Point-of-Care Microfluidic Biochip for Biomarkers Monitoring for Contributing in Early Sepsis Diagnosis

用于生物标志物监测的护理点微流控生物芯片有助于早期脓毒症诊断

• 批准号: 10673974
• 负责人: Rashid Bashir
• 金额: $ 51万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-05 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10673974
• 关键词: Acceleration; Accident and Emergency department; Acquired Immunodeficiency Syndrome; Adult; Affect; American; Antibiotics; Bacteremia; Bacteria; Binding Proteins; Biological Markers; Blood; Blood Cell Count; Blood Circulation; Blood specimen; C-reactive protein; Cause of Death; Cell Surface Proteins; Cells; Cessation of life; Chemicals; Chlamydophila pneumoniae; Chronic Obstructive Pulmonary Disease; Clinic; Clinical; Clinical Research; Collaborations; Computerized Medical Record; Coulter counter; Data; Detection; Devices; Diagnosis; Diagnostic tests; Disease; Drops; Early Diagnosis; Economic Burden; Electrolytes; Engineering; Ensure; Exhibits; Fever; Floor; Foundations; Functional disorder; Future; Goals; Healthcare Systems; Heart Rate; Heart failure; Hospital Costs; Hospitalization; Hospitals; Hour; Hydrogels; Hypotension; Immune response; Immune system; Immunoassay; Immunologic Markers; Infection; Institutional Review Boards; Interleukin-6; Laboratories; Length of Stay; Life; Magnetism; Malignant neoplasm of prostate; Measures; Methods; Microfluidics; Monitor; Morals; Myocardial Infarction; Organ; Organ failure; Pathogen detection; Patients; Persons; Plasma Proteins; Pneumonia; Population; Principal Investigator; Property; Proteins; Reaction Time; Reporting; Sampling; Screening procedure; Sensitivity and Specificity; Sepsis; Septic Shock; Severities; Signal Transduction; Solid; Speed; Stratification; Surface; Survival Rate; Syndrome; Techniques; Technology; Testing; Time; United States; Variant; White Blood Cell Count procedure; Whole Blood; Work; biochip; clinical diagnosis; cost; design; early onset; electric impedance; hospital readmission; improved; innovation; malignant breast neoplasm; mortality; multiplex detection; nano; neutrophil; particle; pathogen; patient population; point of care; procalcitonin; programs; protein biomarkers; risk stratification; septic patients; technological innovation; therapy development

Principal Investigator/Program Director (Last, first, middle): Bashir, Rashid Project Summary: Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection (Sepsis- 3 definition), is the leading cause of death and most expensive condition in hospitals. Annually, > 30 million people affected worldwide, with at least 1.7 million adults developing sepsis (nearly 270K die) at a cost of $24 billion per year in the U.S. Patients diagnosed with sepsis and no ongoing sign of organ failure have about a 15-30% chance of death. However, the mortality rate can increase up to 40-60% for severe sepsis or septic shock patients. One in three patients who die in a hospital have sepsis. One major factor in these rising mortality rates is the inability to accurately and quickly diagnose potentially septic patients. Likewise, sepsis is a leading cause of hospital readmission (higher proportion than hospitalizations for heart attack, heart failure, COPD, and pneumonia in the U.S.). EDs and ICUs rely on monitoring extremely non-specific parameters (e.g. fever, low blood pressure, increased heart rate) to initiate a clinical diagnosis and begin treatment. These crude indicators cause doctors to mistake early stage sepsis with several other diseases. A positive diagnose of early onset sepsis is critical because mortality increases with delays in treatment. Survival rates have been reported to drop by 7.6% every hour that the proper antibiotics are not administered, and these delays compound unnecessary hospital costs. Over the last 30 years, clinics have used different criteria such as SIRS, LODS and SOFA or qSOFA as screening tools to assess the severity of organ dysfunction in a potentially septic patient. Common factors among these criteria are non-specificity and very high false positive rates. For patients with positive criteria, the final diagnostic test is a blood culture that may take up to 5 day for a negative result. Likewise, blood culture has a very high false negative rate (> 60%) and does not work for fastidious pathogens such as Chlamydia pneumoniae. More importantly, blood culture cannot be a gold standard method for sepsis diagnosis. This technique only detects the presence of bacteria in the bloodstream (bacteremia), which does not necessarily indicate illness. Many non-bacteremic infections can also cause life-threatening sepsis. In order to improve the accuracy and sensitivity of sepsis diagnosis, the Sepsis-3 definition underscores the requirements for both pathogen detection and information about the personalized state of the immune system of the patient. Therefore, we propose to focus our efforts on monitoring selective biomarkers of this immune response. However, no single, or even a combination of biomarkers has been validated for the diagnosis of sepsis. Because no single biomarker is specific enough to predict sepsis, we propose to develop a point-of-care microfluidic biochip for measuring cell-surface and plasma-proteins biomarkers that will be used for contributing in early sepsis diagnosis. The microfluidic biochip will provide a complete white blood cell count (WBC), as well as quantification of CD64 expression on neutrophil (nCD64), procalcitonin (PCT), C-Reactive Protein (CRP) and Interleukin 6 (IL-6). Multiple studies have demonstrated the high sensitivity of these biomarkers to sepsis. The proposed device will combine for the first time the analysis of cell-surface proteins and plasma proteins biomarkers from the same sample of blood. Such a device, combined with the routinely test performed in the hospitals, could significantly accelerate the diagnosis of sepsis and as consequence the clinical decision, to provide the correct treatment to the patients.

