ifpac real-time in-line process monitoring of liquid chemical concentration doug nordstrom and dave...

© 2007 Swagelok Company. Swagelok confidential. For internal use only.

IFPACIFPAC

Real-time In-line Process Monitoring of

Liquid Chemical Concentration

Doug Nordstrom and Dave Simko Swagelok Company

IFPAC®- 2008 22nd International Forum Process Analytical Technology

January 27-30, 2008 Baltimore, Maryland


IFPACIFPAC

Outline

• Refractive index and refractometers• General applications• Specific applications

- Ultrahigh-purity liquids- Biopharmaceutical manufacturing

• NeSSI compatibility


IFPACIFPAC

Refractive Index

LIGHT SOURCE

SUBSTANCE

REFLECTED BEAM


IFPACIFPAC

Refractive Index

• Fundamental physical property• Measure of bending of a light beam moving from one medium to a more dense medium• Ratio of sines of angles of incidence and refraction• Constant for pure substance at STP• Influenced by temperature and wavelength


IFPACIFPAC

Refractometers

• Traditional handheld• Digital handheld• Abbe• Inline process


IFPACIFPAC

CR-288® Concentration Monitor


IFPACIFPAC

General Applications

Ultrahigh-purity liquids• Monitoring bulk chemical feed quality and content• Chemical blending, dilution, and spiking• Controlling specific manufacturing processes• Monitoring and controlling waste treatment


IFPACIFPAC

General Applications

Biopharmaceutical manufacturing • Monitoring CIP solutions – chemical

content and endpoint• Chromatographic separation units –

buffers, biological materials, and effluents

• PAT – Monitoring and controlling liquid chemical concentrations from substrate buffers and media to compounding


IFPACIFPAC

TMAH 2.38%

DIW

High Resolution TMAH Measurements


IFPACIFPAC

0

0.01

0.02

0.03

0.04

0.05

0.06

0.07

0.08

0.09

0.1

0 5 10 15 20 25 30 35 40

Time (minutes)

TM

AH

Co

nce

ntr

atio

n

DIW

0.071 % TMAH

0.057 % TMAH

0.049 % TMAH

0.043 % TMAH0.006% change

TMAH Monitor, 2.38% or 0.060%

High Resolution TMAH Measurements


IFPACIFPAC

EKC Continuous Dilution to Process


IFPACIFPAC

EKC265 / CR-288 0 to 5% added H2O shown as IoR

1.451

1.452

1.453

1.454

1.455

1.456

1.457

1.458

1.459

1.460

Time (~2 hours)

IoR

@20

C

40

50

60

70

80

Tem

per

atu

re (

C)

Index of Refraction @20C

Fluid Temp @ Sensor

Baseline EKC-2650% added H2O 1% added H2O

Pump stopped Recirculating

5% added H2O

4% added H2O

3% added H2O

2% added H2O

EKC Dilution Results


IFPACIFPAC

EKC-265 Index of Refraction vs. Conductivity

1.442

1.444

1.446

1.448

1.450

1.452

1.454

1.456

1.458

0% 2% 4% 6% 8% 10% 12% 14% 16% 18%

Concentration of added H2O

IoR

@2

0C

2.80

3.00

3.20

3.40

3.60

3.80

4.00

Co

nd

uct

ivit

y (m

S/c

m)

Index of Refraction @20C

Conductivity

Temp at this data point was 64C while the rest were around 67C

EKC Dilution Results


IFPACIFPAC

Three Chemical Blend with DI Water


IFPACIFPAC

1.33295

1.33315

1.33335

1.33355

1.33375

1.33395

1.33415

1.33435

1.33455

0 500 1000 1500 2000 2500

Time (s)

CR

-288

IoR

DIW Add 30ml chemical A

Add 30 ml chemical B

Add 30ml metal 1

Mixing Spike

Mixing Spike

Add 3 ml chemical B

Photovoltaic Cell Manufacturing


IFPACIFPAC

Feed Forward System - Slurry and H2O2


IFPACIFPAC

8

8.5

9

9.5

10

10.5

11

11.5

12

12.5

0 0.5 1 1.5 2 2.5

Time (hours)

Co

nc

en

tra

tio

n

on

20

21

22

23

24

25

26Slurry Concentration Temperature

lot-to-lot slurry concentration variations



IFPACIFPAC

1.33937

1.33939

1.33941

1.33943

1.33945

1.33947

1.33949

2300 2800 3300 3800 4300 4800 5300 5800 6300

Time (s)

IoR

~0.02% added

~0.02% added

~0.02% added~0.02% added

~0.02% added

~0.02% added

set point



IFPACIFPAC

1.33

1.34

1.35

1.36

1.37

1.38

1.39

1.4

1.41

1.42

1.43

0 5 10 15 20 25 30 35 40 45 50 55

Protein Concentration (g/100 mL)

CR

-28

8 I

oR

Ou

tpu

t

IoR Ovomucoid IoR Urease IoR Hemoglobin

Refractive Index vs. Protein Concentration


IFPACIFPAC

Cholesterol Concentration Expt in TBME:25ml/min Flow Rate

1.3775

1.378

1.3785

1.379

1.3795

1.38

2600 3100 3600 4100

Time (seconds)

RI@

20

C

TC

C =

- 0

.00

03

00

7.03 % w/v 6.679 % w/v 6.327 %w/v 5.975 % w/v 6.116 % w/v 6.257 % w/v

-5%w/v

-10%w/v

-15%w/v

-13%w/v -11%w/v

Cholesterol in TBME


IFPACIFPAC

Ethanol/Proponal Step Gradient10%v/v Steps/20ml/min

1.358

1.36

1.362

1.364

1.366

1.368

1.37

0 5000 10000 15000 20000

Time (sec)

IoR

P1_IoR@20C Zero 10%v/v 20%v/v 30%v/v 40%v/v

Ethanol/Proponal Repeatability


IFPACIFPAC

1.333400

1.333600

1.333800

1.334000

1.334200

1.334400

1.334600

1.334800

1.335000

1.335200

0 5 10 15 20 25 30 35 40

Time

IoR

-5000

0

5000

10000

15000

20000

25000

Co

nd

uc

tiv

ity

CR-288 IoR Conductivity

NaOH 4% phosphoric acid

CIP Solution


IFPACIFPAC1.33365

1.33366

1.33367

1.33368

1.33369

1.3337

1.33371

1.33372

1.33373

1.33374

1.33375

1.33376

1881 1981 2081 2181 2281 2381 2481 2581 2681 2781 2881 2981 3081 3181 3281 3381 3481

Time (s)

IOR

@20

C

1 µL slow manual

2.5 µL @ 150 µL/min

5 µL @ 150 µL/min5 µL @

150 µL/min2.5 µL @ 150 µL/min

5 µL @ 150 µL/min

5 µL fast manual

1 µL slow manual

1 µL fast manual

1 µL slow manual

1 µL fast manual

Ultra Small Scale Leak Detection


IFPACIFPAC

NeSSI Compatibility

ANSI/ISA 76.00.02 FOOTPRINT

CR-288 FOOTPRINT

ifpac real-time in-line process monitoring of liquid chemical concentration doug nordstrom and dave...

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