Lerche1 LUM

Comprehensive particle characterization
by homogeneous-start
centrifugal sedimentation technique
Dietmar Lerche, Prof. Dr. Dr.
LUM Berlin, Germany
Focus User Meeting: The Centrifugal Sedimentation Technique

Bushy House, London; 29 – 30 Nov. 2016
1. Introduction
2. In-situ visualization of separation by STEP-Technology
3. Velocity and size distribution of particles
4. Magnetophoretic velocity
5. Density determination of particles dispersed in liquid
6. Characterization of particle surface properties 1
© 2015 LUM GmbH
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Stability Testing
of Dispersions
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© 2015 LUM GmbH
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for entire life cycles
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1.Particles 2. Dispersions
Materials
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Multi-wavelength
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Real-time Accelerated Efficient and easy
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1. Foöl. LUMiReder
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www.LUMiReader-xr.com
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LUMiINSTRUMENTS are state-of-the-art
3. Composite
1.Particles 2. Dispersions
Materials
Characterization
State,
Stability
Strength
Multisampling
Multi-wavelength
SEPView 6.4 Software SEPView 7
Real-time Accelerated Efficient and easy
ISO/TR 13097, ISO 13317 ISO/TR 13097 EN ISO 4624
ASTM D7827-12 ISO 13318 DIN EN 15870
© 2015 LUM GmbH
In-situ visualization of dispersion state
by STEP-Technology
Conventional Space and Time resolved
“one point” techniques
Extinction Profiles
t1 > t0
12 channels,
l = 870, 470 nm
NIR
VL
Animation see:
X-Ray youtube
© 2015 LUM GmbH
Physical Basics
Partical velocity due to gravity fields
t = t0 t1 > t0 t2 > t1
Stokes law n = shape factor

h 2 Dr . x2. f(a) . . f(a) = hindrance function
v= t =n g RCA
9 h
RCA = CA / g = w² . r [m] / 9.81
Dr > 0, settling, sedimentation =1.1179E-3 * RPM²*r[m]
Dr < 0, creaming, flotation
Limitations: Newtonian Liquids, Re < 0.5
© 2015 LUM GmbH
Software
1. Windows 7 based with Ribbon User Interface
2. plug and play, pack and go
3. Simultaneous analysis for 12 samples
4. Individual user customization
5. Full SOP concept (Creation, capture, data analysis)
6. Seven different tools to understand (quantify) even
the most complicated dispersion::
Time lapse measurement replay
Dispersion fingerprint
Instability index
does for you
Clarification
Phase separation
visualization
Sedimentation and creaming velocities +
Particle density and size distribution
quantification
7. Windows Explorer based data management
8. Comprehensive database security and full audit log
9. Complies with 21 CFR Part 11
The Next STEP® in Dispersion Analysis & Materials Testing www.lum-gmbh.com www.dispersion-letters.com
© 2015 LUM GmbH
STEP-Technology: In-situ visualization of separation behavior
Meniscus Cell Bottom

last = Green
1 = Red
Qualitative: Fingerprints
Quantitative: Instability Index,
Fronttracking, Integration
Particle velocity and size
© 2015 LUM GmbH
Fingerprint:
Monodisperse silica particles
Concentration 10.5% (v/v)
monomodal
Silica, 280 nm,
1100 x g
Concentration 19,8% (v/v)
© 2015 LUM GmbH
Fingerprint: Polydisperse quartz particles
Polydisperse (swarm) sedimentation
Green: Last profil
Quantification by fronttracking
1.3
% 2.3
% 3.3
% 4.6
% 9%
Red: 15
% 21
%
First profile
1100 x g
Residual turbidity
Quartz: 400 nm – 10 µm 30 %
1100 x g, 20 °C
© 2015 LUM GmbH
Fingerprint: Sedimentation types
Polydisperse (Swarm) Sedimentation Zone Sedimenatation

pH = 5, z = 40 mV Aeroxide AluC pH = 9, z = 0 mV
(Evonik)
Colloidal stable Flocculated, Network forming
filling height
Colloidal stable
© 2015 LUM GmbH
In-situ visualization of phase separation
It,p
Transmission Tt,p = Instantanuous profiling of
I0
Transmission,
Clarification,
or
Concentration
changes during
particle separation
from bottom to top!
Clarification Extinction/Concentration
Ct.p = Tt,p - T0 - lg I = Et,p = e . Ct,p . d

