Research
Many biological systems involve the interaction of large numbers of different components, and many of biology’s most pressing questions involve understanding properties that emerge out of this complexity. These questions include, “How do combinations of different microbial species result in community stability?”, “How do different genetic variants combine to give resistance or susceptibility to disease?”, and “How do RNA expression levels give rise to different cell types?”. Answering questions like these will require numbers of experiments commensurate with the complexity of the systems being studied. The Cira lab is developing technologies to enable new scales of experimental throughput and using them to untangle complex biological systems.
Liquid handling
Surface Patterned Omniphobic Tiles (SPOTs)
Coming soon! The Cira Lab has developed Surface Patterned Omniphobic Tiles (SPOTs), a liquid handling platform that makes it cheap and easy to run a wide range of high-throughput experiments. Stay tuned for more details.
This project explored the "food coloring effect", where a mixture of propylene glycol and water (both found in food coloring) forms droplets with unique properties on clean glass. This work extended century-old investigations of surface-tension driven, or Marangoni flows. Key new results include an explanation for lack of pinning force on these droplets, an explanation of vapor-mediated long-range effects, and the creation of numerous droplet-driven machines.
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Cira, Benusiglio & Prakash, "Vapour-mediated sensing and motility in two-component droplets" Nature 2015 519 (7544), 446-50.
Subsequent work explored the effects of confinement on these droplets,
Benusiglio, Cira, Lai, Prakash, "Two-component self-contracted droplets: long-range attraction and confinement effects" 2017 arXiv:1712.00153
refined our understanding of why these droplets move so easily,
Benusiglio, Cira, Prakash, "Two-component Marangoni-contracted droplets: friction and shape" Soft matter 2018, 14, 7724-7730.
and explored this effect in single component droplets:
Shiri, Sinha, Baumgartner, Cira. "Thermal Marangoni Flow Impacts the Shape of Single Component Volatile Droplets on Thin, Completely Wetting Substrates" PRL 127, 024502 2021.
Subsequent work explored the effects of confinement on these droplets,
Benusiglio, Cira, Lai, Prakash, "Two-component self-contracted droplets: long-range attraction and confinement effects" 2017 arXiv:1712.00153
refined our understanding of why these droplets move so easily,
Benusiglio, Cira, Prakash, "Two-component Marangoni-contracted droplets: friction and shape" Soft matter 2018, 14, 7724-7730.
and explored this effect in single component droplets:
Shiri, Sinha, Baumgartner, Cira. "Thermal Marangoni Flow Impacts the Shape of Single Component Volatile Droplets on Thin, Completely Wetting Substrates" PRL 127, 024502 2021.
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In the news
Stanford, Science, New York Times, reddit, Washington Post
Background
For a nice primer on wetting phenomena, see a beautiful set of lectures by David Quere:
part I
part II
Further Developments
Work by Stefan Karpitschka et al combines a numerical model with experiments to predict droplet shape:
Karpitschka, Liebig & Riegler, "Marangoni Contraction of Evaporating Sessile Droplets of Binary Mixtures" Langmuir 2017 33 (19), 4682-4687.
Work by Hack et al clarifies the distinction between autophobing and Marangoni contraction. Hack, Kwieciński, Ramírez-Soto, Segers, Karpitschka, Kooij & Snoeijer. "Wetting of Two-Component Drops: Marangoni Contraction Versus Autophobing" Langmuir 2021, 37, 12, 3605–3611.
Work by Parimalanathan et al shows how non-ideality can lead to Marangoni contraction in counterintuitive cases. Parimalanathan, Dehaeck, Rednikov & Colinet "Controlling the wetting and evaporation dynamics of non-ideal volatile binary solutions" Journal of Colloid and Interface Science Volume 592, 15 June 2021, Pages 319-328.
Stanford, Science, New York Times, reddit, Washington Post
Background
For a nice primer on wetting phenomena, see a beautiful set of lectures by David Quere:
part I
part II
Further Developments
Work by Stefan Karpitschka et al combines a numerical model with experiments to predict droplet shape:
Karpitschka, Liebig & Riegler, "Marangoni Contraction of Evaporating Sessile Droplets of Binary Mixtures" Langmuir 2017 33 (19), 4682-4687.
Work by Hack et al clarifies the distinction between autophobing and Marangoni contraction. Hack, Kwieciński, Ramírez-Soto, Segers, Karpitschka, Kooij & Snoeijer. "Wetting of Two-Component Drops: Marangoni Contraction Versus Autophobing" Langmuir 2021, 37, 12, 3605–3611.
Work by Parimalanathan et al shows how non-ideality can lead to Marangoni contraction in counterintuitive cases. Parimalanathan, Dehaeck, Rednikov & Colinet "Controlling the wetting and evaporation dynamics of non-ideal volatile binary solutions" Journal of Colloid and Interface Science Volume 592, 15 June 2021, Pages 319-328.
