SBIR Phase I: Developing Vibrational spectroscopy with metasurface optics (VISMO) for label-free, high-resolution, high-throughput protein screening

小型企业创新研究(SBIR)第一阶段项目的更广泛影响是促进生物制造的改进和向可持续生物经济的过渡。蛋白质是生物学的工作分子，可用于可持续燃料、制药、塑料和包装材料等产品。基于细胞的制造可以产生数百万种不同的蛋白质，但现有的工具不能提供分辨率、吞吐量或灵敏度来筛选细胞序列和结构。由此产生的服务和产品将减少优化基于蛋白质的产品的时间和成本，朝着可持续的生物经济方向发展，并改善个人和地球健康。这种方法将能够同时对数百万个样本进行微尺度测量，增加了任何可用的技术都无法检测到的分子。这项技术将能够收集有关蛋白质-蛋白质和蛋白质-药物相互作用的动态信息，将大大改善与药物开发和基于蛋白质的产品的合成生物学优化相关的漫长而昂贵的周期，并加速美国生物经济的发展。这项技术可以实现向个性化医疗的过渡，在个性化医疗中，医疗专业人员可以实时访问患者特定的蛋白质组和药物相互作用数据，以保持健康，监测疾病的出现和进展，提高治疗效率，并延长健康跨度。该项目旨在开发具有超表面光学的振动光谱学来筛选蛋白质形式。研究的目标是利用蛋白质的振动散射光谱来确定蛋白质的序列和结构。该项目的目标1将开发一种纳米结构硅芯片，它可以强烈放大蛋白质的振动散射光，用于高灵敏度分析。该项目的目标2将开发尖端的机器学习算法，以提供拉曼光谱的可解释性，包括与蛋白质的一级、二级和三级结构相对应的波数特征。该项目的目标3将开发微流控能力，使高通量样品处理成为可能，每平方厘米分析多达300万个分子。完成后，这个第一阶段项目将降低无标签、高分辨率、高速蛋白质筛选和测序技术的技术基础的风险。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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 I project is to facilitate improved biomanufacturing and the transition to a sustainable bioeconomy. Proteins are the working molecules of biology and can be used for products spanning sustainable fuels, pharmaceuticals, plastics, and packaging materials. Cell-based manufacturing can produce millions of variations of proteins, yet existing tools do not provide the resolution, throughput, or sensitivity to screen the cell sequence and structure. The resulting services and products will reduce the time and cost to optimize protein-based products, en-route to a sustainable bio-based economy and improved personal and planetary health. The approach will enable simultaneous, minute-scale measurement of millions of samples, increasing the suite of detectable molecules beyond any available technology. The technology will enable collection of dynamic information about protein-protein and protein-drug interactions will dramatically improve the lengthy and costly cycles associated with drug development and synthetic biology-based optimization of protein-based products and accelerate advances for the US bioeconomy. The technology may enable the transition to personalized medicine, where medical professionals can access patient-specific proteomic and drug-interaction data in real-time, to maintain wellness, monitor disease emergence and progression, improve treatment efficacy,and extend health spans. This project aims to develop vibrational spectroscopy with metasurface optics to screen for proteoforms. The research objectives are to determine protein sequence and structure, utilizing the vibrational scattering spectra of the protein. Aim 1 of this project will develop a nanostructured silicon chip that strongly amplifies the vibrationally-scattered light from proteins, for high-sensitivity analysis. Aim 2 of this project will develop cutting-edge machine learning algorithms to provide interpretability to the Raman spectra, including the wavenumber features that correspond to the primary, secondary, and tertiary structure of the protein. Aim 3 of this project will develop microfluidic capabilities that enable high-throughput sample processing, with up to 3 million molecules analyzed per square centimeter. Upon completion, this Phase I project will de-risk the technological foundations for label-free, high-resolution, high-speed protein screening and sequencing technologies.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.