Selecting the Best Particle Size Analyzer for your Application

Finding the Best Particle Characterization
Analyzer for your Application

Mark Bumiller
mark.bumiller@horiba.com

© 2010 HORIBA, Ltd. All rights reserved.

First Questions
Why is the measurement being made?
How will the data be used?
Need to match historic data?
Is particle size only enough information?
 Shape, zeta potential, mW

Who will use the instrument?
R&D, QC, students, “the third shift”?

How many samples per day/week/month?


Is it a Particle Size Problem*?
*From Pohl, M., Choosing the right
Particle size analyzer, Powder and
Bulk Engineering, Feb 2008

Technical Problem

Is it a material characterization issue?
Yes

No

Is it a particle characterization issue?
Try other
Analytical
Techniques

No

Use Appropriate
Characterization
Technique


Yes

Is it a Particle Size Problem*?
 Customers complain this batch doesn’t
perform like previous product
 Investigate specific behavior & look for possible
causes
 Chemical or physical difference?

 I have a powder flow problem
 Both particle size & shape influence flow
 But so do other parameters (water content)

 This product isn’t stable
 Could be size and/or zeta potential
 Cause could come from surface chemistry

Choosing the Technique
From Pohl, M., Choosing the right
Particle size analyzer, Powder and
Bulk Engineering, Feb 2008

Is it a particle characterization issue?

Yes

Which technique is most appropriate?
Particle
Size

What are
possible
approaches?

Surface
Area

Zeta
Potential

Porosimetry

Other
Techniques

Particle size distribution is most
common problem/interest


Particle
Counting?

Contamination?
Filtered?
Need conc.?

Particle Counting
Need to know particles/volume
Implies measuring contamination,
typically in a filtered fluid
Particle size analyzers measure your
product, not contamination
Air: use airborne particle counter
Liquid: use liquid particle counter or trap
particles on filter and inspect filter
– Coulter counter, light obscuration, some
dynamic image analyzers


Electrical Sensing Zone
Coulter Principle
 Based on change in
conductivity of aperture as
particle traverses.
 Requires conducting liquid.
 Directly measures particle
volume and counts.
 High resolution
 Used for blood cell counting
now more than industrial
applications


Light Obscuration
 Light Obscuration:

Liquid Flow
Sensing Zone

Light Source
Detector

Light is blocked by single particles as
they traverse the light beam

 Need to know concentration
 Filtered liquids
 Particles/ml @ size


 Particles in water, oil
 USP<788> testing
 High resolution histogram

USP<788> Filter Testing

Load Sample(s)

PSA300 Image Analyzer

Scan Filter

Count/Size all Particles

USP<788> Filter Testing

Mosaic function stitches all scans
Complete fiber is analyzed
Generate Report


Particles or Water in Oil

Flow chambers
50um – 1mm
2mm-6 mm


Droplets vs. Particles

Droplets

Particles

Distinguishing between two would be easy if they looked like this


Droplets vs. Particles

Agglomerated droplets


Sand

 User selects examples
of droplets, iron sulfide,
sand particles
 Software looks at many
size/shape values
 Chooses how to
discriminate
 Bins each particle by
type, counts
 Can calculate ppm


ppm

Pattern Matching Algorithm

time

Surface Area
If surface area influences product
performance
SA-9600: 0.1-2000 m2/g
BET Multi or single point
Quick, easy to use


Particle Sizing Possible Techniques
What are possible techniques?

Direct
Observation

Ensemble
Averaging

Individual
Particle
Counting

Indirect
Observation

Possible
Techniques

Possible
Techniques

Possible
Techniques

Possible
Techniques

Sedimentation

Electrical
Conductivity

Fisher
Sub-sieve
Size

Static Image
Analysis

Static
Light
Scattering

Single Particle
Optical
Spectroscopy

Hegman
Grind
Gauge

Dynamic Image
Analysis

Dynamic
Light
Scattering

Light Scattering
Non-Orifice

Blaine
Permeameter

Optical
Microscope

STEM

AFM

Acoustic
Spectroscopy


Many
Others

Possible Criteria Effecting the Selection








Type of data desired
Sample particle size range
Sample concentration
Sample behavior
Sample type
Industry acceptability


Type of Data Desired
 Particle size (average)
 Particle Size distribution (D10, D50,
D90)
 Particle zeta potential
 Particle shape
 Surface area


Sample Type






Dry powder, suspension, emulsion, aerosol
Size range, upper & lower limit
Sample chemistry
Particle shape
Previous analysis technique


Sample Behavior
 Is the typical sample stable?
 Is the sample stable at elevated or
reduced temperatures?
 Can the sample be diluted without
changing the particle size?
 Is the sample stable following dilution?
 Does the sample adhere to glass, plastic,
metal, etc.?