I0
© 2015 LUM GmbH
STEP - Fingerprints
Suspension Suspension Suspension
monomodal monodisperse tetramodal monodisperse polydisperse
Suspension Emulsion Suspoemulsion

particle – particle - interaction rather monodisperse flotation and sedimentation
First transmission profil: red Last transmission profil: green

© 2015 LUM GmbH
What tell us STEP-Technology ?
Transmission Fingerprints
“Fingerprint” Quantification Particle characterization

100.0 115
Position r [mm] 110
105
50.0
100 1.3 %
2.3 %
3.3 %
95 4.6 %
9%
15 %
90.0 95.0 100.0 105.0 110.0 90 21 %
Radius [mm]
0 100 200 300 400 500

Zeit t [s]
 “Good” or “Bad” product  Phase separation

 Formulation ranking  Particle interaction
 Process optimization  Consolidation
 …  Shelf life prediction
 …
© 2015 LUM GmbH
What tell us STEP-Technology ?
Transmission Fingerprints
“Fingerprint” Quantification Particle characterization
kumulative Volumenverteilung Q3(x) [%]

100.0 115 100 3.0
diff. Volumenverteilung q3(ln x) [-]

Original concentration 110 80
2.5
no dilution, no preparation! q3(ln x)

Position r [mm]
2.0
105 60 Q3(x)
50.0
1.5
100 1.3 %
2.3 % 40
3.3 % 1.0
95 4.6 %
9% 20
0.5
15 %
90.0 95.0 100.0 105.0 110.0 90 21 %
Radius [mm]
0 0.0
0 100 200 300 400 500 0.1 1
Zeit t [s] Partikelgröße x [µm]
 “Good” or “Bad” product  Phase separation  Velocity distribution

 Formulation ranking  Particle interaction  Particle size distribution
 Process optimization  Consolidation  Density distribution
 …  Shelf life prediction  Magnetization
 …  …
© 2015 LUM GmbH
From Particle Characterization…
1.Particle properties of micro- and

nanoparticles
MICROPARTICLES NANOPARTICLES
Multi-wavelength Multi-wavelength
LUMiReader®PSA Dispersion Analyser LUMiSizer®
ISO 13317 ISO 13318

© 2015 LUM GmbH
Classical PSD analysis according to ISO 13318-2
Spatially and time resolved

transmission profiles
T E Time curve of extinction
Constant position
E   ln(T )
tmeas
r t  Dr vs
rmeas
E   ln(T )
E Q size distribution
Q3 Qext
Radial extinction profile
Constant time
Dr  vs  tmeas conversion Qext  Q3 xStokes

requires optical model Cext(xStokes)
Detloff et al., Part.Part.Syst.Charact. 23,2006,184 and Powder Technology 174,2007,50

© 2015 LUM GmbH
Determination of velocity distribution: 2 modes
Mode: Constant time E(t) Mode: Constant position
E(r)
r1 r2 Position r t1 t2 Zeit t
Important: Absolute method, no assumptions, no calibration, no gradient, constant T

Velocity v Particle Concentration

v
Distance rt - r0 Ei
v = = Q( v )i 
Time tm max (E)
Velocity distribution
20
© 2015 LUM GmbH
Fingerprint: Bimodal Silica
Space and Time Resolved Extinction Profils
X50=280 nm
100
Light transmission [%]
50
X50=545 nm
0
92 94 96 98
100 102 104 106 108 110 112 114
Position r [mm]
Mixture by volume A: 66,7%, 280nm; B: 33,3%, 545 nm
© 2015 LUM GmbH
Velocity distribution
Bimodal silica: 280 nm + 545 nm, Ratio: 2/1
1 40
35
Velocity Distribution qv(v)

0.8
Cumulative Velocity
Distribution Qv(v) [-]
30
0.6 25
[s/mm]
20
0.4 15
10
0.2
5
0 0
0.8 0.82 0.84 0.86 0.88 0.9 0.92 0.94
Velocity v [mm/s]
Sepview 6: Mode particle characterization/velocity distribution
© 2015 LUM GmbH
Particle characterization (I)
1. Velocity and velocity distribution
Optimization of milling Mono- & polydispersity
API Red
pigment
pastes
Duration,
Grinding bodies
Detection of oversized Hindrance function and shape

PMMA
PMMA+ 1% oversized
Peng He
(2010)
© 2015 LUM GmbH
Velocity distribution provides PSD for suspensions
and emulsions
1.0
Cumulative volume distribution Q 3(x)

