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# UNIVERSITY COLLEGE LONDON

MODULE CODE

: 'BENG3009

BENG3009A

MODULE NAME

## Computer Aided Bioprocess Engineering

DATE

09-May-11

TIME

10:00

TIME ALLOWED

2 Hours 0 Minutes

ASSESSMENT
PATTERN

2010/11-BENG3009A-001-EXAM-39
2010 University College London

TURN OVER

Answer ALL FOUR QUESTIONS. Marks for each question are distributed as
shown in [J.
1.

## The desired temperature for a large fermenter is 30C and must be

controlled to within 1C. The transfer function of the fermenter
temperature characteristic is

G(s)

30s +1

## It takes more than 90 minutes to increase the temperature from 0 C to

30 C for the open system (i.e., when the feedback loop control system is
not applied).

## Design a control system with a proportional controller to shorten this

settling time and to specify the controller constant Kp so that the settling
time is less than 15 minutes.

[30]

2.

A biotech company has two production processes, one each for drug A
and drug B. The batch time for drug A and drug B are 11 and 8 days
respectively. The gaps between two consecutive batches are 5 days for
drug A and 4 days for drug B. The relationship between operating time
and batch number for a process is as follows:

## Operating time (days) = (batch number 1) X Gap + batch time.

Due to staff constraints, only one process can be operated at any time.
There are 230 working days available in a year. The profits for one
batch of drug A and B are 100,000 and 60,000 respectively. However
the maximum demands for these drugs are 40 batches for drug A and 30
batches for drug B.
a)

## Formulate a Linear Programming problem to help the company

determine the optimal production plan that maximizes the profit and

b)

[15]

## Calculate the optimal number of batches of each drug that should be

produced so as to maximize the profit.

[15]

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3.

## The development team in your company wants to use a simulation study

to identify the optimal operating conditions for a homogenisation step
with subsequent solids removal by centrifugation. Part of the task is to
write MATLAB functions to help simulate the effect of key operating
conditions.
a)

b)

Write a function for calculating the level of protein release, R, given the
pressure, P, and the number of passes N.

Write a function for the grade efficiency curve T(d) of the clarifying
centrifuge at a given flowrate, Q.

c)

[10]

[10]

## Write a program to simulate the impact of P and N upon the levels of

protein release, R, where N is from 1 to 8 and P is from 100 bar to 800
bar. The output of your program should also include graphs showing the

## three curves of the protein release vs. the number of passes at

P= 300 bar, 400 bar and 500 bar.

[10]

Background information:

## 1) Protein release model:

Ln

=K.N.Pa

(1)

where Kp = 4.14X10-8,

d
T(d)=1 exp(-1C,(
)2)
d

(2)

## where d is the solids diameter, (m), Kc is 0.865 and de is determined by the

material properties of the feed stream as well as how the centrifuge is
operated:
1877Q

AlApE(1 COrg

(3)

## where ;I is 0.001 (m2/8), Q is the flowrate (m3/s), hp is 50 (kg/m3) ,

(m2), C is 5 (%), r is 4.6, and g is 9.81 (m/s2).

is 1633

CONTINUED

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4.

## A recombinant protein production process from an E coli strain has been

modelled in BioSolve. The comparison tool has been used to evaluate
the choice of using either stainless steel vessels or single-use systems
(disposables) for the bioreactors and tanks. The results are summarised
in the following table. Discuss the main differences between these two
process routes and the main reasons for the differences in costs between
these two scenarios.

[10]

## PLEASE TURN OVER

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Comparison Analysis
w

Process Definition

O
O

Sizing Basis
Expression (# particles or g/L)
Target Capacity Utilisation
Production Bloreactor Working Volume
Total Number of Production Bioreactors
Production / Seed Train Split
Number of Bioreactors! Batch

Single-Use

Microb Typical

Microb Typical

Gram
2.0E+00
90%
1000 L

Gram
2.0E+00
90%
1000 L

3
2

per unit op
per unit op

per unit op
per unit op

No

No

No
No
No

Yes
Yes
Yes
Liner
Yes
Yes
Yes
3000

## CoG (US\$) Traditional

GON!

W34i1 *
Consumables
Labour

F,c)Wi

Solution Preparation
Media Make-up Basis
Buffer Make-up Basis
Make up Concentrated Buffers

TOTAL

12 88
9 53
4.07
23 53
4 23
54 24

64.38
47 66
20 35
117.64
21 16
271 19

29,898
22,135
9,449
54,632
9,826
125,940

12,646,870
9,363,048
3,996,976
23,109,449
4,156,320
53,272,663

8%
100%

3.91

19 54
43 87
76 32
60 55
5 33
205.60

9,072
20,371
35,446
28,120
2,474
95,483

3,837,609
8,617,075
14,993,454
11,894,908
1,046,409
40,389,455

10%
21%
37%
29%
3%
100%

frtl
tm
Lh

ro

it

t
LI

Liner
No
No
No

3000
No

10

U'

8 77
15 26

10#

Consumables
Labour

12 11

1.07

000gr

TOTAL

41 12

Gthana

No
10

29

48.4

31.4

Comparison
Annual CoG (US\$)
Capital
Materials
Consumables

Labour
Other

53,272,663
12,646,870
9,363,048
3,996,976
23,109,449
4,156,320

8%

43%

## CoG (US\$) Single-Use

Single-Use Systems
Bloreactors (up to 2000L)
Media Preparation (up to 2000L)
Buffer Preparation (up to 2000L)
Type of Buffer Prep System
Media and Buffer Hold (up to 3000L)
intermediate Product Hold (up to 2000L;
Use Stainless Steel above Threshold
Threshold Volume
Membrane Adsorber for Flowthrough
Size of MA Capsule

24%
18%

Single-Use % Change
40,389,455
-24%
3,837,609
-70%
8,617,075
-8%
14,993,454
275%
11,894,908
-49%
1,046,409
-75%

i6

29

146.8

Iv

Vessels
Bags

GGiargkim
2
0

rifl

12
0

12
0

9
0

Other metrics

## Water usage (m3 per batch)

Plastics waste (kg per batch)
Total Installed Capital (US\$M)
Batches per year
Throughput (kg or doses per year)

51.34
31 36
60.39
423
196 44

4.53
146.80
18.32

-91%
368%
-70%

423
196 44

0%
0%

Lar0,04t1Pist*

Vessels
Bags

0
2

0
2

0
12

0
12

1akcet4
0
9