Monitoring transient cell-to-cell interactions in a multi-layered and multi-functional allergy-on-a-chip system.

We have developed a highly integrated lab-on-a-chip containing embedded electrical microsensors, μdegassers and pneumatically-actuated micropumps to monitor allergic hypersensitivity. Rapid antigen-mediated histamine release (e.g. s to min) and resulting muscle contraction (<30 min) is detected by connecting an immune compartment containing sensitized basophile cells to a vascular co-culture model.

[1]  Peter Ertl,et al.  Tomorrow today: organ-on-a-chip advances towards clinically relevant pharmaceutical and medical in vitro models. , 2019, Current opinion in biotechnology.

[2]  G. Rook,et al.  Give us this day our daily germs. , 1998, Biologist.

[3]  A. Beyerle,et al.  Pitfalls in assessing microvascular endothelial barrier function: impedance-based devices versus the classic macromolecular tracer assay , 2016, Scientific Reports.

[4]  J. Schroeder,et al.  Basophils: emerging roles in the pathogenesis of allergic disease , 2011, Immunological reviews.

[5]  Jungkyu Kim,et al.  Pneumatically actuated microvalve circuits for programmable automation of chemical and biochemical analysis. , 2016, Lab on a chip.

[6]  Yuhki Yanase,et al.  Diagnosis of immediate-type allergy using surface plasmon resonance , 2016 .

[7]  Verena Charwat,et al.  Monitoring cellular stress responses using integrated high-frequency impedance spectroscopy and time-resolved ELISA. , 2014, The Analyst.

[8]  M. Schwartz,et al.  ZO-1 controls endothelial adherens junctions, cell–cell tension, angiogenesis, and barrier formation , 2015, The Journal of cell biology.

[9]  Verena Charwat,et al.  Monitoring dynamic interactions of tumor cells with tissue and immune cells in a lab-on-a-chip. , 2013, Analytical chemistry.

[10]  A. Pandey,et al.  Identification of secreted proteins that mediate cell-cell interactions in an in vitro model of the lung cancer microenvironment. , 2008, Cancer research.

[11]  Verena Charwat,et al.  Zirconium dioxide nanolayer passivated impedimetric sensors for cell-based assays , 2015 .

[12]  J. Wedemeyer,et al.  Roles of mast cells and basophils in innate and acquired immunity. , 2000, Current opinion in immunology.

[13]  Richard Novak,et al.  Rapid fabrication of nickel molds for prototyping embossed plastic microfluidic devices. , 2013, Lab on a chip.

[14]  J. Panés,et al.  Leukocyte-endothelial cell interactions: molecular mechanisms and implications in gastrointestinal disease. , 1998, Gastroenterology.

[15]  R. Valenta,et al.  Vaccine development for allergen-specific immunotherapy based on recombinant allergens and synthetic allergen peptides: Lessons from the past and novel mechanisms of action for the future , 2016, The Journal of allergy and clinical immunology.

[16]  Wieland B Huttner,et al.  The cell biology of neurogenesis: toward an understanding of the development and evolution of the neocortex. , 2014, Annual review of cell and developmental biology.

[17]  K. Masaki Early disruption of glial communication via connexin gap junction in multiple sclerosis, Baló's disease and neuromyelitis optica , 2015, Neuropathology : official journal of the Japanese Society of Neuropathology.

[18]  M. White,et al.  The role of histamine in allergic diseases. , 1990, The Journal of allergy and clinical immunology.

[19]  M. Gleave,et al.  Prostate and bone fibroblasts induce human prostate cancer growth in vivo: implications for bidirectional tumor-stromal cell interaction in prostate carcinoma growth and metastasis. , 1992, The Journal of urology.

[20]  Michael J. Cronce,et al.  Organs-on-chips with integrated electrodes for trans-epithelial electrical resistance (TEER) measurements of human epithelial barrier function. , 2017, Lab on a chip.

[21]  Gerhard J Schütz,et al.  The TCR is randomly distributed on the plasma membrane of resting antigen-experienced T cells , 2018, Nature Immunology.

[22]  T. Baudino,et al.  Dynamic cell-cell and cell-ECM interactions in the heart. , 2014, Journal of molecular and cellular cardiology.

[23]  H. Takayanagi,et al.  Osteoclast Biology: Regulation of Formation and Function , 2016 .

[24]  C. Janeway Immunobiology: The Immune System in Health and Disease , 1996 .

[25]  Calman Prussin,et al.  IgE, mast cells, basophils, and eosinophils. , 2003, The Journal of allergy and clinical immunology.

[26]  Andrew G. Clark,et al.  Modes of cancer cell invasion and the role of the microenvironment. , 2015, Current opinion in cell biology.

[27]  I. Lizasoain,et al.  Complexity of the cell–cell interactions in the innate immune response after cerebral ischemia , 2015, Brain Research.

[28]  P. Ertl,et al.  Every Breath You Take: Non-invasive Real-Time Oxygen Biosensing in Two- and Three-Dimensional Microfluidic Cell Models , 2018, Front. Physiol..

[29]  Peter Ertl,et al.  Recent advances in microfluidic technologies for cell-to-cell interaction studies. , 2018, Lab on a chip.

[30]  Erik C Jensen,et al.  Lifting gate polydimethylsiloxane microvalves and pumps for microfluidic control. , 2012, Analytical chemistry.

[31]  Accuracy of serum-specific IgE test with microfluidic array enzyme-linked immunosorbent assay for diagnosing inhalant allergen sensitization in asthma and/or rhinitis allergy patients in Jakarta, Indonesia , 2018, Asia Pacific allergy.

[32]  Christoph A Merten,et al.  Microfluidic single-cell technology in immunology and antibody screening. , 2017, Molecular aspects of medicine.

[33]  Chrysanthi Ainali,et al.  A Systems Model for Immune Cell Interactions Unravels the Mechanism of Inflammation in Human Skin , 2010, PLoS Comput. Biol..

[34]  B. Roysam,et al.  Adult SVZ stem cells lie in a vascular niche: a quantitative analysis of niche cell-cell interactions. , 2008, Cell stem cell.

[35]  P. Ertl,et al.  Engineering of three-dimensional pre-vascular networks within fibrin hydrogel constructs by microfluidic control over reciprocal cell signaling. , 2018, Biomicrofluidics.

[36]  K. Shen,et al.  Transient cell–cell interactions in neural circuit formation , 2009, Nature Reviews Neuroscience.

[37]  The allergy epidemics: 1870-2010. , 2015, The Journal of allergy and clinical immunology.

[38]  R. Murphy,et al.  Eicosanoid Transcellular Biosynthesis: From Cell-Cell Interactions to in Vivo Tissue Responses , 2006, Pharmacological Reviews.

[39]  C. Porta,et al.  The role of the cell–cell interactions in cancer progression , 2015, Journal of cellular and molecular medicine.

[40]  Qasem Ramadan,et al.  In vitro micro-physiological models for translational immunology. , 2015, Lab on a chip.

[41]  A. Sampson,et al.  The immune response and immunosuppressant drugs , 2018 .