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Methods to determine particle properties Chapter 7

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What ranges do we need to measure

Particle Characterization: Light Scattering Methods

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Principles for different methods

1. Visual methods (e.g., optical, electron, and scanning electron microscopy combined with image analysis) 2. Separation methods (e.g., sieving, classification, impaction, chromatography) 3. Stream scanning methods (e.g., electrical resistance zone, and optical sensing zone measurements) 4. Field scanning methods (e.g., laser diffraction, acoustic attenuation, photon correlation spectroscopy) 5. Sedimentation 6. Surface methods (e.g., permeability, adsorption)
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Visual methods Microscopy

Principe of operation Optic or electronic measures Two dimensional projection

Benefits Simple and intuitive Give shape information Reasonable amount of sample

Projection screen or circles Image analysing programs

Measures Feret diameters Equal circles Size range- 0.001-1000 Qm Gives number average,or area average

Drawbacks Statistic relevance tedious if image analyse can not be used Risk for bias interpretation Difficult for high concentrations Sample preparation might be difficult

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Visual methods Estimations by hand

Bjrn B rule of thumb estimate the size of the third largest particle Compare to a known set of circles and count the number of particles in each group. Choose a direction and use 0 and 90 degrees feret diameters Reliability Blind your samples Count enough particles
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Visual Different types of microscope

Light microscope (1-1000 Qm) Fluorescence microscope Confocal laser scanning microscopy Electron microscope SEM (0.05-500 Qm) TEM (-0.1 Qm)

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Visual methods Image analysis

Easy to be fooled Difficult to get god contrast and separation between particles The human eye is much better than any image analysing tool in detecting shapes Example in Image J

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Separation methods

Sieving

Principe of operation stack of sieves that are mechanical vibration for pre-decided time and speed Air-jet sieving - individual sieves with an under pressure and and air stream under the sieve which blows away oversize particles Measures - Projected perimetersquare, circle

Benefits Simple and intuitive Works well for larger particles Drawbacks Can break up weak agglomerates (granulates) Does not give shape information Need substantial amount of material Needs calibration now and then

Size range - 5-125 000 Qm Gives weight average

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Separation methods Powder grades according to BP Description Sieve diameter Qm Sieve that do not allow more than 40% to pass Qm 355 250 180

Coarse Moderate coarse Moderate fine Fine Very fine

1700 710 355 180 125

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Separation methods Chromatography

Measures Hydrodynamic radius Principe of operation Size exclusion (SEC GPC):

Benefits
Short retention times Separation of different fractions Drawbacks Risk for interaction Need detector

porous gel beads Size range -0.001-0.5 Qm

Hydrodynamic Chromatography (HDC)

Quick ime and a decompressor are needed to see this picture.

Flow in narrow space Size range capillary -0.0250 Qm packed column 0,03-2 Qm

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Separation methods FFF Field flow fractionation

Size range 30nm- 1Qm Principe of operation Flow in a chanel effected by an external field

Heat Sedimentation Hydraulic Electric Field

Benefits No material interaction High resolution Good for large polymers Drawbacks Few commercial instrument Still in development stage

uickTime and a decompressor are needed to see this picture.

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Separation methods Cascade impactores

Measure- Aerodynamic volume, Principe of operation The ability for particles to flow an air flow Size range normally 1-10 Qm

uick ime and a decompressor are needed to see this picture

Benefits Clear relevance for inhalation application Can analyse content of particles Drawbacks Particles can bounce of the impactor or interact by neighbouring plates Difficult to deaggregate particles
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Stream Scanning Methods Coulter counter

Measures - Volume diameter

Gives number or massavarge

Size range - 0.1-2000 Qm Principe of operation

Measurement on a suspension that is flowing through a tube, when a particle passes through a small hole in a saphire crystal and the presence of a particle in the hole causes change in electric resistance

Benefits measure both mass and population distributions accurately Drawbacks

Risk for blockage by large particles, More than one particle in sensing zone Particles need to suspended in solution
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Methods to measure particle size Light scattering

Measures - Area diameter or volume diameter, polymers Radius of gyration or molecular mass Principal of operation Interaction with laser light the light are scattered and the intensity of the scattered light are measured Two principals

Static light scattering Dynamic light scattering

Size range- 0.0001-1000 Qm

Benefits Well established instruments are easy to operate yield highly reproducible data Drawbacks Diluted samples-changes in properties Tendency to Oversize the large particles Over estimates the number of small particles

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Static light scattering

Particle size information is obtained from intensity of the scattering pattern at various angles. Intensity is dependent on wavelength of the light Scattering angle particle size relative index of refraction n of the particle and the medium.

Micromeritics Technical Workshop Series (Fall 2000) 16

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Light scattering Small and large particles

uickTime and a decompressor are needed to see this picture.

uickTime and a decompressor are needed to see this picture.

uickTime and a decompressor are needed to see this picture.

Small particles one scattering center < 10 nm Scatter intensity independent of scattering angle (Rayleigh scattering)

are needed toand a decompressorsee this picture. uickTime

Large particles multiple scattering centres Scattering depend on angle and gives diffraction pattern

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Light scattering Mie theory

The complete solution to Maxwells equation for homogeneous sphere

Incident light of only a single wavelength is considered. No dynamic scattering effects are considered. The scattering particle is isotropic. There is no multiple scattering. All particles are spheres. All particles have the same optical properties. Light energy may be lost to absorption by the particles.

Applicable for all sizes Needs to know the refractive index to calculate the size
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Light scattering Fraunhofer theory

Treats that the particle as completely adsorbing disc does not account for light transmitted or refracted by the particle. Only applicable to particles much larger than the wavelength of the light Do not need to know the refractive index Much simpler math

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Light scattering Dynamic light scattering

uickTime and a decompressor are needed to see this picture.

uickTime and a decompressor are needed to see this picture.

Particle size is determined by correlating variations in light intensity to the Brownian movement of the particles Related to diffusion of the particle

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Light scattering Dynamic light scattering the decay function

Monodisperse particles gives a single exponential decay rate Polydisperse samples the self diffusion coefficient is defined by a distribution function that includes number density of species mass M particle form

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Methods to measure particle size Sedimentation

Measures - Frictional drag diameter, stoke diameter

2d 2 g(V v! 18Q

Gives weight average

Principe of operation Sedimentation in gravitational field Sedimentation due to centrifugal force Size range -0.05-100 gm)

Benefits Simple and intuitive Well established Drawbacks Sensitive to temperature due to density of media Sensitive to density difference of particles Orientation of particles to maximize drag bias in the size distribution toward larger particle
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Methods to measure particle size Sedigraph

QuickTi c r ss r t s t is ictur .

              

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Surface area analyse permeability

Measures: Specific area Principe of operation Measures the pressure drop in a particle bed
s(m kg) !
2

1 I3 (P * * kQV 2v (1  I) 2 L

Benefits Simple equipment Relevant for many applications Drawbacks Has to know

Conditions

Porosity Kozenys constant

Laminar flow Know Kozenys constant Homogenous particle bed

Needs uniform density of particles

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Surface area analyse Gas adsorption

Principe of operation Measures the adsorption of gas molecules

Remove adsorbed molecules Introduce gas Measure pressure differences

1 b 1 P P !  * n(P  P0 ) bn m bn m P0

Range 0.01 to over 2000 m2/g. Benefits Well established High precision Gives inner pores Drawbacks Over estimation of available area Experimental difficulties


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