hgms high gradient magnetic separation
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Transcript of hgms high gradient magnetic separation
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 EngineeringMassachusetts institute of Technology
Cambridge MA 02139
Magnetic Nanoparticles
Magnetic CoreSuperparamagneticApplications
Magnetic storage mediaMagnetic drug targetingProtein/Cells separationRNA/DNA purificationMagnetic resonance ImagingCatalystsMR FluidsMass and heat transfer enhancement
8 nm
15-20 nm
Polymer ShellColloidal stability
Functionality
Functionalised Magnetic Nanoparticles
Coating Material FunctionMagneticparticle Perfluorocarbons O2Transfer Enrichment
10 nm15-20 nm
Chiral Moieties Optical Resolutionof Racemic Mixtures
PhospholipidsLigands
Protein Purification
Block Copolymers Removal of OrganicContaminants
Non-volatile, colloidal solventsVery high interfacial areasLow surface activityReadily 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.
Therapeutics High purity High cost Low volumes
Industrial Enzymes Low purity Low cost Large volumes
Purif
icat
ion
Cos
ts(%
of t
otal
Pro
duct
ion
Cos
ts)
100
0
New methods needed for economical protein
production
Protein Adsorption Systems
High ∆PPore diffusion
limitations
Expanded BedShort Contact TimesLimited Flow Range
Can Handle CellsLow Capacity
Low flux
Stirred SystemControlled Contact Times
Fouling of Membranes
Packed BedPlugging
Low VelocitiesDispersionNo cells!
Colloidal Adsorbents
Stable dispersion of adsorbents as colloidal entities
High surface areas
106
107
108
0 10 20 30 40 50 60Are
a pe
r Vol
ume
, m2 /m
3
Colloid Diameter d, nm
0.010.02
0.050.10
A/V = 6φ/d φ, ColloidVolumeFraction
No diffusionalResistances
τ =r2/Dφ2/3 ~ 0.1- 10 ms~ 5 - 50 nm
colloidal entities
Process Overview
N S
Process Overview
N S
Process Overview
N S
Adsorptive Capacity?Particle Stability?Particle Capture?
Cells & Protein
Cells,Protein& MF
RecoveredCells Recovered
Protein
MF RecoveredMF
Cells & Protein
Cells,Protein& MF
RecoveredCells
RecoveredProtein
RecoveredMF
High Gradient Magnetic Separation (HGMS)
Stainlesssteel wire
(50µm)
Magnetic force on particle:
HMVF corecoreomag ∇= µ
Fmag
Fdiff
Fdrag
Clusters Needed for Effective Nanoparticle Capture by HGMS
Small particles - diffusion controlledaffected by bulk concentration
Large clusters - convection controlledno concentration effect18 nm
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 coreReversible recovery
Poly electrolyte coatingTunable adsorption
Easy flow around cellsNo diffusional limitationsColloidally stable
Purification of Drosomycin
Drosomycin least hydrophobic of bound proteins
Elution of nearly pure (90%) drosomycinwith 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 standardOnly 0.1% of particles lost with short (10.5) cm column
1 Voute et al. Bioseparations 8: 115-120, 19992 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)Bubble
Size
Depends on Henry’s Law
Constant
Should not focus on bubble and hydrodynamics!Need to enhance effective Henry’s Law Constant
Mass Transfer Enhancement
2
3
4
5
0 10 20 30 40 50 60
ln (
C*-
Cbu
lk )
Time (min)
φ = 0.005φ = 0
φ = 0.01φ = 0.02
φ = 0.04
0
20
40
60
80
100
0 20 40 60 80 100 120
% O
xyge
n S
atur
atio
n
Time (min)
φ = 0.005φ = 0
φ = 0.01
φ = 0.02
φ = 0.04
DO Probe
N2-Purged suspension exposed
to air at time t=0
Mass Transfer Enhancement
0.8
1
1.2
1.4
1.6
1.8
0 0.01 0.02 0.03 0.04 0.05
Enh
ance
men
t
φ (particle fraction)
1
2
3
4
5
6
0 20 40 60 80 100
Enh
ance
men
t
Temperature (oC)
20 nm, oleic acid coated NP φ = 0.0025
80 nm, PPO-PEO coated NP φ = 0.0025
KLa MeasurementsSulfite Reaction Method
100
1000
10 100
k La (m
mol
/(atm
*L*h
r))
Superficial Velocity ,Vs (cm/min)
φ = 0.01
φ = 0.005
φ = 0.0025
φ = 0 (control)
100
1000
1 10 100
k La (m
mol
/(atm
L h
r))
Power Input per Unit Volume, PG/V
L (HP/1000L)
φ = 0.01
φ = 0.005
φ = 0.0025
φ = 0 (control)
Dtank = 22cm
HL =
14.
