The continued trend toward smaller, more complex electronic systems enables more sophisticated smart products but creates additional challenges in manufacturing. For wearable and medical applications, in particular, concerns about adverse effects on skin and tissue drive a fundamental need for safe adhesive, sealant, coating, and encapsulant compounds. Designed to address these concerns, a class of compounds combines proven biocompatibility and noncytotoxic characteristics with performance properties required for manufacture of medical devices and wearables intended for contact with the human body.

For a wide array of applications, advanced adhesive compounds provide manufacturers with an effective alternative to mechanical fasteners in fabricating mechanical and electronic assemblies. For medical devices and wearable applications, the ability of these compounds to seal gaps and encapsulate assemblies simplifies manufacturing of products resistant to sweat, saline, biofluids, and other liquids. Used in healthcare devices, these compounds provide the essential properties required to withstand the stresses associated with clinical procedures as well as the temperatures or chemicals used with sterilization methods.

Sterilization Stress and Adhesive Compound Requirements

Different microorganisms and molecules like misfolded proteins, or prions, exhibit significantly different levels of resistance to denaturation or destruction (see Figure 1). Prion decontamination of instruments used in neurological procedures, for example, can require long-duration treatments with very strong reagents such as sodium hydroxide (NaOH) or sodium hypochlorite (NaOCl). More typically, hospitals and clinics use sterilization methods that destroy or denature all types of microbes including spores, which lie beyond the destructive capability of disinfectants.

Fig. 1 - The U.S. Centers for Disease Control and Prevention (CDC) categorizes the relative resistance to destruction of pathogenic agents (left) as well as the corresponding methods (right) required to achieve destruction. (Source: CDC)

Among available sterilization methods, conventional steam pressure sterilization in autoclaves is still considered the most effective. In this process, clinical instruments and devices are subjected to saturated steam, using elevated pressure to reach 121 °C for 30 minutes in a gravity displacement sterilizer or to reach 132 °C for four minutes in a vacuum sterilizer.

Despite its effectiveness, this method cannot be used in critical situations involving advanced medical devices and instruments where sustained high temperature can damage heat-sensitive electronic components in these systems. Even when steam pressure sterilization can be used in devices with more complex mechanical assemblies, manufacturers of those devices must ensure that materials such as adhesives used in fabrication can withstand the autoclaving process without compromising the strength of adhesive bonds or integrity of protective coatings. These concerns are further magnified for instrumentation designed for clinical reuse, where repeated steam pressure sterilization cycles might degrade adhesive bonds and seals.

For the sterilization of temperature-sensitive devices and instruments, the healthcare industry employs a wide variety of techniques including exposure to gamma or e-beam radiation as well as use of a number of chemical reagents including ethylene oxide (ETO), hydrogen peroxide (H2O2) gas plasma, liquid peracetic acid (PPA, or CH3CO3H), and many others. Although effective in destroying viruses, bacteria, and other microbial life, these methods each come with their own disadvantages and even represent safety hazards for workers. For example, many states require specific abatement technologies for use of ETO, and OSHA regulates its use to ensure occupational safety. Furthermore, PPA, H2O2, and many other chemicals used in low-temperature sterilization are hazardous to humans and damaging to materials, particularly many materials like copper, brass, and nickel/silver plating and alloys commonly used in electronic assemblies. Accordingly, compounds used to protect assemblies must themselves remain resistant to these chemical agents in one-time sterilization of disposable instruments or in repeated sterilization cycles for reusable instruments and devices.

At the same time, manufacturers of medical devices and wearables built with these compounds need to be confident that their products remain safe for use even with prolonged contact with skin and tissue. Manufacturers need assurance that the adhesive compounds used in product manufacturing will not stand as a roadblock to final product certification — much less prove to be hazardous to humans during long-term use of products manufactured with these compounds. For this reason, adhesives vendors use industry standard testing methods to ensure that these compounds are biocompatible and nontoxic to humans.

