The document discusses process design and scale-up issues related to the continuous flow synthesis of silver nanomaterials. It first summarizes literature on the continuous flow synthesis of silver nanoparticles (AgNPs) and identifies gaps in understanding nucleation rates and separation technologies. The author then examines the mechanism and kinetics of AgNP synthesis via a citrate-based method. Experiments optimizing batch reactor conditions are described. Continuous flow synthesis using multiple continuously stirred tank reactors (CSTRs) is explored to control nucleation and particle size. Centrifugal separation is investigated to recover AgNPs. Finally, the document discusses the continuous flow synthesis of silver nanowires, presenting a proposed reaction mechanism and kinetic rate constants obtained at different temperatures.

1. Process Design and Scale-up of Silver Nanomaterial synthesis
Ph.D Viva Voce
Jaydeep B. Deshpande
PM PhD Fellow
Chemical Engineering and Process Development
& Physical and Material Chemistry Division
AcSIR Roll No. 20EE12A26076
Research Guide:
Dr. Amol A. Kulkarni
1

2. Outline of Presentation
2
1. Introduction to engineering issues in nanomaterial synthesis
2. Engineering issues and continuous flow synthesis of AgNPs
3. Continuous flow synthesis of silver nanowires
4. Two phase flow in small channels
5. Summary

3. What are nanomaterials?
Or by dividing the size of a red blood cell
By 1000
Nano-metre = 10-9 m
In other words, a range of size that you would get by
dividing the thickness of a human hair by 100,000
Or by multiplying the size of an atom by 10

4. Basic research: Types of nanomaterials
Metal
Oxides,
phosphates,etc.
Carbon
Semiconductors
Biomolecules Polymers

5. Basic research: How are nanomaterials made?

6. Bird’s eye view of Nanotechnology driven products
- Nanotechnology based products are
picking up the scale in the market
- Metal nanomaterials dominate the
total number of products
- Metals are primarily used as surface
coatings or in form of active liquids
(inks, paints, gels, etc.)
- Silver nanomaterials hold the largest
share of all the metal based
nanomaterials
- The Silver market is further
bifurcated into electronics based
and biology & life sciences based
products.
Market sizes of various
applications of
nanosilver
6

7. You can be poor and still be born with a silver-spoon
Consider a
cylindrical cup
Dimensions:
Filled height = 10
cm, radius = 5 cm
Volume of a water in the cup = 786 ml
Surface area of silver exposed = 314 sq cm
Surface area/volume = 0.4 cm-1
Surface area of single 10 nm nanoparticle = 3.142x10-12 cm2
Weight of single 10 nm nanoparticle = 5.2x10-18 g
Thus 1 microgram of silver nanoparticles contains 1.9 x 1014
nanoparticles
Surface area of silver exposed = 600 sq cm
Surface area/volume = 0.764 cm-1

8. Basic research/
Pure Science
Chem
Engg
Electronics
Engg
Biomedical
Engg
Materials
Lab
synthesis
Government
Industry
Government
Industry
Products
Products
Bridging
networks
Government
Industry

9. Objectives of the work
Targets:
• To work on solving an industry-academia problem of scaling up AgNP synthesis (PM Fellowship Scheme)
• Understand process development of high value anisotropic systems
• Development of technologies suitable for industrial applications
• Develop further understanding of flow synthesis techniques suitable for nanosynthesis in miniature reactors
Years (starting 2013) 1 2 3 4 5
Tasks
AgNP
Two phase flow
Separation
AgNW
Printing inks
Goal: To understand scale-up issues in nanosynthesis for a one important metal (silver)

10. Part 1: Continuous flow synthesis of AgNPs

11. Part A: Literature analysis

12. Literature analysis
Reaction pathways Continuous flow literature
Author
and year
Mass
balances
Energy
balances
Momentum
balances
Reactor
dosing
Reactor
geometry/type
Heating Separation
/drying
Arndt et
al, 2013
4 2 1 4 3 7 N/A
Dzido et
al, 2011
1 1 2 1 1 7 N/A
Hartleib et
al, 2010
3 4 1 7 4 7 N/A
He et al,
2008
1 1 2 4 1 6 N/A
Horikoshi
et al, 2013
1 4 1 6 6 8 N/A
Haung et
al, 2008 1 3 1 3 1 6
N/A
Lazarus et
al, 2012 1 1 7 8 8 N/A
N/A
Lin et al,
2004
4 4 3 1 1 6 N/A
Kumar et
al, 2009 4 1 1 1 4 4
N/A
Patil et al,
2012
3 1 1 1 1 4 N/A
Liu et al,
2014
8 8 8 1 1 8 N/A
Silvestrini
et al, 2012
1 1 1 1 6 N/A N/A
Scalability Cost Stability Flexibility
Ease and
Greenness
Average
Marks
Turkevich 8 6 10 4 10 7.6
Borohydride 8 6 8 6 10 7.6
Tollen’s
reaction
2 4 8 2 6 4.8
Two-phase
synthesis
2 2 6 6 4 4.4
High
concentration
2 2 6 6 4 4
Gaps in current knowledge on nanomaterial synthesis
• Assessment of suitable reaction path for mass production
• Knowledge of accurate mass balances (eg: total reaction conversion) and reaction/crystallization time
scales, especially the nucleation rates
• Coherent and consistent trends with bulk dimensionless parameters
• Reproducible scalable separation technologies

