This presentation reviews the way flow can effect crystallisation. The presentation also reviews different ways continuous processing can be achieved. Continuous crystallisation is of relevance to a number of technologies including pharmaceutical manufacture.

1. 1
Crystallisation, Flow and Continuous
Processing.
By
Professor Malcolm Mackley
Department of Chemical Engineering and
Biotechnology.
University of Cambridge
UK
Strathclyde 2014
A story that started for me in 1970

2. 2
Crystallisation Flow
Nucleation
Growth
Morphology
Supersaturation Pressure
Supercooling Stirring
Simple shear flow
Extensional flow
Complex flows
Driving forces
Key factors
Flow induced crystallisation depends on all of the above

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Types of Flow
Laminar or Complex flow
Go with the flow!
where
 = density
u = velocity
D = a length scale
h = viscosity
Re < 1 𝐿𝑎𝑚𝑖𝑛𝑎𝑟 𝑅𝑒 ≈ 1 − 1000 𝐶𝑜𝑚𝑝𝑙𝑒𝑥 𝑅𝑒 > 1000 𝑇𝑢𝑟𝑏𝑢𝑙𝑒𝑛𝑡
Reynolds number Re =
𝜌 𝑢 𝐷
𝜂

4. 4
Types of Flow 1
Simple shear (laminar)
Simple shear is not so simple because the flow contains a rotational component
Couette Viscometer
Strain rate 𝛾 =
𝑑𝑢
𝑑𝑦
Velocity u
Distance y

5. 5
Types of Flow 2
Extensional flow (laminar)
Pure extensional flows are not easy to generate in the laboratory
Extension rate 𝜖 =
𝑑𝑢
𝑑𝑥
Velocity u
Distance x
Opposed jets

6. 6
Types of Flow 3
Complex Flows. Time dependant combinations of
simple shear and extensional flow.
Taylor Couette Flow Turbulence
Stirred vessels
Oscillatory Flow Mixing (OFM)
“turbulent” flows are a complex time dependant combinations
of simple shear and extensional; flow

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Solution Crystallisation of Polyethylene (PE)
Polyethylene is chemically the simplist polymer and also the worlds
largest tonnage polymer
“Polymer Single crystals”
Sir Charles Frank Prof Andrew Keller
0.1% PE/Xylene @ 110 0
C 24 hrs @ 80 0
C

8. 8
Solution Crystallisation of Polyethylene (PE)
The structure and morphology of Polyethylene crystals is a work of art
“Perfect Single Crystals”
Self seeding of PE crystals; uniform size
110 0
C 24 hrs @ 80 0
C 4 0
C/hr to 100 0
C 24 hrs @ 80 0
C
D.C.Bassett (1960s)

9. 9
Flow induced PE solution crystallisation
Simple shear, no chain stretching but Extensional Flows stretch’s chains
Simple shear Couette flow. No crystallisation
Taylor vortex Couette flow. Fibrous crystallisation

10. 10
Flow induced PE solution crystallisation
Shish Kebabs are “tasty”; a combination of extended and folded chain crystals
Shish Kebab Fibrous crystals

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Flow induced PE solution crystallisation
Millions of PE polymer chains ordered to form beautiful structures
No Flow
With flow
Chain folded
Single crystals
Shish kebab
Fibrous crystals

12. 1. Can enhance crystal nucleation rates.
2. Can enhance crystal growth rates.
3. Can change crystal morphology.
Flow Induced Crystallisation
Flow usually influences crystallisation in some sort of way
Flow

13. Flow Induced Crystallisation
Some things in life are not simple
Think
• Nucleation conditions (T, P, Composition )
• Growth conditions (T, P, Composition )
• Surface area/ volume ratio.
Surface material of vessel and internals.
Boundary conditions, heterogenieties
• Type of flow
• Batch or continuous

14. Batch vs Continuous Crystallisation
Batch Continuous
• Easy, flexible and universal
• Batch number easy
• Accepted by legislation authorities
• Simple stirrers
• Variation between batches
• Complex flow
• Thermal and shear profiling
not easy to control
• Scale up is tricky
• Not continuous
• Continuous!
• Thermal, chemical and flow
profiling relatively easy
Laminar or Complex flow
• Scale up easier than batch
• Continuous requires front
and back end handling
• Relatively novel and so
acceptance by Companies
and legislation more difficult

15. Batch Crystallisation
No flow Magnetic stirrer Overhead stirrer
Stirred vessel crystallisers can be 500 ml – 20 tonnes in size

16. Continuous Flow Crystallisation
Stirred Vessels
Residence Time Distributions (RTDs)
Chemical Engineers “love” RTDs
Residence time
Fraction
of
tracer
Fraction
of
tracer
Residence time
“Plug flow”
Continuous Stirred Tank
(CST)
𝜏 𝑚 = 𝑚𝑒𝑎𝑛 𝑟𝑒𝑠𝑖𝑑𝑒𝑛𝑐𝑒 𝑡𝑖𝑚𝑒
𝜏 𝑚

17. 17
Ways of achieving “plug” flow.
• Stirred tanks
in series
• Turbulent
tubular flow
• Narrow bore
laminar flow
• Oscillatory
Flow Mixing
(OFM)
Very long tube
v= m/s
Chemical Engineers
normal choice
Long thin tube, less
than about 1mm dia
“There is more than one way to skin a cat.”

