Particle Science Theory and Practice

Ian Haley

Outline of Modules 1
The Basics

Part 1 - What is Particle Size
Part 2 - Presentation Method and Weighting Part 3 The Importance of Shape Part 4 Count-based Measurement

Instrumentation for Particle Characterisation

Part 5 FBRM and The Chord Length Distribution Part 6 Chord Length and Particle Shape Part 7 - An Outline of Different Particle Characterisation Methods and the
Effect of Particle Shape

Outline of Modules
Statistics and Data Handling

Part 8 - Understanding the Mean, Median and Mode of a Particle System
Part 9 Precision and Accuracy Part 10 Correlating FBRM to Other Data Part 11 - Channel Grouping and Statistics Part 12 Signal Aliasing

Practical Aspects of Using FBRM

Part 13 - Probe Location and Orientation Part 14 Standard Procedures

Part 1: What is Particle Size?

Ian Haley

Particle Size

Many particles are complex Three-dimensional objects. Yet we want to represent their size by just one number.

Particle size = 326 m But how was it calculated? And what does this tell us about the particle and others like it?

Size
What is the size of this particle?

10mm

Size
But what is the size of this particle?

50mm

10mm

50 microns? 10 microns? 30 microns? Some other number?

7

What is particle size?

There is no single definition of particle size In this (document), particle size is defined as the diameter of a sphere having the same physical properties; this is known as the spherical equivalent diameter.
(Source: International Standards Organization (ISO 9276-1:1998))

By volume

By surface area

By settling velocity

By sieve analysis

Part 2: Presentation Method and Weighting

Ian Haley

Particle Size and Physical Property

There is no single definition of particle size In this (document), particle size is defined as the diameter of a sphere having the same physical property; this is known as the spherical equivalent diameter.
(Source: International Standards Organization (ISO 9276-1:1998))

By volume

By surface area

By settling velocity

By sieve analysis

The physical property we use has a major effect on the way in which particle size is calculated. 10

Using a Physical Property to Calculate Mean Size

What is the average size of this two-particle system? In other words, What does my PSA lab tell me?

Diameter: 10m Surface area: 314m2 Volume: 524m3

Diameter: 100m Surface area: 31,400m2 Volume: 524,000m3

11

Mean size: calculated statistics for a two-particle system

These numbers are all the correct average size. There are a large number of other methods of calculation that would be correct
as well.

Mean diameter
Number-based dist. = 55.0 m Area-based dist. = 99.1 m

Volume-based dist. = 99.9 m

Diameter: 10m

Diameter: 100m

12

Mean size for equal volumes of 100 m and 10 m particles

Equal Volumes
Number-based dist. = 10.1 m Area-based dist. = 18.2 m

Volume-based dist. = 55.0 m

13

Comparing different physical properties

One 100 m particle
(A) contains the same quantity of material as onethousand 10 m particles (B)

A Total number Diameter Surface area Total volume 1 particle 100 m 31,400 m2 524,000 m3

B 1000 particles 10 m 314,000 m2 524,000 m3

14

Number and Volume Distributions

Number Distribution
12 10

Number

8 6 4 2 0 10 100 1 1

Diameter (m)
1E+06 1E+06

Volume Distribution

Volume (m3)

8E+05 6E+05 4E+05 2E+05 522 0E+00 10 100 522,025

10m

Diameter: 100m

Diameter (m)

15

2006 Mettler-Toledo AutoChem, Inc.

Sensitivity of Each Distribution to Fines

Number Distribution
12 10 10

Sensitive to change in fines!

Number
8 6 4 2 0 10 1000 1

Diameter (m)
1E+06 1E+06

Volume Distribution Insensitive to change fines!

10m
522,025

Volume (m3)

8E+05 6E+05 4E+05 2E+05

Diameter: 100m

5,220
0E+00 10 100

Diameter (m)

16

2006 Mettler-Toledo AutoChem, Inc.

Coarse in the presence of fines

Number Distribution
1200 1000 1000

Number

800 600 400

1000
10m
1

200
0 10 100

Diameter (m)
1E+06 1E+06

Volume Distribution

Volume (m3)

8E+05 6E+05 4E+05 2E+05 0E+00 522025 522025

100m

10

100

Diameter (m)

17

2006 Mettler-Toledo AutoChem, Inc.

Adding one coarse particle

Number Distribution
1200 1000 1000

Number

800 600 400 200 2 0 10 1000

1000
10m

Diameter (m)
1E+06 1E+06

Volume Distribution
1044050

Volume (m3)

8E+05 6E+05 4E+05 2E+05 0E+00 10 100 522025

100m

100m

Diameter (m)

18

2006 Mettler-Toledo AutoChem, Inc.

Detecting breakage in a particle system

Breakage of 1 large particle

into 1000 small particles

Initial particle system Total number Total surface area Total volume Number mean diameter Volume moment mean diameter 27 particles 847,000 m2 14,140,000 m3 100.0 m 100.0 m

After breakage of one particle 1026 particles 1,161,800 m3 14,140,000 m3 12.3 m 96.7 m

Relative change 3700% increase 37% increase 0% 87.7% decrease 3.3% decrease

19

2006 Mettler-Toledo AutoChem, Inc.

Why is the particle distribution range important?

