Chi.Bio: An open-source automated experimental platform for biological science research

Abstract

The precise characterisation and manipulation of in vivo biological systems is critical to their study.1 However, in many experimental frameworks this is made challenging by non-static environments during cell growth,2, 3 as well as variability introduced by manual sampling and measurement protocols.4 To address these challenges we present Chi.Bio, a parallelised open-source platform that offers a new experimental paradigm in which all measurement and control actions can be applied to a bulk culture in situ. In addition to continuous-culturing capabilities (turbidostat functionality, heating, stirring) it incorporates tunable light outputs of varying wavelengths and spectrometry. We demonstrate its application to studies of cell growth and biofilm formation, automated in silico control of optogenetic systems, and readout of multiple orthogonal fluorescent proteins. By combining capabilities from many laboratory tools into a single low-cost platform, Chi.Bio facilitates novel studies in synthetic, systems, and evolutionary biology, and broadens access to cutting-edge research capabilities.

Deep reinforcement learning for the control of microbial co-cultures in bioreactors

“…The same approach could be applied in a range of other culture environments. Over the past several years, a number of low-cost bioreactors have been developed that can operate as both turbidostats or as chemostats [41][42][43][44]. One such system has 78 chambers running in parallel; easily producing the high volume of data required to train our agent [41].…”

“…One such system has 78 chambers running in parallel; easily producing the high volume of data required to train our agent [41]. Another system incorporates online measurement of multiple fluorescence channels, facilitating state measurements at faster intervals than human sampling would allow [44]. Similar devices have been made at a smaller scale, using microfluidics capable of running batch, chemostat and turbidostat cell cultures [45,46].…”

OpenWorkstation: A modular open-source technology for automated in vitro workflows

“…Popular OSH projects, such as the Arduino platform [22] and the RepRap 3D printer [22] , enable fast and inexpensive prototyping to manufacture 3D-printed parts [21] , [23] to accelerate product development cycles [24] . Within the last decade, the number of OSH in scientific journals increased rapidly, ranging from liquid handling robots [25] , [26] , [27] , [28] to a micro syringe autosampler [29] , from positioning stages for automated microscopy [30] , [31] to entire imaging systems [32] , [33] , [34] , from syringe and flow pump solutions [35] , [36] , [37] , [38] to complex microfluidic solutions [39] , [40] , [41] , and to automated experimental platforms for biological research [42] , [43] .…”

From Microbial Communities to Distributed Computing Systems

“…Bioreactors and microfluidic devices allow different scales of control over liquid culture environments, the choice of which plays an important role in the behavior of the populations. Over the past several years a number of low-cost bioreactors have been developed (Takahashi et al, 2015;Hoffmann et al, 2017;Steel et al, 2019). Turbidostats are a class of continuous bioreactor that maintain the culture at a constant optical density (OD) by varying the dilution rate.…”

“…This is of particular interest for implementing distributed systems since gene expression profiles often differ between phases of growth ( Klumpp et al, 2009 ). Some of these bioreactor devices can be configured to measure the output of several fluorescent proteins simultaneously and control multiple inputs dynamically ( Steel et al, 2019 ). Dilution rate has been cited several times as a critical controllable parameter; the rate of removal of molecules from the environment can produce very different population dynamics ( Balagaddé et al, 2008 ; Weiße et al, 2015 ; Yurtsev et al, 2016 ; Fedorec et al, 2019 ).…”