0.8 15 min at 26.000 rpm
rotor-stator homogenizer
0.6
30 min at 24.000 rpm
rotor-stator homogenizer
0.4
0.2 Emulsion A
Emulsion B
0.0
1 10 100 1000
Particle size x in µm
Longer treatment with rotor-stator homogenizer
 Droplet Size of Emulsion B << Emulsion A
© 2015 LUM GmbH
Extinction/volume weighted distribution
18 h F  rt 
Stokes law x  ln  
x (r P  r F ) w  tm  r0 
2
Bimodal silica: 280 nm + 550 nm, Ratio: 2/1

0
- Extinktion x
 k d ln(T )
- Volume ( ) ext (x )
Q3 (x i )  1 
ln Ti
0
x
 k d ln(T )
Ratio: 2 : 1 ( )
ln T0 ext (x )
© 2015 LUM GmbH
Validation
LUMiSizer vs. PCS 173° und SEM
1
cumulative distribution Q(x) [-]
0.8
280 nm LUMiSizer
280 nm PCS 173 °
0.6 550 nm LUMiSizer
550 nm PCS 173 °
0.4 550 nm SEM
1550 nm LUMiSizer
1550 nm PCS 173 °
0.2
1550 nm SEM
0
100 1000 10000
particle size x [nm]
PCS...Photon Correlation Spectroscopy SEM...Scanning Electron Microscopy
© 2015 LUM GmbH
 Reference particles
Spherical micro silica particles with excellent shape stability and narrow size distribution
for use as sedimentation and particle size standard for optical sedimentation analyser
LUMiSizer®
 Specification
Nominal particle sizes:: 170 nm, 250 nm, 550 nm, 1100 nm
Density: 2000 kg/m³
Refractive index: 1.460
Suspension medium: 0.1 % Na4P2O7*10 H2O + 0.05 % NaN3 in ultrapure water
© 2015 LUM GmbH
Klebosol – different measurement techniques
120
LUMiSizer
Mean particle size [nm] 100 XDC
PCS
TEM
80
SEM
60
40
20
0
1508-35 150H50 1630/26
Klebosol
XDC…X-Ray disc centrifuge, PCS…Photon correlation spectroscopy (dynamic light scattering),
TEM…Transmission electron microscope, SEM…Scanning electron microscope
T. Detloff, D. Lerche: Evaluation of particle size analysis by novel centrifugal sedimentation method,
Proceedings and poster Partec 2007 Int. Cong. on Particle Technology, Nuremberg, Germany, 27–29.3.2007
© 2015 LUM GmbH
Round Robin Test, Colloidal silica nanoparticles
2 LUMiSizer
2 Analytical Ultra Centrifuges
1 X-Ray Disc Centrifuge
9 CPS Disc Centrifuges
“Interlaboratory comparison of methods for the measurement of particle size, effective particle density and zeta potential of silica
nanoparticles in an aqueous solution”, Final report, A. Lamberty, K. Franks, A. Braun, V. Kestens, G. Roebben, T. Linsinger, Joint
Research Centre Institute for Reference Materials and Measurements
© 2015 LUM GmbH
Size distribution of Au-NP and Ag-NP by
multiwavelength LUMiSizer compared to SAXS
SAXS (BAM) size: SAXS (BAM) size:

Au NP 8; 54 nm Ag 1; 59 nm
Au NP II; 18 nm Ag 2; 37 nm
Ag 3: 19 nm
Flexibility by variability of optical path and wavelength

o.p. = 1, 2 and 10 mm, l = 470 and 870 nm
Au, Ag1, Ag2: 470 nm, 2 mm Ag3: 870 nm, 10 mm
Sobisch et al., Dispersion Letters 4 (2013) 9-11
© 2015 LUM GmbH
Effect of 53 hours of storage at 25/45 °C
Ostwald ripening
100
Emulsion B (Lemon + WA)
cumulative volume weighted
80
distribution [%]
25°C 45°C
60 x10,3 220 nm 277 nm
x50,3 414 nm 893 nm
40 x90,3 4009 nm 10220 nm
NN 22317 (25°C)
20 NN 22317 (45°C)
0
100 1000 10000
particle size [nm]
Data LUMiSizer 611
© 2015 LUM GmbH
Size distribution of very polydisperse
samples by LUMiSizer NIR
Dispersed brands of MCNT
100
Iolitec
cumulative intensity weihgted

