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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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