5cm
Di = 10cm
VTOTAL = 20L
VWORKING = 5.5L
air to mass spec
42232
2
21 SONaOSONa Cu⎯⎯ →⎯+
+
[SO32-] = 0.67M
[Cu2+] = 1x10-3 M
Catalytic Nanoparticles DesignMagnetite 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
Fe3O4
Stabilizing polymers
Oxime
α-nucleophile: a heteroatom with an unshared electron pair adjacent to the nucleophilic center
α-nucelophiles: oximates, phenolates, etc.
C=N-OHH
Nucleophiles Thus Far Tested
PAM: 2-pyridinealdoxime(common antidotal drug)
p(VPOx-AA): Copolymer of oximatedpoly(4-vinylpyridine) and polyacrylic acid(novel polymeric nucleophile)
N
CH3
HC N OH
CH2
HC C
H2
HC
N
COOH
CH2
C N OH
Decomposition of Organophosphates
O
P(H3C)2HCO
OCH(CH3)2
F
O
PH3C
OCH(CH3)2
F
DFPSarin
O
PH3C F
Soman
OCH(CH3)CH2(CH3)3
Diisopropyl fluorophosphate: model nerve gas
OP+ Nanoparticle gives water-soluble phosphoric acid + fluoride ionNanoparticles are recyclable by HGMS
Method of analysis: continuous detection of F-
Kinetics of Hydrolysis
0.0001
0.001
0.01
0.1
1
10
0.01 0.1 1 10
k obsx1
03 (s-1
)
Concentration (mg/mL)
PAM/M
PAM
p(VPOx-AA)/M
M p(VP-AA)/M
Spontaneous Hydrolysis
Rapid hydrolysis in presence of oximated species
Recycling
0.00
0.10
0.20
0.30
0 1000 2000 3000
-ln(1
-Ct/[D
FP] o)
Time (s)
PAM/M
p(VPOx-AA)/M
1
2
3
1
2
3
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 spillsProtective clothingFilters, membranes, gas masks
Brownian: rotation of particle in fluid
Neel: rotation of magnetic vector within particle
10-810-710-610-5
0.00010.001
0.010.1
1
6 8 10 12 14 16 18
Rel
axat
ion
Tim
e, s
Particle Size, �
Neel
Brownian
τ B =
3Vη0
KT
τ N =
1f0
exp KVkT
⎛⎝⎜
⎞⎠⎟
Relaxation Processes
Magnetic Response of Nanoparticles
λ =µ0 M 2V14kT
≈µ0 χ 2 H0
2V14kT
? 1
20 nm
+ Fe3+ + Fe3+
χshell ≈ 1.3χdist
Magnetite NanoparticlePreparations
Aqueous RouteNucleation of magnetite nanocrystals from a solution of FeCl3 & FeCl2, NH4OH, 80°C. Various stabilizersPros: Cheap, fast, variety of stabilizersCons: broad nanoparticledistribution, irregular shape, average crystallite size fixed
Organic RouteIron-triacetylacetonate reduction by 1-2 hexadecanediol, at 300°C in benzylether,oleic acid+oleyl aminePros: narrow crystallites distribution, regular (controlled) shape, tunable sizeCons: expensive, works only with some organic stabilizers, chemistry poorly understood
20 nm
+ Fe3+ + Fe3+
Magnetophoretic Separation of Nanoparticles in Microfluidic Systems
Decreasing H
Fmag + Fdrag = −µ0Vp M f ∇H − 6πηRU p = 0
Fmag = µ0Vp ( M p − M f )∇H
= −µ0Vp M f ∇H
Fdrag = −6πηRU p
U p = −
µ0Vp M f ∇H6πηR
Magnetic Fluid
Flow Magnetophoresis for Nanoparticle Separations
Nanoparticle Separation and Focusing
Particle Resolution is affected byConvective 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 effectsMagnetic actuators and valves Micromixers, pumps, etc. under a rotating magnetic fieldMagnetic 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 onlygoverned 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 reactionLinking 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 onlyPositively charged bead captures negatively charged nucleated titania efficiently
Tethered Flexible Magnetic Chains
25 µm
50 m No
(c) (d)
50 m
50 m
(a) (b)
50 mNo
25