Enabling Point of Care Screening for Sepsis Using Rapid Single Cell Analysis

使用快速单细胞分析实现败血症的护理点筛查

• 批准号: 9332455
• 负责人: Ajay Shah
• 金额: $ 73.41万
• 依托单位: CYTOVALE, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9332455
• 关键词: Accident and Emergency department; Acquired Immunodeficiency Syndrome; American; Antibiotics; Area; Automation; Bacteria; Biological Assay; Biomechanics; Biophysics; Blood; Blood specimen; Caliber; Calibration; Cause of Death; Cells; Centrifugation; Cessation of life; Chest; Clinical; Clinical Research; Cytometry; Data; Detection; Development; Diagnosis; Diagnostic; Diagnostic tests; Disease; Disease Progression; Emergency Department patient; Emergency Medicine; Ensure; Expenditure; Fingers; Focal Infection; Functional disorder; Grant; Healthcare; Hospitals; Hour; Imaging technology; Immune; Immune response; Immune system; Individual; Infection; Inflammation; Inflammatory; Inpatients; Interview; Label; Leukocytes; Liquid substance; Malignant neoplasm of prostate; Manuals; Measurement; Measures; Mechanics; Methods; Microfluidics; Monitor; Noise; One-Step dentin bonding system; Organ; Organ failure; Outcome; Patient Care; Patient Triage; Patient-Focused Outcomes; Patients; Performance; Phase; Physicians; Population; Preparation; Process; Quality of Care; Reading; Reagent; Reference Standards; Running; Sampling; Savings; Sepsis; Severities; Signal Transduction; Societies; Specificity; Speed; Standardization; System; Techniques; Testing; Time; Triage; Whole Blood; analog; base; clinical decision-making; cost; cost effective; diagnostic accuracy; diagnostic assay; experimental study; fungus; immune activation; improved; improved outcome; indexing; instrument; interest; internal control; killings; leukocyte activation; malignant breast neoplasm; mechanical properties; mortality; novel diagnostics; operation; particle; point of care; point-of-care diagnostics; prevent; rapid detection; response; sample collection; screening; septic; single cell analysis; standard of care; success; therapy design; tool; usability

Project Summary Sepsis, an uncontrolled systemic inflammatory immune response to local infection by bacteria or fungi, is responsible for more deaths than prostate cancer, breast cancer, and AIDS combined, accounts for more than 40% of ICU costs, and is the most expensive inpatient condition in the U.S. (~$20B in annual U.S. healthcare expenditures in 2011). While it has been demonstrated that the time to initiating aggressive treatment is critical to improving outcomes (currently 30-50% mortality) and decreasing costs (>$22,000/case), emergency medicine physicians suffer from a lack of compelling diagnostic tools for detection of sepsis in the emergency department (ED), where >80% of sepsis cases originate in the hospital. CytoVale aims to improve the sepsis treatment paradigm by offering a platform to detect abnormal systemic inflammation at initial presentation. Our diagnostic platform will offer a cost-effective, robust, and rapid sample-to-decision assay (< 10 minutes), in which activated white blood cells that are indicative of uncontrolled systemic inflammation are interrogated in a label-free manner. In order to impact quality of care, the instrument must be situated at the point-of-care (POC), where it can provide rapid results to impact patient care. Currently, this is not feasible, due to manual operations required to prepare samples for the assay (e.g., centrifugation, pipetting) and the lack of an in- sample calibration. Here, we propose to capitalize on the success of our Phase 1 progress of automating the process of sample preparation by now developing a fully integrated module that combines the sample preparation and deformability cytometry microfluidics into a single cartridge and instrument. This will allow for the identification and triaging of patients earlier in their disease process at the ED POC from a finger-prick of blood. Additional cost and patient comfort benefits arise from the ability to track the course of disease and design treatments specific to patient response; saving days spent in the hospital and associated costs. Cytovale also proposes to develop and integrate a deformable sample control. Mechanical standard particles will be used as internal controls within each sample run, to ensure fidelity of the instrument readings and diagnostic accuracy. Not only will this help verify reliability and consistency of experiments, but will also supply a much needed calibration particle to the growing field of cellular biophysics. Combined, these aims will expand accessibility of powerful cell-based assays at the POC.

项目摘要 脓毒症是一种对细菌或真菌局部感染的不受控制的全身炎症免疫反应， 比前列腺癌、乳腺癌和艾滋病加起来还要多， 占ICU费用的40%，是美国最昂贵的住院条件（美国每年的医疗保健费用约为200亿美元 2011年的支出）。虽然已经证明开始积极治疗的时间至关重要， 改善结果（目前死亡率为30-50%）和降低成本（> 22，000美元/例），急诊 内科医生苦于缺乏用于在紧急情况下检测脓毒症的令人信服的诊断工具 科室（艾德），其中>80%的脓毒症病例起源于医院。CytoVale旨在改善败血症 通过提供一个平台来检测异常的全身性炎症在最初的介绍治疗范例。我们 诊断平台将提供一种具有成本效益的，强大的，快速的样品到决策的测定（< 10分钟）， 其中指示不受控制的全身性炎症的活化的白色血细胞在一个 无标签的方式为了影响护理质量，仪器必须位于护理点 (POC)，它可以提供快速的结果来影响患者护理。目前，这是不可行的，由于手动 制备用于测定的样品所需的操作（例如，离心，移液）和缺乏在- 样品校准在这里，我们建议利用我们第一阶段自动化进程的成功， 通过开发一个完全集成的模块， 制备和变形性细胞术微流体到单个盒和仪器中。这将允许 在艾德POC的疾病过程早期， 血额外的成本和患者舒适性益处来自于跟踪疾病进程的能力， 针对患者反应设计治疗方案;节省住院天数和相关费用。 Cytovale还提出开发和集成可变形样品控制。机械标准粒子 将在每次样品运行中用作内部对照，以确保仪器读数的保真度， 诊断准确性。这不仅有助于验证实验的可靠性和一致性，而且还将提供 细胞生物物理学日益发展的领域急需的校准粒子。结合起来，这些目标 扩大POC强大的基于细胞的检测的可及性。