Magnetic Nanofluids for Chemical

and Biological Processing

Andre Ditsch, Bernat Olle, Harpreet Singh,
Lino Gonzalez, Marco Lattuada, Lev Bromberg,
Daniel I.C. Wang, Kenneth A. Smith & T. Alan Hatton

Department of Chemical Engineering

Massachusetts institute of Technology
Cambridge MA 02139
 Magnetic Nanoparticles

Magnetic Core
Applications Superparamagnetic
‹ Magnetic storage media
‹ Magnetic drug targeting Polymer Shell
‹ Protein/Cells separation Colloidal stability
Functionality
‹ RNA/DNA purification
‹ Magnetic resonance
Imaging
‹ Catalysts 8 nm
‹ MR Fluids
‹ Mass and heat transfer 15-20 nm
enhancement
 Functionalised Magnetic
Nanoparticles
Coating Material Function
Magnetic
particle Perfluorocarbons O2Transfer Enrichment
Chiral Moieties Optical Resolution
of Racemic Mixtures
Phospholipids Protein Purification
Ligands
10 nm
15-20 nm Block Copolymers Removal of Organic
Contaminants

Non-volatile, colloidal solvents

Very high interfacial areas
Low surface activity
Readily recovered by magnetic filtration
 Protein Purification
Proteins increasingly used in place of small molecules in industry and
medicine.
‹ Proteins are much more specific and potent than small organic
molecules.
Separations of proteins typically the major processing cost.
‹ Up to 80% of processing costs come from purification.
(% of total Production Costs)

100
New methods needed
Purification Costs

for economical protein

production

0
Therapeutics Industrial Enzymes
High purity Low purity
High cost Low cost
Low volumes Large volumes
 Protein Adsorption Systems

High ∆P
Pore diffusion
limitations

Packed Bed
Plugging
Low Velocities
Dispersion Expanded Bed Low flux
No cells! Short Contact Times
Limited Flow Range Stirred System
Can Handle Cells Controlled Contact Times
Low Capacity Fouling of Membranes
 Colloidal Adsorbents

Stable dispersion of adsorbents as colloidal

colloidal entities
entities
No diffusional
~ 5 - 50 nm Resistances
High surface areas τ =r2/Dφ2/3 ~ 0.1- 10 ms
Area per Volume , m2/m3

108 A/V = 6φ/d φ, Colloid

Volume
Fraction

107 0.10
0.05
0.02
106 0.01

0 10 20 30 40 50 60
Colloid Diameter d, nm
 Process Overview

N S
 Process Overview

N S
 Process Overview

Adsorptive Capacity?
Particle Stability?
Particle Capture?
Cells,
Protein
& MF
MF Cells & Recovered
Protein MF

N S
Recovered
Cells Recovered
Protein
 Cells,
Cells & Recovered Recovered Recovered
Protein
Protein Cells Protein MF
& MF
 High Gradient Magnetic
Separation (HGMS)

Stainless
steel wire
(50µm)

Fdiff
Fmag

Magnetic force on particle:

Fmag = µ oVcore M core ∇H

Fdrag
 Clusters Needed for Effective
Nanoparticle Capture by HGMS
Small particles - diffusion controlled
affected by bulk concentration
Large clusters - convection controlled
18 nm no concentration effect

140 nm
Commercial HGMS Units
Polymer Synthesis

Common, readily available

monomers – scalable process
High charge density at all
relevant pH (SO3-)
Variable hydrophobicity for
additional specificity
(Aromatic ring)
Strong attachment to Fe3O4
(COO-)
Molecular weight from 2kDa to
300kDa with Na2S2O5
Particle Synthesis
 Magnetic Nanoparticles

10 nm

Single crystal magnetic core

Reversible recovery
Poly electrolyte coating
Tunable adsorption
Easy flow around cells
No diffusional limitations
Colloidally stable
Purification of Drosomycin