Industry Acceptability
 Is there an ASTM or ISO Standard already
in place?
 Is there a trade association standard?
 Is there a supplier or end-user
specification?
 Does it meet company standards?
 Is the technique consistent with a QA
procedure development

Size Range by Technique
•ELECTROFORMED MESH •SIEVES
•CENTRIFUGAL

SEDIMENTATION
•PERMEABILITY
•MICROSCOPY
•ELECTRICAL CONDUCTIVITY
•LIGHT OBSCURATION

•DYNAMIC LIGHT SCATTERING
•STATIC LIGHT SCATTERING
0.01µ

0.1µ


1µ

10µ

100µ

1000µ

Size Range by HORIBA Technique


From PQRI Group*

*PQRI Recommendations on Particle-Size Analysis of Drug Substances Used in Oral Dosage Forms
JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 96, NO. 6, JUNE 2007


Sieves
 Weight % sample caught on known
screen sizes
 Solid particles 20 m – 125 mm
 Low equipment cost
 Direct measurement method
 Some automation/calculation available

More information available through www.retsch.com

Sedimentation
Stokes Law
D=

Sedimentation of same density
material in a viscous medium

18 µ Vp
(A - B) G

Vp
G
A
B
D
µ

=
=
=
=
=
=

Settling velocity of discrete particle
Gravity constant
Density of Particle
Density of Carrier Fluid
Diameter of discrete particle
Viscosity of Carrier Fluid

Time

Disc centrifuge

Manual Microscopy
 Inspect particles in a given
field of view
 Repeat process for a
number of fields
 Use graticule to obtain size
 Get size, shape sometimes
count information
 Referee technique: direct
Advantages:
Simple
Inexpensive
Can see shape

Disadvantages:
Slow
Measures very few particles
Very tedious

Need Shape Information?
Two Image Analysis Approaches:
Dynamic:
particles flow past camera


Static:
particles fixed on slide,
stage moves slide

Basic Operations
Objective &
camera

Image Acquisition
and enhancement

Subjective or
automatic

Thresholding

Decisions or
black box

Image Processing

Measurements


Focus, take picture

Separate particles from background

Edge definition, fill particles,
Separate touching particles
Create size & shape distributions

Static Image Analysis: PSA300

Sample preparation
device necessary*
to disperse powders
onto slide(s).
Load powder into nozzle,
pull vacuum, release.
*unless large free flowing powder

Load slide onto automated stage
Move slide, stop, take image, repeat
Higher magnification = smaller particles

Static Image Analysis Applications
Powders, suspensions 0.5 – 1000 µm
Size and shape information
Also count when analyzing filters
API’s

Excipients

Lotions

Aerosols

Widely used in pharmaceutical R&D
But also wherever shape info. required
Abrasives

Filters

Dynamic Image Analysis: CAMSIZER
Size and shape from 30 µm – 30 mm
Particles fall from vibrating
tray through inspection
zone. Two cameras
take images of
particles


Analyze images
Size and shape
distributions

Replace Sieve Analysis

Similar size range, Xcmin matches sieve results, quick + shape


Dynamic Image Analysis Applications
Powders 30 µm – 30 mm
Glass beads

Sugar spheres

Fertilizers

Catalysts

Coating thickness
q3 [%/mm]

Q3 [%]
CoMo2-0,1%Absch_xc_min_001.rdf

90

180

80

160

70

140

60

120

50

100

40

80

30

60

20

40

10

20

0

0
1.4

1.6

1.8

2.0

2.2

2.4

x1

2.6

2.8

x2

x [mm]

Need Widest Dynamic Range?

Laser Diffraction
•Particle size 0.01 – 3000 µm
•Converts scattered light to
particle size distribution
•Quick, repeatable
•Most common technique
•Suspensions & powders


Need Widest Dynamic Range?
Suspension

Powders

30 nm silica

Coffee Results
14

100

90
12
80
10

70

60
q(%)

8
50
6
40

30

4

20
2
10

0
10.00

100.0

1000
Diameter(µm)


0
3000

Sample Volume

10 ml

2mL

35 ml

200 ml

•Wide range of sample cells depending on application
•High sensitivity keeps sample requirements at minimum
•Automatic solvent fill


Small Sample Volume (MiniFlow)

Colloidal Silica (weak scatterer)
Median (D50): 35 nm
Sample Amount: 132 mg

Magnesium Stearate
Median (D50): 9.33 μm
Sample Amount: 0.165 mg

Bio-degradable Polymer
Median (D50): 114 μm
Sample Amount: 1.29 mg


Paste Cell

Unique to HORIBA


Dry Powders
Measure as dry powder using dry
powder feeder
Measure in natural state
Quick, easy, no clean up
Increase air pressure to aid dispersion
Minimum size ~ 0.25 µm

Disperse powder in liquid
Liquids reduce surface tension, add
surfactant, use ultrasound to aid dispersion
Lower detection limit (<30 nm)

Powder: Wet vs. Dry?
POWDER DISPERSION PROCEDURES
Obtain Representative
SAMPLE

Reactivity Check
Reactive in Water
and Organic Liquids

Not Reactive
in Water

Reactive in Water,
Not Reactive in
Organic Solvents
Soluble?