18. 18
More ways of achieving plug flow.
• Static mixer
tubes
• Slug flow in
tubes
• Taylor Couette
flow
• Plastic microcapillary
film (MCF)
Prof Woo-Sik Kim
Korea
Chemical Engineers like tubes and vessels

19. 19
Oscillatory Flow Mixing (OFM)
Inertial mixing flow. Tube diameters, mm - cms
A question of scale!
g/hr, Kg/hr, tonnes/hr
“Discovered” in 1980s

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Oscillatory Flow Mixing (OFM) 1980s;
process
Inventive steps 1979- 1982
Air turbine
generates power

21. 21Chem Eng Sci 1989
Inventive steps. Plug flow residence time

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Heat transfer Chen Eng Sci

23. 23
Mass transfer Cheng Eng Sci

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- Oscillator Base Unit
- Feed inlet section
- Shell and baffled tube vessels
- Product outlet section
Development Stage
Chem Eng Oscillatory Flow Reactor (OFR)
Dr Paul Stonestreet

25. 25
Net Flow In
Net Flow
Out
Biodiesel Reaction Progress
along Reactor

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Prof Xiongwei Ni
Commercialisation

27. 27
Further development OFM Meso Reactor
Nuno Reis, Minghzi Zheng
System configuration
Mesotube,
diameter d
Smoothconstrictions:
spacing3d
Minimumconstriction
diameter 0.4d
2000s
 45º
35 mm, V  4.5 mL
 45º
35 mm, V  4.5 mL
a)
b)
L
d d0


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0 100 200 300 400 500 600 700 800 900
0
0.002
0.004
0.006
0.008
0.01
0.012
0.014
0.016
0.018
0.02
Time (s)
E(t)(-)
b) Exp-E(t)1
Exp-E(t)2
Exp-E(t)3
Fit-E(t)2
(1->2)
Fit-E(t)3
(1->3)
Fit-E(t)
3
(2->3)
Continuous Flow Oscillatory Mesoreactor
Minghzi Zheng
Plug flow meso reactor

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Corrugated Flourinated (FEP) plastic tubing
Parker/Texloc Div. of Parflex USA
Untried plastic fantastic OFM crystalliser ?

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• Viable flow configuration for crystallisation
• Long residence times possible
• Flow, thermal or concentration profiling
possible
Oscillatory Flow Mixing (OFM)

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Microcapillary Films (MCFs)
“Plastic Fantastic”
“Discovered” in 1990s

32. 32
MicroCapillary Films (MCFs) 2000s;
invention
Die land
Polymer flow
Quench bath Extrudate to haul off
Injector
MCF extrudate
Bart Hallmark

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T1 T2 T3 T4
T5 T6P2
Single screw extruder
MCF
extrusion
die
Chilled rollers
Spooling
Guide rollers
Gear pump
MCF
PLAN VIEW
MCF
Chill rollers
Direction of flow
Array of 19 entrainment
nozzles
Entrainment
body
Air inlet
Polymer
melt
Die exit
Quenching length, L
Micro Capillary Film; invention
B. Hallmark, et al. Adv. Eng. Mat., (2005).

34. 34
MCF Development; Pressure Drop
0
2
4
6
8
10
12
14
0 0.2 0.4 0.6 0.8 1
Pressure(bar)
Flow rate (mL/min)
25°C 40°C
55°C 70°C
85°C
Christian Hornung
Polyethylene or FEP

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MCF Development RTD
0
5
10
15
20
25
30
35
40
45
50
0 5 10 15 20 25 30
t [min]
c[mg/l]
inlet
outlet
length = 20 m
flow rate = 0.5 ml/min
Plug flow, laminar flow MCF! Radial dispersion through molecular diffusion

36. MCF Commercialisation
 2 flat silicon heaters (200 W each)
 PID control - Temperature monitoring at top and bottom heater
plates
 Tmax = 150 °C developed by
Lamina Dielectrics Ltd.
& Cambridge University
Teflon coated
hot plates
Temperature control
Reactor disk tray
Patrick Hestor Lamina Ltd

37. MCF Development; Microflow
Organic.
Kerosene, 1.8 mPas
Oil, 27 mPas
Vegetable oil. 50 mPas
Water, 1 mPas, glycerol 10-50 mPas or methanol
Video,
Methanol
into Veg oil
Nuno Reis

38. MCF Development; Slug separation
Scheiff et al. Lab on a Chip. 2011
Slug separation within capillary flow; something new!

39. Bore fluid
Nitrogen
Gas
Cylinder
Polymer
Solution
Die
External
Coagulant
Haul-off
Single Capillary,
MCF membranes
Air-gap
Glass Water
Bath
MCF Development. Microporous MCF membranes
Sina Bonyadi
Microporous MCF; something new

40. Microporous MCFs
2 µm
100 µm
2 µm
1 µm
Bonyadi et al. Journal of Membrane Sci 2012

41. • Potentially viable geometry for continuous
crystallisation
• Narrow bore may cause blockage problems
• Optical interrogation possible during flow
Microcapillary Films (MCFs)

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• Flow can be complicated.
• Crystallisation can be complicated.
• Flow induced crystallisation can be very complicated.
• OFM and MCFs can give plug flow processing.
Message

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http://www.malcolmmackley.com
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