Consistency by design - Microdetection€¦ · Consistency by design V. Thom & M. Hollas ... Consistency by design V. Thom & M. Hollas, ACON, Hanghzou22.06.2006 CONFIDENTIAL 1)Introductionto

Consistency by design

V. Thom & M. Hollas, ACON, Hanghzou 22.06.2006 CONFIDENTIAL

Membrane Development

Volkmar Thom& Markus Hollas, Sartorius AG, Göttingen, Germany



1) Introduction to air cast membranes

2) Consistency by design, with respect to:

� The business unit� Membrane development� Process capability



Introduction to air cast membranes:

From Wood to Membrane



homogeneouspolymer solution

phase inversion:

porous structure

polymer-rich phasepolymer-lean phase

Liquid-Liquid Demixing



Membrane Formation



mixingtank

castingtank

N2tank

solvent tank

casting machine

exhaust

solvent recovery

polymer

Evaporation Process Scheme



Consistency by design=> The diagnostic team



The Diagnostic Team, .....

R&D, Production, Engineering, QA, Customer Support and Management are located within the Göttingen Headquarters

� Effective communication: short ways, fast decisions � Input of 35 membrane scientists

� Team spirit

....Your reliable partner



Consistency by design=> Membrane development



Objective of diagnostic membrane development:

Membrane test performance (in-house hcg & customer testing) � Protein line printability � Line intensity � Line quality (width and shape)� Flow front� Background

Physical Membrane properties� Wicking speed� Protein binding capacity� Wettability� Storability� Surface quality



Membrane casting process � Cross- and down-web homogeneity: intra lot

consistency� Interlot reproducibility� Process capabilities (cpk > 1.3)



Steps of Membrane Development:

1. Develop basic solution recipechoice of suited solvent system, cellulose nitrate grades, additives, mixing, etc.

=>determination of phase diagrams, Statistic Design of experiments

2. Develop casting process on lab machine=> key parameters of drying process; reproducible results

3. Scale-up to production scale Proof of processability of promising recipes



Steps of membrane development (cont.):

4. Evaluate significant control parameters, determine process windows

5. seek external evaluation: alpha (pre-beta) site testing

6. Several large scale reproductions: beta-site samples for external testing

7. Launch



How can consistency be designed into the membrane by raw material?

analytical selection of raw material�Define physical key parameters that influence casting solution �Define and audit your strategic suppliers regularly�Rigorous incoming quality control steps�Recheck influence of lot to lot variations of raw material on membrane properties before release



How can consistency be designed into the membrane by casting solution?

Trübung Video.MOV



What is the ideal casting solution for a consistent membrane production,

clear or turbid?



Characterization of casting solutions: Light transmission

0

10

20

30

40

50

60

70

80

90

100

3 5 4 0 4 5 50 55 6 0

Transmission, [%]

Mix A, reproducible

Mix B, hardly reproducible

Mix C, not reproducibledispersion

Amount of precipitation agent in the mix



Our philosophy of consistency: Start the process on the plateau of a clear

solution



Benefits of clear casting solutions

� Stable solutions, no kinetic influence � Reproducible solutions: transmission plateau

� Longer time for pore growth and membran formation: homogenous structure

outstanding intra- and inter lot consistency



Membrane structure as an indicator for consistency

�Consistent structure: networklike membrane resulting from a clear casting solution

High intra and inter lot consistency



Membrane structure as an indicator for consistency

� inhomogenous globular structure resulting from a turbid casting solution

Lower consistency



Consistency by design=> Process capability



In-house data for diagnsotic membrane production type CN 135 => wicking speed & thickness values (lot:0502854) => very good process capabilities (cpk > 1,3)

0,01

0,52

10

305070

90

9899,5

0 20 40 60 80 100 120 140 160 180

0 20 40 60 80 100 120 140 160 1800

2

4

6

8

10

12

14

16

18

Num

ber

Wickingspeed [s/4cm]

Pro

babi

lity

preliminary upper and lower spec.

