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In In 2) 31 4) 5) W import pandas as pa import nunpy as np You are running a bioreactor in batch mode wit a working volume of 50 L. You are growing induced pluripotent stem cells (/PSCs) for islet ferentiation. As the operator, itis your duty to generate enough cells to innoculate @ $00 L bioveactor. Before starting the run, ‘you want to make sure you have enough reagents. You use previous data fr your celine to simulate your bioreactor run using Monod kinetics. Luckily, the R&D team has done extensive research on the glucose consumption, L-glutamine consumption, lacate producton, and ammonia production of your iPSCs to gve yau everything you need for your simulation Kinetes Cell growth M def mu(munax, c6le, ¢6in, KsGle, Ks6in) return munax © (cle / (@Gle + K-sGle)) * («Gln / (¢_6In + K.s6ln)) Celldeatn W der mu d(mdmin, mud.max, K_sGle, ¢ Cle) return au_d.ein + mi-dmax™* K_sGle/(K_sGle + ¢61c) Glucose consumption M def a.sle(mymax, cle, ¢6In, Ks6le, K.s6In, k Gle) imi = Mu(au_max, ¢_Gic, cin, K_sGic, K sGln) return q.Giemax * ¢6le* ((mi/ (mu + musax)) + 8.5) / (cle + k.Gle) LLalutamine consumption In [6]: W def qGin(c Gln, ¢Gle, a 6ln_max, Kin, a, CGle_the): Sf cle > ¢ Gle_thr: icin 1 alse KpGin = 1+ a * (<_6le_the = le) return Kp ln * q Gln_nax $e Gin /"(c_Gln + k Sn) Lactate production In [7]: W def qtac(ytacgle, Q6te, eu, mimax, @Lac_uptake_max): Qlac = ¥lacgic * @Gle ~ q Lac uptake sax * (Gu_max - mu) / munax return YTacgle * @Gle - @_Lac_uptake fax * (mu_fax ~ mu) / mu_pax ‘Ammonia production In [8]: W def qAmn(y_amgin, Q.6in) return Y_aamgin * 9 Gin Kinetic constants In [9]: W/mudein = 0.0017 #h-2 musdleax = 0.0360 9-2 muleax = 0.0068 7 h-2 KGle = 1.8501 sol /t Cola = 3.7363 armol/t KCsGle = 0.03 gnmol/t KCscin = 0.03 smmol/t @Gle max = 0.07260-9 # mmol /cell/n @GlaLmax = 0.07798-9 # mwol/cell/> Yaengin = 0.6562 Yoacgie = @.4707 @Llacimax = 6.08626-9 nmol /celL/h Klys = 0.0010 Yau know the inital concentrations by taking a measurment at t=O and have recorded the Fndings. In [10]: Wc leo = 44.4 srmol/t c6lnle = 4 fmol XG_0 = 2€7 scells/t cae @ = 9 ennol/t hem = 8 Amol/L ‘You must now cun your simulation. You havea set of ordinary diferental equations (ODEs) that you need to solve in series; therefore, yyou must use an ODE solver. In [11]: W from scipy-integrate import odeint fron scipy inport interpolate an [32] W def odes(x, 1): 4 kinetic constonts mud_nin = 0.0027 #h-2 musdonax = @.0360 9-2 rnu_aax = 0.0669 0 h-1 KGle = 4.8501 #mmot/t kCGin = 3.7363 mol/L KCscle = 6.63 anmal/t KCs6ln = 0.65 rawol/t @Gle_max = 0.0726E-9 # mol /cell/h |@LGIn.max = 0.07786-9 # mmol/celLl/n Yanmgin = @.6562 YLlacgle = 0.4707 qLlaciuptake max = 0,04426-9 snnol/cel/h Kilys = 0.007 #h-2 aes Gatch and Fed-datch Viable Cell Density vs Time Ba dene (ct) Th [36] Mf Glucose Concentration (fed batch vs batch) eatch reactor: plt.plot(t,gle, a's label Baten Reactor") Hed Batch reactor: plt.plot(t_fb, glefb, "y', label = ‘Fed-satch Reactor") pltoxlabel("Tine (hours)', color = ‘darkgreen') plt.ylabel( Concentration of glucose (nel/L)", color = “darkgreen*) plt.title( eaten and Fec-8atch Glucose Concentration vs Tine’, color = ‘darkgreen") pit. legend() out[36]: Batch and Fed-Batch Glucose Concentration vs Time a & Concentration of cre (at) 8 & me H/# U-glutamine Concentration (fed batch vs batch) weatch reactor: plt.plot(t,gln, a's label Baten Reactor") Hed Batch reactor: plt.plot(t_fb, glafb, "y', label = ‘Fed-satch Reactor’) pltoxlabel('Tine hours)", color = ‘dargreen') pltsylabel( ‘concentration’ of L-glutamine (nol/L)", color = ‘darkgreen') plt-title('satch and Fed-satch I-glutanine Concentration vs Time’, color = pit. legend() arkgreen") out[37]: ‘atch and Fedatch H-lutamine Concentration vs Time taine (not) Th (38) out(38): Me Lactate Concentration (fed batch vs batch) eatch reactor: plt.plot(t,1ac, g's label Baten Reactor") Hed Batch reactor: plt.plat(t_fb,12¢_fo, ‘y', label = ‘fed-batch Reactor’) pltoxlabel('Tine (hours)', color = ‘darkgreen') pltsylabel( Concentration of lactate (nol/L)", color = ‘darkgreen') plt.title('gateh and Fec-satch Lactate Concentration vs Tine’, color = ‘darkgreen") pit. legend() Batch and Fed-datch Lactate Concentration vs Time. Tn [39]: W_# Anmonto Concentration (fed batch vs batch) eatch reactor: pit.plot(t,aam, a, label Baten Reactor") sed Batch reactor: plt.plot(t_fbyam_fo, 'y', label = 'Fed-batch Reactor’) pltoxdabel('Tine (hours)", color = ‘darkgreen') pltiylabel( ‘concentration of ansonia (nol/L)', color = ‘darkgreen') plt.title( ‘eaten and Fed-Satch Ancona Concentration vs Tine’, color = ‘darkgreen") pit-legend() out[39]: Batch and Fed-Batch Ammonia Concentration vs Time How many cells do you need fo innoculate& 1000 L reactor? After how many days can you inoculate the 1000 L reactor? In [40]: inital_vol_fo = 50 sin ¢ Flowrate #5 = 15/24 #1/hour volume_f® = inital_vol_fo + (flowrate fo * t_fb) In [41]: M/# want to snnoculate with the same initial cell density (20,000 cels/al) ‘cot_num_cells_fo = Xv. * 1080 prine('The number of cells needed to innoculated 2 1000 reactor:”, int(tot_num_cells fb), cells") The nusber of cells needed to innoculated a 1000L reactor: 29000800000 cells In [42]: W inoc tine fb = np.interp(tot_nun_cells_fb, Xv*volune_fo, t) prine(' after", round(inoe tine f9/24,3) , “days you can inroculate the 1890 Bioreactor.", ) After 2.339 days you can innoculate the 1086. Bioreactor, Export this notebook as por take screen shots and put nto a word document to hand in your workin the drop box.

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