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    Magnetic Separation: Industrial and Lab Scale Applications

    Separation by means of magnetic field has been a mystery until the late 18th

    century

    though magnets were known since 6th

    century BC (Livingston 1997 book). The magical

    flow of the force exerted on a material by iron seemed supernatural in many ways.

    Perhaps, that was the reason it wasnt quite understood and designed for the good

    everyday life.

    Since the industrial revolution and mass production of steel, magnetic control became a

    crucial piece of modern technology. Electronics, communication was in high demand of

    magnetic technology as similar as the way magnetic ore refinement industry solely relied

    on. Magnetic force seemed best petted into magnetic separation where its uncontrollable

    power would be very handy. But it was only 1792 when a patent was filed by William

    Fullarton on separating iron minerals with a magnet (Gunther 1909, Parker 1977).

    The applications were in great interest mainly because magnetic force didnt let the

    gravity be the monopoly of the natural forces. In 1852, magnetite was separated from

    apatite by a NY company on a conveyor belt separator (Gunther 1909). Later, with the

    proven methods of beneficiation and refinement especially in the ores and minerals, a

    new line of separators were introduced for separation of iron from brass fillings, turnings,

    metallic iron from furnace products and magnetite from plain gangue (Gunther 1909). A

    brief timeline can be seen in Figure 1.

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    FirstPatenton MS

    1792 1852 1909 1973 2006

    NY companybuilt a conveyorbelt separator

    Over 300patents filedon MS

    First nanoseparationspaper

    First sizedependentmagneticseparation

    200019001800

    Figure 1. Timeline of magnetic separation technology

    A very broad but fitting and clear classification of magnetic separations can be done as

    follows (Parker 1977):

    1. Low intensity dry magnetic separations

    2. Low intensity wet magnetic separations

    3. High intensity dry magnetic separations

    4. High intensity wet magnetic separations (i.e. High Gradient Magnetic Separation

    (HGMS))

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    A. Value of Magnetic Separation

    Although the magnetic field would make no distinction between various magnetic

    particles, magnetic separation handpicks those with magnetic affinity from physically

    similar mixtures, i.e. in terms of density, shape, and size (Svoboda 2003).

    Among many applications well discuss briefly in the following pages, the following

    ones would give a sense of how valuable magnetic separation could be. As early as 1970s

    Delatour and Kolm (Delatour 1973 and 1975) treated water samples from the Charles

    River (Fe3O4 seeding, 5ppm Al

    3+

    ) with a high flow velocity HGMS (Vo= 136 mms

    -1

    ,

    Ho=1T) to obtain the following reductions:

    - coliform bacteria from 2.2x105/l to 350/l

    - turbidity by 75%

    - color by 95%

    - suspended solids by 78% (Gerber 1983 p 153)

    Later, Bitton and Mitchell removed 95% of the viruses from water by magnetic filtration

    following a 10 minutes of contact period with magnetite (added to be 250 ppm) (Gerber

    1983 p 153). The following years, Boliden Kemi AB reduced phosphorus of water

    supplies at least 87%. (Gerber 1983 p 154).

    B. Physics of the process

    a. Introduction of the concept

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    Magnetic separation, particularly the high gradient magnetic separation (HGMS), is the

    method of entrapping magnetic particles from a non-magnetic medium by the virtue of

    high gradient magnetic fields. The high gradients are obtained as a consequence of

    distortion of the magnetic field by ferromagnetic wire matrix present in a separation

    column.

    b. Comparison to magnetic separation and applications which could not be done by

    normal magnetic separation.

    HGMS methods have been successful in separating weakly paramagnetic materials of the

    order of microns, efficiently unlike traditional magnetic separation techniques (Parker

    1981). HGMS has been successfully applied to remove cells (Safarik, 1999) and proteins

    (Bucak 2003), organic (Moeser 2002) and inorganic contaminants using functionalized

    magnetic materials, all of which will be exemplified in the related applications sections.

    c. Physics and Fluid dynamics of the method.

    Magnetic separation occurs on account of the force balance between the various

    competing forces acting on a magnetic particle like hydrodynamic drag arising due to the

    flow velocity, magnetic force due the applied field, diffusion force and inter-particle

    forces like Helmotz double layer interaction, dipole-dipole interaction and Van Der

    Waals attraction. The diffusion forces become important in the nanometer regime

    because the energy required to move a particle, attains comparability with the thermal

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    energy of the Brownian motion, hence setting up a number density gradient (Fletcher

    1998). Hence, the magnetic, dipole-dipole interaction and Van Der Waals forces aid the

    process of separation, whereas, diffusion, double layer interaction and drag force act

    against the separation.