0,01

0,52

10

305070

90

9899,5

0 20 40 60 80 100 120 140 160

0 20 40 60 80 100 120 140 1600

10

20

30

40

50

60

Thickness [µm]

Cp = 1,67Cpk = 1,57

Cp = 1,60Cpk = 1,53



cross web

down web

wicking thickness

0

20

40

60

80

100

120

140

160

180

roll number

wic

king

[sec

/4cm

]

0

20

40

60

80

100

120

140

160

180

1 2 3 4 5 6

zone

wic

king

[sec

/4cm

]

0

20

40

60

80

100

120

140

160

roll number

thic

knes

s [µ

m]

0

20

40

60

80

100

120

140

160

1 2 3 4 5 6

zone

thik

ness

[µm

]

In-house data for diagnsotic membrane production type CN 135=> wicking speed & thickness values (lot:0502854)



0,00

0,10

0,20

0,30

0,40

0,50

0,60

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

roll number

prot

ein

bind

ing

[a.u

.]

0,00

0,10

0,20

0,30

0,40

0,50

0,60

1 2 3 4 5 6

zone

prot

ein

bind

ing

[a.u

.]

cross web(first & last roll)

down web(one zone)

In-house data for diagnsotic membrane production type CN 135=> protein binding (lot:0502854)



0

200

400

600

800

1000

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

roll number

test

line

inte

nsity

[a.u

.]

In-house data for diagnsotic membrane production type CN 135=> test line intensity (lot:0502854)



Consistency by design=> Production process

Membrane performance: customer data



position 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47

start

3 m X X X X X X X

10 m X X X X X X X

18 m X X X X X X X

end

zone = final roll

Consistent hcg test performance across a master roll: customer data

Test Line Response @ 25 mIU/mL hCG @ 3 Minutes

0.000

0.005

0.010

0.015

0.020

0.025

1030

300 8

0337

7

Zone 3

-2m

Zone 3

-10m

Zone 3

-18m

Zone 1

1-2m

Zone 1

1-10

m

Zone 1

1-18

m

Zone 1

4-2m

Zone 1

4-10

m

Zone 1

4-18

m

Zone 2

4-2m

Zone 2

4-10

m

Zone 2

4-18

m

Zone 3

1-2m

Zone 3

1-10

m

Zone 3

1-18

m

Zone 3

8-2m

Zone 3

8-10

m

Zone 3

8-18

m

Zone 4

5-2m

Zone 4

5-10

m

Zone 4

5-18

m

Sca

nner

Res

ult

Control Line Response @ 3 Minutes

0

0.01

0.02

0.03

0.04

0.05

0.06

0.07

0.08

0.09

0.1

1030

300 8

0337

7

Zone 3

-2m

Zone 3

-10m

Zone 3

-18m

Zone 1

1-2m

Zone 1

1-10

m

Zone 1

1-18

m

Zone 1

4-2m

Zone 1

4-10

m

Zone 1

4-18

m

Zone 2

4-2m

Zone 2

4-10

m

Zone 2

4-18

m

Zone 3

1-2m

Zone 3

1-10

m

Zone 3

1-18

m

Zone 3

8-2m

Zone 3

8-10

m

Zone 3

8-18

m

Zone 4

5-2m

Zone 4

5-10

m

Zone 4

5-18

m

Sca

nner

Res

ut



master roll 1 2 3 4 5 6

12

3

4

5

6 X X X7

89

101112 X X X131415161718192021222324 X X X25262728

zone

Consistent performance across a lot: customer data

cross web

dow

n w

eb

0,000

0,002

0,004

0,006

0,008

0,010

0,012

0,014

0,016

finalroll

6 12 24 6 12 24 6 12 24

masterroll

4 4 4 8 8 8 12 12 12

Test

line

inte

nsit

y [a

.u.]



Possible root causes for false-positive test lines

Thank You!!



Membrane Development

Volkmar Thom& Markus Hollas, Sartorius AG, Göttingen, Germany

Documents

Consistency by design - Microdetection€¦ · Consistency by design V. Thom & M. Hollas ... Consistency by design V. Thom & M. Hollas, ACON, Hanghzou22.06.2006 CONFIDENTIAL 1)Introductionto