Individual Control and Quantification of 3D Spheroids in a High-Density Microfluidic Droplet Array

Tomasi, Raphaël F.-X.; Sart, Sébastien; Champetier, Tiphaine; Baroud, Charles N.

doi:10.1016/j.celrep.2020.107670

Cited by 83 publications

(129 citation statements)

References 74 publications

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“…Programmable DNA gels could also find applications in single-cell sequencing (where gel beads and droplet microfluidics are already routine) for instance to extract from a cellular the transcripts belonging to a specific cellular type [ 9 ]. In tissue engineering, DNA gel beads could support complex engineering of spheroids [ 86 ], for instance to spatially organize multicellular spheroid, to select spheroid with given phenotypes, or to massively screen culture conditions [ 87 , 88 ]. Lastly, it could also find application at the intersection of regenerative medicine and drug delivery.…”

Section: Discussionmentioning

confidence: 99%

Morphological Manipulation of DNA Gel Microbeads with Biomolecular Stimuli

et al. 2021

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Hydrogels are essential in many fields ranging from tissue engineering and drug delivery to food sciences or cosmetics. Hydrogels that respond to specific biomolecular stimuli such as DNA, mRNA, miRNA and small molecules are highly desirable from the perspective of medical applications, however interfacing classical hydrogels with nucleic acids is still challenging. Here were demonstrate the generation of microbeads of DNA hydrogels with droplet microfluidic, and their morphological actuation with DNA strands. Using strand displacement and the specificity of DNA base pairing, we selectively dissolved gel beads, and reversibly changed their size on-the-fly with controlled swelling and shrinking. Lastly, we performed a complex computing primitive—A Winner-Takes-All competition between two populations of gel beads. Overall, these results show that strand responsive DNA gels have tantalizing potentials to enhance and expand traditional hydrogels, in particular for applications in sequencing and drug delivery.

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Section: Discussionmentioning

confidence: 99%

Morphological Manipulation of DNA Gel Microbeads with Biomolecular Stimuli

et al. 2021

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“…The microfluidic chips were fabricated using the protocols detailed in previous studies. [17,21,25] Briefly, the chip consisted of a top part made with poly(dimethylsiloxane) (PDMS, SYLGARD 184, Dow Corning, 1:10 w/w ratio of curing agent to bulk material) on which was imprinted a flow focusing device connected to an emulsification channel (serpentine), diverging rails, and terminated by a culture chamber; the bottom part of the chip was a PDMS layer (about 400 µm thick) etched with an array of capillary traps, which was bonded on a microscopy glass slide ( Figure 1A). The top and bottom parts of the chip were assembled after plasma treatment (Harrick, Ithaca, USA).…”

Section: Microfabricationmentioning

confidence: 99%

High‐Throughput Measurements of Intra‐Cellular and Secreted Cytokine from Single Spheroids Using Anchored Microfluidic Droplets

Saint-Sardos

Sart

Lippera

et al. 2020

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communication and help regulate the function on the scale of whole organs and organism. The different types of molecules are present at different concentrations in vivo and act over a range of time scales, from seconds to days. Indeed, variations in the rate of secretion of different molecules indicate the state of the cells, for example, as a response to changes in their environment. Standard methods for measuring secreted molecules in typical cell culture experiments, however, require the presence of a large number of molecules, which translates into volumes of tens to hundreds of µL and give information at the level of large populations of cells. As a result, these techniques hide the heterogeneities that may exist on the scale of individual cells. It is becoming increasingly clear, however, that these heterogeneities are present and play a determining role in many biological processes, such as the immune response to an unknown pathogen, [1] or as a prognostic marker for some cancer types. [2] 2002303 (2 of 11)

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“…This data-driven approach allowed the heterotopic 3D cell culturing behaviour to be monitored and linked single-cell measurements with population measurements. 100 This platform yielded time-resolved, single-cell data, revealing a dynamic response regulated at the spheroid level. This was achieved by introducing a new asymmetric design for the anchors, which led to a qualitative transformation in the functionality of the microfluidic approach for a range of biological applications, including tissue engineering, models of immuno-therapies, and understanding host-pathogen interactions.…”

Section: Aqueous Two-phase System (Atps)mentioning

confidence: 99%