Development of A Novel Nanoparticle Biosensor for Rapid, Point-of-Care Sepsis Diagnosis and Risk Assessment

开发新型纳米颗粒生物传感器，用于快速护理点脓毒症诊断和风险评估

基本信息

批准号：
10602155
负责人：
Ke Liu
金额：
$ 22.41万
依托单位：
NAMI DIAGNOSTICS LLC
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-06-14 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10602155
关键词：
Address Adult Affect Affinity Antibodies Architecture Assessment tool Bacteria Biological Assay Biosensing Techniques Biosensor Biotechnology Biotinylation Blinded Blood Blood Tests Blood specimen Caring Cause of Death Cell Culture Techniques Cells Cessation of life Chemistry Clinical Collaborations Consumption Cost efficiency Coupled Data Data Analyses Dedications Detection Development Devices Diagnosis Diagnostic Diagnostic Reagent Kits Diagnostic tests Disease Disease Progression Economics Escherichia coli O157:H7 Evaluation Flow Cytometry Food Goals Health Health care facility Healthcare Systems Hematology Hospitalization Hour Human Human Resources Immune Targeting Immunoassay Infrastructure Intervention Length Leukocytes Magnetism Manufacturer Measurement Medical Metals Methods Microfluidic Microchips Microfluidics Monitor Morbidity - disease rate Outcome Outcome Measure Pathway interactions Patients Phase Pilot Projects Primary Care Procedures Process Production Prognosis Protocols documentation Race Rapid diagnostics Recurrence Research Design Resource-limited setting Resources Risk Risk Assessment Salmonella Sampling Sensitivity and Specificity Sepsis Signal Transduction Streptavidin Sulfides Survival Rate Survivors System Systemic Inflammatory Response Syndrome Technology Test Result Testing Texas Time United States Universities Validation Whole Blood antibody conjugate antimicrobial biomarker validation commercial application commercialization diagnostic assay diagnostic platform diagnostic strategy diagnostic tool experience magnetic beads manufacture mortality nano nanoparticle novel novel diagnostics particle pathogen patient population phase 1 study point of care portability predict clinical outcome prevent prognostic value prototype response sensor septic septic patients skills specific biomarkers success

项目摘要

Abstract. In the United States, about 1.7 million adults affected by sepsis annually, which leads to more than 270,000 deaths per year. If sepsis cannot be diagnosed and treated early, it not only causes high morbidity and mortality rates, but also poses a major burden to the healthcare system since septic patients are generally hospitalized for extended stay and rarely discharged from ICU before 2-3 weeks. In response to this health problem, NaMi Diagnostics collaborates with Texas Tech University to develop a nanoparticle-based electrochemical testing kit to pinpoint early sign of sepsis before it progresses systemic inflammatory response syndrome (SIRS) and other serious complications. Our technology features include high sensitivity, fast turnaround results, multiplexing capability, quantitative measurement, cost-efficiency, and portability. The proposed study design is adapted from a prototype sensor architecture that has been previously applied to detect food pathogens such as E. coli O157:H7 and Salmonella yet utilizes sepsis-specific cell markers validated in a microfluidic platform by our project collaborator. Specifically, the key component of our testing platform includes functionalized magnetic particles for isolation of target immune cells specific to sepsis and employs different types of modified metal sulfide nanoparticles for identification and detection, producing nearly real-time diagnostic answers, enabling prompt medical intervention, and allowing long-term monitoring of sepsis survivors to prevent the recurrence of sepsis. The proposed workflow is simple, requiring minimal infrastructure and labor, and can be readily implemented in point-of-care and resource-limited settings. The goal of upcoming Phase I project at NaMi Diagnostics will be demonstrating the feasibility for sensitive and simultaneous detection of leukocytes with upregulated CD64 and CD69 expression as proof-of-concept for early and accurate sepsis diagnosis. To validate the prognostic value for severe disease, correlation between testing result and clinical outcome in sepsis patients will be also explored in this study.

抽象的。在美国，每年约有 170 万成年人患有败血症，这导致超过每年有 27 万人死亡。脓毒症如果不能及早诊断和治疗，不仅会导致高发病率和死亡率，但也给医疗保健系统带来了重大负担，因为脓毒症患者通常住院时间延长，很少在 2-3 周内从 ICU 出院。为了回应这种健康问题，NaMi Diagnostics 与德克萨斯理工大学合作开发基于纳米颗粒的电化学检测试剂盒可在脓毒症发展为全身炎症反应之前查明脓毒症的早期症状综合征（SIRS）和其他严重并发症。我们的技术特点包括高灵敏度、快速周转结果、复用能力、定量测量、成本效率和便携性。这拟议的研究设计改编自先前应用于的原型传感器架构检测食物病原体，例如大肠杆菌 O157:H7 和沙门氏菌，并利用脓毒症特异性细胞标记物我们的项目合作者在微流体平台上进行了验证。具体来说，我们测试的关键组成部分平台包括功能化磁性颗粒，用于分离脓毒症特异性靶免疫细胞和采用不同类型的修饰金属硫化物纳米颗粒进行识别和检测，产生近实时诊断答案，实现及时的医疗干预，并允许长期监测脓毒症幸存者预防脓毒症复发。所提出的工作流程很简单，需要最少的基础设施和劳动力，并且可以在护理点和资源有限的环境中轻松实施。这 NaMi Diagnostics 即将进行的第一阶段项目的目标将是展示敏感和同时检测 CD64 和 CD69 表达上调的白细胞作为概念验证早期、准确的脓毒症诊断。为了验证严重疾病的预后价值，本研究还将探讨脓毒症患者的检测结果和临床结果。