SBIR Phase I: Broadband focusing for non-invasive cell metabolomics

SBIR 第一阶段：宽带聚焦非侵入性细胞代谢组学

• 批准号: 2221721
• 负责人: Adam Hanninen
• 金额: $ 27.5万
• 依托单位: TRESTLE OPTICS LLC
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-15 至 2025-02-28
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2221721&HistoricalAwards=false
• 关键词: SBIR; Phase; Broadband; focusing; non

The broader impact of this Small Business Innovation Research (SBIR) Phase I project is aimed toward advancing sustainable production of chemicals using synthetic biology. Here, single-cell microbes are engineered to produce valuable metabolites using enzymes rather than sourcing these chemicals from petroleum. Developing genetically engineered cell strains with high yield remains an ongoing effort due to the complexities in how genetic code leads to phenotype expression. This problem is addressed using a bottom-up approach to screen microbe populations at the single-cell level. The method deployed to identify metabolite content in individual cells is based on infrared (IR)-absorption spectroscopy which is label-free, quantitative, and non-destructive. Synthetic biology is poised to disrupt the chemical value-chain by providing an alternative to petroleum-based chemicals that is sustainable and carbon-neutral. Once a highly productive cell is identified it can be selectively propagated to create enriched cell lines. Innovations in optical microscopy are required to improve the performance of the cell screening instruments, which will allow high-resolution focusing across a broad spectral range. The upgraded platform will optimize yield more quickly, providing value by reducing the upfront cost to develop new industrial cell strains. The proposed project emphasizes optical engineering to develop a microscope designed for high-resolution chemical imaging based on molecular vibrational IR-absorptions. This is achieved by deploying focusing elements that operate over a broad spectral range that extend standard optical microscopes to include mid-infrared light sources. The optical instrument will be used to evaluate chemical content in industrial microbe strains and develop enriched cell lines. These single-cell microbe populations are engineered to produce enzymes used to catalyze the synthesis of valuable metabolites. Yields from individual cells, however, are variable due to genetic mutations in the population. Therefore, a quantitative analytical tool based on IR-spectroscopy that can non-destructively identify highly productive cells for selective propagation is extremely desirable. This bottom-up approach for metabolomic cell screening and directed evolution is an innovation as it is label-free, non-invasive, and has strong chemical specificity. In this project, the team will study an industrial microalgae strain used as a low-cost feedstock supplement and identify cells rich in protein content to enhance the overall protein yield.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.

这项小型企业创新研究（SBIR）I期项目的更广泛影响旨在使用合成生物学推进化学物质的可持续生产。在这里，单细胞微生物经过设计，可以使用酶产生有价值的代谢产物，而不是从石油上采购这些化学物质。由于遗传代码如何导致表型表达的复杂性，开发具有高产量的基因工程细胞菌株仍然是一项持续的努力。使用自下而上的方法来解决此问题，以筛选单细胞级别的微生物种群。用于鉴定单个细胞中代谢物含量的方法是基于红外（IR）吸收光谱，该光谱不含标签，定量和无损。 合成生物学有望通过提供可持续性且与碳中性的基于石油的化学物质的替代品来破坏化学价值链。 一旦确定了高生产的细胞，就可以选择性地传播以创建富集的细胞系。需要光学显微镜的创新来改善细胞筛选仪器的性能，这将允许在广泛光谱范围内进行高分辨率聚焦。升级的平台将更快地优化产量，从而通过降低开发新的工业细胞菌株的前期成本来提供价值。拟议的项目强调了基于分子振动IR-ABSorptions的高分辨率化学成像设计的光学工程。这是通过部署在广泛光谱范围内运行的焦点元素来实现的，该元素将标准光学显微镜扩展到包括中红外光源。光学仪器将用于评估工业微生物菌株中的化学含量并发展富集的细胞系。这些单细胞微生物种群经过设计，用于生产用于催化有价值代谢物的合成的酶。但是，由于种群的基因突变，来自单个细胞的产量是可变的。因此，基于IR-光谱的定量分析工具，可以非破坏性地识别高生产性细胞以进行选择性传播。代谢组细胞筛查和定向进化的自下而上的方法是一种创新，因为它是无标签，无创的，并且具有很强的化学特异性。在该项目中，该团队将研究一种用作低成本原料补充剂的工业微藻菌株，并鉴定富含蛋白质含量的细胞以提高整体蛋白质的产量。该奖项反映了NSF的法定任务，并被认为是通过基金会的知识分子优点和更广泛影响的审查标准来通过评估来通过评估来支持的。