Biocompatibility and Cytotoxicity

For some types of materials, contact with human tissue can cause an immunological response such as a rash or even cause failure of tissue cell membranes and organelles, typically resulting in eventual cell death, or necrosis. The use of biocompatible, nontoxic materials to avoid these and other pathological effects has become an important factor in the manufacture of medical devices and even consumer wearables. In fact, failure to address these concerns has forced manufacturers of mainstream consumer wearables to withdraw some products found to result in cases of skin rash or worse.

To demonstrate that their products and materials exhibit no adverse effects, manufacturers of adhesive compounds and other materials used in manufacturing comply with two primary testing standards: United States Pharmacopeia (USP) Class VI for biocompatibility and ISO 10993-5 for cytotoxicity. USP Class VI uses a variety of in vivo testing methods to demonstrate that the material under test does not leach chemicals that could result in an immunological response or other adverse reaction. ISO 10993-5 provides additional rigor in that this testing standard uses in vitro methods to determine if the material under test exhibits cytotoxic effects that cause cell damage.

Table 1. ISO 10993-5 testing reactivity grades. (Source: Toxikon Final Report)

To pass ISO 10993-5 testing, manufacturers submit samples of their materials to independent testing labs. In this testing process, the independent testing lab combines the material under test with mammalian cells in a nutrient suspension. Laboratory technicians observe the cells in this suspension for signs of reactivity after 24 hours and again after 48 hours. In these studies, reactivity is defined in five different grades corresponding to different degrees of degradation of cell morphology (see Table 1).

Adhesives manufacturers have responded to the need for compounds that pass USP Class VI testing and ISO 10993-5 cytotoxicity testing while nevertheless providing the range of performance characteristics required in each application. As with other applications, the electronics assemblies at the heart of medical devices and consumer wearables need compounds able to meet a wide range of requirements for performance and workability. For example, an endoscope used for exploratory procedures needs adhesives and sealants that not only provide biocompatibility and noncytotoxic characteristics but also exhibit the strength and flexibility required to withstand handling and usage without bond or seal failure as well as the thermal or chemical resistance required to withstand repeated sterilization cycles without swelling or becoming brittle. In addition, some devices may levy critical requirements for thermal and electrical conductivity, requiring adhesive compounds created with specific fillers such as silver for assemblies that need both thermal and electrical conductivity or aluminum oxide for applications that require thermal conductivity but electrical insulation. Still other applications may require adhesive and sealing compounds with special color requirements or optical characteristics designed to selectively block or pass specific wavelengths of light.

Along with varied performance requirements, manufacturers require adhesive compounds able to bond or adhere to a wide range of materials while supporting a wide range of processing requirements. In some cases, fabrication requirements may require compounds with unlimited working, or pot life. In others, manufacturers may need the ability to rapidly tack an assembly with UV or LED light before fully curing the assembly with heat. Similarly, these dual-cure compounds may be a critical requirement for assemblies with shadowed areas that UV or LED light cannot reach. Similarly, processing requirements may dictate use of pre-measured two-part adhesive systems designed for rapidly prototyping an assembly or one-part premixed adhesive systems designed for simple application.

Epoxies, Silicones, and UV/LED Curable Chemistries

Despite the broad range of requirements for performance characteristics and processing properties, manufacturers can find suitable solutions among a number of medically safe adhesive systems available in a wide variety of chemistries including epoxies, silicones and UV/LED-curable compounds.

Table 2. ISO 10993-5 testing results for Master Bond EP42HT-2Med. (Source: Toxikon Final Report)

For example, epoxy systems such as Master Bond EP3HTMed, Master Bond EP42HT-2Med, and Master Bond EP42HT-2Med Black each meet USP Class VI biocompatibility and ISO 10993-5 cytotoxicity specifications for medical device assemblies. Independent laboratory tests show that systems such as Master Bond EP42HT-2Med can achieve a reactivity grade of 0 according to the definitions of reactivity defined in Table 1 (see Table 2).

