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

基本信息

批准号：
10462484
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
项目类别：
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/10462484
关键词：
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 Cell surface 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 Gold 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 base biochip clinical diagnosis cost design early onset electric impedance hospital readmission improved innovation malignant breast neoplasm mortality multiplex detection nanomagnetic neutrophil particle pathogen patient population point of care procalcitonin programs protein biomarkers response biomarker risk stratification septic patients technological innovation therapy development

项目摘要

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.

首席研究员/项目总监（最后、第一、中间）：Bashir、Rashid 项目摘要：脓毒症，一种由宿主对感染反应失调引起的危及生命的器官功能障碍（脓毒症- 3 定义），是死亡的主要原因，也是医院最昂贵的疾病。每年有超过 3000 万人受到影响在全球范围内，美国至少有 170 万成年人患败血症（近 27 万人死亡），每年造成 240 亿美元的损失。被诊断患有败血症且没有持续器官衰竭迹象的患者死亡几率约为 15-30%。然而，严重败血症或败血性休克患者的死亡率可增加高达 40-60%。三分之一在医院死亡的患者有败血症。死亡率上升的一个主要因素是无法准确、快速地诊断潜在的疾病脓毒症患者。同样，败血症是再入院的主要原因（比例高于因心脏病住院的比例）发作、心力衰竭、慢性阻塞性肺病和美国的肺炎）。急诊科和重症监护室依赖的监测极其不具体参数（例如发烧、低血压、心率加快）以启动临床诊断并开始治疗。这些粗略的指标导致医生将早期败血症误认为是其他几种疾病。早发的阳性诊断脓毒症至关重要，因为死亡率随着治疗的延误而增加。据报道存活率下降了 7.6% 每小时都没有给予适当的抗生素，这些延误增加了不必要的医院费用。超过过去 30 年，诊所使用不同的标准，如 SIRS、LODS 和 SOFA 或 qSOFA 作为筛查工具来评估潜在脓毒症患者器官功能障碍的严重程度。这些标准的共同因素是非特异性和误报率非常高。对于符合阳性标准的患者，最终的诊断测试是血培养，可能需要阴性结果需要 5 天。同样，血培养具有非常高的假阴性率（> 60%），并且不适用于挑剔的病原体，如肺炎衣原体。更重要的是，血培养不能成为金标准方法用于脓毒症诊断。该技术仅检测血液中细菌的存在（菌血症），而不能检测血液中是否存在细菌（菌血症）。必然表明有病。许多非菌血症感染也可能导致危及生命的败血症。为了改善为了提高脓毒症诊断的准确性和敏感性，Sepsis-3 定义强调了对两种病原体的要求检测和有关患者免疫系统个性化状态的信息。因此，我们建议重点关注我们致力于监测这种免疫反应的选择性生物标志物。然而，没有单一的，甚至是组合的生物标志物已被验证可用于脓毒症的诊断。因为没有任何一种生物标志物具有足够的特异性来预测脓毒症，我们建议开发一种用于测量细胞表面和血浆蛋白生物标志物的即时微流控生物芯片，将用于促进脓毒症的早期诊断。微流控生物芯片将提供完整的白细胞计数 (WBC)，以及中性粒细胞 CD64 表达 (nCD64)、降钙素原 (PCT)、C 反应蛋白的定量 (CRP) 和白细胞介素 6 (IL-6)。多项研究表明这些生物标志物对脓毒症具有高度敏感性。这拟议的设备将首次结合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。这种设备与医院进行的常规测试相结合，可以显着加速脓毒症的诊断，从而加快临床决策，为患者提供正确的治疗。