Drosomycin least hydrophobic of bound

proteins
Elution of nearly pure (90%) drosomycin
with pH=7, 0.5M NaCl

Complete elution of all proteins at

pH=10, 0.5M NaCl
Allows re-use of particles
 Comparison with other methods

(Capacity) x (speed) 30x better than best found in literature, 100x standard
Only 0.1% of particles lost with short (10.5) cm column
1 Voute et al. Bioseparations 8: 115-120, 1999
2 Ganetsos and Barker Preparative and Production Scale Chromatography Marcel Dekker 1993
 Oxygen Transfer in Fermentation

Xmax= X0e µt

NA = Xmaxµ/YC/O ~ 425 mmole O2/L hr

= kLa(C* - CL)~ 105 mmole O2/L hr

(DO2/δ) Depends on
Bubble Henry’s Law
Size Constant

Should not focus on bubble and hydrodynamics!

Need to enhance effective Henry’s Law Constant
 Mass Transfer Enhancement
100

% Oxygen Saturation
φ =0
80 φ =0.005
φ = 0.01
60
φ =0.02
40 φ = 0.04

20
DO Probe
0
0 20 40 60 80 100 120
Time (min)
5
φ =0
φ =0.005
φ =0.01
4
)
N2-Purged φ =0.02
bulk

φ = 0.04
ln ( C* -C

suspension exposed
to air at time t=0 3

2
0 10 20 30 40 50 60
Time (min)
 Mass Transfer Enhancement
1.8

1.6
Enhancement

1.4

1.2

1
6
0.8 20 nm, oleic acid coated NP
0 0.01 0.02 0.03 0.04 0.05 5 φ = 0.0025

Enhancement
φ (particle fraction)
4

2 80 nm, PPO-PEO coated NP

φ = 0.0025
1
0 20 40 60 o 80 100
Temperature ( C)
 KLa Measurements
Sulfite Reaction Method
φ =0.01

k a (mmol/(atm L hr))
1000 φ =0.005
air to mass spec
φ =0.0025
Di = 10cm
φ =0 (control)

100

L
HL = 14.5cm

1 10 100
VTOTAL = 20L Power Input per Unit Volume, P /V (HP/1000L)
G L
VWORKING = 5.5L
1000
φ =0.01

k a (mmol/(atm*L*hr))
Dtank = 22cm φ =0.005

φ =0.0025

1 2+
Na 2 SO3 + O2 ⎯Cu
⎯⎯→ Na 2 SO4 φ =0 (control)
2
100
L

[SO32-] = 0.67M
[Cu2+] = 1x10 -3 M
10 100
Superficial Velocity ,Vs (cm/min)
 Catalytic Nanoparticles Design
Magnetite nanoparticles:
• Modified with moieties containing highly nucleophilic groups
• Selectively attack electrophilic groups such as P-O bonds
found in toxic organophosphates
• Contain charged group on the surface: colloidally stable in
water

Stabilizing α-nucleophile:
polymers H a heteroatom with an unshared
electron pair adjacent to the
C=N-OH nucleophilic center
α-nucelophiles:
Oxime oximates, phenolates, etc.

Fe3O4
 Nucleophiles Thus Far Tested
H H
C C C C
H2 H2
COOH

N
HC N OH
N
CH3
CH2
PAM: 2-pyridinealdoxime
(common antidotal drug) C N OH

p(VPOx-AA): Copolymer of oximated

poly(4-vinylpyridine) and polyacrylic acid
(novel polymeric nucleophile)
 Decomposition of
Organophosphates
O O O

H3C P F H3C P F (H3C)2HCO P F

OCH(CH3)2 OCH(CH3)CH2(CH3)3 OCH(CH3)2

Sarin Soman DFP

Diisopropyl fluorophosphate: model nerve gas

OP+ Nanoparticle gives water-soluble phosphoric acid + fluoride ion

Nanoparticles are recyclable by HGMS
Method of analysis: continuous detection of F-
 Kinetics of Hydrolysis

10
PAM/M
1
kobsx103 (s-1)

0.1 PAM

0.01 p(VPOx-AA)/M

M p(VP-AA)/M
0.001
Spontaneous Hydrolysis
0.0001
0.01 0.1 1 10
Concentration (mg/mL)

Rapid hydrolysis in presence of oximated species

 Recycling
0.30

PAM/M
3
-ln(1-Ct/[DFP]o)

