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:
- 金额:$ 51万
- 依托单位:
- 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:
- 关键词:Accident and Emergency departmentAcquired Immunodeficiency SyndromeAdultAffectAmericanAntibioticsBacteremiaBacteriaBinding ProteinsBiological MarkersBloodBlood Cell CountBlood CirculationBlood specimenC-reactive proteinCause of DeathCell Surface ProteinsCell surfaceCellsCessation of lifeChemicalsChlamydophila pneumoniaeChronic Obstructive Pulmonary DiseaseClinicClinicalClinical ResearchCollaborationsComputerized Medical RecordCoulter counterDataDetectionDevicesDiagnosisDiagnostic testsDiseaseDropsEarly DiagnosisEconomic BurdenElectrolytesEngineeringEnsureExhibitsFeverFloorFoundationsFunctional disorderFutureGoalsGoldHealthcare SystemsHeart RateHeart failureHospital CostsHospitalizationHospitalsHourHydrogelsHypotensionImmune responseImmune systemImmunoassayImmunologic MarkersInfectionInstitutional Review BoardsInterleukin-6LaboratoriesLength of StayLifeMagnetismMalignant neoplasm of prostateMeasuresMethodsMicrofluidicsMonitorMoralsMyocardial InfarctionOrganOrgan failurePathogen detectionPatientsPersonsPlasma ProteinsPneumoniaPopulationPrincipal InvestigatorPropertyProteinsReaction TimeReportingSamplingScreening procedureSensitivity and SpecificitySepsisSeptic ShockSeveritiesSignal TransductionSolidSpeedStratificationSurfaceSurvival RateSyndromeTechniquesTechnologyTestingTimeUnited StatesVariantWhite Blood Cell Count procedureWhole BloodWorkbasebiochipclinical diagnosiscostdesignearly onsetelectric impedancehospital readmissionimprovedinnovationmalignant breast neoplasmmortalitymultiplex detectionnanomagneticneutrophilparticlepathogenpatient populationpoint of careprocalcitoninprogramsprotein biomarkersresponse biomarkerrisk stratificationseptic patientstechnological innovationtherapy 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.
主要研究者/项目负责人(最后一名、第一名、中间名):Bashir、Rashid
脓毒症,一种由宿主对感染的反应失调引起的危及生命的器官功能障碍(脓毒症-
3定义),是死亡的主要原因和医院最昂贵的条件。每年有超过3000万人受到影响
在全球范围内,至少有170万成年人患败血症(近27万人死亡),在美国每年花费240亿美元。
被诊断为败血症且没有持续器官衰竭迹象的患者有约15-30%的死亡机会。但
严重脓毒症或脓毒性休克患者的死亡率可增加至40-60%。三分之一死于医院的病人
得了败血症这些死亡率上升的一个主要因素是无法准确和快速地诊断潜在的
败血症患者。同样,败血症是再次入院的主要原因(比例高于心脏病住院)
在美国,心脏病发作、心力衰竭、COPD和肺炎)。急诊科和重症监护室依赖于监测极不特异性的
参数(例如发热、低血压、心率增加),以启动临床诊断并开始治疗。这些
粗糙的指标使医生将早期败血症与其他几种疾病相混淆。早期发病的阳性诊断
脓毒症是关键的,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%
每隔一个小时,没有给予适当的抗生素,这些延误加剧了不必要的医院费用。来
在过去的30年里,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。这些标准中的共同因素是非特异性,
非常高的假阳性率。对于阳性标准的患者,最终的诊断测试是血培养,
5天为阴性结果。同样,血培养具有非常高的假阴性率(> 60%),并且对
苛养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。这种技术只能检测血液中细菌的存在(菌血症),而不能检测血液中细菌的存在。
这必然意味着疾病。许多非菌血症感染也可导致危及生命的败血症。为了提高
脓毒症诊断的准确性和敏感性,脓毒症-3定义强调了两种病原体的要求
检测和关于患者的免疫系统的个性化状态的信息。因此,我们建议将重点
我们致力于监测这种免疫反应的选择性生物标志物。然而,没有一个单一的,甚至是一个组合,
生物标志物已被验证用于脓毒症的诊断。因为没有单一的生物标志物能够特异性地预测脓毒症,
我们建议开发一种用于测量细胞表面和血浆蛋白质生物标志物的即时微流控生物芯片,
将有助于脓毒症的早期诊断。微流控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(nCD 64)、降钙素原(PCT)、C反应蛋白表达的定量
(CRP)和白细胞介素6(IL-6)。多项研究已经证明这些生物标志物对脓毒症的高敏感性。的
所提出的设备将联合收割机首次结合细胞表面蛋白和血浆蛋白生物标志物的分析,
同样的血液样本这样的设备,结合在医院进行的常规测试,
加快脓毒症的诊断,从而加快临床决策,为患者提供正确的治疗。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Rashid Bashir其他文献
Rashid Bashir的其他文献
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{{ truncateString('Rashid Bashir', 18)}}的其他基金
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 - 财政年份:2021
- 资助金额:
$ 51万 - 项目类别:
Smartphone-linked system for diagnosis and epidemiological reporting of pathogens at the point of care
智能手机连接系统,用于在护理点诊断和流行病学报告病原体
- 批准号:
10462690 - 财政年份:2019
- 资助金额:
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High accuracy optical growth assay of 3D cellular systems
3D 细胞系统的高精度光学生长测定
- 批准号:
10330571 - 财政年份:2019
- 资助金额:
$ 51万 - 项目类别:
Smartphone-linked system for diagnosis and epidemiological reporting of pathogens at the point of care
智能手机连接系统,用于在护理点诊断和流行病学报告病原体
- 批准号:
10241489 - 财政年份:2019
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Atomically-thin diode integrated into a nanopore DNA Sensor
集成到纳米孔 DNA 传感器中的原子薄二极管
- 批准号:
9808985 - 财政年份:2019
- 资助金额:
$ 51万 - 项目类别:
Multiplexed Pathogen Detection from Whole Blood for Rapid Detection of Sepsis
全血多重病原体检测可快速检测脓毒症
- 批准号:
9809870 - 财政年份:2019
- 资助金额:
$ 51万 - 项目类别:
LLISA: ???Liposome-Linked Immunosorbant Assay??? for Detection of HIV Viral Load
LLISA:???脂质体连接免疫吸附测定???
- 批准号:
8514874 - 财政年份:2013
- 资助金额:
$ 51万 - 项目类别:
"LLISA:'Liposome-Linked Immunosorbant Assay' for Detection of HIV Viral Load at Point-of-Care"
“LLISA:用于护理点 HIV 病毒载量检测的‘脂质体联免疫吸附测定’”
- 批准号:
8721331 - 财政年份:2013
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$ 51万 - 项目类别:
Measurements of BPDE-DNA adducts by solid state nonopore and deep sequencing (PQ
通过固态非孔和深度测序 (PQ
- 批准号:
8534070 - 财政年份:2012
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Measurements of BPDE-DNA adducts by solid state nonopore & deep sequencing (PQ3
通过固态非孔测量 BPDE-DNA 加合物
- 批准号:
8384743 - 财政年份:2012
- 资助金额:
$ 51万 - 项目类别:
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