Probability (%)

All three distributions have the same mean but significantly different distributions!

Particle dimension (m) 20

Defining Number and Square Weighting

What is the mean of this distribution?

21

Weighted vs. Unweighted Distributions, Part I

Which distribution is the most sensitive in your application?
Mean = 7.1 m Mean = 9.2 m

Example: A Population of Cubes

Mean = 12.2 m

Mean = 15.2 m

The size distribution is presented as: a) Total number b) Total length (based on projected area) c) Total surface area d) Total volume of particles within each size classification

Number, Length, Area, Volume Distributions

Presentation method determines sensitivity to different regions of the population. (Example: Population of Cubes)

Number Distribution

Length Distribution

Area Distribution

Volume Distribution

23

Data presentation of cube distribution

The statistic choice/presentation method determines the sensitivity to different regions of the population.

Sq Weighted vs. Unweighted Distributions

Example: A population of cubes

FBRM No Weight
Emphasizes changes to the fine (small) end of the distribution

Mean = 12.2 m FBRM = 15.2 m Mean Square Weight

Emphasizes changes to the coarse (large) end of the distribution

25

Weighted vs. Unweighted Distributions (1)

No Weighted Distribution
Time=0 min

Square weighted Distribution

Time=0 min

Time=90 min
Time=180 min

Time=90 min
Time=180 min

On Left: No Weighted FBRM

distributions at 3 time points show a decrease in count and an increase in dimension
Unweighted distribution is sensitive to
fine particles population

On Right: Square Weighted FBRM

distribution for same 3 time points show enhanced resolution to growth in coarse particle dimension
Square weighted distributions is
sensitive to coarse particle dimension

26

FBRM Distributions and Trended Statistics

Unweighted Distribution #/s <50 m
Time=0 min Time=90 min Time=180 min

#/s 50-1000 m

Square Weighted Distribution

Time=0 min Time=90 min Time=180 min

Mean180 = 141m Mean90 = 82m Mean0 = 75m

27

Weighted vs. Unweighted Distributions, (1)

Distribution weighting (by
number, length, area, or volume) can significantly enhance or reduce the resolution to change.

Selecting the appropriate

weighting function will enhance the changes that directly relate to the application goal.

In this example, the squareweighted distribution does not detect small changes in the concentration of fine material.

However, the unweighted

distribution is very sensitive to the amount of fine material present.

28

Weighted vs. Unweighted Distributions, (2)

Distribution weighting (by
number, length, area, or volume) can significantly enhance or reduce the resolution to change.

Selecting the appropriate

weighting function will enhance the changes that directly relate to the application goal.

However, the squareweighted distribution is very sensitive to the amount of coarse material.

In this example, the

unweighted distribution does not detect small changes in the concentration of coarse material.

29

Definitions: Fines vs. Coarse

Our descriptions of fine and coarse
material are relative

Terms are used to describe the

smallest and largest particles in a given system

Definitions are system specific

Fines

Coarse

30

When talking particles, size is a generic term

Reporting of particle size must include definitions of:

The physical property selected to characterize size of the particles, for example:
Diameter Chord length Projected area Surface area Volume Settling rate Response of electrical, optical, or acoustical field Number-based distribution Length-based distribution Area-based distribution Volume-based distribution Scale (log vs. linear) Channel grouping Count vs. normalized

Statistical calculations and display, for example:

Assumptions, for example:

- Shape - Refractive index - Coincidence effects

31

Sensitivity to a given particle system trait depends on the chosen statistic

Distribution mean depends on both the property measured and the

calculation used to characterize the particle distribution.

- Property
Sphere having the same settling rate Sphere fitting through the same-size sieve aperture Sphere producing a similar diffraction pattern No shape assumption - Chord length distribution Calculation Number Length Area Volume

Different techniques use different properties to calculate size. None are

fundamentally wrong, they just measure different properties of the particles.
32

Part 3: The Importance of Shape

Ian Haley

The Volume Spherical Equivalent Diameter (VSED)

10 m

Calculate the diameter of a sphere with the same volume as a needle

24.7 m

100 m

The surface area of the needle is 60% greater than that of the sphere.

34

Why do we assume all particles are spherical?

Simplicity: A sphere is the only shape that can be described by
one unique number (the diameter), regardless of the particles orientation.

35

How can particle size be calculated for non-spheres?

5 m 18 m

50 m

Calculate the diameter of a sphere with the same volume as the cylinder
A spherical equivalent diameter based on volume (VSED)

How does the VSED relate to the length and width of this particle? The surface area of the cylinder is 73% greater than the sphere! A needle will handle and flow differently to a sphere!
36

How can particle size be calculated for non-spheres?