Nanocyl
80 Polytech&Net
Soft silica shell magnetic core NP
distribution [%]
Particle recharging by PEI 60
Stable-flocculation-stable
40
PEI-to-iron w/w ratio (%):
cumulative size distribution Q3 [%]
0 4 6 8 10 12
100 20
Volume weighted
80 0
300 500 1000 2000 3000 5000 10000 2000
60
equivalent particle diameter [nm]
40
20 Note: Large dynamic range

from 10 nm to 50 µm
0
(LUMiSizer)
10 100 1000 100000
Hydrodynamic diameter [nm] .
© 2015 LUM GmbH
LUMiSizer - Measurement Repetition
Median x50,0 of different colloidal silica suspensions
Klebosol 1508-35 150H50 1630/26
1 “batch” / 49 nm  0.05 nm 84 nm  0.27 nm 102 nm  0.42 nm

6 repetitions =  0.1 % =  0.3 % =  0.4 %
49 nm  0.54 nm 84 nm  0.33 nm 103 nm  0.63 nm

6 “batches”
=  1.1 % =  0.4 % =  0.6 %
T. Detloff, D. Lerche: Evaluation of particle size analysis by novel centrifugal sedimentation method, Proceedings
and poster Partec 2007 International Congress on Particle Technology, Nuremberg, Germany, 27–29.3.2007
© 2015 LUM GmbH
Particles dispersed in different sucrose solutions
0,03 % m/m 1.1 µm polysterene in 0% - 30% m/m sucrose solutions, 4°C, 2000 rpm,
Fluid density and viscosity according to Stokes taken into account
Cumulative volume distriution Q3(x) in %
100
x50,3 = 1.081 µm
 0.012 µm
80  1.07 %
0%
60 4.1 %
8.3 %
16.5 %
40
20.6 %
28.9 %
20
0
0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0
Particle size x in µm
© 2015 LUM GmbH
Particle size distribution at high concentration
Correction for only Correction for mulitiple
mulitiple scattering scattering and hindrance
100 100
Silica 175 nm
100 Silica 175 nm
distribution Q3(x) [%]
Cum. vol.-weighted particle size
Cum. vol.-weighted
Cum. vol.-weighted particle size

80 80 80
particle size
distribution Q3(x) [%]
distribution Q 3 (x) [%]

60
60 40 60
20
40 0 40
50 100 150 200 250 300
20 20 x [nm]
Particle size
0 0
50 100 150 200 250 300 50 100 150 200 250 300
Particle size x [nm] Particle size x [nm]
9.9% 7.2% 5.2% 3.2% 2.2%

1.1% 0.7% 0.4% 0.2% SEM
Detloff et al., Powder Technology 174,2007,50

© 2015 LUM GmbH
Concentration profile analysis by AUC approaches
Direct boundary method (DBM)
polydisperse silica polydisperse silica, different grades

„S“ = 0.1-0.5µm „M“ = 0.15-0.6µm „L“= 0.2…1.2µm
Walter et al., Nanoscale, measured by K. Obata, Y. Mori

7(17):6574-6587, 2015 (Doshisha University, Kyoto, Japan)
The Next STEP® in Dispersion Analysis & Materials Testing www.lum-gmbh.com www.dispersion-letters.com LUM workshop 2016,
Berlin
© 2015 LUM GmbH
Investigation of Multimodal Distributions
 Investigation of trimodal gold nanoparticle mixture with AC and dynamic

light scattering experiment (DLS)
Walter et al., Nanoscale (2015)

 Direct Boundary Model reduced noise and determines meniscus (start-line) more
accurate
 Individual sizes nicely reproduced, superior resolution by AC combined with DBM
© 2015 LUM GmbH
Particle Size Distributions obtained by
LUMiSizer
1. Velocity Distribution Qv(v), qv(v)
 Direct measurement  no calibration / no material properties
 Information directly related to separation processes
 Sufficient for quality control
 Qualitative information about particle size distribution (PSD)
2. Extinction Weighted Particle Size Distribution QInt(x), qInt(x)

 Quantitative information about particle size
3. Volume Weighted Particle Size Distribution Q3(x), q3(x)

 Quantitative information about particle size
and volume fraction of each class
 Comparison with other measurement methods possible
 Conversion into mass or number distribution
© 2015 LUM GmbH
Material properties to be known for PSD
Note: Velocity Distribution, no Parameters required!
Extinction Weighted Volume Weighted

