Understand and Detect Sepsis: Pathogen Isolation, Biochemistry Assay, and Optofluidic Sensing

了解和检测脓毒症：病原体分离、生物化学检测和光流控传感

• 批准号: 10275269
• 负责人: Ke Du
• 金额: $ 36.63万
• 依托单位: ROCHESTER INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10275269
• 关键词: Address; Antimicrobial Resistance; Bacteria; Bacterial Infections; Biochemistry; Biological Assay; Biological Markers; Biomedical Research; Blood specimen; Cells; Clinical; Clustered Regularly Interspaced Short Palindromic Repeats; Collection; Communities; Consumption; Detection; Diagnosis; Disease; Early treatment; Emergency Situation; Engineering; Fluorescence; Foundations; Goals; Home; Interdisciplinary Study; Label; Laboratories; Lead; Life; Liquid substance; Malignant Neoplasms; Methods; Microfluidic Microchips; Molecular Diagnosis; Nanostructures; Nucleic Acids; Patients; Postdoctoral Fellow; Preparation; Prevention; Property; Public Health; Publishing; Research; Research Personnel; Resistance; Retrieval; Risk; Sampling; Sensitivity and Specificity; Sepsis; Septic Shock; Students; Technology; Testing; Tissues; Virus; Virus Diseases; Vision; Whole Blood; Work; accurate diagnosis; advanced disease; antimicrobial; bacterial resistance; base; disease diagnosis; doctoral student; interdisciplinary approach; isothermal amplification; journal article; miniaturize; mortality; nanodevice; nanomaterials; nervous system disorder; pathogen; programs; rapid diagnosis; response; small molecule; undergraduate student; whole blood bacteria

Project Summary Background: Sepsis is a life-threatening emergency, normally caused by the body’s response to a bacterial infection. Without early treatment, sepsis can lead to septic shock with approximately 50% mortality rate. Rapid and accurate diagnosis of sepsis is the key to decrease the mortality rate. However, there is no global standard for sepsis testing due to the inadequate sensitivity and specificity of the current technologies. The PI has the ambition to address the critical and far-reaching bottlenecks specifically of concern in sepsis testing: 1) a rapid and simple method to isolate and concentrate bacteria from whole blood sample, 2) a sensitive and one-step CRISPR microfluidic chip to detect the nucleic acid biomarkers of the pathogens, and 3) a multiplexing and miniaturized optofluidic waveguide platform to enhance the fluorescence based detection. Overview of the laboratory: The PI established his own lab at RIT in 2018. With the overwhelm start-up support by the home department, the PI is leading an active and interdisciplinary research group with 1 postdoc researcher, 4 Ph.D. students, 2 Master students, and a couple of undergraduate students. Within 2 years, the lab has published ~10 journal articles in the fields of bacteria/virus isolation, CRISPR biochemistry assay, and optofluidic sensing. Exploiting interdisciplinary approach, the lab is working on technologies to quickly identify antimicrobial resistant bacteria in whole blood sample. As more strains become resistant to available therapies, the risk for people developing life-threatening sepsis is increasing. The research topic we are working on will be the key for clinicians to provide quick clinical decisions and increase the chances of survivals. In addition, the technologies developed in our lab will also lay the foundation for the diagnosis and treatment of many different kinds of diseases such as cancer, viral infection, and neurological diseases. Goals for the next 5 years: Our first goal is to develop a fully automated nanodevice that can collect and concentrate bacteria from whole blood with a retrieval efficiency of 99% and a concentration factor of 10,000. We will begin with spiked sample and then proceed to clinical sample. Leveraging the unique properties of nanomaterials and nanostructures, the second goal is to develop a one-step and isothermal CRISPR chip for low concentration (1 CFU/mL) bacteria detection without front end target amplification. Towards the end of the fifth year, we will integrate the sample preparation chip and the CRISPR detection chip as a single and compact unit for the testing of clinical samples. The third goal is to develop a liquid-core, superhydrophobic nanostructure cladding waveguide platform for multiplexing bacteria detection. The high fluorescence collection efficiency will enable sensitive sepsis detection with microliter level sample consumption. Overall vision of the research program: The technologies we are developing will have a broad impact to the biomedical research communities to understand and engineering small molecules, cells, and tissues. The proposed work will also advance disease diagnosis, prevention, and treatment.

项目摘要 背景：脓毒症是一种危及生命的紧急情况，通常是由身体对细菌的反应引起的。 感染如果没有早期治疗，脓毒症可导致脓毒性休克，死亡率约为50%。快速 脓毒症的准确诊断是降低死亡率的关键。然而，没有全球标准 由于目前技术的灵敏度和特异性不足，私家侦探有 目标是解决脓毒症检测中特别关注的关键和深远的瓶颈：1）快速 方法简便、灵敏、一步到位 CRISPR微流控芯片检测病原体的核酸生物标志物，以及3）多路复用和 小型化的光流体波导平台，以增强基于荧光的检测。 实验室概述：PI于2018年在RIT建立了自己的实验室。有了大量的创业支持 由内政部，PI是领导一个积极的和跨学科的研究小组与1博士后 研究员，4位博士学生，2名硕士生，和一对夫妇的本科生。两年内， 实验室在细菌/病毒分离、CRISPR生物化学测定和 光流体传感利用跨学科的方法，该实验室正在研究技术，以快速识别 全血样本中的抗菌药物耐药菌。随着越来越多的菌株对现有疗法产生耐药性， 人们患上危及生命的败血症的风险正在增加。我们正在研究的课题将是 临床医生提供快速临床决策和增加生存机会的关键。此外该 我们实验室开发的技术也将为许多不同的疾病的诊断和治疗奠定基础。 癌症、病毒感染和神经系统疾病等多种疾病。 未来5年的目标：我们的第一个目标是开发一种完全自动化的纳米设备，可以收集和 从全血中浓缩细菌，回收率为99%，浓缩倍数为10，000。 我们将开始加标样品，然后继续临床样品。充分利用 纳米材料和纳米结构，第二个目标是开发一步和等温CRISPR芯片， 低浓度（1 CFU/mL）细菌检测，无需前端靶标扩增。快结束时 第五年，我们将样品制备芯片和CRISPR检测芯片集成为一个单一的紧凑型芯片。 临床样本检测单元。第三个目标是开发一种液核超疏水纳米结构 包层波导平台用于多路细菌检测。高荧光收集效率将 能够以微升水平的样品消耗进行灵敏的脓毒症检测。 研究计划的总体愿景：我们正在开发的技术将对未来产生广泛的影响。 生物医学研究社区了解和工程小分子，细胞和组织。的 拟议的工作还将促进疾病诊断，预防和治疗。