5 m

24 m

100 m

Calculate the diameter of a sphere with the same volume as the cylinder
A spherical equivalent diameter based on volume (VSED)

The cylinder has doubled in length; but the diameter of the equivalent
sphere has only increased by 33%
37

Is the Spherical Equivalent Diameter practical?

YES!

NO!

38

Can the SED help improve a process?

Run 3
Very different morphologies for three batches of the same process

Run 5

Run 5

Run 6

Would a SED provide meaningful

information about the process?

Could it help improve the process?

39

Even if a true spherical equivalent diameter was measured

In a chemical process, do spherical and non-spherical particles

behave the same way?

Can spheres be used to model the behavior of non-spherical

particles?

- They do not have the same surface area or flow properties.

40

Shape: If particles are not spherical, what happens?

Most instruments will assume that the signal is derived from a spherical
particle, and in turn derive a spherical equivalent diameter based on this incorrect assumption.

At this point, there are no successful correction factors in commercial

software (excluding some image analysis packages) that account for non-spherical shapes. Most will generally track growth or reduction of shaped particles, but not in an absolute sense.

The further particle shape moves away from a sphere, the less accurate
instruments based on a spherical equivalent model become.

41

Part 4: Count-based Measurement

Ian Haley

Count-Based Particle Size Measurement

Instruments and techniques used to measure particle size fall into

two key groups:

A measurement is made on a cloud or ensemble of particles simultaneously.
Particles are not measured individually The distribution is expressed as size vs percentage or distribution density These are normalised techniques

Conversely.
Some instruments derive their data by measuring particles individually The data is sensitive to changes in population The distribution is expressed as size vs number These are count-based techniques

43

Normalized vs. Count-Based Distributions, Part 1

In this example, particle dimension is
held constant as the concentration of the dispersed phase increases.

While the number of measured

chords increases, the normalized distribution shows that the size and shape of the particles remain relatively unchanged.

Count-based distributions display

changes in particle dimension and/or changes in the numberbased particle concentration.

Normalization removes particle

population information from the data.

44

Normalized vs. Count-Based Distributions, Part 2

Each channel in a count-based
distribution is independent of change occurring in other ranges of the distribution.

Each channel in a normalized

distribution is dependent on changes occurring in other regions of the distribution.

The normalized, unweighted

distribution indicates dramatic relative change in this size region.

The count-based distribution

shows that the actual number of particles measured in this range did not change.

45

Count-Based Particle Size Measurement

Allows you to measure particle population You can track changes in particle concentration
Track absolute changes in isolated size regions, independent of other

size regions

But, normalized techniques:

Hide the effect of concentration
Only relative changes in concentration can be tracked

46

Part 5: FBRM and The Chord Length Distribution

Ian Haley

How does FBRM work?

Cutaway view of FBRM In-process Probe PVM image illustrating the view from the FBRM Probe Window

Laser source fiber Detection fiber Beam splitter

Rotating optics FBRM FBRM Probe Tube Sapphire Window

Probe installed in process stream

Focused beam

48

What is FBRM Technology?

Enlarged view

PVM image illustrating the view from the FBRM Probe Window

Path of Focused Beam

Probe detects pulses of Backscattered light And records measured Chord Lengths

This core patented technology is called Focused Beam Reflectance Measurement [FBRM]

49

FBRM Method of Measurement

What is FBRM Technology ?

Enlarged view Typical FBRM applications include: -Crystallization -Formulations -Precipitation Path of -Polymerization Focused -Emulsification Beam -Microencapsulation -Dissolution and disintegration -Flocculation -Fermentation Thousands of Chord Lengths are measured each second to produce the FBRM Chord Length Distribution :

51

FBRM Instrument Configuration Standard Focal Position

Standard Focal Position - -0.02 mm (20m inside the
window) measured from outside surface of probe window.

Rotating Lens Focused Beam Sapphire Window

Advantages - In majority of cases, provides

excellent sensitivity to realtime change in count and dimensions of particle population. - Minimizes noise from properties of the system that are not under investigation.

Process flow direction

52

What Happens if the Focal Point is Outside the Window?

Outbound:

Return:

Intensity of focused beam is

degraded by

Return signal is also degraded by

- Absorption by the carrying fluid. - Attenuation due to particles between
the window and measuring zone.

- Absorption by the carrying fluid. - Attenuation due to particles in front of

the measuring zone.

Note: Particles between the window and the measuring zone will reflect light that will be detected as background signal. This will significantly degrade the signalto-noise ratio.

53

Chord Lengths from a Sphere

Chords are Measured from every Aspect

54

Chord length Probability: A Graphical Approach

10 9 8 7 6 5 4 3 2 1

Counts
1 2 3 4 5 6 7 8 9 10 Chordlength [a.u.]
55

Part 6: Chord Length and Particle Shape

Ian Haley

Chord Lengths Measurements, FBRM

Chords are Measured from every Aspect

57

FBRM Particle Shape

A chord length distribution is a function of average shape and dimension of particles and particle structures as they actually exist in process.

