Magnetic Separation: Industrial and Lab Scale Applications
Magnetic Separation: Industrial and Lab Scale Applications
Magnetic Separation: Industrial and Lab Scale Applications
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<strong>Magnetic</strong> <strong>Separation</strong>: <strong>Industrial</strong> <strong>and</strong> <strong>Lab</strong> <strong>Scale</strong> <strong>Applications</strong><br />
<strong>Separation</strong> by means of magnetic field has been a mystery until the late 18 th century<br />
though magnets were known since 6 th century BC (Livingston 1997 book). The magical<br />
flow of the force exerted on a material by iron seemed supernatural in many ways.<br />
Perhaps, that was the reason it wasn’t quite understood <strong>and</strong> designed for the good<br />
everyday life.<br />
Since the industrial revolution <strong>and</strong> mass production of steel, magnetic control became a<br />
crucial piece of modern technology. Electronics, communication was in high dem<strong>and</strong> of<br />
magnetic technology as similar as the way magnetic ore refinement industry solely relied<br />
on. <strong>Magnetic</strong> force seemed best petted into magnetic separation where its uncontrollable<br />
power would be very h<strong>and</strong>y. But it was only 1792 when a patent was filed by William<br />
Fullarton on separating iron minerals with a magnet (Gunther 1909, Parker 1977).<br />
The applications were in great interest mainly because magnetic force didn’t let the<br />
gravity be the monopoly of the natural forces. In 1852, magnetite was separated from<br />
apatite by a NY company on a conveyor belt separator (Gunther 1909). Later, with the<br />
proven methods of beneficiation <strong>and</strong> refinement especially in the ores <strong>and</strong> minerals, a<br />
new line of separators were introduced for separation of iron from brass fillings, turnings,<br />
metallic iron from furnace products <strong>and</strong> magnetite from plain gangue (Gunther 1909). A<br />
brief timeline can be seen in Figure 1.
First<br />
Patent<br />
on MS<br />
1800<br />
NY company<br />
built a conveyor<br />
belt separator<br />
Over 300<br />
patents filed<br />
on MS<br />
1900<br />
First nano<br />
separations<br />
paper<br />
First size<br />
dependent<br />
magnetic<br />
separation<br />
1792 1852 1909 1973 2006<br />
Figure 1. Timeline of magnetic separation technology<br />
A very broad but fitting <strong>and</strong> clear classification of magnetic separations can be done as<br />
follows (Parker 1977):<br />
1. Low intensity dry magnetic separations<br />
2. Low intensity wet magnetic separations<br />
3. High intensity dry magnetic separations<br />
4. High intensity wet magnetic separations (i.e. High Gradient <strong>Magnetic</strong> <strong>Separation</strong><br />
(HGMS))<br />
2000
A. Value of <strong>Magnetic</strong> <strong>Separation</strong><br />
Although the magnetic field would make no distinction between various magnetic<br />
particles, magnetic separation h<strong>and</strong>picks those with magnetic affinity from physically<br />
similar mixtures, i.e. in terms of density, shape, <strong>and</strong> size (Svoboda 2003).<br />
Among many applications we’ll discuss briefly in the following pages, the following<br />
ones would give a sense of how valuable magnetic separation could be. As early as 1970s<br />
Delatour <strong>and</strong> Kolm (Delatour 1973 <strong>and</strong> 1975) treated water samples from the Charles<br />
River (Fe3O4 seeding, 5ppm Al 3+ ) with a high flow velocity HGMS (Vo= 136 mms -1 ,<br />
Ho=1T) to obtain the following reductions:<br />
- coliform bacteria from 2.2x10 5 /l to 350/l<br />
- turbidity by 75%<br />
- color by 95%<br />
- suspended solids by 78% (Gerber 1983 p 153)<br />
Later, Bitton <strong>and</strong> Mitchell removed 95% of the viruses from water by magnetic filtration<br />
following a 10 minutes of contact period with magnetite (added to be 250 ppm) (Gerber<br />
1983 p 153). The following years, Boliden Kemi AB reduced phosphorus of water<br />
supplies at least 87%. (Gerber 1983 p 154).<br />
B. Physics of the process<br />
a. Introduction of the concept
<strong>Magnetic</strong> separation, particularly the high gradient magnetic separation (HGMS), is the<br />
method of entrapping magnetic particles from a non-magnetic medium by the virtue of<br />
high gradient magnetic fields. The high gradients are obtained as a consequence of<br />
distortion of the magnetic field by ferromagnetic wire matrix present in a separation<br />
column.<br />
b. Comparison to magnetic separation <strong>and</strong> applications which could not be done by<br />
normal magnetic separation.<br />