13. Reaction conditions:
1. Silver nitrate: 1 mmol/L
2. Trisodium citrate: 3-6 mmol/L
3. Temperature: 85-94oC
Batch reactor was optimized for mixing performance.
Final optimized batch reactor specifications:
1) Type: Baffled with jacket
2) Volume = 50 ml, base without jacket ~ 4 cm
3) Stirrer: Magnetic stirrer with 3.5 cm octagonal stirring bead
at ~ 500 rpm
4) Mixing time ~ 5s (measured using conductivity)
Measurement of kinetics:
1. Uv-vis spectrophotometer
2. Atomic absorption spectrometer 13
Citrate based synthesis of silver nanoparticles

14. Part B: Mechanism

15. Mechanism of reaction
Evidence of heterogeneous nucleation
60
65
70
75
80
85
90
95
100
N/A 0.5 1 2 3 4 6 8 12 15
Citrate
concentration
(%
of
initial
conc)
Time (min)
colour appears at 4 min
Intermediate 1: wire-like Intermediate 2: globule/droplet
Chemical analysis of the intermediate
- Nanoparticles seem to preferentially nucleate
heterogeneously in pockets and not homogenously within
the solution

16. Mechanism of reaction
Insights from MD simulations
In collaboration with Dr Suman Chakraborty

17. Part C: Scale-up and continuous flow

18. Nucleation and growth
Silver ionic concentration Uv absorbance
𝐴 → 𝐵 → [𝐶]𝑆𝑚𝑎𝑙𝑙𝑒𝑟 𝑁𝑎𝑛𝑜𝑝𝑎𝑟𝑡𝑖𝑐𝑙𝑒𝑠 …(i)
[𝐶]𝑆𝑚𝑎𝑙𝑙𝑒𝑟 𝑁𝑎𝑛𝑜𝑝𝑎𝑟𝑡𝑖𝑐𝑙𝑒𝑠 + 𝐴 → [𝐶]𝑙𝑎𝑟𝑔𝑒𝑟 𝑛𝑎𝑛𝑜𝑝𝑎𝑟𝑡𝑖𝑐𝑙𝑒𝑠 …(ii)
Equations:
A: silver ions, B: intermediate, C: nanoparticles

19. Nucleation and growth
𝑑𝐴
𝑑𝑡
= −𝑘1[𝐴] …(2)
𝑑𝐵
𝑑𝑡
= 𝑘1 𝐴 − 𝑘2[𝐵] …(3)
𝑑𝐶
𝑑𝑡
= 𝑘2 𝐵 + 𝑘3 𝐴 𝑠∗
[𝐶] …(4)
𝑑𝐴
𝑑𝑥
= 𝐵𝑜
𝑑2𝐴
𝑑𝑥2
− 𝜏1[𝐴] …(2)
𝑑𝐵
𝑑𝑥
= 𝐵𝑜
𝑑2𝐵
𝑑𝑥2 + 𝜏1 𝐴 − 𝜏2[𝐵] …(3)
𝑑𝐶
𝑑𝑥
= 𝐵𝑜
𝑑2𝐶
𝑑𝑥2 + 𝜏2 𝐵 + 𝜏3 𝐴 𝑠∗
[𝐶] …(4)
Bo =
𝑎𝑥𝑖𝑎𝑙 𝑑𝑖𝑠𝑝𝑒𝑟𝑠𝑖𝑜𝑛 𝑡𝑖𝑚𝑒
𝑟𝑒𝑠𝑖𝑑𝑒𝑛𝑐𝑒 𝑡𝑖𝑚𝑒