Sphere

Sphere

- No shape is assumed. - Affect of shape on FBRM

measurement is known. In most cases the affect of shape on measurement can be filtered out or enhanced to track the change.

Needle Needle

Platelet

Platelet

58

Monodispersed Distribution of Spheres, SED 500 m

59

Normal Distribution of Spheres, Mean SED 200 m, Std Dev 25 m

60

Normal Distribution of Needles AR 2:1, Mean SED 200 m, Std Dev 25 m

61

Normal Distribution of Needles AR 4:1, Mean SED 200 m, Std Dev 25 m

62

Modelling Chord Length Distributions 1

growth of a needle

Ruf, A., Worlitschek, J, Mazzotti, M. Modeling and Experimental Analysis of PSD Measurements through FBRM. Part & Part Syst Characterization. 17 (4), 167-179, 2001.

63

Modelling Chord Length Distributions 2

growth of a needle

Ruf, A., Worlitschek, J, Mazzotti, M. Modeling and Experimental Analysis of PSD Measurements through FBRM. Part & Part Syst Characterization. 17 (4), 167-179, 2001.

64

Modelling Chord Length Distributions 3

growth of a needle

Ruf, A., Worlitschek, J, Mazzotti, M. Modeling and Experimental Analysis of PSD Measurements through FBRM. Part & Part Syst Characterization. 17 (4), 167-179, 2001.

65

Distributions
How do we define a collection of particles of differing size and/or shape?

66

Number, Length, Area, Volume Distributions

Presentation method determines sensitivity to different regions of the population. (Example: Population of Cubes)
No Wt
600

500

400

Count/sec

300

200

100

0
1 3 5 7 15 Dimension 25 40 65

Which statistics are sensitive to length or width?

67

Part 7: An Outline of Different Particle Characterisation Methods and the Effect of Particle Shape

Ian Haley

In-Situ Particle Characterization Tools

10 m droplets FBRM Technology

Focused Beam Reflectance Measurement Track real-time changes in particles and droplets as they naturally exist in the process

PVM Technology
Particle Video Microscope Microscope quality images, in-process and in real time

Characterize particle systems from 0.5m

to 3mm

Characterize particle systems from 2m

to 1mm

69

Imaging and Image Analysis

METTLER TOLEDO PVM enables qualitative and quantitative particle
system characterization

70

Tracking the shape change with FBRM

The following schematic represents the change in morphology. Long Needles Short cubic/diamond crystals

9 chords 1 long chord 8 fine chords

5 chords 5 medium chords

PVM Shows Seed Morphology

PVM images show metastable seeds
are long needle shaped crystals

t=10mins

72

PVM and FBRM Identify Habit Shift (Form Conversion)

At 25mins - polymorphic transformation
occurs

The habit shifts from needles to blocks

t=25mins

73

FBRM and PVM Identify When Conversion is Complete

After 45mins the transformation is
complete

The FBRM distribution is narrower and

tighter

t=45mins

74

How Laser Diffraction Works

Dilute sample (0.01% wt or lower) of particles
added to Laser Diffraction bench top system

They are circulated to the measurement zone

(particles can break, dissolve, etc during this step)

Particles are illuminated by a laser beam in

transmission.
Laser Dilute Particles Detector

The particles scatter this light in all direction,

the light scatter on the detector is collected (diffraction pattern)

A mathematical model (Mie and/or

Fraunhofer theory) is used to fit a diffraction pattern of spheres with the measured diffraction pattern

For Internal Use Only

What does the Laser Diffraction size data look like?

Volume Based Distribution

Normalized distribution
Distribution Assuming all
particles are spheres

77

Sample 1: Bimodal distribution of Glass Spheres

78

Laser Diffraction

Laser Diffraction Electro Sensing Zone Image Analysis

79

Sample 3: Needle like crystals

80

Laser Diffraction Electro Sensing Zone Image Analysis

81

Impact of Particle Shape on Sieving

Sieving will size based on the 2nd largest particle dimension Particles of the same width will be sized the same Particles of different shapes but the same width will be sized the same
82

Determining the appropriate method of measurement

What is the process or product parameter of concern? Critical
parameters may include:

- Downstream processing efficiency

Filtration Milling Drying Flow properties Product yield and purity Bulk Product quality properties Dissolution Bulk density Formulation properties

What region of the particle population directly affects the critical

parameters?

What instrument permits us to monitor this critical parameter? Is sampling or safety an issue?
83

Part 8: Understanding the Mean, Median and Mode of a Particle System

Objective for this Module

Understand how the mean, median and mode are calculated Study how particle system changes impact the mean and median Understand the best statistic to choose for a given objective

85

A sample distribution of particles

9m

25m

50m
25m

32m

Mean

= 28m (9+25+25+32+50)/5

Median = 25m (50% greater than this size; 50% smaller than this size) Mode = 25m (most common occurrence)
86

What happens when we add two coarse particles?

