thereby minimize the transmission of HAIs and CAIs. It can be integrated into existing surfaces without making their use difficult. The developed heating film is scalable in size and versatile in design and can have many applications. For examples it can be placed over a hospital door handle, on a taxi door handle, on a stair railing in a concert hall, on the floor, on surgical instruments and medical instruments to ensure the efficient killing of pathogens. The fast heating and cooling behavior makes it safe for use by the public. Potentially low manufacturing costs and minimal maintenance also make it an ideal solution for use on any high touch surface. Validation of working Principle using Experiments

We fabricated a heating film by depositing a 12 microns thick layer of Cu on a 500 microns thick FR4 substrate (Figure 5A). A protective polymeric layer (~ 30 microns thick) was deposited on top of the microheaters to protect the Cu layer. We connected the film to a DC power supply and using a Proportional- Integral-Derivative (PID) controller, we activate it at different power levels. The PID was programmed to supply initially the maximum electric power to the film until the desired temperature was reached. When that happened, the duty cycle of the PID was reduced in order to maintain that temperature of the film.

The time-dependent temperature behavior of the microheater layer is shown in figure 5B, where the desired temperature is reach reached in 6-7 seconds depending on the applied voltage and duty cycle of the PID.

In this specific experiment, the duty cycle was decreased by the PID after the maximum temperature was reached.

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41. CN104622542B, (WANG YANJUN, 15/2/2017

42.CN204484251U, (WANG YANJUN), 22/7/2015

43.CN108543103A, (ZHOU ZHIYI), 18/9/2018

44.CN111852182, (ZHOU ZHIYI), 30/10/2020