Monitoring peripheral blood leukocyte and immune responses in health and disease

监测健康和疾病中的外周血白细胞和免疫反应

• 批准号: 9096011
• 负责人: Bruce D Levy
• 金额: $ 38.91万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-23 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9096011
• 关键词: Acute; Address; Anemia; Biological Assay; Biomedical Engineering; Blood; Blood Platelets; Blood Tests; Blood Volume; Cells; Chronic; Clinical; Clinical Medicine; Clinical assessments; Complete Blood Count; Complex; Coupled; Data; Development; Diagnostic; Diagnostic tests; Disease; Dose; Engineering; Erythrocytes; Fractionation; Health; Hospitals; Human; Hypersensitivity; Immune; Immune response; Immunologic Monitoring; Immunosuppressive Agents; Infection; Inflammatory; Inflammatory Response; Label; Laboratories; Leukocytes; Lymphocyte Function; Malignant Neoplasms; Measurement; Measures; Medical; Medicine; Methods; Microfluidic Microchips; Microfluidics; Monitor; Morbidity - disease rate; Opportunistic Infections; Patients; Peripheral; Plasma; Property; Regimen; Routine Diagnostic Tests; Sampling; Secondary to; System; Testing; Therapeutic; Transplantation; Venous; White Blood Cell Count procedure; Whole Blood; adaptive immunity; base; cell type; cellular targeting; clinical practice; cost; design; immune function; immunoregulation; long term hospitalization; milliliter; neutrophil; novel; novel strategies; peripheral blood; research study; response

 DESCRIPTION (provided by applicant): The proposed experiments will test the hypothesis: The separation of leukocytes by their intrinsic properties using Dean Flow Fractionation will enable analyses of innate and adaptive immune responses in microliter quantities of whole blood. Acute and chronic inflammatory responses are integral to the clinical expression of many diseases, yet routine clinical assessment of immune function is based solely on leukocyte count. This is typically measured with a complete blood count and leukocyte differential count. In current clinical practice, critical clinical decisions regarding immune modulation are made based on the count of leukocytes and leukocyte subclasses without assessment of leukocyte function. In addition, the measurement of a peripheral venous complete blood count uses 3-5 mL. Based on the significant blood volume required for the complete blood count and other routine laboratory testing, patients can develop iatrogenic anemia. There is a critical need to develop assays that enable assessment of immune function and require significantly smaller volumes of blood. In preliminary results, we have developed an inertial microfluidic approach to selectively separate diverse cellular targets that is based on non-labeled, cell type specific physical features. From peripheral venous blood, this new approach can separate leukocytes from erythrocytes and platelets, leukocyte subclasses and distinguish activated neutrophils from unactivated cells by tandem iso-dielectric separation. This multi-functional, extracorporeal separation system is high throughput and capable of preparatory separation of leukocytes prior to coupled analyses of systemic and cellular immune function. To address our hypothesis, two specific aims are proposed: 1. Design microliter scale preparatory inertial microfluidic separation of leukocytes in peripheral blood; 2. Determine microliter scale assays of systemic and cell-based immune function. Recent advances in high-throughput microfluidic engineering enable this project, paving the way for a new approach to complex immune monitoring.

 描述（由适用提供）：拟议的实验将测试假设：使用院长流量分馏的白细胞通过其内在特性分离，将使整个血液中的先天和适应性免疫剂分析。急性和慢性炎症反应是许多疾病的临床表达不可或缺的一部分，但是，免疫功能的常规临床评估仅基于白细胞计数。这通常是通过完整的血细胞计数和白细胞差异计数来测量的。在当前的临床实践中，关于免疫调节的关键临床决策是根据白细胞和白细胞亚类的计数做出的，而无需评估白细胞功能。另外，外周静脉全血细胞计数的测量使用3-5 mL。基于全血细胞计数和其他常规实验室测试所需的大量血液体积，患者可以发展医源性贫血。迫切需要进行评估，以评估免疫功能，并且需要大量的血液。在初步结果中，我们开发了一种惯性的微流体方法，可以选择性地分离基于未标记的细胞类型特定物理特征的各种细胞靶标。从周围静脉血液中，这种新方法可以将白细胞与红细胞和血小板，白细胞亚类分开，并通过串联的ISO-射线分离将活化的中性粒细胞与未激活的细胞区分开。这种多功能的体外分离系统是高通量的，能够在全身和细胞免疫学函数的耦合分析之前制备白细胞分离。为了解决我们的假设，提出了两个具体目标：1。设计微尺度制备惯性微流体分离 外周血中的白细胞； 2。确定系统性和基于细胞的免疫征功能的微尺度评估。高通量微流体工程的最新进展使该项目为复杂的免疫监测提供了新的方法。