9m

25m

50m
25m

80m

32m

120m
Mean = 49m (9+25+25+34+50+80+120)/7 Median = 32m (50% greater than this size;50% smaller than this size) Mode = 25m (most common occurrence)
87

What happens when we add 4 fine particles?

9m

25m

50m
25m

32m
5m 5m

5m

5m

Mean

= 18m (5+5+5+5+9+25+25+34+50)/9

Median = 9m (50% greater this size;50% smaller than this size) Mode = 5m (most common occurrence)
88

The best stat depends on your region of interest

Mean: +75%
Median: +22% 89

Mean: -35%

Median: -64%

Tracking Real Particle Attrition

Mean: -40%
PVM

Median: -67%

90

Tracking Real Particle Attrition

Particle Count >20m: + 185%

Mean: -40%

Median: -67%

91

Conclusions
The mean, median and mode are all averages used to characterize
particle systems

The mean is sensitive to outliers a small number of very large (or

very small) particles; for example large boulders during milling

The median is sensitive to changes in particle number; especially at

the fine end of the distribution; for example secondary nucleation

Particle count in certain size classes is also a powerful statistic to

study

92

Part 9: Precision and Accuracy

Ian Haley

Precision & Accuracy Defined

Precision
- The ability of the instrument to yield the same
response to repeated measurements of the same unchanging sample.

Accuracy
- The ability of an instrument to yield results that are as
close as possible to the absolute properties possessed by a sample.

- The ability of an instrument to yield results that are as

close as possible to a recognized Reference or Standard Method

94

Accuracy
When discussing accuracy it is important to specify:
- The absolute property in question. (e.g. absolute chord length, true
diameter, etc)

- The reference technique by which that absolute property is

independently determined.

95

Precision and Accuracy Explained

A. Both Precise and Accurate. B. Measurement capable of monitoring
and control: Precise measurement with a consistent offset (bias). Good sensitivity to change.

C. Poor measurement for process

monitoring and control. Poor sensitivity to change. Average (x) of all measurements will approach the true value.

D. Measurement with both random error

and offset.

96

Precision and Accuracy Explained (2)

Two goals of FBRM instrument
design:

1) To ensure high instrument to

instrument repeatability, so instruments are repeatable and can be validated across sites and during scale up (lab to plant).

2) To ensure high repeatability

instrument to itself, so measurements of the same system will always measure the same distribution and provide opportunity for control, quality by design, and process optimization.

97

High Precision and High Accuracy

Case A (Ideal):
Accurate and Precise
100% 80% 60% 40% 20% 0% 0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0

True Mean = 4.0 Measured Mean =

4.0

95% Confidence
Interval = +/-5.0%
8.0

Measured Value

6.0 4.0 2.0 0.0

0.0 1.0 2.0 3.0 4.0 5.0

98

Poor Precision and High Accuracy

Case C: Accurate Measurement, poor precision
25% 20% 15% 10% 5% 0% 0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0

True Mean = 4.0 Measured Mean = 4.0 95% Confidence Interval = +/50%

8.0

Measured Value

6.0 4.0 2.0 0.0

0.0 1.0 2.0 3.0 4.0 5.0

Time (minutes)

99

High Precision and Poor Accuracy

Case B: Precise Measurement with an Offset
100% 80% 60% 40% 20% 0% 0.0
8.0

True Mean = 4.0 Measured Mean = 6.0 95% Confidence Interval = +/5.0%

1.0

2.0

3.0

4.0

5.0

6.0

7.0

8.0

Measured Value

6.0 4.0 2.0 0.0

0.0 1.0 2.0 3.0 4.0 5.0

100

Precision Depends on the Selected Statistic

Why is this true? Any given statistic is primarily the function some specific region of the chord length distribution. Some regions may have more or less counts depending on the particle system.

101

Sensitivity Defined
The ability to of the instrument to respond to a real change in the process parameter of interest. The higher the sensitivity, the smaller the real change in process the instrument is able to detect.

102

Precision and Sensitivity to Change

Is this noise?
Or is there insufficient information to provide a signal of sufficient stability (precision)?

8.0

Measured Value

6.0 4.0 2.0 0.0

0.0 1.0 2.0 3.0 4.0 5.0

103

Precision and Sensitivity to Change

A 0.1% increase in the solids concentration resulted in a corresponding 0.1% increase in the output signal.

104

Precision and Measurement Duration

Increasing single measurement duration improves measurement precision.

FBRM Count, 88-298m (chords/sec)

2 sec.

5 sec.
10 sec. 1 min.

5 min.

Elapsed Time (hr:min) 105

Precision and the Effect of Averaging

Increasing number of measurements to average (navg) improves measurement precision.