HGMS methods have been successful in separating weakly paramagnetic materials of the<br />
order of microns, efficiently unlike traditional magnetic separation techniques (Parker<br />
1981). HGMS has been successfully applied to remove cells (Safarik, 1999) <strong>and</strong> proteins<br />
(Bucak 2003), organic (Moeser 2002) <strong>and</strong> inorganic contaminants using functionalized<br />
magnetic materials, all of which will be exemplified in the related applications sections.<br />
c. Physics <strong>and</strong> Fluid dynamics of the method.<br />
<strong>Magnetic</strong> separation occurs on account of the force balance between the various<br />
competing forces acting on a magnetic particle like hydrodynamic drag arising due to the<br />
flow velocity, magnetic force due the applied field, diffusion force <strong>and</strong> inter-particle<br />
forces like Helmotz double layer interaction, dipole-dipole interaction <strong>and</strong> Van Der<br />
Waals attraction. The diffusion forces become important in the nanometer regime<br />
because the energy required to move a particle, attains comparability with the thermal
energy of the Brownian motion, hence setting up a number density gradient (Fletcher<br />
1998). Hence, the magnetic, dipole-dipole interaction <strong>and</strong> Van Der Waals forces aid the<br />
process of separation, whereas, diffusion, double layer interaction <strong>and</strong> drag force act<br />
against the separation.<br />
Since the magnitude of magnetic (Fm), drag (Fh) <strong>and</strong> diffusional (Fd) forces are<br />
prominent, we shall consider these for the force balance.<br />
Fm + Fh + Fd = 0<br />
Fm = μ VpMp<br />
o ∇<br />
H<br />
where µo is the permeability of free space, Vp is the particle volume, Mp is the core<br />
magnetization of the particle <strong>and</strong> grad H is the magnetic field gradient(order of Ms/a -<br />
Parker 1981) in the vicinity of a capture center (e.g Ferromagnetic wire) (Gerber <strong>and</strong><br />
Birss, 1983).<br />
Fh = 6πηbv<br />
Where η is the viscosity of the solvent in which the nanosized magnetite particles are<br />
dispersed, b is the particle radius <strong>and</strong> v is the flow velocity.
kT<br />
Fd = − ∇n<br />
n<br />
W ⎛ K<br />
n = no<br />
exp( ⎜<br />
kT ⎝ 2ra<br />
4<br />
1<br />
+<br />
ra<br />
2<br />
⎞<br />
⎟<br />
⎠<br />
Where, ‘n’ denotes the particle number density, no is the bulk particle density away from<br />
the wire, k the Boltzmann constant, T is the temperature, W = 2πMsHob3/3, K= Ms/2µoHo<br />
<strong>and</strong> ra = r/a. (Fletcher 1991)<br />
Gradient also given as dH/dx = -2Bo a 2 /b 3 (Oberteuffer 1974)<br />
Explanation of force figure <strong>and</strong> graph will take one more paragraph.<br />
C. <strong>Industrial</strong> (Column) <strong>Applications</strong><br />
As briefly mentioned above, separation by means of a magnet gained strong grounds<br />
when high gradient magnetic separation (HGMS) was introduced. Its ability of h<strong>and</strong>ling<br />
particles down to nanometer scale on a large scale <strong>and</strong> high flow rate with affordable cost<br />
even inspired engineers to say: “Virtually every process in the chemical engineering<br />
industry is a potential application (for HGMS). Many previously unthinkable processes<br />
will now become practical, <strong>and</strong> many previously practical ones will become unthinkable.<br />
It has already happened in the kaolin industry, <strong>and</strong> is beginning to happen elsewhere.”<br />
(Henry Kolm, September 1975)(Kolm 1975 IEEE). Apart from kaolin, the “elsewhere”<br />
would mainly be steel related applications. Thanks to the construction of industrial plants<br />
where steel is heavily used, almost all piping builds up iron particulates. These can be<br />
cleaned most efficiently by a magnet preferably with a ferromagnetic matrix, in other
words with a high gradient magnetic separator. Table 1 summarizes the general use of<br />
magnetic separation in industry.<br />
Fields of Application Objective<br />
Chemical <strong>and</strong> allied industries<br />
Food, drink <strong>and</strong> tobacco manufacturing<br />
Coal processing<br />
Metals industries<br />
<strong>Industrial</strong> raw materials processing<br />
(cement, refractory materials, glass s<strong>and</strong>s,<br />
etc.)<br />
Removal of tramp metal for machinery<br />
protection <strong>and</strong> avoidance of wear<br />
Extraction of ferrous contamination,<br />
including free iron, ferrosilicon, magnetite,<br />
etc.<br />
Mineral dressing industries Extraction or enrichment of magnetic ores<br />
(magnetite, hematite, ilminite, etc.<br />
Table 1. <strong>Industrial</strong> applications of magnetic separation (From Parker 1977 Contemp<br />
