https://orbilu.uni.lu/bitstream/10993/21149/1/Advantages%20and%20challenges%20of%20microfluidic%20cell%20culture%20in%20polydimethylsiloxane%20devices.pdf

Advantages and challenges of microfluidic cell culture in polydimethylsiloxane devices.

Many drugs have progressed through preclinical and clinical trials and have been available – for years in some cases – before being recalled by the FDA for unanticipated toxicity in humans. One reason for such poor translation from drug candidate to successful use is a lack of model systems that accurately recapitulate normal tissue function of human organs and their response to drug compounds. Moreover, tissues in the body do not exist in isolation, but reside in a highly integrated and dynamically interactive environment, in which actions in one tissue can affect other downstream tissues. Few engineered model systems, including the growing variety of organoid and organ-on-a-chip platforms, have so far reflected the interactive nature of the human body. To address this challenge, we have developed an assortment of bioengineered tissue organoids and tissue constructs that are integrated in a closed circulatory perfusion system, facilitating inter-organ responses. We describe a three-tissue organ-on-a-chip system, comprised of liver, heart, and lung, and highlight examples of inter-organ responses to drug administration. We observe drug responses that depend on inter-tissue interaction, illustrating the value of multiple tissue integration for in vitro study of both the efficacy of and side effects associated with candidate drugs.

/pdf/multi-tissue-interactions-in-an-integrated-three-tissue-57t2dedidt.pdf

Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform

Organoid-on-a-chip and body-on-a-chip systems for drug screening and disease modeling.

The recent advent of microphysiological systems - microfluidic biomimetic devices that aspire to emulate the biology of human tissues, organs and circulation in vitro - is envisaged to enable a global paradigm shift in drug development An extraordinary US governmental initiative and various dedicated research programs in Europe and Asia have led recently to the first cutting-edge achievements of human single-organ and multi-organ engineering based on microphysiological systems The expectation is that test systems established on this basis would model various disease stages, and predict toxicity, immunogenicity, ADME profiles and treatment efficacy prior to clinical testing Consequently, this technology could significantly affect the way drug substances are developed in the future Furthermore, microphysiological system-based assays may revolutionize our current global programs of prioritization of hazard characterization for any new substances to be used, for example, in agriculture, food, ecosystems or cosmetics, thus, replacing laboratory animal models used currently Thirty-six experts from academia, industry and regulatory bodies present here the results of an intensive workshop (held in June 2015, Berlin, Germany) They review the status quo of microphysiological systems available today against industry needs, and assess the broad variety of approaches with fit-for-purpose potential in the drug development cycle Feasible technical solutions to reach the next levels of human biology in vitro are proposed Furthermore, key organ-on-a-chip case studies, as well as various national and international programs are highlighted Finally, a roadmap into the future is outlined, to allow for more predictive and regulatory-accepted substance testing on a global scale

/pdf/biology-inspired-microphysiological-system-approaches-to-3xy0ougun5.pdf

Biology-inspired microphysiological system approaches to solve the prediction dilemma of substance testing.

The terms biosurfactant and bioemulsifier have often been used interchangeably to describe surface active biomolecules. However, it is important to note that there are marked differences between them especially based on their physico-chemical properties and physiological roles. Although bioemulsifiers and biosurfactants are both amphiphilic in nature and are produced by a wide range of microorganisms, each exhibit characteristic roles in nature. These microbial surfactants have recently received increased scientific attention due to their unique characteristics relative to chemically derived surfactants. Their unique features include; non-toxicity, biodegradability, biocompatibility, efficiency at low concentrations and their synthesis from natural substrates under mild environmental conditions.

/pdf/bioemulsifiers-are-not-biosurfactants-and-require-different-1g3vvql37c.pdf

Bioemulsifiers are not biosurfactants and require different screening approaches

A low-cost microBR (microbioreactor) made from PTFE [poly(tetrafluoroethylene)] was used to cultivate a model organism, Pseudomonas aeruginosa DS10-129. The progress of bioprocessing was monitored by comparing the growth of the organism in a microBR, a conventional bench scale bioreactor and a shake flask. Under the microBR conditions, the organism produced 23 mg/ml of pyocyanin that had antimicrobial effects against Bacillus subtilis, Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas teessidea and Pseudomonas clemancea. Furthermore, it produced a total of 106 microg/ml of effective biosurfactants consisting of dirhamnolipids (RL2) and monorhamnolipids (RL1). The biosurfactants reduced the surface tension of distilled water from 72 to 27.9 mN/m and emulsified kerosene by 71.30%. The pyocyanin and rhamnolipids were produced during the exponential and stationary phases of growth respectively. The results of the microBR were comparable to those obtained using conventional scale methods.

