Robotic automation of droplet microfluidics

Tm, Tran; Kim, Samuel; Ar, Abate

doi:10.1101/278556

Cited by 3 publications

(6 citation statements)

References 34 publications

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“…Reproducibility is key to successful lab work as well as automation. 4 To seamlessly connect a 1 mL pipette tip with the outlet of the microfluidic channel, we added a 4 mm long rubber O-ring at the lower part of the pipette tip. The conical shape of the 1 mL pipetting tip prevents the rubber O-ring from sliding along the tip and locks it in place.…”

Section: Resultsmentioning

confidence: 99%

“…Microfluidic technologies have seen some general automation approaches, such as pressure-controlled valving 1 and programmatically reconfigurable devices. 2 Most of these, however, require substantial infrastructure outside of the microfluidic device, [3][4][5][6][7] and only very few (e.g., the Fluidigm integrated fluidic circuits) can be readily interfaced with general laboratory robotics such as liquid-handling robots.…”

Section: Introductionmentioning

confidence: 99%

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Rapid Production and Recovery of Cell Spheroids by Automated Droplet Microfluidics

Langer

Joensson

2020

SLAS Technology

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The future of the life sciences is linked to automation and microfluidics. As robots start working side by side with scientists, robotic automation of microfluidics in general, and droplet microfluidics in particular, will significantly extend and accelerate the life sciences. Here, we demonstrate the automation of droplet microfluidics using an inexpensive liquid-handling robot to produce human scaffold-free cell spheroids at high throughput. We use pipette actuation and interface the pipetting tip with a droplet-generating microfluidic device. In this device, we produce highly monodisperse droplets with a diameter coefficient of variation (CV) lower than 2%. By encapsulating cells in these droplets, we produce cell spheroids in droplets and recover them to standard labware containers at a throughput of 85,000 spheroids per microfluidic circuit per hour. The viability of the cells in spheroids remains high throughout the process and decreases by >10% (depending on the cell line used) after a 16 h incubation period in nanoliter droplets and automated recovery. Scaffold-free cell spheroids and 3D tissue constructs recapitulate many aspects of functional human tissue more accurately than 2D or single-cell cultures, but assembly methods for spheroids (e.g., hanging drop microplates) have limited throughput. The increased throughput and decreased cost of our method enable spheroid production at the scale needed for lead discovery drug screening, and approach the cost at which these microtissues could be used as building blocks for organ-scale regenerative medicine.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Rapid Production and Recovery of Cell Spheroids by Automated Droplet Microfluidics

Langer

Joensson

2020

SLAS Technology

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“…Unfortunately, PDMS chips used as part of automated workflows based on pipettors and liquid handling robots create additional problems related to the lack of reproducibility as those elements are frequently manufactured in low quantities, usually directly by hand -introducing a great human error. And reproducibility is the critical element of successful lab work and the automation 39,4 . To address those issues and connect seamlessly 1ml pipette tip with the outlet of the microfluidic channel we have added an approximately 4 mm rubber O-ring at the lower opening of the pipette tip.…”

Section: Resultsmentioning

confidence: 99%

“…Microfluidic technologies have seen some general automation approaches such as pressure-controlled valving 1 , and programmatically reconfigurable devices 2 . However, most of these have required substantial infrastructure outside of the microfluidic device 3,4,5,6,7 and only very few, such as, e.g. the Fluidigm integrated fluidic circuits can be readily interfaced with general laboratory robotics such as liquid handling robots.…”

Section: Introductionmentioning

confidence: 99%

DRAFT - Robotic automation of production and the recovery of cell spheroids

Langer

Jönsson²

2019

Preprint

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Droplet microfluidics enables high throughput cell processing, analysis and screening by miniaturizing the reaction vessels to nano-or pico-liter water-in oil droplets, but like many other microfluidic formats, droplet microfluidics have not been interfaced with or automated by laboratory robotics. Here we demonstrate automation of droplet microfluidics based on an inexpensive liquid handling robot for the automated production of human scaffold-free cell spheroids, using pipette actuation and interfacing the pipetting tip with a droplet generating microfluidic chip. In this chip we produce highly mono-disperse 290µm droplets with diameter CV of 1.7%. By encapsulating cells in these droplets we produce cell spheroids in droplets and recover them to standard formats at a throughput of 85000 spheroids per microfluidic circuit per hour. The viability of the cells in spheroids remains high after recovery only decreased by 4% starting from 96% after 16 hours incubation in nanoliter droplets. Scaffold-free cell spheroids and 3D tissue constructs recapitulate many aspects of functional human tissue more accurately than 2D or single cell cultures, but assembly methods for spheroids, e.g. hanging drop micro-plates, has had limited throughput. The increased throughput and decreased cost of our method enables spheroid production at the scale needed for lead discovery drug screening and approaches the cost where these micro tissues could be used as building blocks for organ scale regenerative medicine.

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“… 71 Newly, the possibility of full automation and integration of the microfluidic workflow was demonstrated using a system composed of 3 components: (i) a robotic liquid handler; (ii) syringe pumps with valves, which can withdraw and pump fluid; (iii) microfluidic unit operations, such as droplet generation, merging, and sorting. 72 Such a system can perform all of the steps required for directed evolution and shows a high level of flexibility.…”

Section: Variant Selectionmentioning

confidence: 99%

Directed Evolution in Drops: Molecular Aspects and Applications

et al. 2021

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The process of optimizing the properties of biological molecules is paramount for many industrial and medical applications. Directed evolution is a powerful technique for modifying and improving biomolecules such as proteins or nucleic acids (DNA or RNA). Mimicking the mechanism of natural evolution, one can enhance a desired property by applying a suitable selection pressure and sorting improved variants. Droplet-based microfluidic systems offer a high-throughput solution to this approach by helping to overcome the limiting screening steps and allowing the analysis of variants within increasingly complex libraries. Here, we review cases where successful evolution of biomolecules was achieved using droplet-based microfluidics, focusing on the molecular processes involved and the incorporation of microfluidics to the workflow. We highlight the advantages and limitations of these microfluidic systems compared to low-throughput methods and show how the integration of these systems into directed evolution workflows can open new avenues to discover or improve biomolecules according to user-defined conditions.

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Robotic automation of droplet microfluidics

Cited by 3 publications

References 34 publications

Rapid Production and Recovery of Cell Spheroids by Automated Droplet Microfluidics

Rapid Production and Recovery of Cell Spheroids by Automated Droplet Microfluidics

DRAFT - Robotic automation of production and the recovery of cell spheroids

Directed Evolution in Drops: Molecular Aspects and Applications

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