Phys.)<br />
a. Kaolin (clay) decolorization<br />
Kaolin (a.k.a. china clay) is a clay mixture with the main component kaolinite<br />
(Al2O2SiO2.2H2O or Al2Si2O5(OH)4) mineral (Gerber 1983 p131). Named from the<br />
Kaoling Hills of the city of Ching-te chen where fine Chinese porcelains were produced,<br />
kaolin quickly found its place in industries where resistance to acids <strong>and</strong> alkalis was<br />
necessary. In today’s world, however, it’s mostly used (80%) for paper manufacturing<br />
industry where it plays dual role:<br />
1. as a filler between the pulp fibers<br />
2. as a surface coating for a white glossy finish
(Saikia 2003, Iannicelli 2000, Gerber 1983 p132, China Clay Producers<br />
Association)<br />
Naturally colored due to the iron containing micas, tourmaline, pyrite, anatase <strong>and</strong> rutile,<br />
kaolin needs to be magnetically cleaned before used in paper or porcelain (Oder 1973,<br />
Oder 1976 IEEE, Gerber 1983 p132, Lofthouse 1981). Since the first magnetic removal<br />
of impurities by J. M. Huber Corp. in 1969, kaolin is processed for coating quality<br />
throughout the world with continuous high gradient magnetic separator (Figure 2).<br />
Competing with the leaching process, where chemical resistance of impurities limits<br />
usage, HGMS h<strong>and</strong>les 75% of world production (Oder 1976). A typical plant would<br />
have an HGMS with a filter diameter of about 2 m <strong>and</strong> capacity up to 20 tons/h<br />
(Hirschbein 1982). Figure 3 shows kaolin mineral before <strong>and</strong> after the decolorization<br />
process.
Figure 2. Metso® High Gradient <strong>Magnetic</strong> Separators (HGMS) are designed to recover<br />
weakly magnetic material from non-magnetic matter <strong>and</strong> can be used for many<br />
applications including the processing of clays, iron ores, rare earths <strong>and</strong> industrial<br />
minerals. In addition to the strongly magnetic minerals of Fe, Co, <strong>and</strong> Ni, a vast number<br />
of weakly magnetic minerals, which are not normally treatable by ordinary magnetic<br />
separators, may be processed by High Gradient <strong>Magnetic</strong> Separators. Metso HGMS<br />
separators are able to remove even weakly paramagnetic materials. (From Metso<br />
Minerals)
Figure 3. Kaolin decolorizes to white after magnetic separation . Courtesy of<br />
R.Weller/Cochise College <strong>and</strong> U.S. Geological Survey.<br />
b. Steel production<br />
Conventional methods for cleaning steel mill waste <strong>and</strong> process waters include<br />
sedimentation, flocculation followed by sedimentation, <strong>and</strong> fixed bed filtration.<br />
Sedimentation methods require large areas for settling tanks <strong>and</strong> clarifiers (Oberteuffer<br />
1975). Table 2 lists some of the contaminants generated in a steel production process. On<br />
average 1 ton of steel needs 151 tons of water for cooling, cleaning purposes. Apparently,<br />
the process generates many magnetic particulates. Those particles, especially the ones in<br />
the gas <strong>and</strong> hot water streams, need vast space <strong>and</strong> heavy machinery for removal by<br />
regular methods, filtration, flocculation, etc. <strong>Magnetic</strong> separation, instead, offers great<br />
time, space <strong>and</strong> cost savings (Oberteuffer 1975, Harl<strong>and</strong> 1976, Gerber 1983 p133). In a<br />
sample treatment at Kawasaki Steel Corporation of Japan, a 3 kOe field strength, 2.1 m
diameter magnetic filter removes 80% of contaminants from the cooling wastewater of<br />
vacuum degassing process (Hirschbein 1982).<br />
Sources Contaminants<br />
Coke production Non-magnetic particles, dissolved organics, oil<br />
Iron making <strong>Magnetic</strong> particles, dissolved organics<br />
Steel making <strong>Magnetic</strong> particles<br />
Hot forming <strong>Magnetic</strong> particles, oil, acids<br />
Cold finishing <strong>Magnetic</strong> particles, oil<br />
Table 2. Sources of contaminants in a steel production process (Oberteuffer 1975).<br />
Power plants (both conventional <strong>and</strong> nuclear) with wastewater, steam <strong>and</strong> cooling<br />
systems often requires filtering off the ferromagnetic or paramagnetic particulates<br />
clumping on the thermal, process streams (Berger 1983 book page).<br />
Fly ash from coal power plants has 18% iron oxides. <strong>Magnetic</strong> filtration is capable of<br />
saving 15% of fly ash <strong>and</strong> recycling it. Estimates show that this can replace some of the<br />
magnetite used in industry (Hirschbein 1982). Figure 4 shows an example of a ball mill<br />
separator used in these operations.