Particle Size Particle Size Depends on
Distribution Distribution
Particle Density -
Fluid Density Temperature
Fluid Dynamic Viscosity Temperature
Particle Refractive
- Light Wavelength
Index (complex)
Temperature,
- Fluid Refractive Index
Light Wavelength
© 2015 LUM GmbH
Characterization of magnetic properties
(responsiveness) of magnetic particles
1. Superposition of ambient/high gravity fields and magnetic fields
Gravity Magnetic
fields fields
2. Determination of particle migration velocity distribution

by STEP-Technology in dependence on magnetic fields/gradients
3. Result: Magnetophoretic mobility distribution and magnetic

responsiveness of magnetic particles and assemblies.
O. Mykhaylova, D. Lerche et al., IEEE Magnetic Letters, 6 (2015), Open source
© 2015 LUM GmbH
STEP-Mag: Measurement principle
Customized LUMiReader
Magnetic fields and gradients in a
measuring window:
from 1÷200 mT and 0.5÷10 T/m)
500 µl, h=10 mm
Y
Optical window 40 mm
Resolution < 30 µm
DT = 0.1 s to hours
3 Wavelengthes
Magnetic
1000 Profiles Z Force
Different optical cells
30 °C – 60 °C d
Operation and quant-
ification by SEPView
Variable distance
MP1 magnetic nanoparticle 20µgFe/ml, between magnet sets
© 2015 LUM GmbH
Choice of the conditions for registration of the clarification in
applied magnetic fields (Sedimentation vs. Magnetophoresis)
Unstable suspension, Settling of MP6 under gravity
No magnets 84.1 mm between magnets
D470 nm averaged through the profile and normalized

Mesurment duration 15 min Mesurment duration 15 min
Microparticles MP6, 20µgFe/ml
24.5 mm
34.4 mm
43.6 mm
53.4 mm
63.4 mm
73.4 mm
no MF
0 200 400 600 800 1000

Time (s)
Magnetophoresis Sedimentation
© 2015 LUM GmbH
Magnetic particles and nano-assemblies exhibit
large range of magnetophoretic velocities
© 2015 LUM GmbH
LUMiReader-Mag: In-situ visualization of MP-migration
due to magnetic and/or gravity fields
0.4 2 magnet discs at bottom
0.3
B [T]
0.2
<B   0.1 T
0.1
0.0
-14 -12 -10 -8 -6 -4 -2 0 2 4
X [mm]
0
1st derivative of "B" [T/m]

< dB/dx  19.4 T/m
Averaged over
-20
probe height
-40
NeoDeltaMagnet® (NdFeB),
IBSMagnets NE155; -60
Magnet disc:
D=15,0 mm, h=5,0 mm -14 -12 -10 -8 -6 -4 -2 0 2 4
X [mm]
© 2015 LUM GmbH
Determination of magnetophoretic mobility distribution
MP 11,
(Monodisperse)
No dependence
on wavelength
No magnetic field Magnetic field: 0.104 T, 19.4 T/m

Integral extinction
Integral extinction
Time (s) Time (s) v (µm/s)
© 2015 LUM GmbH
Magnetophoretic mobility analysed
at different wavelengthes
MP 1,
Polydisperse, < B  0.16 T
< dB/dx  33.5 T/m
Blue light data
Averaged over
focus more on sample height
410 nm
small particles
Normalized Integral Extinction

1.2 l = 410 nm
1.0 l = 630 nm
l = 870 nm
0.8
630 nm
0.6
0.4
0.2
870 nm
0.0
-0.2
0 20 40 60 80 100
Time (s)
© 2015 LUM GmbH
Magnetophoretic velocity of SO-Mag-NP viral complexes
does not depend on viral objects
84 µgFe/ml, B = 0.421 T,
33 min
Self-assembling of MNP
with viral complexes:
SO-Mag6-12 with
Adenoviral (Ad)
and VSV-particles
© 2015 LUM GmbH
Hydrodynamic density determination
of nano- @ microparticles dispersed in a liquid
1. „Zero interpolation separation velocity”
(Archimedian) approach (ISO/WD 18747-1):
Density determination by „keeping particles in suspense“,

