Eirini Velliou

Application and validation of the TTI based chill chain management system SMAS (Safety Monitoring and Assurance System) on shelf life optimization of vacuum packed chilled tuna.

The objective of the study was to establish a validated kinetic model for growth of spoilage bacteria on vacuum packed tuna slices in the temperature range of 0 to 15 degrees C and to evaluate the applicability of the TTI (Time Temperature Integrators) based SMAS (Safety Monitoring and Assurance System) system to improve tuna product quality at the time of consumption in comparison to the conventional First In First Out (FIFO) approach. The overall measurements of total flora and lactic acid bacteria (LAB) on the tuna samples used in a laboratory simulated field test were in close agreement with the predictions of the developed kinetic model. The spoilage profile of the TTI bearing products, handled with SMAS, was improved. Three out of the thirty products that were handled randomly, according to the FIFO approach, were already spoiled at the time of consumption (logN(LAB)>6.5) compared to no spoiled products when handled with the SMAS approach.

Design and characterization of a scalable airlift flat panel photobioreactor for microalgae cultivation

A novel flat panel photobioreactor prototype with bulk liquid flow driven by an external airlift was designed, modeled, and experimentally characterized for the purpose of developing scalable industrial photobioreactors. Baffles were built inside the flat panel part of the reactor, directing the liquid bulk flow in a serpentine way, and the external airlift drove the liquid flow and facilitated gas mass transfer. The gas holdup, liquid flow velocity, and oxygen mass transfer of this prototype were experimentally determined and mathematically modeled, and the performance of the reactor was tested by cultivating two species of microalgae, Scenedesmus obliquus and Chlorella sorokiniana. The model-predicted trends correlated well with experimental data, indicating that the reactor might be scaled up using these models. A high cell concentration of C. sorokiniana was achieved under controlled indoor cultivation conditions although serious biofouling occurred in the case of S. obliquus cultivation. The results favor the possibility of scaling up the reactor to industrial scales, based on the models employed, and the potential advantages and disadvantages of the reactor are discussed regarding this industry-oriented photobioreactor configuration in comparison with current industrial photobioreactors.

A framework for the design, modeling and optimization of biomedical systems

Abstract We present an overview of the key building blocks of a design framework for modeling and optimization of biomedical systems with main focus on leukemia, that we have been developing in the Biological Systems Engineering Laboratory and the Centre for Process Systems Engineering at Imperial College. The framework features the following areas: (i) a three-dimensional, biomimetic, in vitro platform for culturing both healthy and diseased blood; (ii) a novel, hollow fiber bioreactor that upgrades this in vitro platform to enable expansion and continuous harvesting of healthy and diseased blood; (iii) a global optimization-based approach for the design and operation of the aforementioned bioreactor; (iv) a pharmacokinetic / pharmacodynamic model representing patient response to Acute Myeloid Leukemia treatment; (v) an experimental framework for cell cycle modeling and quantitative analysis of environmental stress. This manuscript recapitulates the progress made in the different areas as well as the way in which these areas are connected, finally leading to a hybrid in vitro/in silico platform which allows the optimization of the ex vivo expansion of healthy and diseased blood.

A mathematical model of subpopulation kinetics for the deconvolution of leukaemia heterogeneity

Acute myeloid leukaemia is characterized by marked inter- and intra-patient heterogeneity, the identification of which is critical for the design of personalized treatments. Heterogeneity of leukaemic cells is determined by mutations which ultimately affect the cell cycle. We have developed and validated a biologically relevant, mathematical model of the cell cycle based on unique cell-cycle signatures, defined by duration of cell-cycle phases and cyclin profiles as determined by flow cytometry, for three leukaemia cell lines. The model was discretized for the different phases in their respective progress variables (cyclins and DNA), resulting in a set of time-dependent ordinary differential equations. Cell-cycle phase distribution and cyclin concentration profiles were validated against population chase experiments. Heterogeneity was simulated in culture by combining the three cell lines in a blinded experimental set-up. Based on individual kinetics, the model was capable of identifying and quantifying cellular heterogeneity. When supplying the initial conditions only, the model predicted future cell population dynamics and estimated the previous heterogeneous composition of cells. Identification of heterogeneous leukaemia clones at diagnosis and post-treatment using such a mathematical platform has the potential to predict multiple future outcomes in response to induction and consolidation chemotherapy as well as relapse kinetics.