FBRM Count, 88-298m (chords/sec)

Elapsed Time (hr:min) 106

Precision vs Response Time

1000

10.0%

Minimum Response Time (= t m) [sec]

100

10

1.0%

0.1 0.1 1 10 100

0.1% 1000

Single Measurement Duration (t m) [sec]

107

Precision (95% confidence limits) [%]

Measurement Duration and Sensitivity to Change

Increasing the Measurement Duration (with no averaging) provides more stable data, but will increase the minimum response time.

FBRM Count (18.6-149 m)

1450 1400 1350 1300 1250 1200 -1.0 0.0 1.0 2.0 3.0 4.0 + 1.0 % by weight, SMD = 1 sec Step Change in Concentration

FBRM Count (18.6-149 m)

1500

1500 1450 1400 1350 1300 1250 1200 -1.0 0.0 1.0 2.0 3.0 4.0 + 1.0 % by weight, SMD = 10 sec Step Change in Concentration

Elapsed Time (min)

Elapsed Time (min)

FBRM Count (18.6-149 m)

1500 1450 1400 1350 1300 1250 1200 -1.0 0.0 1.0 2.0 3.0 4.0 + 1.0 % by weight, SMD = 60 sec Step Change in Concentration

FBRM Count (18.6-149 m)

1500 1450 1400 1350 1300 1250 1200 -1.0 0.0 1.0 2.0 3.0 4.0 + 1.0 % by weight, SMD = 120 sec Step Change in Concentration

Elapsed Time (min)

Elapsed Time (min)

108

Effect of Averaging on Response Time

Increasing the number of measurements to average (navg) improves precision. However, response is dampened with increased averaging.

FBRM Count (18.6-149 m)

1450 1400 1350 1300 1250 1200 -1.0 0.0 1.0 2.0 3.0 4.0 + 1.0 % by weight, Average = 10 Step Change in Concentration

FBRM Count (18.6-149 m)

1500

1500 1450 1400 1350 1300 1250 1200 -1.0 0.0 1.0 2.0 3.0 4.0 + 1.0 % by weight, Average = 30 Step Change in Concentration

Elapsed Time (min)

Elapsed Time (min)

FBRM Count (18.6-149 m)

1450 1400 1350 1300 1250 1200 -1.0 0.0 1.0 2.0 3.0 4.0 + 1.0 % by weight, Average = 60 Step Change in Concentration

FBRM Count (18.6-149 m)

1500

1500 1450 1400 1350 1300 1250 1200 -1.0 0.0 1.0 2.0 3.0 4.0 + 1.0 % by weight, Average = 120 Step Change in Concentration

Elapsed Time (min)

Elapsed Time (min)

109

Goal of Successful Instrument Implementation

Provide a precise measurement that reflects the smallest
change of interest to the process or product parameter of concern.

Precision is of greater concern than Accuracy

110

Part 10: Correlating FBRM to Other Data

Ian Haley

112

FBRM vs. Laser Diffraction

240

220

LD Vol Mean (microns)

200

180

160

140

120

100 50 70 90 110 130 150

FBRM Mean Chord Sqr. Wt. (Microns)

113

114

Isothermal Batch: FBRM,PVM,LD & FBRM Prediction

350

Extrapolating LD data
300

250

Mean (D 4,3)

200

150

100

50

LD Mean FBRM Mean Sqr. Wt. LD Extrapolation PVM Dimension

0 0 200 400 600 800 1000 1200 1400 1600 1800

Time (s)

115

Sieve Correlation with FBRM

116

Sieve Correlation with FBRM

117

Sieve and Coulter Counter Correlation with FBRM

118

Correlation to downstream product quality or process efficiency

How close does the FBRM instrument response come to the measurement of product quality or process efficiency

Bruce A. Keiser, Ph.D. Nalco Chemical Company

119

Optimizing Filtration and Scale-up

1) A correlation is made between specific cake resistance (filterability) and both the dimension and number of particles 2) One can measuring the in-situ particle dimension and count with FBRM and predict downstream filtration rates. 3) FBRM is highly successful in predicting filtration because of its high sensitivity to changes in the number of fine particles

Optimization of Pharmaceutical Batch Crystallization for Filtration and scale-up Brian K. Johnson, Carol Szeto, Omar Davidson and Art Andrews AIChE Annual Meeting, Los Angeles, CA, November 1997

2009 METTLER TOLEDO

Relating settling rate to chord length

AJ Parker CRC for Hydrometallurgy
25

Hindered settling rate (m h -1)

20

15

200 rpm
10

100 rpm
5

0 0 100 200 300 400 500

Mean square-weighted chord length (m)

121
The Use of FBRM in the Study of Flocculation Processes Phil Fawell, CSIRO

Correlating biomass & ethanol production with FBRM

SPSC 01 (Ge et al 2004)

Correlation between first FBRM

peak (flocs) biomass
122

Correlation between second

FBRM peak (bubbles) and ethanol production

Part 11: Channel Grouping and Statistics

Ian Haley

How to Choose the Right Channel Grouping for Your Work & the Affect of the Chosen Grouping on Statistics

Channel Grouping*

124

Channel A Definition

A bin with a specific upper and lower limit in microns. Counts with a chord length measured between those limits are put in that specific channel.