Figure 4. A ball mill separator from Eriez. <strong>Separation</strong> of ball mill grinding ball segments<br />
from the discharge.<br />
c. Enrichment of ores – Mineral Beneficiation<br />
Treatment of ores with magnetic separation carried out mostly for 2 purposes:<br />
Enrichment of iron ores or cleaning non-iron ores from iron species. The very similar<br />
density of transition metal minerals makes it challenging to use conventional methods of
separation. The magnetic nature of iron species, therefore, plays a crucial role in the<br />
beneficiation of the ores.<br />
Among the iron ores taconite leads for the need of magnetic beneficiation. From a<br />
taconite ore (33% iron) kell<strong>and</strong> (kell<strong>and</strong> 1973) was able to recover iron at 95% on a 5<br />
cm/sec flow rate. Today, Metso Minerals, Inc. (formerly Sala International AB) offers<br />
magnetic separators that can separate iron from ores up to 100% (depending on the<br />
particulate sizes, magnetic field <strong>and</strong> flow rate). Figure 5 shows a successful continuous<br />
HGMS separator.<br />
Figure 5. Continuous High Gradient <strong>Magnetic</strong> <strong>Separation</strong> for many low susceptibility<br />
minerals that are associated with other minerals or have extra Fe in the crystals, <strong>and</strong> are<br />
hence often possible to separate. (From Metso Minerals)
<strong>Magnetic</strong> separation of pyrite (FeS2) from coal for desulfurization is also very much<br />
practiced by industrial means (Maxwell 1978). The weakly magnetic nature of pyrite,<br />
however, led to pretreatments for better removal. The most useful procedure was found to<br />
be the thermal conversion of pyrite (FeS2, Ms=0.3 emu/g) to pyrrohite (Fe7S8, Ms=22<br />
emu/g). Up to 91% removal of sulfur from coal was achieved by microwave heating<br />
followed by a magnetic separation (Uslu 2003). Figure 6 shows a picture of Eugene Hise<br />
testing magnetic separation on pulverized coal. Figure 7 has an industrial scale drum<br />
separator used in large scale applications.<br />
Figure 6. Eugene Hise pours crushed coal into a magnetic separator designed to remove<br />
contaminants from pulverized coal. (Courtesy of Oak Ridge National <strong>Lab</strong>oratory<br />
(ORNL). Ref: ORNL Review 1992 Vol 25 (3-4) Chapter 7)
Figure 7. An industrial scale drum separator used in large scale applications. From Eriez<br />
manual.<br />
d. Food industry
General use of magnetic separation in food industry is removing rare earth elements<br />
from food ingredients. Similar to the ore beneficiation or desulfurization, the target<br />
substances are weakly magnetic <strong>and</strong> need high magnetic fields applied to a continous<br />
process of food production line.<br />
Bunting <strong>Magnetic</strong>s Co. offers magnetic metal separators <strong>and</strong> metal detectors for the<br />
quality of food <strong>and</strong> extended service life of the processing equipment, especially for<br />
cheese processing, chocolate plants, pet food processing, flour mills, spice plants,<br />
vegetable processing. Removal of both ferrous <strong>and</strong> nonferrous tramp metals is achieved<br />
by their line of food safety products for the food processing industry (For more<br />
information visit www.buntingmagnetics.com). Figure 8, 9 <strong>and</strong> 10 show case studies<br />
from Greenwood <strong>Magnetic</strong>s Ltd. (For more information visit<br />
www.greenwoodmagnetics.com).<br />
Figure 8. A single row easy-clean grid box was supplied to a major international food<br />
producer. Manufactured to specification, the grid was fitted with a perspex inspection
window <strong>and</strong> safety switches. The high-density rare earth easy-clean magnetic tubes<br />
filter loose tea with a flow rate of 5tph. Internally the welds were fully laid, ground<br />
smooth <strong>and</strong> crack <strong>and</strong> crevice free to food industry st<strong>and</strong>ards.<br />