Production of rhamnolipid biosurfactants by Pseudomonas aeruginosa DS10-129 in a microfluidic bioreactor.

The use of microfluidic bioreactor platforms for cell culturing holds considerable promise for a range of fields which include drug discovery, tissue engineering, bioprocessing optimisation and cell based screening studies. Microflu- idic bioreactor systems have length scales that are well matched to the physical dimensions of most cells and microorgan- isms. In view of this, microfluidic bioreactors have attractive features which make them ideal to study the behaviour of cells and their internal organisation in their native microenvironment. Due to their small footprint microbioreactor plat- forms offer a number of advantages over conventional macroscale systems including improved biological function, higher quality cell-based data, reduced volume of reagents, ease of integration and lower cost. This review highlights the basic concepts, designs and operational requirements of microbioreactors for cell based studies. An illustrative outline of differ- ent applications of microbioreactors and some indication of new trends and progress in recent years are provided. Specific examples of applications of microbioreactors are drawn for cytotoxicity assays, tissue engineering, stem cells, microbial fermentations, single cell analysis and in vitro fertilisation.

/pdf/microfluidic-bioreactors-for-cell-culturing-a-review-37zxxjhko5.pdf

Microfluidic Bioreactors for Cell Culturing: A Review

A simple microbioreactor for high-throughput bioprocessing made from low cost polymer polytetrafluoroethylene (PTFE) tubes with a working volume of 1.5 ml is described. We have developed a microfluidic system that handles a small population of cells of a model microorganism, Pseudomonas aeruginosa DS10-129. Under the conditions of the microbioreactor, the organism produced extracellular secondary metabolites by using nutrient broth modified with glycerol. Pyocyanins were isolated from the fermented medium as a metabolite of interest. Antibiotic properties of pyocyanin were effective against a number of microorganisms such as Staphylococcus aureus, S. epidermis, Bacillus subtilis, Micrococcus luteus and Saccharomyces cerevisiae. Batch fermentation of the model organism in the microbioreactor was compared to shake-flask and conventional bench fermenter methods. Results obtained from the microbioreactor compared favourably with the conventional processes.

/pdf/development-of-a-simple-and-low-cost-microbioreactor-for-43clkh4gn3.pdf

Development of a simple and low cost microbioreactor for high-throughput bioprocessing

https://research.tees.ac.uk/ws/files/6359267/347108.pdf

Low cost microfluidic cell culture array using normally closed valves for cytotoxicity assay.

A prototype membrane aerated polydimethylsiloxane (PDMS) microbioreactor integrated with a photodiode detector was developed for monitoring intracellular green fluorescent protein ultraviolet (GFPUV) expression in Escherichia coli. The developed system is compact, simple and inexpensive and ideal for economical on chip detection of fluorophores in aqueous solution and intracellular GFPUV expression. The detection limit for cell free GFPUV was found to be 4.8 × 10 -8 M. Intracellular GFPUV expression in E. coli cells was monitored for 12 h and the lowest detectable signal was recorded from a cell concentration of 2.7 × 10 7 cells/mL with signal to noise ratio (SNR) value of 3. The performance of the photodiode detector was benchmarked with a CCD spectrophotometer and results showed favorable comparison. A miniaturized microbioreactor for monitoring intracellular dynamics in real time is demonstrated. Keywords— photodiode, fluorescence, microbioreactor, intracellular GFPUV

Godfrey Pasirayi

Papers

Production of rhamnolipid biosurfactants by Pseudomonas aeruginosa DS10-129 in a microfluidic bioreactor.

Microfluidic Bioreactors for Cell Culturing: A Review

Development of a simple and low cost microbioreactor for high-throughput bioprocessing

Low cost microfluidic cell culture array using normally closed valves for cytotoxicity assay.

Microbioreactor with Photodiode Detection for Monitoring Intracellular GFPUV Expression in E. coli