125

Hardware & Channel Grouping

The FBRM hardware is based on 4096 linear 0.25 micron channels,
so the primary x-axis is this linear scale.

Software display provides user with options to group the distribution

channels.

FBRM logarithmic scales are calculated from the linear scale channel
data.

The choice between linear and log scales will change your statistics
Many other particle size instruments use hardware based on a log
scale. They do not provide statistics based on a linear scale.

126

Logarithmic Grouping
Each channel width is progressively wider than the
preceding channel width.

The distance between channel midpoints is

proportionate to their logarithms.

High resolution is provided on the small-particle side

of the distribution.

Significantly lower resolution (progressively wider

channels) is provided on the large-particle side of the distribution.

127

Linear Grouping

All channels have equal width. The distance between the channel midpoints is also equal. Equal resolution is provided throughout the distribution. Each channel has an equal probability of a count being
placed in it.

128

Logarithmic Grouping
100-Channel Log Grouping (same data set as linear):

129

Linear Grouping
100-Channel Linear Grouping (same data set as log):

130

Grouping Effect on Statistics

Comparison of statistics (linear vs. logarithmic channel grouping for the same data set):
Statistic #/sec #/meas Median Mean Mode 10th Percentile 100 Linear, 0-1000 m 501,000 1,002,000 500.00 m 500.00 m 495.00 m 223.28 m 100 Log, 1-1000 m 500,998 1,001,996 499.96 m 500.12 m 520.79 m 223.17 m % Difference 0.0004% 0.0004% 0.008% 0.024% 5.21% 0.05%

50th Percentile
90th Percentile
12.525th Percentile

500.00 m
776.72 m 250.00 m 12.525% 87.475% 204.35 m

499.96 m
778.21 m 249.96 m 12.53% 87.47% 204.72 m

0.008%
0.2% 0.016% 0.04% 0.006% 0.18%

%<250 m %>=250 m StdDev

131

Choosing Channel Grouping

The more counts per channel, the better the statistical stability.
The fewer channels chosen, the more counts there will be per channel.

The more channels chosen, the higher the potential resolution of

change and the more counts required for statistical stability.

The fewer channels chosen, the lower the potential resolution of

change and the less counts required for statistical stability.

132

Channel Grouping
Rules of Thumb:

Select the smallest channel range possible that

encompasses all the data.

Use/explore linear and log channel groupings.

133

Log v. Linear Mostly fine particles

Exp. 1: Mostly Fine - Linear Scale
70
60 50 Count 40 30 20 10 0 0 200 400 600 Dimension (m) 800 1000 Count t = 5mins t = 10mins

Exp. 1: Mostly Fine - Log Scale

70
60 50 40 30 20 10 0 1 10 Dimension (m) 100 1000 t = 5mins t = 10mins

In this example most of the particle counts are less than 100m with an
increase in the number of particles in this range over time

Using a linear scale one-tenth of the channels are for particles less than
100m not very sensitive to change in this region

Using a logarithmic scale two-thirds of the channels are for particles less than
100m much more sensitive to change in this region*

Alternatively, zoom in on the linear channel

*NOTE: The caveat is for channels narrower than the actual data (0.25 um), the data is interpolated 134
Internal usage only

Log v. Linear Mostly coarse particles

Exp 2: Mostly Coarse - Linear Scale
100 90 80 70 60 50 40 30 20 10 0
0 t = 5mins t = 10mins

Exp 2: Mostly Coarse - Log Scale

100 90 80 70 60 50 40 30 20 10 0
1 t = 5mins t = 10mins

Count

200

400 600 Dimension (m)

800

1000

Count

10 Dimension (m)

100

1000

In this example most of the particle counts are greater than 100m with an
increase in the number of particles in this range over time

Using a linear scale nine-tenths of the channels are for particles greater than
100m very sensitive to change in this region

Using a logarithmic scale one-third of the channels are for particles greater
than 100m much less sensitive to change in this region

135

Internal usage only

Log scale

136

Internal usage only

Linear scale

Isolate region of change easily when looking at a

linear scale

137

Internal usage only

Linear scale

Isolate region of change easily when looking at a

linear scale

138

Internal usage only

Part 12: Signal Aliasing

Ian Haley

Signal Aliasing

If a process shows periodic oscillations, the issue of

aliasing can be important.

Under certain conditions a combination of the process

oscillation time, instrument response time, data lag and averaging can conspire to present a misleading result

The following slides explain.

