Homework Assignment 7.docx - Bioengineering 161A Fall 2018...

Unformatted text preview: Bioengineering 161A Fall 2018 Homework #7 Due November 20th by the end of class to the TAs 1. Chemostat with Recycle and Cell Concentration Glucose Feed F SoXo NaHCO3 Feed Fb So,bXo,b VR qp µnet Effl uent Har vest SX SXh Recy cle SXr You are running a 1000L chemostat with recycle, but your cells keep dying. Upon investigation, you discover that the effluent media is highly acidic, so you add a second feed for the continuous delivery of sodium bicarbonate, which maintains the reactor at an optimal pH and solves your problem. Bicarbonate acts as a buffer and is not involved in the reaction. Both feeds are sterile, the glucose feed concentration is 2.0 g/L with flow rate 100 L/hr, and the bicarbonate feed concentration is 3.5 g/L with flow rate 50 L/hr. The recycler has a volume recycle ratio of 0.2 and a cell concentration factor of 2.0. The yield coefficient YX/S is 0.5 g cells/g S and the growth is described by kinetic parameters Ks = 100 mg/L and µm = 0.3 hr -1. Assume kd = 0. The recycler does not concentrate glucose or bicarbonate. a) In the boxes above, write the expressions for the flow rate of the Effluent, Recycle, and Harvest streams. b) At steady state, derive an expression for the specific rate of cell growth, µg. Calculate the dilution rate and µg and compare them. c) Derive an expression for the steady state concentration of cells in the reactor. Calculate for qp = 0. 2. Immobilized Cell Bioreactor The liver bioreactor shown below is a fluidized-bed reactor, where primary liver cells from pigs have been seeded onto spherical plastic particles. The cells form a Catapano and Gerlach Bioreactors for Liver Tissue Engineering biomatrix (biofilm) of average thickness L = 0.15mm. When fat-soluble toxins in the patient’s blood encounter the cells in the bioreactor, they are converted into watersoluble toxins that are removed downstream by a membrane separation process with 100% efficiency. The patient’s blood is being pumped through the bioreactor at a flow rate of 300ml/hr and the concentration of toxins in this feed stream is 0.025mg/ml. The conversion of the toxins follows MichaelisMenten kinetics with the assumption of first order reaction kinetics (e.g. relatively 3 Fig. 3. Clinical treatment of an ALF patient with the Modular Extracorporeal Liver Support (MELS) low substrate concentration). Vmax = 0.50mg toxins/mmBAL hr and Ks = 0.25mg utilizing the bioreactor developed by Gerlach et al. [51] loaded with 600 g of primary porcine cells. 3 toxins/mm . The specific surface area of the biofilm in the reactor is 1.25 mm2/mm3. The diameter of the column is 100mm and the height is 500mm. In 1997, Flendrig et al. proposed another packed-bed bioreactor with decentralized oxygen supply permitting direct of high allowable density liver cells with low nutrientsof concentration a.) If theperfusion maximum concentration toxins in the blood leaving the bioreactor and returned totothe patient is 0.005mg/ml, what does the gradients [75]. Primary porcine liver cellsbeing were cultured attached the fibers of a spiral wound average factor throughout 3D polyester non-woven fabriceffectiveness packed in a cylindrical acrylic enclosure, andthe werecolumn directly need to be? perfused with medium or plasma flowing along the bioreactor length (Figure 2d). Microporous b.) Calculate the yieldfabric coefficient YP/Sforfor the bioreactor. membranes interposed in between adjacent layers provided a distributed oxygen Assume all fat-soluble toxin Hepatocytes consumed isreported converted into water-soluble toxin at a 1:1 (wt/wt) ratio supply and CO 2 removal. were to arrange in the fabric in in vivo-like and cell growth is negligible. aggregates, to synthesize urea and proteins, and to transform lidocaine into MEGX and xilidine for up to 2 weeks. Use of the bioreactor for the EC treatment of animal models of ALF caused a significant enhancement of the survival rate of small and large laboratory animals [109] and was proven safe in the treatment of ALF patients [118]. Recently, Ambrosino et al. proposed to 3. Fed-batch Culture couple the polyester fabric with a porcine autologous biomatrix to enhance cell attachment to the 3D scaffold [99].asked In 1996,by Naruse et al. [94] to anddesign later on Morsiani et al. [103]to modified this You are your boss a bioreactor produce concept by arranging the fabric in an annular packed-bed bioreactor and by flowing medium or plasma radially across the fabric to enhance oxygen transport to the cells and reduce the bioreactor inlet/outlet pressure drop (Figure 2e). Up to ca. 230 g primary hepatocytes could be cultured in such bioreactor in a high metabolically active state [120]. BALs based on this bioreactor are under clinical testing. an antibiotic. a.) Name two advantages of using a fed-batch process over CSTR production. (5pts) b.) Using mass balances on cells and substrate, i.e. starting from and dX t dSt dt dt t t where X and S stand for the total amount of biomass in the reactor and the total amount of substrate in the reactor respectively, derive the following function: X t X 0t FYXM/ s S0t ...
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