1 L U N D U N I V E R S I T Y Methods to determine particle properties Chapter 7

2 L U N D U N I V E R S I T Y What ranges do we need to measure Particle Characterization: Light Scattering Methods

3 L U N D U N I V E R S I T Y 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)

4 L U N D U N I V E R S I T Y

5 Benefits – “Simple” and intuitive – Give shape information – Reasonable amount of sample Drawbacks – Statistic relevance “tedious” if image analyse can not be used – Risk for bias interpretation – Difficult for high concentrations – Sample preparation might be difficult Visual methods Microscopy Principe of operation – Optic or electronic measures – Two dimensional projection Projection screen or circles Image analysing programs Measures – Feret diameters – Equal circles Size range  m Gives number average,or area average

6 L U N D U N I V E R S I T Y Visual methods Estimations by hand Björn 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

7 L U N D U N I V E R S I T Y Visual Different types of microscope Light microscope (  m) Fluorescence microscope Confocal laser scanning microscopy Electron microscope – SEM (  m) – TEM (Å-0.1  m)

8 L U N D U N I V E R S I T Y 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

9 L U N D U N I V E R S I T Y 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 perimeter- square, circle – Size range  m Gives weight average 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

10 L U N D U N I V E R S I T Y Separation methods Powder grades according to BP Description Sieve diameter  m Sieve that do not allow more than 40% to pass  m Coarse Moderate coarse Moderate fine Fine180 Very fine125

11 L U N D U N I V E R S I T Y Separation methods Chromatography Measures – Hydrodynamic radius Principe of operation – Size exclusion (SEC GPC): porous gel beads Size range  m – Hydrodynamic Chromatography (HDC) Flow in narrow space Size range capillary  m packed column 0,03-2  m Benefits – Short retention times – Separation of different fractions Drawbacks – Risk for interaction – Need detector

12 L U N D U N I V E R S I T Y Separation methods FFF Field flow fractionation Size range 30nm- 1  m Principe of operation – Flow in a chanel effected by an external field Heat Sedimentation Hydraulic Electric Benefits – No material interaction – High resolution – Good for large polymers Drawbacks – Few commercial instrument – Still in development stage Field

13 L U N D U N I V E R S I T Y Separation methods Cascade impactores Measure- Aerodynamic volume, Principe of operation – The ability for particles to flow an air flow Size range normally 1-10  m 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 de- aggregate particles

14 L U N D U N I V E R S I T Y Stream Scanning Methods Coulter counter Measures - Volume diameter Gives number or massavarge – Size range  m – 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

15 L U N D U N I V E R S I T Y 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  m 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

16 L U N D U N I V E R S I T Y 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)

17 L U N D U N I V E R S I T Y Light scattering Small and large particles Small particles one scattering center < 10 nm Scatter intensity independent of scattering angle (Rayleigh scattering) Large particles multiple scattering centres Scattering depend on angle and gives diffraction pattern

18 L U N D U N I V E R S I T Y 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

19 L U N D U N I V E R S I T Y 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

20 L U N D U N I V E R S I T Y Light scattering Dynamic light scattering Particle size is determined by correlating variations in light intensity to the Brownian movement of the particles Related to diffusion of the particle

21 L U N D U N I V E R S I T Y 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

22 L U N D U N I V E R S I T Y Methods to measure particle size Sedimentation Measures - Frictional drag diameter, stoke diameter Gives weight average – Principe of operation Sedimentation in gravitational field Sedimentation due to centrifugal force – Size range £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

23 L U N D U N I V E R S I T Y Methods to measure particle size Sedigraph

24 L U N D U N I V E R S I T Y Surface area analyse permeability Measures: – Specific area Principe of operation – Measures the pressure drop in a particle bed – Conditions Laminar flow Know Kozenys constant Homogenous particle bed Benefits – Simple equipment – Relevant for many applications Drawbacks – Has to know Porosity Kozenys constant – Needs uniform density of particles

25 L U N D U N I V E R S I T Y Surface area analyse Gas adsorption Principe of operation – Measures the adsorption of gas molecules Remove adsorbed molecules Introduce gas Measure pressure differences Range – 0.01 to over 2000 m2/g. Benefits – Well established – High precision – Gives inner pores Drawbacks – Over estimation of available area – Experimental difficulties