Semi-automated on-demand control of individual droplets with a sample application to a drug screening assay

Hébert, Marie; Courtney, Matthew; Ren, Carolyn L.

doi:10.1039/c9lc00128j

Cited by 28 publications

(21 citation statements)

References 39 publications

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“…The lower cost should help microfluidics become more accessible to researchers in a broad range of fields, including chemistry, biology, material science, etc. As an open-source system with full access to, and understanding of, the detailed construction and operation, it also shows promise in less developed areas of microfluidics such as active control of individual droplets [12] , [13] .…”

Section: Hardware In Contextmentioning

confidence: 99%

“…In one application it is being used as a standalone system for a study in continuous flow electrophoresis using microchannels and pressure-driven flow for control. Another fundamental study in active-controlled droplet microfluidics uses µPump as an embedded system as part of a feedback control system [13] . Lastly, AES Life Sciences, a company focused on protein characterization and analysis solutions is using a two-channel µPump as an embedded system for various tests and applications.…”

Section: Validation and Characterizationmentioning

confidence: 99%

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µPump: An open-source pressure pump for precision fluid handling in microfluidics

Gao¹,

Hébert²,

Huissoon

et al. 2020

HardwareX

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Section: Hardware In Contextmentioning

confidence: 99%

Section: Validation and Characterizationmentioning

confidence: 99%

µPump: An open-source pressure pump for precision fluid handling in microfluidics

Gao¹,

Hébert²,

Huissoon

et al. 2020

HardwareX

Self Cite

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“…[27,29] Droplet-based assays that enable studies under controlled cell growth through controlled nutrient supply are scarce. Programmable devices have been developed [31][32][33] that could facilitate controlled microbial growth inside droplets that are spatially fixed on a chip, allowing sequential addition of nutrients by ondemand formation of nutrient-containing droplets, transport to the cell-containing droplets and induction of coalescence.…”

Section: Introductionmentioning

confidence: 99%

“…Droplet‐based assays that enable studies under controlled cell growth through controlled nutrient supply are scarce. Programmable devices have been developed [ 31–33 ] that could facilitate controlled microbial growth inside droplets that are spatially fixed on a chip, allowing sequential addition of nutrients by on‐demand formation of nutrient‐containing droplets, transport to the cell‐containing droplets and induction of coalescence. Jakiela and co‐workers [ 34 ] as well as Jian and co‐workers [ 35 ] in separate studies have used an alternative approach in which cell‐containing droplets were circulated on chip and periodically flown through part of the circuit designed to split off part of the droplet and merge it with a nutrient droplet.…”

Section: Introductionmentioning

confidence: 99%

Fed‐Batch Droplet Nanobioreactor for Controlled Growth of Cyberlindnera (Pichia) jadinii: A Proof‐Of‐Concept Demonstration

Totlani

Wang

Bisschops

et al. 2021

Adv Materials Technologies

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Improvement of the microorganism's product yield on feedstock is possible by targeted genetic modification, which requires a solid understanding of the species metabolism and genetics. Alternatively, genetic modifications can be introduced randomly such that the chance that a resulting mutant performs better than the original one is small. Consequently, many mutants need to be created and subsequently screened in order to identify the best performing ones. [1] Given the large number of experiments, it is common practice to grow and study all the different mutants in individual microliter-sized wells on microtiter plates. While this allows for parallel screening in an automated fashion using pipetting robots and plate readers, conventional microtiter plates lack the ability to feed nutrients and control pH by base or acid addition. It is indeed challenging to feed liquids at flow rates in the nanoliter per hour range to all the individual wells of a microtiter plate and to do so accurately. Therefore, screening of mutants is commonly performed under batch conditions with all feedstock present from the start and no further control over feedstock concentration and pH. In contrast, more than 80% of the processes in industrial biotechnology are operated under so called fed-batch conditions with control over feedstock concentration and pH. [2,3] This incompatibility between the physiological conditions during screening and industrial operation not only leads to selection of false positives which fail to generate competitive yields at industrial scale, but also fails to identify the best mutants for fed-batch conditions. [4][5][6] The effectiveness of screening hence greatly benefits from a technology that enables growing and studying a large number of microorganisms under precisely controlled conditions representative of industrial bioreactors. Besides screening of mutants, optimization of process conditions, a second important aspect in bioprocess development, also benefits from such a technology. [7] Although there has been progress in recent years, there remains both need and opportunity to cost-effectively and with fidelity miniaturize fermentation to screen under fed-batch conditions.Several strategies have been developed to study microorganisms under controlled growth conditions. One strategy is to A key bottleneck in bioprocess development is that state-of-the-art tools used for screening of cells and optimization of cultivation conditions do not represent the conditions enforced at industrial scale. At industrial scale, cell growth is strictly controlled ("fed-batch") to optimize the metabolites produced by the cells. In contrast, cell growth is uncontrolled ("batch") in microwells commonly used for bioprocess development due to the difficulty to continuously supply minute amounts of nutrients to the cells in these wells over the course of the cultivation experiment. This work addresses this bottleneck through the development of a droplet-based fed-batch nanobioreactor.A key challenge addressed in this work is ...

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“…Digital acquisition by a photodiode was also developed for evaluating droplet size . Recently, an image processing software was utilized as an efficient tool for droplet size measurement, but a sophisticated setup and an expensive camera were needed . These requirements make it hard for the non‐experts to use for real‐time droplet detection and the droplet size measurement.…”

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confidence: 99%

A micrometer head integrated microfluidic device for facile droplet size control and automatic measurement of a droplet size

Bui

Seo

2019

Electrophoresis

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Semi-automated on-demand control of individual droplets with a sample application to a drug screening assay

Abstract: Automated control of individual droplets in microfluidic channels offers tremendous potential for applications requiring high accuracy and minimal user involvement.

Cited by 28 publications

References 39 publications

µPump: An open-source pressure pump for precision fluid handling in microfluidics

µPump: An open-source pressure pump for precision fluid handling in microfluidics

Fed‐Batch Droplet Nanobioreactor for Controlled Growth of Cyberlindnera (Pichia) jadinii: A Proof‐Of‐Concept Demonstration

A micrometer head integrated microfluidic device for facile droplet size control and automatic measurement of a droplet size

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