Analytica chimica acta · 2026
Quantitative assessment of neutrophil chemotactic migration under coexisting intermediate and terminal chemokine gradients in a microfluidic environment: Applications for immune dysfunction and prognostic evaluation in sepsis.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Zhu Zhuoyi, Yang Xiao, Yao Yuhang, Fang Ming, Shao Min, Zha Yutao, Zhao Jun, Cui Junsheng, Ren Xiaoou, Zhu Ling, Pu Xuexue, Li Qiuling, Yang Ke
Аннотация
BACKGROUND: Sepsis remains a life-threatening condition, largely due to immune dysregulation and the difficulty of accurately assessing patient prognosis. Neutrophils, as central innate immune effectors, migrate through complex chemokine landscapes in vivo, responding to both intermediate chemokines (e.g., IL-8, LTB4) and terminal chemokines (e.g., fMLP, C5a) to coordinate effective antimicrobial and inflammatory responses. Existing in vitro assays, however, are limited in their ability to recapitulate physiologically relevant dual-gradient environments and fail to provide quantitative, high-throughput analysis of neutrophil migration dynamics. This limitation hampers the mechanistic understanding of neutrophil dysfunction in sepsis and constrains the development of predictive immune monitoring strategies.
RESULTS: We developed a six-channel Dual-gradient Neutrophil Chemotaxis chip (DNC-chip) capable of simultaneously generating paired chemokine gradients within each assay unit (units 1-3: 100 nM LTB4 + 100 nM fMLP; units 4-6: 100 nM LTB4 + 10 nM C5a). This platform enabled high-throughput, quantitative assessment of neutrophil migration. Using samples from healthy controls (NH = 20) and sepsis patients (NS = 20), we extracted multidimensional migration parameters, including Euclidean distance, chemotactic index, stop ratio, and peak velocity, to construct a Neutrophil Migration Kinetics Comprehensive (NMKC) index. The NMKC index also exhibited strong predictive performance for mortality, with AUC values of 0.786 for the LTB4 + fMLP gradient and 0.813 for the LTB4 + C5a gradient.
SIGNIFICANCE: The DNC-chip establishes a robust platform for functional immune phenotyping under complex dual-chemokine landscapes. Integrated with the NMKC index, it provides a quantitative framework for objective immune monitoring and mortality risk stratification in sepsis, highlighting its potential for clinical translation and warranting validation in larger patient cohorts.
RESULTS: We developed a six-channel Dual-gradient Neutrophil Chemotaxis chip (DNC-chip) capable of simultaneously generating paired chemokine gradients within each assay unit (units 1-3: 100 nM LTB4 + 100 nM fMLP; units 4-6: 100 nM LTB4 + 10 nM C5a). This platform enabled high-throughput, quantitative assessment of neutrophil migration. Using samples from healthy controls (NH = 20) and sepsis patients (NS = 20), we extracted multidimensional migration parameters, including Euclidean distance, chemotactic index, stop ratio, and peak velocity, to construct a Neutrophil Migration Kinetics Comprehensive (NMKC) index. The NMKC index also exhibited strong predictive performance for mortality, with AUC values of 0.786 for the LTB4 + fMLP gradient and 0.813 for the LTB4 + C5a gradient.
SIGNIFICANCE: The DNC-chip establishes a robust platform for functional immune phenotyping under complex dual-chemokine landscapes. Integrated with the NMKC index, it provides a quantitative framework for objective immune monitoring and mortality risk stratification in sepsis, highlighting its potential for clinical translation and warranting validation in larger patient cohorts.