20. Nucleation and growth in Continuous flow
Nucleation (10min) +
Growth(25min RT)
Particle
size in nm
(DLS)
Bo CSTRs
assigned
to
complex
formation
CSTRs
assigned
to
particle
formation
1 2 [50 ml CSTRs(nuc)] + 3 [50
ml(gr)]
120+/-22 10 2 2
2 1 [100 ml] + 2 [50 ml CSTRs(nuc)]
+ 3 [50 ml(gr)]
105+/-56 12 3 1
3 3 [50 ml CSTRs(nuc)] + 3 [50
ml(gr)]
84+/-17 12 3 1
4 5 [50 ml CSTR(nuc)] + AMAR3
(gr)
78+/-17 40 3 2
5 Batch 68+/-15 Inf
Five 50 ml CSTRs One 100 ml CSTRs followed by
five 50 ml CSTRs
Six 50 ml CSTRs Five 50 ml CSTRs followed by
AMAR3 flow reactor
Particles produced in
batch
Particles produced in
continuous

21. Nucleation and growth in Continuous flow
0.0E+0
2.0E-4
4.0E-4
6.0E-4
8.0E-4
1.0E-3
1.2E-3
1.4E-3
1.6E-3
1.8E-3
0 500 1000 1500 2000
E(1/s)
Time (s)
5 50 ml
3 50 ml
1 100ml, 2 50 ml
2 50 ml
120 nm
105 nm
84 nm
78 nm
Axial dispersion as function of number of
CSTRs allocated to nucleation
0
20
40
60
80
100
120
140
0 50 100 150 200
Intensity
(A.U.)
hydrodynamic size (nm)
Nucleation in 2 50 ml CSTRs
nucleation in 1 100ml and 2 50 ml CSTRs
nucleation in 3 50 ml CSTRs
nucleation in 5 50 ml CSTRs
Batch
Particle size and polydispersity as a
function of number of CSTRs allocated to
nucleation

22. Recommendations
1) Temperature controlled at 90oC
2) pH at 7.8, rapid stirring in the first reactor
3) Smaller but larger number of CSTRs for nucleation, Bo > 10
4) Premixing of reagents
5) Monitoring the silver concentration

23. Part D: Separation

24. Nanoparticle separation
24
Separation of nanoparticles
Magnetic field is
probably the easiest way
for separation. It is not
applicable to silver.
Separation by Electric
fields can cause
agglomeration at
electrode
Separation by
gravitational field is
effective
Separation by filtration is
too slow for a low
concentration reaction
scheme

25. Separation of silver nanoparticles in continuous flow
• For particles to flow out of the centrifuge
continuously and avoid
agglomeration/deposition, particles must be
collected not on the wall of the centrifuge
but on a mobile interface which can be
easily manipulated.
• Liquid-liquid interface can be used for this
purpose after functionalizing the
nanoparticles with appropriate groups
𝑑𝐶𝑝𝑣𝑝
𝑑𝑡
= 𝑘𝑙𝑎 (𝐶𝑝𝑣𝑝 − 𝐶∗
)
𝐷𝑎𝑠 =
𝐿𝐾
𝑣
𝑣 =
2
9
(𝜌𝑝 − 𝜌𝑤 )
𝜇
𝑔𝑅2
𝑣 =
2
9
(𝜌𝑝 − 𝜌𝑤 )
𝜇
𝑔𝑅2

26. Separation of silver nanoparticles in continuous flow
Nanoparticle
size (nm)
Separation
efficiency
Separation
time
(min)
Das
90 0.6 45 242.02
120 0.72 28 136.13
150 0.8 17 87.13
200 0.9 11 49.01
300 0.95 5 21.78
500 0.98 2 7.84
1000 0.99 1 1.96
• Batch model predicted
concentration of nanoparticles was
45%. However 30% recovery was
obtained from ACE. The difference is
attributed to increased mixing at the
liquid-liquid interface in the ACE
• 8 stages would be required for near
complete separation making the
operation costlier for small particles.
• Separation efficiency is best for Da ~
1

27. MIC (ppm)
Bacteria
0% PVP
1000 ppm
silver
(sample
1)
8% PVP
1000 ppm
silver
(sample 2)
4% PVP
1000 ppm
silver
(sample 3)
1% PVP
1000 ppm
silver
(sample 4)
0.1% PVP
500 ppm
silver
(sample
5)
PVP
stabilizer
E.coli - 600 300 300 150 No
activity
S.enterica - 400 500 400 300-400 No
activity
A.junii - 600 500 500 Not
tested
No
activity
Effect of Separation on antimicrobial activity
In collaboration with Dr Mahesh Dharne

28. Part 2: Silver nanowires production

29. Synthesis of 1D nanosilver in continuous flow

30. Polycrystalline AgNPs
Monocrystalline AgNPs
Monocrystalline
AgNWs
Silver ions
km1
kn2
kn1
km2
A
B
M
M
Reaction mechanism of glycol synthesis