DRY
ANALYSIS

Water Solubility?

Organic Liquid Check
Not Reactive,
Insoluble

Insoluble

Select
Distilled/D.I. Water

Select
Organic Liquid

Reactive
or
Soluble

DRY
ANALYSIS

No
Wettable?

Select
Surfactant

Yes
Not Dispersed

Dispersed
Dispersion Check

Dispersed
Ultrasonic Energy
Treatment

Dispersion Check

Not Dispersed

Select Different
Surfactant


WET SLURRY
ANALYSIS

Dry Powder Feeder Reproducibility
Direct flow of powder down to cell
Auto feedback controls feed rate
Constant mass flow = robust results


Automatic ISO13320
calculations

HORIBA Diffraction Systems
LA-950: 0.01-3000 µm wet or dry
Modular, range of samplers, advanced
software including Method Expert

LA-300: 0.1 – 600 µm wet only
Smaller, more portable, less expensive


Measuring at Process Concentration
Light scattering typically requires dilution
Does PSD change with dilution?
Concern when studying dispersion
Some samples are better analyzed without
any alteration
 Implies no sample preparation
 Dispersion stability studies often include zeta
potential and other parameters





 Size, zeta potential, pH, conductivity, temp,
surfactant concentration, titration studies


Acoustic Spectroscopy
Pulsed electric field applied
to sample
Sound interacts with sample
Attenuation converted to size

Advantages:
 Can accommodate high
sample concentrations
 Also zeta potential, pH,
conductivity, conc.


Applications:
 Emulsions &
suspensions
 Dispersion stability
with zeta potential

Dispersion Stability
 Want stable dispersion
 Either suspensions or
emulsions
 Suspensions sediment &
flocculate
 Emulsions phase
separate, creaming or
coalescence

good

bad

good

bad

Zeta Potential
 If surface has + charge,
then - ions attracted to
surface
 + ions attracted to – ions,
builds electric double
layer
 Slipping plane: distance
from particle surface
where ions move with
particle
 ZP = potential (mV) at
slipping plane

Electroacoustics – Zeta Potential
Piezo crystal

Electrodes

A
Zeta Potential Probe
ColloidVibrationCurrent

 p  m
 d P
CVI  C
m

DynamicMobility
..

 m  o (  p   s )  m K s
d 
 ( p   m ) s K m

Hardware Configurations

Size
Zeta
Conductivity
Titration
burettes


pH Titration of Rutile 7%vl & Alumina 4%vl
85 nm

300 nm
PSD unstable @ IEP
aggregates form


DT-1201 System
 Particle size analysis 5 nm – 1000 m
 High concentration ~2- 40 wt%
 Dispersion stability studies
 Used in formulation to study effect of surface
chemistry on product stability and performance

 Fantastic research tool or just
best option for particle size
without dilution


Dynamic Light Scattering (DLS or PCS)
Most common technique for sub-micron sizing
Range: 1 nm – 1 m*

Frequency Shifted Signal

Frequency-Intensity
Distribution

Stokes-Einstein R H 
* Density dependent, when does settling become prominent motion?

kT
6  D

Zeta potential Measurement
Mobility

U

＋

－

 d

2 E・ n・ sin  2 
・

U
Zeta potential

ν0


ν0+νd

3U・ 
ζ　

2・ f (ka)

DLS Applications
 Particle size of suspension 1 nm – 1 m
 Both ends extended depending on sample

 Zeta potential of dilute suspensions
 Only suspensions, small particles

 Molecular weight, second virial coefficient
Proteins


Nanoparticles

Biomolecules

Conclusions
One general purpose particle size
analyzer: laser diffraction
Flexible, quick, easy

Want additional shape information:
image analysis
Static: 0.5-1000 µm
Dynamic: 30 µm – 30 mm
– Replace sieve analysis

All particles < 1 µm: DLS, acoustics

Conclusions
Measure without dilution: acoustic
spectroscopy: 3 nm – 1000 µm
Size, zeta potential, conductivity, microrheology

Talk to our applications experts
Have samples run on system of interest
It’s rare for one application to be equally
suited to more than one instrument


Selection Table


Why Only One Method?
Good idea to have several techniques
If > 1 µm use microscope for reference
Sieves useful to confirm presence of
large particles or to remove particles too
large for another technique
Beware: Use a different technique = get
a different answer
It is important to understand how
analysis methods differ in order to know
how to compare data

Thank-you
Visit the website: www.horiba.com/us/particle
Product information
Many application notes
Previous webinars


Selecting the Best Particle Size Analyzer for your Application

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Selecting the Best Particle Size Analyzer for your Application