then density of the particle equals density of the fluid
Following slides see also: Woehlecke et al., Dispersion Letters 3 (2012) 12-15
© 2015 LUM GmbH
Determination of oil droplet density by
zero velocity interpolation approach
200
particle velocity y × viscosity h
sedimentation creaming
150
droplet density
100
in µm/s × mPa·s
Interpolation y = 0
rP = 1139,6 kg/m³
50
-50
-100
-150
1000 1050 1100 1150 1200 1250
liquid density rL in kg/m³
Birch oil droplets. LUMiSizer, 25 °C, 2 mm glass cells, Sucrose solutions
© 2015 LUM GmbH
Density, Viscosity of sodium polytungstate solution
3000 25°C 60
Viscosity h in mPa s
Density r in kg/m³
Density
Viscosity 50
2500
40
2000 30
20
1500
10
1000 0
0 20 40 60 80
Sodium polytungstate concentration in % m/m
TC-Tungsten Compounds, Germany

© 2015 LUM GmbH
Determination of PMMA particle density by
zero velocity interpolation approach
100
80
particle velocity y × viscosity h
60
40 Density does
in µm/s × mPa·s
rP = 1202 kg/m³
not depend
20 on particle size
0 and shape (not
shown)
-20
-40
-60
-80
-100
1050 1100 1150 1200 1250 1300 1350
liquid density rL in kg/m³
Continuous phase polytungstate solution

LUMiReader PSA, T = 30 °C, 10 mm PC cells
© 2015 LUM GmbH
Hydrodynamic density determination
of nano- @ microparticles dispersed in a liquid
1. „Zero interpolation separation velocity”
(Archimedian) approach (ISO/WD 18747-1):
Density determination by „keeping particles in suspense“,

then density of the particle equals density of the fluid
2. „Two separation velocity” approach

(ISO/WD 18747-2) :
Density determination by measuring separation velocities

of dispersed particles in two continuous phases with
different density
© 2015 LUM GmbH
2. Principle: „multi- separation velocity“ approach
Starting point: Stokes Law
Methodical approach: Determination of Stokes velocity of same

particles in two different continuous phases*
Monodisperse particles
v1 
(r P  rF,1 )  x 2
 w2
r
18  h1
v1  h1  rF,2  v 2  h2  rF,1
rP 
v1  h1  v 2  h2
v2 
(r P  rF,2 )  x 2  w2
r
18  h2
* First application Mc Cromeck, later Mächtle, 1984
© 2015 LUM GmbH
2. Principle: „multi-separaton velocity“ approach
0.03 % m/m 1.1 µm Polystyrene in:
0%, 4.1%, 8.3%, 16.5%, 20.6% and 28.9 % Sucrose solution, LUMiFuge RCA, 11.5 °C
Density calculated based on any pairs of sedimentation velocities (vi, vj)
1100
Particle density rP in kg/m³
v1  h1  rF,2  v 2  h2  rF,1
1080 rP 
v1  h1  v 2  h2 Density
Mean value:
1060
r= 1053 kg/m³
1040 s.d. = 0.4 %
1020 r = 1055 kg/m³

(supplier data)
1000
980
Dr12 Dr13 Dr14 Dr15 Dr23 Dr2 Dr25 Dr34 Dr35
4
Density difference Dr
© 2015 LUM GmbH
2. Principle: „Multi-separation velocity“ approach
Creaming of loaded beverage droplets dispersed in H2O and D2O
LUMiSizer data, Velocity distribution, 4000 rpm, 7°C
Cum. intensity distribution Q(v) in %

100
80
H2O D2O
(r = 997 kg/m³) (r = 1100
60 kg/m³)
40
20
0
0,1 1 10 100
Creaming velocity v in µm/s
© 2015 LUM GmbH
2. Principle: „two separation velocity“ approach
Density distribution of loaded droplets calculated based
on creaming velocity distribution in H2O and D2O
960
v1(Q( v ))  rF,2  v 2 (Q( v ))  rF,1
rP 
Particle density rP in kg/m³
v1(Q( v ))  v 2 (Q( v ))
955 Small droplets,
more dense
950
945
Large droplets,
less dense
940
0 20 40 60 80 100
Quantile velocity distribution Q(v) in %
© 2015 LUM GmbH
Density determination of nanoparticles:
different colloidal silica
in concentrated sodium polytungstate solution in H2O and D2O
55 % H2O
72 % D2O
„zero velocity extrapolation” „two velocity“
Ludox 50 nm 2012 kg/m³ 1950 kg/m³
Koestrosol 15 – 20 nm 2037 kg/m³ 2026 kg/m³
*results were obtained in cooperation with the Institute for Reference Materials and Measurements (IRMM)
which is part of the Joint Research Centre (JRC) of the European Commission (EC).
© 2015 LUM GmbH
Characterization of particle surface properties
a) Electrostatic properties
DLOV-Theory
Repulsion El.- Interaction
Total
Attraction VW- Interaction
Source: Wikimedia Common
© 2015 LUM GmbH
Electrostatic surface structure of
„electrokinetic soft particles“ are not
assessible by Zeta
By Oshima
Contradictions to Smoluchowski:
1. 3D distribution of charges (radial, circumferential), volume charge
density [As/m³]
2. 3D-surface structure comparable to Debye-Hueckel length
3. Ion penetrable surface layer of e.g. polyelectrolytes
© 2015 LUM GmbH
Decoration of plain SO-Mag5 with branched 25 kD
polyethylene imine (PEI) to recharge surface
MS = 94 emu/g iron;
PO4 sites 8.4/nm² SO-Mag5 SO-Mag6-n
Zeta = -34 +/- 2mV
25 kD branched polyethylene imine n=PEI-to-iron
w/w ratio (%)
Primary CS-MNP Final Viral-MNP-Complex

