Deformability-based microfluidic cell pairing and fusion

Dura, Burak; Liu, Yaoping; Voldman, Joel

doi:10.1039/c4lc00303a

Cited by 80 publications

(80 citation statements)

References 31 publications

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“…Monitoring early signaling events requires generation of defined cell pairs with controlled timings. We previously demonstrated a deformabilitybased cell-pairing approach that allowed sequential capture and pairing of fibroblasts in parallel (17). Here, as a first step to a microfluidic cell-cell interaction assay, we extended this cellpairing technique to immune cells by developing microfluidic devices suitable for cell types with a wide size range (cell diameters ∼9-25 μm).…”

Section: Resultsmentioning

confidence: 99%

Longitudinal multiparameter assay of lymphocyte interactions from onset by microfluidic cell pairing and culture

Dura

Servos

Barry

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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104

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Resolving how the early signaling events initiated by cell-cell interactions are transduced into diverse functional outcomes necessitates correlated measurements at various stages. Typical approaches that rely on bulk cocultures and population-wide correlations, however, only reveal these relationships broadly at the population level, not within each individual cell. Here, we present a microfluidics-based cell-cell interaction assay that enables longitudinal investigation of lymphocyte interactions at the single-cell level through microfluidic cell pairing, on-chip culture, and multiparameter assays, and allows recovery of desired cell pairs by micromanipulation for off-chip culture and analyses. Well-defined initiation of interactions enables probing cellular responses from the very onset, permitting singlecell correlation analyses between early signaling dynamics and later-stage functional outcomes within same cells. We demonstrate the utility of this microfluidic assay with natural killer cells interacting with tumor cells, and our findings suggest a possible role for the strength of early calcium signaling in selective coordination of subsequent cytotoxicity and IFN-gamma production. Collectively, our experiments demonstrate that this new approach is well-suited for resolving the relationships between complex immune responses within each individual cell.microfluidics | cell pairing | single-cell analysis | cell-cell interactions | multiparameter assay I nitiation and progression of immune responses require direct cell-cell interactions. Molecular interactions at the contact interface mediate cellular cross-talk and trigger a series of wellorchestrated downstream signaling events. The magnitude and dynamics of these signals promote and coordinate immune cell activation, and underlie a broad array of functional outcomes, such as target cell elimination, secretory activity, and proliferation (1, 2). Understanding how these early signaling events are transduced into functional responses demands correlated measurements at different stages as these responses unfold.Typically, these relationships are probed by first activating cells in bulk cocultures, often mixing cell populations and initiating contacts via a brief centrifugal cosedimentation, and then piecing together measurements from independent assays performed at different time points. This approach may determine broad outcomes of intercellular interactions, but it suffers from three major limitations. First, individual assay measurements are averaged over many different combinations of interactions due to the uncontrolled and indefinite nature of cell-cell interactions in bulk cocultures. For example, varying times of initiation and duration of contacts (1, 3), number of interacting partners (4), and differences in antigen presenting cells (5) can all modulate immune cell responses. Unpredictable variation is therefore introduced into measured responses, masking the true intrinsic cellular heterogeneity and blurring the correlations. Second, conventional as...

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Section: Resultsmentioning

confidence: 99%

Longitudinal multiparameter assay of lymphocyte interactions from onset by microfluidic cell pairing and culture

Dura

Servos

Barry

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

104

View full text Add to dashboard Cite

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Section: Defining Intercellular Interactionsmentioning

confidence: 99%

“…The first group of such systems utilize high-density hydrodynamic cell trap arrays within flowthrough channels [28][29][30][31]32 ] (Figure 1d). In particular, we developed a method, termed 'microfluidic cell pairing' [29,31,32 ], that uses microfabricated capture-cups to properly isolate and pair thousands of cells in parallel using a multistep cell loading procedure. This approach generates one-to-one enduring interactions at high efficiencies (up to 80%), and proper choice of cell density and flow rates enable highly synchronous contact formation (<40 s variation across the entire array) with a defined time point, providing the opportunity to probe into emerging cellular responses beginning from the contact time.…”

Section: Defining Intercellular Interactionsmentioning

confidence: 99%

Spatially and temporally controlled immune cell interactions using microscale tools

Dura

Voldman

2015

Current Opinion in Immunology

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Many critical immunological responses are mediated by cell-cell interactions. Despite their capabilities, traditional techniques that rely on snapshot analysis or ensemble measurements can only provide a fragmentary picture of the complexity of these interactions. Emerging classes of new and versatile microscale tools hold great potential for enabling detailed investigation of these interactions with precise control in space and time, multiplexed measurement capability and high-throughput single-cell analysis. These features allow new ways of examining immune cell interactions that are not possible with traditional methods, improve the extent of information extracted from experiments, and reveal new findings. Here, we review recent developments in microscale tools that are paving the way for comprehensive analyses of cell-cell interactions in the immune system.

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“…Another common method for pairing cells is using a microfluidic cell trap or structure to control the pairing of cells (Fig 1C). These traps commonly utilize either hydrodynamic traps 56–58 or some type of structure to hold the cell 59,60 . Another method of manipulating cells, either vertically or horizontally, is using acoustofluidics 61,62 .…”

Section: Short Distance Communicationmentioning

confidence: 99%

Bridging the gap: microfluidic devices for short and long distance cell–cell communication

Castro

Qin

2017

Lab Chip

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Cell-cell communication is a crucial component of many biological functions. For example, understanding how immune cells and cancer cells interact, both at the immunological synapse and through cytokine secretion, can help us understand and improve cancer immunotherapy. The study of how cells communicate and form synaptic connections is important in neuroscience, ophthalmology, and cancer. But in order to increase our understanding of these cellular phenomena, better tools need to be developed that allow us to study cell-cell communication in a highly controlled manner. Some technical requirements for better communication studies include manipulating cells spatiotemporally, high resolution imaging, and integrating sensors. Microfluidics is a powerful platform that has the ability to address these requirements and other current limitations. In this review, we describe some new advances in microfluidic technologies that have provided researchers with novel methods to study intercellular communication. The advantages of microfluidics have allowed for new capabilities in both single cell-cell communication and population-based communication. This review highlights microfluidic communication devices categorized as “short distance,” or primarily at the single cell level, and “long distance,” which mostly encompasses population level studies. Future directions and translation/commercialization will also be discussed.

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Deformability-based microfluidic cell pairing and fusion

Cited by 80 publications

References 31 publications

Longitudinal multiparameter assay of lymphocyte interactions from onset by microfluidic cell pairing and culture

Longitudinal multiparameter assay of lymphocyte interactions from onset by microfluidic cell pairing and culture

Spatially and temporally controlled immune cell interactions using microscale tools

Bridging the gap: microfluidic devices for short and long distance cell–cell communication

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