We created a synthetic community by inserting DNA barcodes into E. coli cells. We serially passaged this community in parallel experiments with different fractions of migrants. When migration was high, selection could be ignored, but when migration was low, selection must be considered. This resulted in two regimes, one where neutral theories of ecology apply and a second where selection must be taken into account, however, the neutral regime is only relevant for very large migration fractions due to the magnitude of typical fitness differences, even in this simple system.
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Cira, Pearce, Quake. "Neutral and niche dynamics in a synthetic microbial community" 2018 PNAS.
Subsequent work by Kim Vasquez, et al from the KC Huang lab applied these barcoded strains to measure key fundamental parameters of mouse microbiome communities:
Vasquez, Willis, Cira, Ng, Pedro, Aranda-Díaz, Rajendram, Yu, Higginbottom, Neff, Sherlock, Xavier, Quake, Sonnenburg Good, Huang "Quantifying rapid bacterial evolution and transmission within the mouse intestine" Cell Host & Microbe
Volume 29, Issue 9, 8 September 2021, Pages 1454-1468.e4
Subsequent work by Kim Vasquez, et al from the KC Huang lab applied these barcoded strains to measure key fundamental parameters of mouse microbiome communities:
Vasquez, Willis, Cira, Ng, Pedro, Aranda-Díaz, Rajendram, Yu, Higginbottom, Neff, Sherlock, Xavier, Quake, Sonnenburg Good, Huang "Quantifying rapid bacterial evolution and transmission within the mouse intestine" Cell Host & Microbe
Volume 29, Issue 9, 8 September 2021, Pages 1454-1468.e4
Microfluidics
This work developed a self powered device that takes in a fluid sample, divides it into numerous isolated subsamples for parallel experimentation. We used this device to measure minimum inhibitory concentrations of antibiotics against bacteria and perform rapid bacterial species typing.
Cira, Ho, Dueck, Weibel. "A self-loading microfluidic device for determining the minimum inhibitory concentration of antibiotics" Lab on a Chip 2012 12, 1052-1059. Ho, Cira, Crooks, Baeza, Weibel. "Rapid Identification of ESKAPE Bacterial Strains Using an Autonomous Microfluidic Device" PLoS One 2012 7 (7). Weibel, Cira. "Self-Loading Microfluidic Device and Methods of Use." U.S. Patent No. 20150321194A1, 2015. |
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Background
This device relies on vacuum stored in solid PDMS to move liquid reagents, which has since been referred to in the field as "degas-driven", "vacuum driven", or "power-free ". The first description of this effect to actuate liquids can be found in Hosokawa et al:
Hosokawa, Sato, Ichikawa, Maeda. "Power-free poly (dimethylsiloxane) microfluidic devices for gold nanoparticle-based DNA analysis" 2004 Lab on a Chip 4 (3).
Further Developments
Subsequently, devices similar to this were independently extended to include nucleic acid amplification by Lars Renner et al from the Weibel lab and Charlie Yeh et al from the Lee lab:
Renner, et al. "Detection of ESKAPE Bacterial Pathogens at the Point of Care Using Isothermal DNA-Based Assays in a Portable Degas-Actuated Microfluidic Diagnostic Assay Platform" 2017 Applied and environmental microbiology 83 (4).
Yeh, Fu, Hu, Thakur, Feng, Lee. "Self-powered integrated microfluidic point-of-care low-cost enabling (SIMPLE) chip" 2017 Science Advances 3 (3).
This device relies on vacuum stored in solid PDMS to move liquid reagents, which has since been referred to in the field as "degas-driven", "vacuum driven", or "power-free ". The first description of this effect to actuate liquids can be found in Hosokawa et al:
Hosokawa, Sato, Ichikawa, Maeda. "Power-free poly (dimethylsiloxane) microfluidic devices for gold nanoparticle-based DNA analysis" 2004 Lab on a Chip 4 (3).
Further Developments
Subsequently, devices similar to this were independently extended to include nucleic acid amplification by Lars Renner et al from the Weibel lab and Charlie Yeh et al from the Lee lab:
Renner, et al. "Detection of ESKAPE Bacterial Pathogens at the Point of Care Using Isothermal DNA-Based Assays in a Portable Degas-Actuated Microfluidic Diagnostic Assay Platform" 2017 Applied and environmental microbiology 83 (4).
Yeh, Fu, Hu, Thakur, Feng, Lee. "Self-powered integrated microfluidic point-of-care low-cost enabling (SIMPLE) chip" 2017 Science Advances 3 (3).
This work combined electronics with fludics to create an electrically controlled microfluidic valve. Heating causes thermal expansion of an elastomer layer which is "focused" by adjacent rigid confining layers into amplified displacements which are used to seal a microfluidic channel.
Cira, Khoo, Jain, Andraka, Paull, Thomas, Aliado, Viergever, Yu, Li, Nguyen, Robles, Araci, Quake. "Elastomeric Focusing Enables Application of Hydraulic Principles to Solid Materials in Order to Create Micromechanical Actuators with Giant Displacements". arXiv 2017, In review. Cira, Quake, Robles, Khoo. Elastomeric Focusing Valves. U.S. Patent 20170321821A1, 2017. |
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Currently In review