Adenovirus-MNP-Assemblies
200 nm
The Next STEP® in Dispersion Analysis & Materials Testing P TEM

harm Res.
www.lum-gmbh.com Mykhaylyk et al., AFM
www.dispersion-letters.com
DOI 10.1007/s11095-011-0661-9
© 2015 LUM GmbH
„Stability“ characterization by naked eye,
electrokinetic potential, and particle size (DSL)
Decoration of plain SO-Mag5

with branched 25 kD
polyethylene imine (PEI)
to recharge surface
n= 0 1 1.5 2 4 6 8 10 12
Electrokimetic potential [mV]
Conclusion: Ratio 4 – 5 is o.k. but clinical evaluation didIntensity

not proof!
Hydrodynamic diameter [nm]

PSD 10000
50 NumberPSD
Nanosizer data
25 1000
0
100
-25 In water
10
-50
0 5 10 15 0 2 4 6 8 10 12
Pharm Res. Mykhaylyk et al.,
PEI-to-Iron w/w ratio n [%] DOI 10.1007/s11095-011-0661-9
© 2015 LUM GmbH
PEI-to-Iron w/w ratio n [%]
0 1 1.5
z  −34 ± 2mV
Transmission (%)
2 4 6
+35 mV to +39 mV
8 10 12
SO-Mag5, n=0 Position

The Next STEP® in Dispersion Analysis & Materials Testing
(mm)
www.lum-gmbh.com www.dispersion-letters.com
© 2015 LUM GmbH
Stabilization of recharged SO-Mag for Magnetoinfection need
higher PEI decoration than predicted by Zetapotential
Behavior of concentrated (original) MNP dispersion
SO-Mag5 SO-Mag6-6 SO-Mag6-12
Particel analysis of diluted MNP dispersion

PEI-to-iron w/w ratio (%): PEI-to-Iron w/w ratio
cumulative size distribution Q3 [%]
0 4 6 8 10 12 0 12 1 1.5
120
distribution function [%]
100 2 4 6 8 10 256
100 128
Mean magnetophoretic
Volume weighted
80
64
Cumulative
80
mobility [µm/s]
60 32
60 16
40 40 8
4
20 20
2
0 0
1
10 100 1000 10000 1 10 100 1000 0 2 4 6 8 10 12
Hydrodynamic diameter [nm] Magnetophoretic mobility [µm/s] PEI-to-Iron w/w ratio [%]
© 2015 LUM GmbH
Characterization of particle surface properties
b) Hansen Solubilty Parameters (HSPs)
Good Affinity = Particles easy to disperse and stay dispersed
Bad Affinity = Particles difficult to disperse, state unstable
Characterization of solubility (1936)
Hansen:
Dispersion forces (dD),
Polar interactions (dP),
Hydrogen bonding (dH).
Prediction: 1. Measure the dispersibility of nano particles in different