Figure 9. The Bullet magnet was specified by a leading flour producer. Flour flows<br />
upwards through the 5” pipe <strong>and</strong> any ferrous contamination is removed by the high<br />
intensity rare earth bullet magnet (8500 gauss min). This particular customer specified a<br />
bolted flat door, so that the magnet could be completely removed when required.<br />
Figure 10. A water-jacketed pipeline magnet was supplied to Fox’s Biscuits.<br />
Manufactured to suit a 4” pipeline pressure resistant up to 10bar, nine high intensity rare<br />
earth magnets (11500 gauss) filter liquid chocolate flowing at 300l/minute. The
pressurised heated water-jacket maintains the temperature of the chocolate. All 316<br />
stainless steel, <strong>and</strong> manufactured to food industry st<strong>and</strong>ards.<br />
e. Arsenic removal – Water treatment (JT)<br />
[in progress]<br />
D. Biotechnological (Batch) <strong>Applications</strong><br />
The ability to control remotely inspired many biotechnologists <strong>and</strong> medical scientists to<br />
investigate magnetic solutions for several biochemical processes, such as protein <strong>and</strong> cell<br />
separations <strong>and</strong> purifications, magnetic drug targeting <strong>and</strong> delivery, <strong>and</strong> enzyme based<br />
bio-catalysis. Unlike industrial applications, in-lab or batch applications require tailor-<br />
made magnetic materials but remain fine with steady, not continuous, bench-top or batch,<br />
process solutions. First, we will give key components of a magnetic material to be used in<br />
vivo <strong>and</strong> then review some of the biological applications of magnetic separation.<br />
a. Materials requirement<br />
In vivo applications of magnetic materials require biocompatibility. Thus, biochemists<br />
tend to use naturally existing minerals, such as magnetic iron oxides (magnetite, Fe3O4<br />
<strong>and</strong> maghemite, γ-Fe2O3), due to their biologically safe nature i.e. in the ferrofluids<br />
(Tartaj 2003 J of Phy).
A summary of key requirements for a bio-magnetic separation material is as follows (also<br />
depicted in Figure 8):<br />
1. Biocompatibility<br />
2. Suitable linkers<br />
3. Functional layers on magnetic core<br />
4. Protective layer<br />
5. Antigen detection<br />
6. Shape recognition<br />
7. Fluorescent signaling
Figure 11. On a single particle, several necessary sections of a magnetic material that<br />
could be used in biological systems is summarized. (from ref. [Salata 2004 Review] with<br />
permission)<br />
b. Protein purification<br />
<strong>Magnetic</strong> separation of biological entities proven to be rapid <strong>and</strong> more effective for over<br />
30 years now (Robinson 1973 Biotech, Lilly 1974 Biotech, Guesdon 1977<br />
Immunochem, Hirschbein 1982 ApplBiochem, Hubbuch 2001). Proper coating <strong>and</strong><br />
labeling of the magnetic particles <strong>and</strong> the target species would yield hassle-free <strong>and</strong><br />
time-saver purifications with reduced costs (Setchell 1985, Safarik 2004<br />
BiomagResTech). Although very effective, magnetic affinity separations need to be<br />
very specific. Immobilization of lig<strong>and</strong>s on the magnetic adsorbents for the capture of<br />
the target species is crucial <strong>and</strong> perhaps because of this, though st<strong>and</strong>ard liquid column<br />
chromatography is currently the most often used technique, magnetic separations will<br />
prevail with significant research in magnetic affinity separations <strong>and</strong> biochemical<br />
analysis (Safarik 2004 BiomagResTEch). Recent studies on magnetic materials for<br />
protein separations involve silica coated magnetite with amino functionality for salmon<br />
sperm DNA elution (Bruce 2005 Langmuir), phospholipid coated magnetite for<br />
myoglobin recovery (Bucak 2003 BiotechnolProg), polyethylenimine coated magnetite<br />
