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Probing basophil function in microfluidic systems for allergic disease diagnosis

探测微流体系统中的嗜碱性粒细胞功能以诊断过敏性疾病

基本信息

批准号：
10302059
负责人：
Sindy Kam-Yan Tang
金额：
$ 22.07万
依托单位：
STANFORD UNIVERSITY
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：
2021-08-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10302059
关键词：
Address Adoption Adverse reactions Allergens Allergic Allergic Disease Allergic Reaction Anaphylaxis Basophils Behavior Biological Assay Blood Blood specimen Cells Charge Chemotaxis Clinical Color Complement Coupled Cytoplasmic Granules Data Development Diagnosis Diagnostic Diagnostic tests Disease Disease model Dose Epidemic Flow Cytometry Food Food Hypersensitivity Frequencies Goals Gold Grant Healthcare Human Hypersensitivity Immune Immunology Immunotherapy In Vitro Label Leukocytes Life Measurement Measures Mediator of activation protein Medical Care Costs Methods Microfluidics Monitor National Institute of Biomedical Imaging and Bioengineering Oral Outcome Patient risk Patients Pilot Projects Play Predictive Value Proteoglycan Reaction Recording of previous events Risk Role Sensitivity and Specificity Severities Signaling Molecule Source Stratification Surface System Testing Time Tissues Validation Whole Blood Work base biochip companion diagnostics cost design disease diagnosis electric impedance food allergen food challenge food standard high risk improved innovation microfluidic technology migration mouse model patient stratification rapid test tool

项目摘要

PROJECT SUMMARY Basophils play important roles in allergic diseases: their activation is increasingly used for food allergy diagnosis, and their migration into tissues has been correlated with the onset of anaphylaxis. However, since basophils are rare, they are less studied and utilized for diagnostics than other leukocytes, especially in ex vivo microfluidic systems. The overall goal of this project is to fill this gap by developing enabling microfluidic technologies to better quantify basophil function, and by using food allergy as a model disease. Food allergy has reached epidemic proportions and has become a significant source of healthcare burden. Common in vitro allergy tests lack sufficient accuracy. Oral food challenge, the gold standard for food allergy assessment, is often not performed as it places the patient at risk of anaphylaxis. As such, food allergy is often identified only after an adverse reaction that could be life-threatening. In addition, there is no reliable correlation between the onset of anaphylaxis and a minimum offending dose of allergen. Metrics to predict anaphylaxis risk in a patient are essentially non-existent. Our long-term goal is to address these challenges by developing 1) allergy diagnostic tests that are accurate, safe, rapid, and accessible, and 2) metrics to better stratify patients at high risk of anaphylaxis. The overall objective of this pilot grant is to test the hypotheses that: 1) impedance changes in basophils upon activation, which exposes negatively-charged exteriorized granule proteoglycans, is an accurate and simple label-free indicator for basophil activation, and 2) basophil migration and secretion profile correlates with reaction severity. Our approach includes using whole blood samples from clinically-proven and well-characterized peanut allergic subjects and healthy controls, and leveraging our interdisciplinary team's expertise in innovative microfluidic technology and human immunology. We will: (Aim 1) design and validate a label-free impedance-based basophil activation test using whole blood in the presence of food allergen ex vivo, and (Aim 2) design and validate a coupled basophil migration and multiplexed secretion assay ex vivo to determine the correlation with patient history of anaphylaxis.

项目总结