SBIR Phase II: Large-Scale Synthesis of Hollow Metal Nanospheres: Conversion of Batch Synthesis to Continuous Flow

这个小企业创新研究（SBIR）第二阶段项目的广泛影响是基于建立一个一致的、可靠的高质量空心金属纳米颗粒来源，从而使其在明显优于传统同类产品的应用中得到商业应用。其中一个应用是使用点测试：通过切换到空心金属纳米颗粒，横向流动分析将达到更高的灵敏度和更低的检测极限，从而改善对环境污染的现场测试；农业中的毒素和病原体检测；以及在临床和兽医护理中的早期疾病识别。将其整合到COVID-19等高度传染性疾病的快速抗体和抗原检测中应该会产生特别大的影响，因为由此产生的更高灵敏度将减少假阴性结果的发生，从而改善快速检测的性能（和公众的看法）。至关重要的是，它还将改善农村和服务不足人群的基线检测可获得性，这些人群无法获得配备pcr的临床实验室。它们也可以应用于许多其他行业。这个小型企业创新研究二期项目将推进等离子体纳米材料连续流合成技术的发展。纳米颗粒合成是一个高度敏感的过程，以前获得高质量的先进结构样品需要劳动密集型的小批量工艺，与大规模生产不相容。简单地扩展传统的批量技术导致产品质量差，成本过高。该项目推进了一个原型反应器，该反应器已经证明了中空等离子体纳米粒子的高通量生产，可以控制尺寸和颜色，同时保持结构均匀性（15% CV）。重要的是，与小批量合成相比，每升产品的人工成本降低了950%。该项目将提高保真度，进一步扩大产量，后期处理和稳定最终产品，并对其光学性能进行基准测试。由此产生的生产规模反应器将具备为LFA制造商提供即用型先进彩色标签所需的能力。它将通过创造具有良好控制物理特性的高性能等离子体纳米结构的持续商业供应，从而实现新的研究和新的纳米器件。制造用于使用点测试应用的中空金属纳米颗粒也将为其扩展到其他行业铺平道路，这些行业也将受益于其有利的光学和光热等离子体特性，如光催化，水净化和光治疗。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact of this Small Business Innovation Research (SBIR) Phase II project is based upon establishing a consistent, reliable source of high-quality hollow metal nanoparticles, thus enabling their commercial adoption in applications where they markedly outperform their conventional counterparts. One such application is point-of-use testing: by switching to hollow metal nanoparticles, lateral flow assays will reach higher levels of sensitivity and lower limits of detection, improving field testing for environmental contamination; detection of toxins and pathogens in agriculture; and early disease identification in clinical and veterinary care. Integration into rapid antibody and antigen tests for highly contagious diseases such as COVID-19 should prove particularly impactful, as the resulting higher sensitivity would reduce the occurrence of false negative results, thereby improving the performance (and public perception) of rapid testing. Critically, it would also improve baseline testing availability for rural and under-served populations who do not have access to PCR-equipped clinical laboratories. They can be applied to many other industries as well. This Small Business Innovation Research Phase II project will advance the state of the art of continuous flow synthesis of plasmonic nanomaterials. Nanoparticle synthesis is a highly sensitive process, and obtaining high quality samples of advanced architectures has previously required labor-intensive, small-batch processes incompatible with large-scale production. Simply scaling traditional batch techniques has led to product with poor quality and prohibitive costs. This project advances a prototype reactor that has demonstrated high-throughput production of hollow plasmonic nanoparticles with control over size and color, while maintaining structural uniformity (15% CV). Importantly, it reduced the cost of labor per liter of product by 950% from that of small batch synthesis. The proposed project will increase fidelity, further scale production volume, post-process and stabilize the final product, and benchmark its optical performance. The resulting production-scale reactor will have the capacity necessary to supply LFA manufacturers with ready-to-use, advanced color labels. It will enable new research and new nano-enabled devices by creating a consistent commercial supply of high performance plasmonic nanostructures with well-controlled physical properties. The manufacture of hollow metal nanoparticles for point-of-use testing applications will also pave the way for their expansion into other industries that would also benefit from their advantageous optical and photothermal plasmonic properties, such as photocatalysis, water purification, and phototherapeutics.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.