Robust Superstructure Optimisation of a Bioreactor that Produces Red Blood Cells

Abstract Recent work developed a novel, biomimetic, cost effective 3D hollow fibre bioreactor for growing healthy red blood cells ex vivo ( Panoskaltsis et al., 2012 ). This promising bioreactor recapitulates the architectural and functional properties of erythrocyte formation and thereby reduces the need for expensive growth factors by more than an order of magnitude. The optimal bioreactor configuration has not been defined; design choices include: number of bioreactors run in parallel, number of hollow fibres in each reactor, size and aspect ratio of each bioreactor. Individual experiments on the bioreactor are cost- and labour-intensive, so we propose global, robust, superstructure optimisation for designing and operating the bioreactor. Beyond this individual bioreactor, robust superstructure design has the potential to more generally enable bioprocess optimisation.

BiOnto: An Ontology for Biomass and Biorefining Technologies

This paper presents design and implementation of the BiOnto ontology in the domain of biorefining. The ontology models both biomass types and composition and biorefining processing technologies. The designed ontology is verified by a case study in the domain of Industrial Symbiosis.

Sonodynamic therapy combined with novel anti-cancer agents, sanguinarine and ginger root extract: Synergistic increase in toxicity in the presence of PANC-1 cells in vitro

The presence of ultrasound-induced cavitation in sonodynamic therapy (SDT) treatments has previously enhanced the activity and delivery of certain sonosensitisers in biological systems. The purpose of this work was to investigate the potential for two novel anti-cancer agents from natural derivatives, sanguinarine and ginger root extract (GRE), as sonosensitisers in an SDT treatment with in vitro PANC-1 cells. Both anti-cancer compounds had a dose-dependent cytotoxicity in the presence of PANC-1 cells. A range of six discreet ultrasound power-frequency configurations were tested and it was found that the cell death caused directly by ultrasound was likely due to the sonomechanical effects of cavitation. Combined treatment used dosages of 100μM sanguinarine or 1mM of GRE with 15s sonication at 500kHz and 10W. The sanguinarine-SDT and GRE-SDT treatments showed a 6% and 17% synergistic increase in observed cell death, respectively. Therefore both sanguinarine and GRE were found to be effective sonosensitisers and warrant further development for SDT, with a view to maximising the magnitude of synergistic increase in toxicity.

Designing a bio-inspired biomimetic in vitro system for the optimization of ex vivo studies of pancreatic cancer

Pancreatic cancer is one of the most aggressive and lethal human malignancies. Drug therapies and radiotherapy are used for treatment as adjuvants to surgery, but outcomes remain disappointing. Advances in tissue engineering suggest that 3D cultures can reflect the in vivo tumor microenvironment and can guarantee a physiological distribution of oxygen, nutrients, and drugs, making them promising low-cost tools for therapy development. Here, we review crucial structural and environmental elements that should be considered for an accurate design of an ex vivo platform for studies of pancreatic cancer. Furthermore, we propose environmental stress response biomarkers as platform readouts for the efficient control and further prediction of the pancreatic cancer response to the environmental and treatment input.

Key environmental stress biomarker candidates for the optimisation of chemotherapy treatment of leukaemia

The impact of fluctuations of environmental parameters such as oxygen and starvation on the evolution of leukaemia is analysed in the current review. These fluctuations may occur within a specific patient (in different organs) or across patients (individual cases of hypoglycaemia and hyperglycaemia). They can be experienced as stress stimuli by the cancerous population, leading to an alteration of cellular growth kinetics, metabolism and further resistance to chemotherapy. Therefore, it is of high importance to elucidate key mechanisms that affect the evolution of leukaemia under stress. Potential stress response mechanisms are discussed in this review. Moreover, appropriate cell biomarker candidates related to the environmental stress response and/or further resistance to chemotherapy are proposed. Quantification of these biomarkers can enable the combination of macroscopic kinetics with microscopic information, which is specific to individual patients and leads to the construction of detailed mathematical models for the optimisation of chemotherapy. Due to their nature, these models will be more accurate and precise (in comparison to available macroscopic/black box models) in the prediction of responses of individual patients to treatment, as they will incorporate microscopic genetic and/or metabolic information which is patient-specific.

Biophysical interactions between pancreatic cancer cells and pristine carbon nanotube substrates: Potential application for pancreatic cancer tissue engineering

Novel synthetic biomaterials able to support direct tissue growth and retain cellular phenotypical properties are promising building blocks for the development of tissue engineering platforms for accurate and fast therapy screening for cancer. The aim of this study is to validate an aligned, pristine multi-walled carbon nanotube (CNT) platform for in vitro studies of pancreatic cancer as a systematic understanding of interactions between cells and these CNT substrates is lacking. Our results demonstrate that our CNT scaffolds-which are easily tuneable to form sheets/fibers-support growth, proliferation, and spatial organization of pancreatic cancer cells, indicating their great potential in cancer tissue engineering.