Furthermore, each system offers excellent resistance to steam pressure sterilization as well as both radiation and chemical low-temperature sterilization methods. Manufacturers can use either epoxy system to meet a wide range of performance requirements for physical strength and bonding properties.

Manufacturers can nevertheless meet specific processing requirements using either of these epoxy systems. Because it is a one-part system, Master Bond EP3HTND-2Med Black requires no mixing and maintains contact with little sagging when applied to vertical assemblies thanks to its non-drip consistency. Furthermore, it offers an unlimited working life, curing only when heated to 250 °F for 20–30 minutes. This system can also cure within 5–10 minutes at 300 °F. If the application requires an epoxy with a lower cure temperature, the two-part Master Bond EP42HT-2Med Black system can cure in 48–72 hours at room temperature or in as little as 2–3 hours at 200 °F.

When a high flexible bond or seal is required for endoscopes and other medical devices, manufacturers can opt for suitable silicone systems such as the two-component Master Bond MasterSil 151Med or the one-part Master Bond MasterSil 912Med silicone systems. Besides meeting USP Class VI biocompatibility and ISO 10993–5 cytotoxicity standards, MasterSil 151Med and MasterSil 912Med each provide exceptional elongation characteristics at 120–150 percent and 250–350 percent, respectively.

Each of these silicone systems can withstand low-temperature sterilization with radiation or certain chemical agents. For applications involving optical assemblies, MasterSil 151Med remains optically clear and offers excellent wavelength transmission properties. To meet different assembly requirements, MasterSil 912Med provides a fast tack time solution with a tackfree time of 15–30 minutes at room temperature with full cure in 7 days. In contrast, MasterSil 151Med can cure in 24–48 hours at room temperature or in only 1–2 hours at 200 °F.

In some cases, an assembly may require a fast cure system but cannot tolerate elevated temperatures. For these cases, Master Bond LED405Med provides an effective one-part solution with its ability to cure in as few as 15–30 seconds on exposure to a blue (405 nm) LED. Ideally suited to optical medical instruments, Master Bond LED405Med is optically clear and bonds to a wide array of substrates including metals, plastics, and glass. At the same time, this system meets ISO 10993-5 standards for cytotoxicity and withstands the full range of sterilization methods, including radiation and chemical treatments.

Other types of temperature-sensitive assemblies might include structures that block light from reaching internal bonds or other areas that also require curing. For these applications, manufacturers can opt for a dual cure system such as Master Bond UV15DC80Med, which can cure on exposure either to a UV (320–365 nm) light source or 80–120 °C temperature. In fact, manufacturers can use a combination of both methods — using UV light for a rapid initial cure and adding heat to complete the cure. Finally, this one-part epoxy system passes both USP Class VI biocompatibility and ISO 10993–5 cytotoxicity standards and withstands steam pressure, radiation, and chemical sterilization methods.

Conclusions

Each type of medical and wearable device brings its own unique requirements for adhesive properties and processing characteristics. Fortunately, assembly manufacturers can find a wide range of adhesive systems able to meet today’s specific requirements.

Even so, new requirements for adhesive systems will continue to arise. The emergence of novel substrates for flexible and textile electronics promises to enable new types of medical devices and consumer wearables — and bring a wave of new sterilization techniques required to deal with these products. At the same time, the evolution of semiconductor technologies and fabrication techniques promises to enable further integration and miniaturization of devices. In turn, manufacturers dealing with more highly integrated components and denser systems will need correspondingly more effective adhesive solutions able to address enhanced requirements for thermal, mechanical, and conductive properties as well as workability characteristics.

More advanced adhesive systems will continue to emerge to match unique performance requirements while main taining biocompatibility and noncytotoxic characteristics. Using these adhesive systems, manufacturers will continue to meet broad challenges associated with next-generation medical devices, wearables, and other mobile consumer devices designed to operate in close contact with the human body.

This article was written by Christine Desplat, R&D Engineer for Master Bond, Hackensack, NJ. For more information, click here .


Medical Design Briefs Magazine

This article first appeared in the October, 2020 issue of Medical Design Briefs Magazine.

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