for purification of plasmid DNA from bacterial cells (Chiang 2005 J ChromatogB),<br />
magnetic separation of erbium (III) attached biological particles (Evans 1981 Science),<br />
magnetic polyacrylamide-agarose beads for measuring rabbit antibody (Guesdon 1977),
magnetic polymer latexes for isolation of trypsin from pancreatic extract (Khng 1998),<br />
ProtA-immobilized magnetic immunomicrospheres for immunoaffinity purification of<br />
antibodies IgG2a from mouse ascites (Liu 2004 JApplPolS), silica coated magnetite<br />
with iminodiacetic acid functionality for bovine hemoglobin (BHb) <strong>and</strong> bovine serum<br />
albumin (BSA) (Ma 2006 Coll), streptavidin-functionalized magnetic nanoparticles for<br />
stimulant biotoxin (Mertz 2005 JMMM), magnetite <strong>and</strong> nickel particles for the<br />
immobilization of a-chymotrypsin (Munro 1975 IEEE), Nickel-NiO-BSA-chymotrypsin<br />
for casein hydrolysis (Munro 1981 BiotechBioeng), magnetic affinity support for<br />
adsorption of lysozyme (Tong 2001 BiotechProg), streptavidin-biotin coated magnetic<br />
beads for DNA-RNA isolation (Uhlen 1989 Nature), polyethyleneimine coated<br />
magnetite for virus capture (Veyret 2005 AnalBiochem), carboxyl-modified magnetic<br />
nanobeads for the isolation of genomic DNA from human whole blood (Xie 2004<br />
JMMM), TeNT-linked iron oxide nanobeads with dextran coating for explaining the<br />
relative capacity of the specific compartments of a cell resulting from endocytosis<br />
through different receptors that promote antigen presentation <strong>and</strong> immune (Perrin-<br />
Cocon 2001 JMMM). Figure 8 describes a st<strong>and</strong>ard setup for a bench-top magnetic<br />
separation (Tartaj 2003 Review). Figure 9 shows a summary of the available magnetic<br />
separators (Safarik 2004 BiomagResTech).
Figure 12. A simple, st<strong>and</strong>ard representation of a bio-magnetic separation. (From Tartaj<br />
2003)
Figure 13. Examples of batch magnetic separators applicable for magnetic separation of<br />
proteins <strong>and</strong> peptides. A: Dynal MPC -S for six microtubes (Dynal, Norway); B: Dynal<br />
MPC – 1 for one test tube (Dynal, Norway); C: Dynal MPC – L for six test tubes<br />
(Dynal, Norway); D: magnetic separator for six Eppendorf tubes (New Engl<strong>and</strong><br />
Bio<strong>Lab</strong>s, USA); E: MagneSphere Technology <strong>Magnetic</strong> <strong>Separation</strong> St<strong>and</strong>, two position<br />
(Promega, USA); F: MagnaBot Large Volume <strong>Magnetic</strong> <strong>Separation</strong> Device (Promega,<br />
USA); G: MagneSphere Technology <strong>Magnetic</strong> <strong>Separation</strong> St<strong>and</strong>, twelve-position<br />
(Promega, USA); H: Dynal MPC – 96 S for 96-well microtitre plates (Dynal, Norway);<br />
I: MagnaBot 96 <strong>Magnetic</strong> <strong>Separation</strong> Device for 96-well microtitre plates (Promega,<br />
USA); J: BioMag Solo-Sep Microcentrifuge Tube Separator (Polysciences, USA); K:<br />
BioMag Flask Separator (Polysciences, USA); L: MagneSil <strong>Magnetic</strong> <strong>Separation</strong> Unit<br />
(Promega, USA); M: MCB 1200 processing system for 12 microtubes based on MixSep<br />
process (Sigris Research, USA); N: PickPen magnetic tool (Bio-Nobile, Finl<strong>and</strong>).<br />
Reproduced with the permission of the above mentioned companies; the photos were<br />
taken from their www pages. (REF: Safarik 2004 Protein Review)<br />
In an excellent review, Safarik <strong>and</strong> Safarikova discuss advantages <strong>and</strong> the equipment for<br />
a successful protein purification via magnetic means with a full scan of magnetic<br />
separation applications in isolation of enzymes, antibodies <strong>and</strong> proteins (Safarik 2004<br />
Biomag Res Tech). The efforts for the industrial scale applications are noteworthy <strong>and</strong><br />
can be applied for a few biological molecules (Hubbuch 2002 BiotechBioeng, Safarik<br />
