Manufacturing of cell therapy products requires sufficient understanding of the cell culture variables and associated mechanisms for adequate control and risk analysis. The aim of this study was to apply an unstructured ordinary differential equation‐based model for prediction of T‐cell bioprocess outcomes as a function of process input parameters. A series of models were developed to represent the growth of T‐cells as a function of time, culture volumes, cell densities, and glucose concentration using data from the Ambr®15 stirred bioreactor system. The models were sufficiently representative of the process to predict the glucose and volume provision required to maintain cell growth rate and quantitatively defined the relationship between glucose concentration, cell growth rate, and glucose utilization rate. The models demonstrated that although glucose is a limiting factor in batch supplied medium, a delivery rate of glucose at significantly less than the maximal specific consumption rate (0.05 mg 1 × 106 cell h−1) will adequately sustain cell growth due to a lower glucose Monod constant determining glucose consumption rate relative to the glucose Monod constant determining cell growth rate. The resultant volume and exchange requirements were used as inputs to an operational BioSolve cost model to suggest a cost‐effective T‐cell manufacturing process with minimum cost of goods per million cells produced and optimal volumetric productivity in a manufacturing settings. These findings highlight the potential of a simple unstructured model of T‐cell growth in a stirred tank system to provide a framework for control and optimization of bioprocesses for manufacture.

Cell therapy manufacturing is limited by lack of online tools capable of realtime in-process monitoring, particularly of simultaneous changes in multiple orthogonal (mutually independent) parameters. Here, we studied changes in CD36 expression, number density and size (area) of erythroblasts through different stages of erythropoiesis in vitro using a quartz crystal resonator (QCR), integrated with a microscope, and flow cytometry in parallel. An analytical model was developed extending the Kanazawa-Gordon theory. Based on this model, independent correlations were established between changes in each QCR parameter, dissipation (ΔΓ) and resonance frequency (−Δf0), and CD36 expression (from flow cytometry) and cell area (from microscope). The correlation functions were used to derive an acoustic signature (−ΔΓ/Δf0) of the differentiation process that uniquely mapped the relative changes in CD36 expression and late-stage enucleation-related deviations. A method to quantify relative changes in cell area purely from the acoustic parameters was also proposed. This work demonstrated for the first time the potential of an electromechanical tool for online monitoring of concurrently varying orthogonal phenotypic parameters in cell therapy manufacturing.

The National Botanic Garden of Wales at Middleton Hall in the parish of Llanarthne, Carmarthenshire is a recent creation in the landscapes of West Wales, but it contains within its bounds the earthworks and historical ecology of two previous designed landscapes. One consists of the extensive parklands and remnant buildings of an important Picturesque landscape created by William Paxton at the end of the eighteenth century. The other was the location of the original Middleton Hall and its formal gardens, laid out in the early seventeenth century, probably on a previous medieval site and reduced to earthworks by the Paxton creation. This article presents a new plan of those early formal gardens together with a brief summary of small-scale excavations, and seeks to place them in the wider context of the Carmarthenshire historic landscapes. Perhaps, however, the most important element of the historic narrative for the future of the Botanic Garden is the role of the Middleton family in the early exploitation and trade in plants from the other side of the world as founder captains of the East India Company. This resonates well with the Botanic Garden’s long-term aims, and the historic landscape is now a key element of new developments in this nationally important institution.

Large-scale manufacture of human embryonic stem cells (hESCs) is prerequisite to their widespread use in biomedical applications. However, current hESC culture strategies are labor-intensive and employ highly variable processes, presenting challenges for scaled production and commercial development. Here we demonstrate that passaging of the hESC lines, HUES7, and NOTT1, with trypsin in feeder-free conditions, is compatible with complete automation on the CompacT SelecT, a commercially available and industrially relevant robotic platform. Pluripotency was successfully retained, as evidenced by consistent proliferation during serial passage, expression of stem cell markers (OCT4, NANOG, TRA1-81, and SSEA-4), stable karyotype, and multi-germlayer differentiation in vitro, including to pharmacologically responsive cardiomyocytes. Automation of hESC culture will expedite cell-use in clinical, scientific, and industrial applications.