The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project will result from reducing overall COVID-19 mortality, and reducing the incidence of morbid secondary infections in intubated patients such as ventilator-acquired pneumonia (VAP). The market for antifouling/antimicrobial indwelling endotracheal tubes (ETTs) was estimated at $1.85 billion in 2017 with 6.6% annual growth, and further increases are likely due to the outbreaks of COVID-19 and other respiratory diseases. More than 50% of COVID-19 deaths are attributable to acute respiratory distress syndrome (ARDS) from secondary healthcare-acquired infections, such as VAP. Unfortunately, ETTs used for ventilation do not prevent bacterial settlement upon their surfaces (biofouling). To date there is only one FDA-approved antimicrobial ETT that does not target fouling as the root cause of VAP, leaving this critical issue unaddressed. The proposed technology advances the development of ETTs with novel coatings and can potentially be used in other indwelling biomedical medical devices, including urinary-, central venous-, and hemodialysis catheters (estimated market size: $77.7 billion by 2026). A ~10% reduction infection rate with this technology could prevent 1.7 million healthcare-acquired infections, annually saving 99,000 lives and $28-45 billion associated-cost in the US. This technology will also support research in antimicrobial interactions with surfaces. This SBIR Phase I project proposes to establish the feasibility of gemini-surfactant inspired coatings on ETTs to reduce COVID-19 mortality. Current approaches to prevent biofouling in ETTs involve incorporation of biocidal Ag+ ions or deposition of hydrophilic polymers resembling traditional surfactants to the surface. However, such biocide-release coatings liberate Ag+ ions that are cyto- and genotoxic and are subject to gradual depletion of the active agent. Meanwhile, the polymers are limited by both intrinsically hydrophobic regions in their backbones and the low surface activities of conventional “parent” surfactants. This project will advance the development of a new class of antifouling coatings combining structural elements of powerful gemini surfactants displaying surface activities orders of magnitude higher than their conventional counterparts, with the molecularly precise and durable surface modification technique of silanization. By mimicking the structures of gemini surfactants, incorporating multiple ionic “head” groups into the coating via silanization, hydrophilicity and antifouling/antimicrobial properties will be greatly increased relative to conventional antifouling coatings.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.