31. Rate constant data
Temp(oC)Reactio
n rate (1/s)
Reduction rate
(polycrystalline
particles)
kn1
Oxidation rate
(polycrystalline
particles)
kn2
Reduction rate
(monocrystalline
material)
km1
Oxidation rate
(monocrystalline
material)
km2
130 1.50E-04 0.5 1.00E-03 0.1
140 1.00E-03 3 3.00E-03 0.1
150 2.50E-03 8 3.50E-03 0.1
Temp(oC)Crystalli
zation rate (1/s)
Nucleation rate
(monocrystalline
material)
km1
Oxidation rate
(monocrystalline
material)
km2
130 3.00E-09 1.00E-03
140 1.00E-05 2.00E-03
150 1.00E-05 5.00E-03
Polycrystalline AgNPs
Monocrystalline AgNPs
Monocrystalline
AgNWs
Silver ions
km1
kn2
kn1
km2
A
B
M
M
Data suggests:
• Growth dominates at lower temperatures
• Oxidation rates for polycrystalline and
monocrystalline are rapid and mixing
dependent
• Oxidation rates will compete at low
temperatures. Low temperatures are
expected to be mixing sensitive
31

32. Type of
salt
Property 40k 360k:55k(1
:1)
360k 1300k:5
5k(1:1)
1300k
FeCl3
(0.6
mM)
D (nm)
L (um)
Aspect
ratio
~80
~3.8
~48
56+/-6
21.8+/-10
390
50+/-12
20.2+/-12.6
404
~ 76
16 +/- 9
207
156+/-14
29.7 +/-15
190
NaCl
(1.8
mM)
D (nm)
L (um)
Aspect
ratio
~86
~4.1
~48
53+/-9
5+/-1.5
94
64.2+/-8.3
1.8+/-0.5
28
~ 85
5 +/- 1.5
58
114+/-28
14.9+/-3.8
130
Optimization of the PVP grade

33. Effect of temperature at slow mixing rate (~1 min mixing time)
33
140oC 120oC 110oC
Decreasing
temperature
Length ~ 8 microns
Diameter ~ 50-60 nm
Length ~ 30 microns
Diameter ~ 100 nm
Length ~ 60 microns
Diameter ~ 100 nm
Optimization of temperature

34. 15.5 um
5.8 um
60 um
16 um
40 um
12 um
38 nm
72 nm
80 nm
144 nm
120 nm
65 nm
6.00E-08 6.00E-07 6.00E-06 6.00E-05
20
40
60
80
100
120
140
160
0
10
20
30
40
50
60
70
5.00E-08 5.00E-07 5.00E-06 5.00E-05
nucleation rate (1/s)
nanowire
diameter
(nm)
nanowire
length
(microns)
nucleation rate (1/s)
Master plot

35. Continuous flow optimization
No. Configuration FeCl3
Conc
mM
Bo Length of
nanowire
(microns)
Diameter of
nanowire
(nm)
1 100 ml flow reactor 0.6 4 10 700
2 1700 ml volume flow
reactor
0.6 14 27 188
3 1700 ml volume flow
reactor
0.8 14 38 157
4 1700 ml volume flow
reactor
0.5 14 37 440
5 1700 ml volume flow
reactor
0.9 14 51 351
6 1450 ml volume flow
reactor
0.6 32 ~10 ~40-60

36. Application as TCF
Authors Transmittance (%),Resistance (Ohm/sq)
(best value)
Minimal required 80%, 100 Ohm/Sq
Xie et al 2018 81%, 130 Ohm/Sq
J ia et al 2016 95%, 35 Ohm/Sq
Triyana et al 2017 89.5%, 12 Ohm/Sq
Dai et al 2018 >91%, 40 Ohm/Sq
Marus et al 2018 93%, 100 Ohm/sq
Wang et al 2018 79%, 9.6 Ohm/sq
Choo et al 2015 93%, 50 Ohm/sq
J eong et al 2018 86%, 28 Ohm/sq
Li et al 2018 88%, 19 Ohm/sq
Menamparambath et al
2015
96.4%, 24 Ohm/sq
Batch method 94%, 75 Ohm/sq
Continuous flow method 90%, 86 Ohm/sq

37. Application as printing material

38. Part 3: Understanding two-phase flow in small channels

39. 39
• Liquid-liquid segmented flow comprises intensely mixed compartments of immiscible liquids
progressing consecutively through channel.
Such a flow is utilized for rapid & efficient liquid-liquid extraction and the axial dispersion values
from cold flow studies are utilized for mass balance
• Extraction of solute will lead to variation in physicochemical properties of both solvents and also
in varying slug lengths inside the capillary
• The axial dispersion will hence change along the length of the capillary and existing cold flow
correlations cannot be applied to the system
• The effect of mass transfer on the mass balances hence needs to be investigated
Effect of mass transfer on axial dispersion occurring in segmented flow

