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Integrating Immunology and Microfluidics for Single Immune Cell Analysis Integrating immunology and microfluidics for single immune cell analysis Citation for published version (APA): Sinha, N., Subedi, N., & Tel, J. (2018). Integrating immunology and microfluidics for single immune cell analysis. Frontiers in Immunology, 9, [2373]. https://doi.org/10.3389/fimmu.2018.02373 DOI: 10.3389/fimmu.2018.02373 Document status and date: Published: 16/10/2018 Document Version: Publisher’s PDF, also known as Version of Record (includes final page, issue and volume numbers) Please check the document version of this publication: • A submitted manuscript is the version of the article upon submission and before peer-review. There can be important differences between the submitted version and the official published version of record. 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If the publication is distributed under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license above, please follow below link for the End User Agreement: www.tue.nl/taverne Take down policy If you believe that this document breaches copyright please contact us at: [email protected] providing details and we will investigate your claim. Download date: 06. Oct. 2021 REVIEW published: 16 October 2018 doi: 10.3389/fimmu.2018.02373 Integrating Immunology and Microfluidics for Single Immune Cell Analysis Nidhi Sinha 1,2, Nikita Subedi 1,2 and Jurjen Tel 1,2* 1 Laboratory of Immunoengineering, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands, 2 Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, Netherlands The field of immunoengineering aims to develop novel therapies and modern vaccines to manipulate and modulate the immune system and applies innovative technologies toward improved understanding of the immune system in health and disease. Microfluidics has proven to be an excellent technology for analytics in biology and chemistry. From simple microsystem chips to complex microfluidic designs, these platforms have witnessed an immense growth over the last decades with frequent emergence of new designs. Microfluidics provides a highly robust and precise tool which led to its widespread application in single-cell analysis of immune cells. Single-cell Edited by: analysis allows scientists to account for the heterogeneous behavior of immune cells Jorge Bernardino De La Serna, which often gets overshadowed when conventional bulk study methods are used. United Kingdom Research and Innovation, United Kingdom Application of single-cell analysis using microfluidics has facilitated the identification of Reviewed by: several novel functional immune cell subsets, quantification of signaling molecules, and Li Tang, understanding of cellular communication and signaling pathways. Single-cell analysis École Polytechnique Fédérale de research in combination with microfluidics has paved the way for the development of Lausanne, Switzerland Alex James Tipping, novel therapies, point-of-care diagnostics, and even more complex microfluidic platforms Adaptimmune, United Kingdom that aid in creating in vitro cellular microenvironments for applications in drug and toxicity Alireza Mashaghi, Harvard University, United States screening. In this review, we provide a comprehensive overview on the integration *Correspondence: of microsystems and microfluidics with immunology and focus on different designs Jurjen Tel developed to decode single immune cell behavior and cellular communication. We have [email protected] categorized the microfluidic designs in three specific categories: microfluidic chips with cell traps, valve-based microfluidics, and droplet microfluidics that have facilitated the Specialty section: This article was submitted to ongoing research in the field of immunology at single-cell level. T Cell Biology, a section of the journal Keywords: immunoengineering, microfluidics, single-cell analysis, cellular heterogeneity, cellular communication Frontiers in Immunology Received: 29 May 2018 Accepted: 24 September 2018 INTRODUCTION: IMMUNOENGINEERING Published: 16 October 2018 The human immune system recognizes myriads of environmental triggers and is highly flexible Citation: in generating a variety of signaling responses over time (1, 2). Several types of cells collaborate Sinha N, Subedi N and Tel J (2018) Integrating Immunology and with antibodies and cytokines to generate an appropriate immune response (3). The spatial Microfluidics for Single Immune Cell organization and migration of cells within tissues as well as the dynamic nature of cellular Analysis. Front. Immunol. 9:2373. communication enhances the complexity of our immune system and determines the type of doi: 10.3389/fimmu.2018.02373 response (4–7). The nature and magnitude of an immune response is dependent on dynamic Frontiers in Immunology | www.frontiersin.org 1 October 2018 | Volume 9 | Article 2373 Sinha et al. Integrating Single-Cell Technology and Microfluidics molecular and cellular interactions where well-orchestrated and most noteworthy examples of major discoveries within cellular communication is the key factor to maintain it (8). The the field of immunoengineering, specially immunotherapy, are question arises whether all immune cells fight all pathogens and the development of chimeric antigen receptor T-cells and tumors similarly in order to leverage this broad flexibility and artificial antigen presenting cell systems (38–40). Moreover, diversity. Even though there are multiple subsets of immune immunoengineering also involves mathematical models that cells, with each subset responding to specific stimuli, responses describe the functioning of the immune system, technologies are often initiated by individual cells within each subset and to monitor and track the migration of immune cells and communicated in order to establish a more complex population engineering tools to understand immune cell function at the level response (9). Stochastic expression of genes (influenced systemic level in health and disease (41–43). The field of by a cellular microenvironment) or pre-defined molecular immunoengineering can, and has been described by various drivers (as in case of B-cell and T-cell receptors) are driving definitions, e.g., for the current issue in Frontiers “Application of factors behind heterogeneity in the human immune system systems immunology to engineering the tumor immunological (9). Numerous studies over the last decades established that microenvironment, aiming at predicting lymphocyte receptor’s heterogeneity is a trademark of the human immune system (10, recognition patterns. Building sophisticated mimetic in vitro 11). The identification of heterogeneity requires systems beyond models, for instance by means of optical and magnetic tweezers conventional biological methods like ELISA, western blot, and to develop novel immuno-oncotherapeutics paving the way others that do not allow the required spatial and temporal toward personalized and predictive medicine.” The Center for manipulation of biological cells (12–14). Technologies such Immunoengineering at Georgia Tech University defined this as microsystems and microfluidics, have allowed scientists to field as follows: “The field that applies engineering tools and study the individual behavior of immune cells, identify signaling principles to quantitatively study the immune system in health pathways, map distinct immune cell subsets, quantify secreted and disease, and to develop new therapies or improve existing molecules and characterize the immune response under varied therapies by precisely controlling and modulating a patient’s conditions (15–17). Research on immune cells with technology immune response.” The field of immunoengineering has been integration has contributed toward innovative immunotherapy- described in excellent reviews with a focus on engineering based treatment modalities with lower treatment-related toxicity approaches to augment immunotherapy (44–48). In this review and side effects (18–20). They provide better alternatives to article, we highlight one aspect of immunoengineering and we more conventional treatment modalities e.g., chemotherapy, particularly discuss various microfluidic and microsystems and radiotherapy or targeted therapy. At the same time, microfluidic focus on their advantages over conventional methods especially based models have assisted in the development of novel therapies, for decoding heterogeneous immune cell behavior and cellular discovery of new drugs, and monitoring the clinical efficacy of interactions. new treatments (21–23). Microfluidic devices are also used
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