Microfluidic Bioreactors for Cell Culturing: A Review

Pasirayi, Godfrey; Auger, V.; Scott, Simon M.; Rahman, Pattanathu; Islam, Meez; O׳Hare, Liam; Ali, Zulfiqur

doi:10.2174/1876402911103020137

Cited by 42 publications

(27 citation statements)

References 278 publications

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“…The potential importance of microfluidic platforms in drug development has been widely recognised [2]. Microfluidic cell culture platforms integrated with key functional elements such as microvalves, mixers, gradient generators, detectors and heating elements are applicable for a variety of applications including a microchemostat [3].…”

Section: Introductionmentioning

confidence: 99%

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

Pasirayi

Scott

Islam

et al. 2014

Talanta

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A reusable low cost microfluidic cell culture array device (MCCAD) integrated with a six output concentration gradient generator (cGG) and 4×6 arrays of microchamber elements, addressed by a series of row and columnar pneumatically actuated normally closed (NC) microvalves was fabricated for cell-based screening of chemotherapeutic compounds. The poly(dimethylsiloxane) (PDMS) device consists of three layers: fluidic, control and membrane which are held by surface contact and made leak-proof by clamping pressure. The NC valves are actuated by a thick PDMS membrane that was created by a novel method based on the self-assembly of PDMS pre-polymer molecules over a denser calcium chloride solution. The membrane actuated the valves reliably and particulates such as alumina particles (3 µm) and MCF-7 cells (20-24 µm) (2×10(5) cells/mL) were flowed through the valves without causing blockage or leakage and consequently avoiding contamination of the different cell culture elements. The MCCAD was cast and assembled in a standard laboratory without specialist equipment and demonstrated for performing quantitative cell-based cytotoxicity assays of pyocyanine on human breast cancer (MCF-7) cells and assessed for toxic effect on human hepatocyte carcinoma (HepG2) cells as an indicator for liver injury. Then, the MCCAD was demonstrated for sequential drug combinatorial screening involving gradient generation of paclitaxel doses followed by treatment with aspirin doses on the viability of MCF-7 cells. The interaction between paclitaxel and aspirin was evaluated by using the Bliss independence predictive model and results showed reasonable agreement with the model. A robust, portable, easily fabricated and low cost device is therefore shown to conveniently carry out culturing of multiple cell lines for high throughput screening of anti-cancer compounds using minimal reagents.

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Section: Introductionmentioning

confidence: 99%

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

Pasirayi

Scott

Islam

et al. 2014

Talanta

Self Cite

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“…[247] Sensing and control elements are key components to manufacture effective microfluidic bioreactors with the ability to monitor and/or control in real time relevant process parameters such as temperature, optical density, dissolved oxygen, and flow rate. [218] Regarding optical sensors, a wide class of detection methods can be found in the literature, which depends on the optical properties to be measured. Absorption, fluorescence, chemiluminescence, and surface plasmon resonance (SPR) are some example of techniques commonly used in microbioreactors.…”

Section: Materials and Fabrication Methods Of Microfluidic Bioreactorsmentioning

confidence: 99%

Physically Active Bioreactors for Tissue Engineering Applications

et al. 2020

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Tissue engineering (TE) is a dynamic and growing scientific field that merges the knowledge of different areas such as biology, physics, medicine, and engineering. [1] The TE discipline was first coined at a National Science Foundation sponsored meeting in 1987, thus originating a field that employs life sciences and engineering with the purpose of developing biologic or synthetic supports to restore, keep, or enhance tissue functions or damaged organs. [2] The classical TE approach has been mainly focusing on associating cells with a supporting matrix, also called biomaterials or scaffolds, that essentially acts as a passive template for tissue formation in vitro by allowing cells to adhere, migrate, differentiate, and produce tissue. Usually, the cells are seeded onto the scaffolds and, occasionally, growth factors are also added. The combination of cells, growth factors, and scaffold is often referred as the TE triad. [3] Nevertheless, novel approaches in TE that include the application of a biophysical stimuli to the scaffolds through the use of a bioreactor are emerging. [4] Tissue engineering (TE) is a strongly expanding research area. TE approaches require biocompatible scaffolds, cells, and different applied stimuli, which altogether mimic the natural tissue microenvironment. Also, the extracellular matrix serves as a structural base for cells and as a source of growth factors and biophysical cues. The 3D characteristics of the microenvironment is one of the most recognized key factors for obtaining specific cell responses in vivo, being the physical cues increasingly investigated. Supporting those advances is the progress of smart and multifunctional materials design, whose properties improve the cell behavior control through the possibility of providing specific chemical and physical stimuli to the cellular environment. In this sense, a varying set of bioreactors that properly stimulate those materials and cells in vitro, creating an appropriate biomimetic microenvironment, is developed to obtain active bioreactors. This review provides a comprehensive overview on the important microenvironments of different cells and tissues, the smart materials type used for providing such microenvironments and the specific bioreactor technologies that allow subjecting the cells/ tissues to the required biomimetic biochemical and biophysical cues. Further, it is shown that microfluidic bioreactors represent a growing and interesting field that hold great promise for achieving suitable TE strategies.

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“…There is increasing effort on the development of miniaturised bioreactors, typically at the milliliter (mL) scale, as part of a broader drive to increase the chemical and biological information about bioprocesses. 2,3 Previously, we have used an ultra-low-cost approach with a simple PTFE tube and a syringe pump for inoculum and nutrient feed. 4,5 The large surface area to volume ratio can offer rapid heat and mass transfer, but the approach is limited in the complexity of bioprocessing and had no integrated sensing.…”

Section: Introductionmentioning

confidence: 99%