Abstract
Rapid and frequent screening of cytokines as immunomodulation agents is necessary for precise interventions in severe pathophysiological conditions. In addition to high-sensitivity detection of such analytes in complex biological fluids such as blood, saliva, and cell culture medium samples, it is also crucial to work out miniaturized bioanalytical platforms with potential for high-density integration enabling screening of multiple analytes. In this work, we show a compact, point-of-care-ready bioanalytical platform for screening of cytokines such as interleukin-4 (IL-4) and interleukin-2 (IL-2) based on one-dimensional ion-sensitive field-effect transistors arrays (nanoISFETs) of silicon fabricated at wafer-scale via nanoimprint lithography. The nanoISFETs biofunctionalized with receptor proteins alpha IL-4 and alpha IL-2 were deployed for screening cytokine secretion in mouse T helper cell differentiation culture media, respectively. Our nanoISFETs showed robust sensor signals for specific molecular binding and can be readily deployed for real-time screening of cytokines. Quantitative analyses of the nanoISFET-based bioanalytical platform was carried out for IL-4 concentrations ranging from 25 fg/mL (1.92 fM) to 2.5 μg/mL (192 nM), showing a limit of detection down to 3–5 fM, which was found to be in agreement with ELISA results in determining IL-4 concentrations directly in complex cell culture media.Graphical abstract
Highlights
Cytokines are secreted by immune cells such as lymphocytes (T cells) and epithelial cells, as low molecular weight proteins which are responsible for management of various host defense
IL-4 plays a crucial role in differentiation of naïve CD4+ T cells by promoting Th2 cell differentiation acting against parasitic infections and rheumatoid arthritis [1, 2]
Labelling-based methods are performed for qualitative tissue analysis while enzyme-linked immunosorbent spot (ELISpot) and enzyme-linked immunosorbent assay (ELISA) are employed for quantitative analysis [1, 7]
Summary
Cytokines are secreted by immune cells such as lymphocytes (T cells) and epithelial cells, as low molecular weight proteins which are responsible for management of various host defense. IL-2 have essential role in key immune response mechanisms where they directly impact the differentiation of T cells, effector T cells, and memory T cells, helping the immune system act against infection [5, 6]. Due to highly dynamic and heterogeneous secretion profiles in different tissues, precise monitoring of cytokine during a disease progression and treatment pose a real challenge. Given ultrafast and efficient screening of cell-secreted cytokines, personalized care in different inflammatory conditions, such as sepsis, cancer, lupus, and graft-versus-host disease (GVHD), is expected to be critically improved [7, 9]
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