2001 BiotechLett).
<strong>Magnetic</strong> separation based protein analysis <strong>and</strong> detection systems on chips are of great<br />
interest for early diagnosis for fatal infections. Biobarcoded magnetic beads (Nam 2003<br />
Science), microfluidic biochemical detection system (Choi 2002 <strong>Lab</strong>OnaChip),<br />
micromachined magnetic particle separator (Ahn 1996) are prominent examples of this<br />
field.<br />
Recently, nanorods of Ni with Au edges were successfully used to remove His-tagged<br />
proteins with 90% recovery (Lee 2004 Angew<strong>and</strong>te).<br />
c. Cell separation<br />
Similar to protein purifications, magnetic separations offer rapid quantification, high<br />
cell recovery when compared to the conventional methods, i.e. centrifugation (Chang<br />
2005 J Ind Microbiol). As early as 1977, 99% recovery of neuroblasioma cells was<br />
obtained in a matter of minutes (Kronick 1977 Science). Same year, magnetic separation<br />
of red blood cells <strong>and</strong> lymphoid cells were also introduced (Molday 1977 Nature).<br />
<strong>Magnetic</strong> separation of cells is advantageous over the conventional methods mainly<br />
because it lets target cells to be isolated directly from the medium, i.e. blood, bone<br />
marrow, tissue homogenates, stool, cultivation, media, food, water, soil etc (Safarik<br />
1999 JChromB).
<strong>Lab</strong>eled cells, i.e. neural progenitor cells (Lewin 2000 Nature Biotech), red blood cells<br />
(Haukanes 1993 Nature Biotech, Takayasu 2000, Zborowski 2003 BiophysicalJ, Seesod<br />
1997 Am J Trop Med Hyg), tumor cells (Wang 2004 NanoLett), malarial parasites<br />
(Melville 1981 IEEE), baker’s yeast (Azevedo 2003 IEEE), can be targeted to magnetic<br />
beads which can therefore be separated (Pankhurst 2003). <strong>Magnetic</strong> moment or giant<br />
magnetoresistance of the magnetic particle-cell assembly can tell us about the location<br />
<strong>and</strong> even the count of the cells that are present (Pankhurst 2003).<br />
With efforts to take magnetic cell separation to industrial level, Berger <strong>and</strong> coworkers<br />
were able to develop a micro cell separator (Berger 2001 Electrophoresis), Haik<br />
introduced a magnetic device for continuous separation of red blood cells (Haik 1999<br />
JMMM) <strong>and</strong> Zborowski applied a magnetic quadrupole flow sorter on a model cell<br />
system of human peripheral lymphocytes targeted with commercial monoclonal<br />
antibodies <strong>and</strong> iron-dextran colloid (Zborowski 1999 JMMM). Figure 14 <strong>and</strong> 15 shows<br />
two examples of magnetic devices for cell separations.<br />
Recently, magnetic nanowires were experimented with cell separation techniques <strong>and</strong><br />
found to be four times better in purity (80 %) <strong>and</strong> recovery (85%) yields (Hultgren 2004<br />
IEEE).
Figure 14. <strong>Magnetic</strong>ally labeled cells can be separated on a gravity feed through a high<br />
gradient magnetic separator (HGMS). From ref (Berger 2001 Electrophoresis)
Figure 15. A magnetic device for separation of red blood cells. (from ref [Haik 1999<br />
JMMM])<br />
d. Drug Delivery
Bio-distribution of pharmaceuticals always faces a big challenge: Unspecific, evenly<br />
distribution of the drugs all over the body. This requires a large amount of the dose<br />
to get enough of it to the target which also brings a side effect of the non-specific<br />
toxicity in healthy sectors. Among other drug targeting methods, magnetic targeting<br />
offers one of the most viable solutions to the targeting problem (Torchilin 2000<br />
Europ J Pharm). To our knowledge, first applications in magnetic drug targeting<br />
date back to late 1970s (Mosbach 1979 <strong>and</strong> Senyei 1978, Widder 1978).<br />
For a successful delivery, a carrier must also be fully controllable. Aggregation,<br />
clogging or intrinsic, permanent magnetic behavior is completely unacceptable.<br />
Superparamagnetic iron oxides, therefore, offer both requirements for being an<br />
excellent shuttle for a successful drug delivery. Figure 12 explains how a<br />
magnetically targeted carrier would work.