Considering Signal Aliasing

Case A (measurement interval = 30 sec)

Ideal. The output signal closely approximates the

process variable.
Process Variable Measured Data Points Instrument Output Reconstructed Signal

a) Measurement Interval = 30 sec

Process Variable

Time (minutes)

141

Measurement Precision without Aliasing

Case B (30sec MD 5 measurement average= 150 sec)

Process dynamics are maintained, but the time

lag is increased and the amplitude of the oscillations is dampened.
Process Variable
b) Averaging = 5 measurements

Time (minutes)

142

Considering Signal Aliasing

Case C (measurement interval = 120 sec)

Process dynamics are maintained, but the time

lag is increased and the amplitude of the oscillations is dampened.
b) Measurement Duration = 120 sec

Process Variable

Time (minutes)

143

Considering Signal Aliasing

Case D (measurement interval = 240 sec)

Aliasing. Process dynamics are misrepresented for a

measurement interval greater than 175 seconds (half the period of the process oscillations).
c) Measurement Interval = 240 sec

Process Variable
0.0

5.0

10.0

15.0

20.0

25.0

30.0

Time (minutes)

144

Measurement Precision without Aliasing

Case C (30sec MD 10 measurement average = 300 sec)

Aliasing does not occur, even as the total measurement

duration approaches the period of the process.

Note: At TMD = 350 seconds, the measured signal shows

no dynamics.

Process Variable

c) Averaging = 10 measurements

10.0

15.0

20.0

25.0

30.0

35.0

40.0

Time (minutes)

145

Part 13: Practical Aspects of Using FBRM: Probe Location and Orientation

Ian Haley

The Typical FBRM System

FLANGE WELDED TO DIP PIPE BY CUSTOMER EXHAUST TUBE RETAINING FLANGES

REACTOR TOP

LENGTH

ADAPTER WELDED TO DIP PIPE BY CUSTOMER

375MM 14.75IN

147

Why is Probe Location and Orientation Important?

FBRM is a point measurement Particles passing that point must be sufficiently

representative of the process for process changes to be tracked.

The instrument can only measure what it can see.

Choosing a probe location

Probe insertion: 30-60
angle to the flow

- Presents probe tip with

fresh slurry - Maintains a clean probe window

149

Probe Orientation

Probe orientation becomes more important with:

- Extremes in individual particle density (very low or very high in relation to the carrying solution). Lower solids concentration. Lower carrying solution viscosity. A larger median particle size. A wider particle size distribution. Greater particle shape deviation from a sphere.

Probe Orientation

More flexibility in probe location is allowed by:

Smaller differences between particle density and carrying solution density. Higher solids concentration (dispersed-phase liquid). A smaller median particle size. A narrower particle size distribution. Smaller differences between average particle shape and a sphere.

Ideal Probe Location in a Pipeline

Probe installed in a vertical, up-flow pipe,
three to five pipe diameters from the top of the last elbow:

- Provides an ideal length of obstruction-free

6

5 7

pipe upstream of the probe - Offers the most uniformly random and representative presentation of the dispersed phase to the measurement zone - Keeps the probe window residue-free

2 4 FLOW 3

152

Typical Pipeline Installation: FBRM D600S

153

Mounting in Stirrer Vessels

FLANGE HELD IN PLACE ON THE PROBE WITH SCREWED-ON FLANGE ADAPTOR EXTENDED PROBE HOUSING

The goal is to provide a

well-mixed, representative sample to the probe

Choose a mounting location

that will present the material of interest to the probe tip

MIXER

PROBE TIP

BAFFLE

ROTATION (FLOW DIRECTION)

154

Mounting in Stirred Vessels

Avoid areas that are not
completely homogeneous

If the probe is inserted from the

Leading Side of Baffle Mixer Rotation

top of the reactor, locate it near the leading side of the baffle

Avoid the trailing side of the

baffle, as this is where there are dead areas and eddies where particles may settle or segregate

Trailing Side of Baffle

TOP VIEW OF MIXED REACTOR

155

Down- vs. up-flow impeller

Location of the probe within the
vessel must take into account the vertical direction of the flow. (Is the flow upward or downward at the vessel wall?)

Leading Side of Baffle

Mixer Rotation

For example, if the probe is

inserted from the top of the vessel, the probe must be installed in a location where the flow is in a generally upward direction.

Trailing Side of Baffle

TOP VIEW OF MIXED REACTOR

156

Part 14: Standard Procedures

Ian Haley

D600L Performance Verification

Instrument Repeatability Assurance
Assessment of instrument measurement performance

Initial instrument OQ
Uses PVC Reference Standard & Fixed Beaker Stand Unique PVC Standard prepared and measured on new instrument in

Lasentec factory
Standard delivered with instrument to customer Standard measured and compared with factory reference data

Continued instrument PQ
Uses PVC Reference Standard & Fixed Beaker Stand Measure Standard at regular intervals and compare with factory reference

data

158

Calibration Verification through Measurement of the PVC Reference Standard

PVC Measurement:
at the Factory at startup (IQ/OQ) after 3 months (PQ)

159

D600 Window Reference Procedure

Correct focus position of the laser is important

Reproducibility Best quality data

Window Reference Position is on the window surface

Minimises effect of light scattering or refractive difference changes on

quality of data

Over time, window position may drift

Procedure for locating correct Window Reference Position
Precision micrometer used to adjust focus position

160