0.20
1 1

2
0.10
2
3
p(VPOx-AA)/M
0.00
0 1000 2000 3000
Time (s)

Particles can be recovered and recycled with no

loss of catalytic effectiveness
 Applications

Catalytic decomposition of organophosphates:

‹ Numerous OP pesticides and insecticides
‹ Warfare agents such as sarin, soman, and VX
Drainwaters, industrial runoffs and spills
Protective clothing
Filters, membranes, gas masks
 Magnetic Response of
Nanoparticles
Relaxation Processes
1
Brownian: rotation of particle in fluid 0.1

Relaxation Time, s
3V η0
0.01 Neel
τB = 0.001
KT 0.0001
-5
Neel: rotation of magnetic vector within particle 10
-6
10
Brownian
1 ⎛ KV ⎞ 10
-7

τ N = exp ⎜
⎝ kT ⎟⎠
-8
10
f0 6 8 10 12 14 16 18
Particle Size,

+ Fe3+ + Fe3+ µ0 M 2V µ0 χ 2 H 02V

λ= ≈ ? 1
14kT 14kT

20 nm

χ shell ≈ 1.3χ dist

 Magnetite Nanoparticle
Aqueous Route
‹ Nucleation of magnetite
nanocrystals from a solution of
FeCl3 & FeCl2, NH4OH, 80°C.
Various stabilizers
‹ Pros: Cheap, fast, variety of
stabilizers
‹ Cons: broad nanoparticle
distribution, irregular shape,
average crystallite size fixed
Preparations
Organic Route
‹ Iron-triacetylacetonate reduction
by 1-2 hexadecanediol, at 300°C in
benzylether,oleic acid+oleyl amine
‹ Pros: narrow crystallites
distribution, regular (controlled)
shape, tunable size
‹ Cons: expensive, works only with
some organic stabilizers,
chemistry poorly understood

+ Fe3+ + Fe3+

20 nm
 Magnetophoretic Separation of
Nanoparticles in Microfluidic Systems
Decreasing H

Fdrag = −6πη RU p Magnetic Fluid

Fmag = µ0V p ( M p − M f )∇H

= − µ0V p M f ∇H

Fmag + Fdrag = − µ0V p M f ∇H − 6πη RU p = 0

µ0V p M f ∇H
Up = −
6πη R
Flow Magnetophoresis for
Nanoparticle Separations
 Nanoparticle Separation and
Focusing

Particle Resolution is affected by

Convective dispersion (non-uniform velocity profiles)
Non-uniform lateral field distributions
 Magnetic Shells
Use layer-by-layer technique to coat polystyrene beads with
polyelectrolytes and then adsorb magnetic nanoparticles.
Polymer core can be dissolved out using solvent.
 Applications of Magnetic Chains
and Rods

Fundamental studies on behavior under fixed and rotating

magnetic field
Magneto-rheological effects
Magnetic actuators and valves
Micromixers, pumps, etc. under a rotating magnetic field
Magnetic nanowires (Bibette &Vivoy)
Magnetic pillars can be used for separations (currently used in
separation of DNA (Doyle's research))
Functionalized chains can be used for separations
‹ Molecular movement of a molecule through the maze of chains only
governed by size and interactions with chains...
Separation of paramagnetic species
 Bead Alignment and Coupling

Beads can be aligned in microchannel under magnetic

field and joined together either using sol-gel chemistry or
chemical coupling with appropriate linker.
 Rigid Magnetic Chains

Sol Gel kinetics (Titanium

isopropoxide as precursor)
‹ Extremely fast hydrolysis
reaction
‹ Linking requires preferential
nucleation on the bead surface
Magnetite beads coated with
PDAMAC and resuspended in
anhydrous ethanol; Kpw = 60
‹ Water of hydration in the
PDAMAC shell ensures reaction
on the bead surface only
‹ Positively charged bead
captures negatively charged
nucleated titania efficiently
 Tethered Flexible Magnetic Chains

(a) (b)

25

50 m 50 m
No

(c) (d)

25 µm
50 m 50 m
No