Figure 16. <strong>Magnetic</strong> Targeted Carriers (MTC) offer a target oriented drug delivery.<br />
(Courtesy of FeRx Inc. from Saiyed 2003)<br />
Researchers at FeRx Inc. were able to craft iron particles with activated carbon (1-2<br />
μm) <strong>and</strong> attach Doxorubicin, an anti-cancer drug (Wilson 2004 Radiology). They<br />
used the magnetic particle – drug assembly to cure cancer tumor in a reversible drug<br />
release fashion (Saiyed 2003, http://www.magneticsmagazine.com/e-<br />
prints/ReRx.pdf). Sadly, FeRx, Inc. is now out of business <strong>and</strong> laid off most of its<br />
employees (For more information visit<br />
http://www.biotechcareercenter.com/FeRx.html,<br />
http://www.9news.com/acm_news.aspx?OSGNAME=KUSA&IKOBJECTID=c17c<br />
7125-0abe-421a-00b3-c79476c2f9f1&TEMPLATEID=0c76dce6-ac1f-02d8-0047-<br />
c589c01ca7bf).<br />
As can be clearly seen in FeRx example, physical (magnetic properties to drug<br />
binding capacity) <strong>and</strong> physiological (target position to body weight) limitations for<br />
the in vivo studies resulted unsuccessful clinical trials which only encouraged more<br />
in depth research (Dobson 2006 DDT). For this reason, using epirubicin, an<br />
anticancer drug, Lubbe <strong>and</strong> coworkers identified the potential of ferrofluids (Lubbe<br />
1999 JMMM). More theoretical studies followed: a mathematical model for<br />
magnetic targeted drug delivery (Grief 2005 JMMM), a hypothetical magnetic drug<br />
targeting system using FEMLAB simulations with the high gradient magnetic<br />
separation (HGMS) principles (Ritter 2004 JMMM), a two-step targeted drug
delivery system (Rosengart 2005 JMMM), <strong>and</strong> a new method for locally targeted<br />
drug delivery with magnetic implants in the cardiovascular system (Yellen 2005<br />
JMMM). Regardless, anti-cancer drug delivery via magnetic carriers increases drug<br />
concentration at the tumor site <strong>and</strong> limits the systemic drug concentration, by which<br />
it enhances the drug activity to multiples of magnitude (Neuberger 2005 JMMM).<br />
Recent treatments with magnetic drug targeting involved using of MTCs (<strong>Magnetic</strong><br />
Targeted Carriers) in liver <strong>and</strong> lung (Goodwin 1999 JMMM), treatment of squamous<br />
cell carcinoma in rabbits with FFs (ferrofluids) bound to mitoxantrone (FF-MTX)<br />
that was concentrated with a magnetic field (Alexiou 2000 Cancer Res, Alexiou<br />
2005 JMMM), preparation of magnetic liposomes containing submicron-sized<br />
ferromagnetic particles encapsulating the muscle relaxant drugs, diadony or<br />
diperony, for local anesthesia (Kuznetsov 2001 JMMM), an improved method for<br />
the physical delivery of rAAV vectors in vivo in which virion particles are<br />
conjugated to microsphere supports (Mah 2002 Mol Therapy), thrombosis treatment<br />
using a composition of ferrofluid with fibrinolytic enzyme (Rusetski 1990 JMMM),<br />
nucleic acid delivery with magnetically labeled non-viral vectors (Schillinger 2005<br />
JMMM)<br />
e. Biocatalysis<br />
This newly developing field is strictly bound to the control of the magnetic beads<br />
that can immobilize several bio-catalysts, mainly enzymes, such as β-lactamase
(Gao 2003 ChemComm) <strong>and</strong> peroxidase (Yang 2004 Anal Chem). Figure 17 shows<br />
how an enzyme can be immobilized on a nano iron oxide.<br />
Figure 17. Preparation of enzyme immobilized, silica coated nano iron oxide.<br />
(courtesy of Gao 2003 CC)<br />
E. Acknowledgements<br />
The authors would like to thank the NSF (EEC-0118007) Center of Biological <strong>and</strong><br />
Environmental Nanotechnology <strong>and</strong> the Robert A. Welch Foundation (C-1349) for<br />
funding <strong>and</strong> XYZ for their invaluable help.
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