40. 40
Kerosene-water system was used with water was the continuous phase
Effect of varying slug sizes on axial dispersion in segmented flow without mass transfer

41. Varying physicochemical properties with mass transfer
0.0008
0.001
0.0012
0.0014
0.0016
0.0018
0 20 40 60
viscosity(N-m)
Capillary length (cm)
0.4kac,0.5w
0.4kac,0.9w
0.4kac,1.7w
0.4kac,2.5w
800
802
804
806
808
810
812
0 10 20 30 40 50 60
Density
of
the
continuous
phase
(kg/m3)
Capillary length (cm)
0.4kac,0.5w
0.4kac,0.9w
0.4kac,1.7w
0.4kac,2.5w
41
50% solution of kerosene-acetone and water were used as the two phases in segmented flow. Acetone acts as the solute and
completely transfers from kerosene to water. Aqueous phase was the continuous phase in all the experiments.

42. Both factors lead to an increase in axial dispersion for slug flow
with mass transfer
0
0.01
0.02
0.03
0.04
50 100 150 200 250
E
(1/s)
Time (s)
ker-ac-water
ker water
1.E-06
1.E-05
1.E-04
1.E-03
0.00001 0.0001
D
(m2/s)
Film thickness (dimensionless)
3.44 mm k-w
3.44 mm k-ac
42

43. Summary

44. 44
Acknowledgement
Access to instruments for analysis:
1. Dr. B.L.V. Prasad and Dr Nandini Devi (uv-vis)
2. Dr. Mahesh Dharne (antimicrobial activity)
3. Dr. Krishnamoorthy (spin coater)
4. Dr. Manjusha Shelke (4-point conductivity measurement)
5. Dr. Satish Ogale (FE-SEM)
6. Dr. Shashank Gaikwad (Continuous centrifugal extractor)
7. NCL central facilities
8. Dr. Jayakannan (IISER-Pune) (DLS)
9. Dr. Arnab Bhattacharya (TIFR) (optical measurements)

45. Research guide
Dr. Amol A. Kulkarni
DAC members
Dr. Ashish K. Lele
Dr. Vivek V. Ranade
Dr. B.L.V. Prasad
Dr. Pankaj Doshi
Dr. Vinay Bhandari
Acknowledgement
45
Head of Department, CEPD, CSIR-NCL
Director, CSIR-NCL
CSIR for funding
Labmates and teachers from NCL
Shalini Sharma(SERB), Dr. Kohli (DST), and
Neha Gupta (CII) for organizing the PM
fellowship
Collaborators
Dr. Aditya Pattani (NanoXpert
Technologies)
Dr. Suman Chakrabarty,
Dr. Mahesh Dharne

46. 0
2
4
6
8
10
12
14
0 20 40 60
Drop
length
(mm)
Capillary length (cm)
0.4kac,0.5w
0.4kac,0.9w
0.4kac,1.7w
0.4kac,2.5w
0.4k,0.5w
0.4k,0.9w
0.4k,1.7w
Varying slug lengths
46

47. Effect of drop-wall bridge
0
2
4
6
8
10
12
0 0.2 0.4 0.6
length
of
drop-wall
bridge
(mm)
capillary length travelled (m)
0.2kac- 0.5w
0.3 kac- 0.5 w
0.5 kac - 15 w
0.5 kac -20 w
The bridge represents the area at which the contact
angle of the drop with the hydrophilic wall reduces
significantly due to the presence of a hydrophilic
solute
Drop detachment is a function of velocity as well as
mass transfer
Bridging on the upper wall leads to
bypass of tracer from beneath the slug
47

48. Size selective separation and purification:
Diameter 64.2+/-8.3
Length 1.8+/-0.5
Aspect ratio 28
Diameter 60+/-12
Length 25.2+/-12.6
Aspect ratio 416
Varying aspect ratio at fixed diameter
Large scale production
(1.5kg/day for 1L reactor)
48
Synthesis process highlights

49. Mechanism of reaction
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
1.1
0 100 200 300 400 500 600
%
silver/citrate
ions
time (s)
𝐷𝑎 = 𝜏𝑘 =
𝑚𝑖𝑥𝑖𝑛𝑔 𝑡𝑖𝑚𝑒
𝑟𝑒𝑎𝑐𝑡𝑖𝑜𝑛 𝑡𝑖𝑚𝑒