solvents with known HSP.
2. Calculate HSP (HDP) for particles.
© 2015 LUM GmbH
General SOP:
3. Calculate sedimentation time (ST)
based on Integral Extinction
ST = time to
reach
E0 + 0.15
Sedimentation time
E0 = extinction of
pure liquid
© 2015 LUM GmbH
Absolute sedimentation times
of particles dispersed in
different continuous phases
General SOP: 𝑡s 𝜌m − 𝜌s
4. Relative sedimen- 𝑅𝑆𝑇 =
𝜂
tation times RST
to eliminate
density and
viscosity effects
© 2015 LUM GmbH
General SOP: 6. Calculate HSP
5. Score RST to 0, 1 HSP-value: Finn Talc 15
Score 0, 1
Normalization of RST
𝑅𝑆𝑇
𝑅𝑆𝑇norm =
𝑅𝑆𝑇max
δd =12.1 MPa0.5; δP =17.7 MPa0.5
δh =3.9 MPa0.5; R0 =9.1 MPa0.5
by HSPiP-software, Abbott
Lerche et al., Dispersion Letters (2015)
74
© 2015 LUM GmbH
Summary: Particle Characterization
by Analytical Centrifugation
with STEP-Technology
Particle sedimentation or creaming

Separation velocity distribution
Particle size distribution
Particle density (distribution)
Particle magnetization
Surface characterization of particles
© 2015 LUM GmbH
Thank you so much for spending your time
with us !!!
More Information: See exhibition by Adaptive Instruments (Colin Jenkins).

D.Lerche@LUM-GmbH.de
www.LUM-GmbH.com, www.adaptive-instruments.com
www.Dispersion-Letters.com
© 2015 LUM GmbH

Lerche1 LUM

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Comprehensive particle characterization

Focus User Meeting: The Centrifugal Sedimentation Technique

SEPView 6.4 Software SEPView 7

Units placed in 45 countries all over the world

Stokes law n = shape factor

Meniscus Cell Bottom

Concentration 19,8% (v/v)

Polydisperse (swarm) sedimentation

Green: Last profil

Polydisperse (Swarm) Sedimentation Zone Sedimenatation

Ct.p = Tt,p - T0 - lg I = Et,p = e . Ct,p . d

Suspension Emulsion Suspoemulsion

First transmission profil: red Last transmission profil: green

“Fingerprint” Quantification Particle characterization

Position r [mm] 110

0 100 200 300 400 500

 “Good” or “Bad” product  Phase separation

“Fingerprint” Quantification Particle characterization

kumulative Volumenverteilung Q3(x) [%]

diff. Volumenverteilung q3(ln x) [-]

no dilution, no preparation! q3(ln x)

 “Good” or “Bad” product  Phase separation  Velocity distribution

1.Particle properties of micro- and

ISO 13317 ISO 13318

Spatially and time resolved

Dr  vs  tmeas conversion Qext  Q3 xStokes

Detloff et al., Part.Part.Syst.Charact. 23,2006,184 and Powder Technology 174,2007,50

Important: Absolute method, no assumptions, no calibration, no gradient, constant T

Velocity Distribution qv(v)

Detection of oversized Hindrance function and shape

Cumulative volume distribution Q 3(x)

Bimodal silica: 280 nm + 550 nm, Ratio: 2/1

2 Analytical Ultra Centrifuges

1 X-Ray Disc Centrifuge

9 CPS Disc Centrifuges

SAXS (BAM) size: SAXS (BAM) size:

Flexibility by variability of optical path and wavelength

cumulative intensity weihgted

20 Note: Large dynamic range

Median x50,0 of different colloidal silica suspensions

Klebosol 1508-35 150H50 1630/26

1 “batch” / 49 nm  0.05 nm 84 nm  0.27 nm 102 nm  0.42 nm

49 nm  0.54 nm 84 nm  0.33 nm 103 nm  0.63 nm

Cum. vol.-weighted particle size

distribution Q 3 (x) [%]

9.9% 7.2% 5.2% 3.2% 2.2%

Detloff et al., Powder Technology 174,2007,50

polydisperse silica polydisperse silica, different grades

Walter et al., Nanoscale, measured by K. Obata, Y. Mori

 Investigation of trimodal gold nanoparticle mixture with AC and dynamic

Walter et al., Nanoscale (2015)

2. Extinction Weighted Particle Size Distribution QInt(x), qInt(x)

3. Volume Weighted Particle Size Distribution Q3(x), q3(x)

Note: Velocity Distribution, no Parameters required!

Extinction Weighted Volume Weighted

Fluid Density Temperature

Fluid Dynamic Viscosity Temperature

2. Determination of particle migration velocity distribution

3. Result: Magnetophoretic mobility distribution and magnetic

D470 nm averaged through the profile and normalized

Microparticles MP6, 20µgFe/ml

0 200 400 600 800 1000

1st derivative of "B" [T/m]