We used continuous flow micro-devices as bioreactors for the production of a glycosylated pharmaceutical product (a monoclonal antibody). We cultured CHO cells on the surface of PMMA/PDMS micro-channels that had been textured by micromachining and coated with fibronectin. Three different micro-channel geometries (a wavy channel, a zigzag channel, and a series of donut-shape reservoirs) were tested in a continuous flow regime in the range of 3 to 6 μL min(-1). Both the geometry of the micro-device and the flow rate had a significant effect on cell adhesion, cell proliferation, and monoclonal antibody production. The most efficient configuration was a series of donut-shaped reservoirs, which yielded mAb concentrations of 7.2 mg L(-1) at residence times lower than one minute and steady-state productivities above 9 mg mL(-1) min(-1). These rates are at about 3 orders of magnitude higher than those observed in suspended-cell stirred tank fed-batch bioreactors.
We report a proof-of-principle for the use of micro-devices as continuous bioreactors for the production of monoclonal antibodies. We culture CHO cells on the surface of PMMA "zigzag" channels textured with semi-spherical cavities coated with fibronectin, observing steady-state productivities 100 times higher than those observed in full scale systems.
Microscale electrokinetic techniques have great potential for the separation and sorting of microorganisms, and could solve the need for rapid and early detection of pathogens in medical diagnostics and food safety applications. Presented here is the application of micro particle image velocimetry for the characterization of electrokinetic transport of three types of microorganisms: Escherichia coli, Ankistrodesmus spiralis, and Saccharomyces cerevisiae. The electrokinetic behavior of these microorganisms was characterized employing a straight glass microchannel and direct current electric fields (50-300 V cm -1). The effects of the type and size of microorganism, electric field magnitude, and suspending medium characteristics were analyzed. Additionally, electrokinetic differentiation was achieved when a sample containing a mixture of the three types of microorganisms was analyzed by generating an electropherogram in one minute, identifying that three different species were present. These results demonstrate that fast and effective detection, and differentiation of intact microorganisms can be achieved employing microscale electrokinetic techniques.
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