In situ characterisation and manipulation of biological systems with Chi.Bio

Steel, Harrison; Habgood, Robert; Kelly, Ciarán L.; Papachristodoulou, Antonis

doi:10.1371/journal.pbio.3000794

Cited by 46 publications

(65 citation statements)

References 41 publications

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“…DIY mini-bioreactor systems have recently been developed by different labs to enable such real-time measurements and, most importantly, contain illumination setups. These systems include the eVOLVER [ 57 ] ( Figure 3 b) and Chi.Bio [ 58 ] systems, both of which work with at least 30 mL culture volumes, are customizable, and allow fluidic inputs and illumination at various wavelengths, as well as optical density measurements, and stirring and temperature control. Both devices are open-source projects, freely providing all details regarding the construction steps and components used.…”

Section: Scale-up Instrumentsmentioning

confidence: 99%

The Promise of Optogenetics for Bioproduction: Dynamic Control Strategies and Scale-Up Instruments

et al. 2020

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Progress in metabolic engineering and synthetic and systems biology has made bioproduction an increasingly attractive and competitive strategy for synthesizing biomolecules, recombinant proteins and biofuels from renewable feedstocks. Yet, due to poor productivity, it remains difficult to make a bioproduction process economically viable at large scale. Achieving dynamic control of cellular processes could lead to even better yields by balancing the two characteristic phases of bioproduction, namely, growth versus production, which lie at the heart of a trade-off that substantially impacts productivity. The versatility and controllability offered by light will be a key element in attaining the level of control desired. The popularity of light-mediated control is increasing, with an expanding repertoire of optogenetic systems for novel applications, and many optogenetic devices have been designed to test optogenetic strains at various culture scales for bioproduction objectives. In this review, we aim to highlight the most important advances in this direction. We discuss how optogenetics is currently applied to control metabolism in the context of bioproduction, describe the optogenetic instruments and devices used at the laboratory scale for strain development, and explore how current industrial-scale bioproduction processes could be adapted for optogenetics or could benefit from existing photobioreactor designs. We then draw attention to the steps that must be undertaken to further optimize the control of biological systems in order to take full advantage of the potential offered by microbial factories.

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Section: Scale-up Instrumentsmentioning

confidence: 99%

The Promise of Optogenetics for Bioproduction: Dynamic Control Strategies and Scale-Up Instruments

et al. 2020

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“…Custom algorithms were developed and implemented in python to automatically gate and deconvolve cytometry data on the fly. Two versions of the platform were assembled, using either a custom bioreactor setup (left photos) or Chi.Bio reactors 4 16 . Three different ON-OFF blue light temporal profiles were applied (bottom) and cytometry was acquired every 45 minutes.…”

Section: Figure 2 Reacsight-based Assembly Of a Fully Automated Platform Enabling Reactive Optogenetic Control And Single-cell Resolved Cmentioning

confidence: 99%

“…Small-scale, low-cost bioreactors are emerging as powerful tools for microbial systems and synthetic biology research [1][2][3][4] . They allow tight control of cell culture parameters (e.g.…”

Section: Introductionmentioning

confidence: 99%

“…We first use ReacSight to assemble a platform enabling cytometry-based characterization and reactive optogenetic control of parallel yeast continuous cultures. Importantly, we built two versions of the platform, using either a custom-made bioreactor array or the recent low-cost, open-hardware, optogenetic-ready commercially available Chi.Bio bioreactors 4 . We then demonstrate its usefulness on three case studies.…”

Section: Introductionmentioning

confidence: 99%

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Enhancing bioreactor arrays for automated measurements and reactive control with ReacSight

Bertaux

Sosa-Carrillo

Fraisse

et al. 2020

Preprint

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New small-scale, low-cost bioreactor designs provide researchers with exquisite control of environmental parameters of microbial cultures over long durations, allowing them to perform sophisticated, high-quality experiments that are particularly useful in systems biology, synthetic biology and bioengineering. However, existing setups are limited in their automated measurement capabilities, primarily because sensitive and specific measurements require bulky, expensive, stand-alone instruments (for example, most single-cell resolved measurements require a cytometer or a microscope). We present here ReacSight, a generic and flexible strategy to enhance multi-bioreactor platforms for automated measurements and reactive experiment control. We use ReacSight to assemble a platform for single-cell resolved characterization and reactive optogenetic control of parallel yeast continuous cultures. We demonstrate its usefulness by achieving parallel real-time control of gene expression with light in different bioreactors and by exploring the relationship between fitness, nutrient scarcity and cellular stress density using highly-controlled and informative competition assays.

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“…Although each measurement may not be as accurate as a measurement on a dedicated system, such loss of fidelity is more than compensated for by enhanced understanding of the interactions between parameters. For example, with the Chi-Bio bioreactor, Steel and colleagues [1] made use of the sensor histidine kinase-CcaS-and its cognate response receptor-CcaR-to form an optogenetic system coupled to green fluorescent protein (GFP) expression. They were able to drive the quantity of GFP in a culture of cells so it tracked an externally defined profile.…”

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confidence: 99%

Controlling control—A primer in open-source experimental control systems

Forman

2020

PLoS Biol

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Biological systems are composed of countless interlocking feedback loops. Reactor control systems-such as Chi-Bio (https://chi.bio/), recently published in PLOS Biology-enable biologists to drive multiple processes within living biological samples, using a single experimental framework. Consequently, the dynamic relationships between many biological variables can be explored simultaneously in situ. Similar multivariable experimental reactors are employed beyond biology in the study of active matter and non-equilibrium chemical reactions, in which physical systems are maintained far from equilibrium through the continuous introduction of energy or matter. Inexpensive state-of-the-art components enable open-source implementation of such multiparameter architectures, which represent a move away from expensive systems optimised for single measurements, towards affordable and reconfigurable multi-measurement systems. The transfer of well-understood engineering knowledge into the hands of biological and chemical specialists via open-source channels allows rapid cycles of experimental development and heralds a change in experimental capability that is driving increased theoretical and practical understanding of out-of-equilibrium systems across a wide range of scientific fields. Multiparameter measurement and feedback systems Soyuz and Space X capsules allow mission specialists to reach orbit. Along similar lines, wellconceived open-source control systems and high-quality state-of-the-art components give specialists the ability to construct sophisticated experimental configurations with little to no engineering expertise, bringing domain-specific knowledge closer to the laboratory equipment design process. The demand for such capabilities has resulted in the development of core control systems into which a range of high-quality state of the art sensors, actuators, and control algorithms can be inserted with minimal effort. Instead of many separate machines optimised for single measurements-such as ultraviolet to visible (UV-Vis) light spectrometers, or microscopes-these generalised frameworks allow for simultaneous measurement and control of multiple experimental parameters, under the complete direction of the end-user. Such systems are made affordable by the diverse range of extremely cheap-yet high-quality-components available on the consumer market, from supply companies such as Mouser, RS, or Digikey. Multiparameter experimental arrangements introduce the possibility of sophisticated feedback loops to investigate coupling between several measurable quantities. By modifying an

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In situ characterisation and manipulation of biological systems with Chi.Bio

Cited by 46 publications

References 41 publications

The Promise of Optogenetics for Bioproduction: Dynamic Control Strategies and Scale-Up Instruments

The Promise of Optogenetics for Bioproduction: Dynamic Control Strategies and Scale-Up Instruments

Enhancing bioreactor arrays for automated measurements and reactive control with ReacSight

Controlling control—A primer in open-source experimental control systems

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