首席调查员/计划总监（最后，第一，中间）：巴希尔，拉希德 项目摘要：败血症，一种威胁生命的器官功能障碍，是由宿主对感染的失调反应引起的（败血症 - 3定义），是医院死亡的主要原因和最昂贵的状况。每年，> 3000万人受到影响 在全球范围内，美国至少有170万成年人（死亡近27万），每年为240亿美元 被诊断出患有败血症和持续的器官衰竭迹象的患者的死亡机会约为15-30％。但是， 对于严重的败血症或败血性休克患者，死亡率可以增加40-60％。三分之一的患者在医院死亡 有败血症。这些死亡率上升率的主要因素之一是无法准确，快速诊断可能 化粪池患者。同样，败血症是医院再入院的主要原因（比心脏的住院比例高 在美国的攻击，心力衰竭，COPD和肺炎）。 EDS和ICU依赖于监视极其非特异性的 参数（例如发烧，低血压，心率增加）以启动临床诊断并开始治疗。这些 原始指标导致医生将早期败血症与其他几种疾病误认为。早期发作的积极诊断 败血症至关重要，因为死亡率随着治疗的延迟而增加。据报道，存活率下降了7.6％ 每小时都没有服用适当的抗生素，并且这些延误会使不必要的医院费用。在 最近30年，诊所使用了不同的标准，例如SIRS，LOD和SOFA或QSOFA作为筛查工具来评估 潜在的化粪池患者的器官功能障碍的严重程度。这些标准之间的常见因素是非特异性和 非常高的误报率。对于具有积极标准的患者，最终的诊断测试是一种血液培养 到5天，结果负面结果。同样，血液培养具有很高的假阴性率（> 60％），不起作用 诸如衣原体肺炎等挑剔的病原体。更重要的是，血液培养不能成为黄金标准方法 用于败血症诊断。该技术仅检测到血液中的细菌存在（菌血症），而不是 必然表明疾病。许多非细菌感染也会引起威胁生命的败血症。为了改善 败血症诊断的准确性和敏感性，SEPIS-3定义强调了两种病原体的要求 有关患者免疫系统个性化状态的检测和信息。因此，我们建议集中精力 我们在监测这种免疫反应的选择性生物标志物方面的努力。但是，没有单一，甚至没有组合 生物标志物已通过诊断败血症进行验证。因为没有单个生物标志物的特异性足以预测败血症，所以 我们建议开发一种用于测量细胞表面和质量蛋白生物标志物的护理点的微流体生物芯片，该生物标志物 将用于败血症早期诊断。微流体生物芯片将提供完整的白色血细胞 计数（WBC）以及中性粒细胞（NCD64），降钙素（PCT），C反应蛋白上CD64表达的定量 （CRP）和白介素6（IL-6）。多项研究表明，这些生物标志物对败血症的敏感性很高。这 建议的装置将首次合并细胞表面蛋白和血浆蛋白生物标志物的分析 相同的血液样本。这样的设备，结合在医院中进行的常规测试，可以显着 加速败血症的诊断，并因此是临床决定，为患者提供正确的治疗方法。

项目成果

Electrochemical point-of-care devices for the diagnosis of sepsis.

• DOI: 10.1016/j.coelec.2023.101300
• 发表时间: 2023-04
• 期刊: Current opinion in electrochemistry
• 影响因子: 8.5
• 作者: E. Valera;Victoria Kindratenko;Aaron M Jankelow;J. Heredia;A. Y. Kim;Thomas W. Cowell;Chih-Lin Chen;K. White;Hee-Sun Han;Rashid Bashir

Droplet Microfluidics for High-Resolution Virology.

• DOI: 10.1021/acs.analchem.2c00615
• 发表时间: 2022-05
• 期刊: Analytical chemistry
• 影响因子: 7.4
• 作者: Wenyang Jing;Hee-Sun Han