SBIR Phase I: Culture-independent Rapid Bacterial Isolation and Identification

SBIR 第一阶段：不依赖培养物的快速细菌分离和鉴定

• 批准号: 1819613
• 负责人: Rajesh Krishnamurthy
• 金额: $ 22.5万
• 依托单位: 3I Diagnostics, Inc.
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1819613&HistoricalAwards=false
• 关键词: SBIR; Phase; Culture; independent; Rapid

This SBIR Phase I project aims to develop and demonstrate the feasibility of a system that can identify a broad range of bacteria in 1 hour directly from blood. Existing diagnostic systems require 2-6 days to identify the bacteria, which delays treatment using appropriate antibiotics. Sepsis, which is often caused by a bacterial infection, contributes to up to half of all hospital deaths in the US largely due to complications arising from delays or inappropriate treatment (which is mainly because of lack of information regarding the infection-causing bacteria). It is the most expensive hospital-treated condition in the United States ? representing $20.3 billion in healthcare costs. The proposed system aims to sharply reduce the time to provide information needed by physicians, enabling them to initiate treatment using the appropriate antibiotic rapidly. This is expected to lead to significant reductions in costs, complications, and mortality. Further, by eliminating the need for culturing, new insights into bacterial behavior can be acquired contributing to additional fundamental knowledge of bacteria. This knowledge will aid antibiotic discovery efforts, improve understanding of mechanisms of drug resistance, support new biomanufacturing processes through faster detection of bacterial contamination of pharmaceutical products and foods, and characterization of the microbiome.The challenges of rapid bacterial identification are primarily in two areas ? sample preparation, that eliminates the need for culturing, and multiplex identification, to cover the diverse range of bacterial species capable of causing infection. The proposed work is based on leveraging the differential response between bacteria and the cells in a sample matrix to selectively break down the sample matrix, but not bacteria, such that the largest lysis debris is smaller than intact bacteria. The debris is subsequently separated from intact bacteria using a size-based technique enabling rapid isolation of a broad range of bacteria directly from the sample. A novel Fourier-transform infrared microspectroscopy system is then used to identify the isolated bacteria at clinically relevant concentrations. No bacteria-specific reagents are employed. The proposed Phase I work addresses the highest risk technical hurdles in the process. Isolating and detecting low concentration of bacteria directly from blood is accomplished through the three objectives of this project that optimize the purification and bacterial recovery from the sample, identification accuracy, and performance of the integrated system relative to the traditional culturing-based method.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.

该SBIR第一阶段项目旨在开发并演示一种系统的可行性，该系统可以在1小时内直接从血液中识别多种细菌。现有的诊断系统需要2-6天来识别细菌，这会延迟使用适当抗生素的治疗。脓毒症通常由细菌感染引起，在美国占所有医院死亡人数的一半，主要是由于延迟或不适当治疗引起的并发症（主要是因为缺乏有关感染致病细菌的信息）。这是美国最昂贵的医院治疗条件？相当于203亿美元的医疗费用。拟议的系统旨在大幅减少医生提供所需信息的时间，使他们能够迅速使用适当的抗生素开始治疗。预计这将导致成本、并发症和死亡率的显著降低。此外，通过消除对培养的需要，可以获得对细菌行为的新见解，从而有助于细菌的额外基础知识。这些知识将有助于抗生素发现工作，提高对耐药性机制的理解，通过更快地检测药品和食品的细菌污染和微生物组的表征来支持新的生物制造过程。样品制备，无需培养和多重鉴定，以涵盖能够引起感染的各种细菌种类。所提出的工作是基于利用细菌和样品基质中的细胞之间的差异反应来选择性地分解样品基质，而不是细菌，使得最大的裂解碎片小于完整的细菌。随后使用基于大小的技术将碎片与完整的细菌分离，从而能够直接从样品中快速分离出广泛的细菌。一种新的傅里叶变换红外显微光谱系统，然后用于识别临床相关浓度的分离细菌。未使用细菌特异性试剂。拟议的第一阶段工作解决了这一过程中风险最高的技术障碍。本项目通过优化样品的纯化和细菌回收、鉴定准确性、以及集成系统相对于传统养殖的性能-该奖项反映了NSF的法定使命，并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。