SBIR Phase I: A Microbial Enrichment Device to Reduce the Cost of Sequencing Metagenomes

这个小企业创新研究（SBIR）项目的更广泛的影响/商业潜力将是通过更广泛地采用整个宏基因组和元转录组测序来加速微生物组科学的发现。这些DNA和RNA测序技术是基于微生物组的药物和诊断数据生成的黄金标准，但对于大规模研究工作来说过于昂贵。高成本是由于两个因素：首先，客户需要对大量DNA和RNA进行测序，以充分分析微生物组;其次，由于样品吞吐量较低，研究项目的周转时间较长。拟定产品将富集微生物细胞，并在测序分析开始前去除污染物。如果成功，该产品对最终用户的商业影响将是大幅节省成本和扩大客户群的能力，使科学进步能够加速微生物组研究。通过证明一次性使用器械和工作台的可行性证明，实现第一阶段提案中规定的技术目标将显著降低公司商业化工作中的技术风险。在宏基因组测序之前能够富集微生物的顶级仪器。SBIR第一阶段项目提出开发微生物富集工具，以显著降低使用DNA和RNA分析微生物组的成本和难度测序 目前，测序实验室主任只能以巨大的成本分析微生物组，因为样品被来自宿主细胞的DNA和RNA高度污染。所提出的解决方案是一种一次性盒和一种控制仪器，使实验室人员能够直接从样品中快速富集微生物，而无需使用引入偏倚的生物工程标签或标记，并能够生成主要由细菌DNA和RNA组成的测序文库。该提案中的技术挑战是将先前证明的用于富集细菌的当前实验室方法转换为台式仪器，该台式仪器使用与当前测序工作流程兼容的简单一次性装置，其需要最少的操作员步骤。该系统在第一阶段的性能将使用加标样品与细菌分离物和模拟社区来模拟现实的微生物组进行评估。该奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project will be the acceleration of discoveries in microbiome science by wider adoption of whole metagenomic and metatranscriptomic sequencing. These DNA and RNA sequencing techniques are the gold standard for data generation in microbiome-based drugs and diagnostics, but are prohibitively expensive for large-scale research efforts. The high cost is due to two factors: First, customers are required to sequence large quantities of DNA and RNA to adequately analyze the microbiome; and second, research projects are plagued by long turnaround times due to lower sample throughput. The proposed product will enrich microbial cells and will remove contaminants before the sequencing analysis begins. If successful, the commercial impact of this product for end-users will be substantial cost savings and the ability to expand their customer base, enabling scientific progress to accelerate in microbiome research. Accomplishing the technical aims set forth in this Phase I proposal will significantly reduce technical risk in the company's commercialization efforts by demonstrating proof-of-feasibility for a single-use device and bench-top instrument capable of enriching microbes prior to metagenomic sequencing.This SBIR Phase I project proposes to develop a microbial enrichment tool to significantly reduce the cost and difficulty of analyzing microbiomes using DNA and RNA sequencing. At present, sequencing laboratory directors only are able to analyze microbiomes at tremendous expense because samples are highly contaminated with DNA and RNA derived from host cells. The proposed solution is a disposable cartridge and a control instrument that will enable lab personnel to rapidly enrich microbes directly from samples without the use of bioengineered tags or labels that introduce bias, and enable the generation of sequencing libraries composed primarily of bacterial DNA and RNA. The technical challenges in this proposal are to convert the current laboratory method for enriching bacteria demonstrated previously into a bench-top instrument that uses a simple and disposable device compatible with current sequencing workflows that requires minimal operator steps. The system's performance in Phase I will be evaluated using spike-in samples with bacterial isolates and mock communities to simulate realistic microbiomes.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.