    Since the magnitude of magnetic (Fm), drag (Fh) and diffusional (Fd) forces are

    prominent, we shall consider these for the force balance.

    0=++

    FdFhFm

    HMVFm ppo =

    whereo is thepermeability of free space, Vp is the particle volume,Mp is the core

    magnetization of the particle andgrad His the magnetic field gradient(order ofMs/a -

    Parker 1981) in the vicinity of a capture center (e.g Ferromagnetic wire) (Gerber and

    Birss, 1983).

    bvFh 6=

    Where is the viscosity of the solvent in which the nanosized magnetite particles are

    dispersed, b is the particle radius and v is the flow velocity.

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    +=

    =

    24

    1

    2exp(

    aa

    o

    rr

    K

    kT

    Wnn

    nn

    kTFd

    Where, n denotes the particle number density, no is the bulk particle density away from

    the wire, k the Boltzmann constant, T is the temperature, W = 2MsHob3/3,K= Ms/2oHo

    and ra = r/a. (Fletcher 1991)

    Gradient also given as dH/dx = -2Bo a2/b

    3(Oberteuffer 1974)

    Explanation of force figure and graph will take one more paragraph.

    C. Industrial (Column) Applications

    As briefly mentioned above, separation by means of a magnet gained strong grounds

    when high gradient magnetic separation (HGMS) was introduced. Its ability of handling

    particles down to nanometer scale on a large scale and high flow rate with affordable cost

    even inspired engineers to say: Virtually every process in the chemical engineering

    industry is a potential application (for HGMS). Many previously unthinkable processes

    will now become practical, and many previously practical ones will become unthinkable.

    It has already happened in the kaolin industry, and is beginning to happen elsewhere.

    (Henry Kolm, September 1975)(Kolm 1975 IEEE). Apart from kaolin, the elsewhere

    would mainly be steel related applications. Thanks to the construction of industrial plants

    where steel is heavily used, almost all piping builds up iron particulates. These can be

    cleaned most efficiently by a magnet preferably with a ferromagnetic matrix, in other

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    words with a high gradient magnetic separator. Table 1 summarizes the general use of

    magnetic separation in industry.

    Fields of Application Objective

    Chemical and allied industries

    Food, drink and tobacco manufacturing

    Coal processing

    Metals industries

    Removal of tramp metal for machinery

    protection and avoidance of wear

    Industrial raw materials processing

    (cement, refractory materials, glass sands,

    etc.)

    Extraction of ferrous contamination,

    including free iron, ferrosilicon, magnetite,

    etc.

    Mineral dressing industries Extraction or enrichment of magnetic ores

    (magnetite, hematite, ilminite, etc.

    Table 1. Industrial applications of magnetic separation (From Parker 1977 Contemp

    Phys.)

    a. Kaolin (clay) decolorization

    Kaolin (a.k.a. china clay) is a clay mixture with the main component kaolinite

    (Al2O2SiO2.2H2O or Al2Si2O5(OH)4) mineral (Gerber 1983 p131). Named from the

    Kaoling Hills of the city of Ching-te chen where fine Chinese porcelains were produced,

    kaolin quickly found its place in industries where resistance to acids and alkalis was

    necessary. In todays world, however, its mostly used (80%) for paper manufacturing

    industry where it plays dual role:

    1. as a filler between the pulp fibers

    2. as a surface coating for a white glossy finish

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    (Saikia 2003, Iannicelli 2000, Gerber 1983 p132, China Clay Producers

    Association)

    Naturally colored due to the iron containing micas, tourmaline, pyrite, anatase and rutile,

    kaolin needs to be magnetically cleaned before used in paper or porcelain (Oder 1973,

    Oder 1976 IEEE, Gerber 1983 p132, Lofthouse 1981). Since the first magnetic removal

    of impurities by J. M. Huber Corp. in 1969, kaolin is processed for coating quality

    throughout the world with continuous high gradient magnetic separator (Figure 2).

    Competing with the leaching process, where chemical resistance of impurities limits

    usage, HGMS handles 75% of world production (Oder 1976). A typical plant would

    have an HGMS with a filter diameter of about 2 m and capacity up to 20 tons/h

    (Hirschbein 1982). Figure 3 shows kaolin mineral before and after the decolorization

    process.

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    Figure 2. Metso High Gradient Magnetic Separators (HGMS) are designed to recover

    weakly magnetic material from non-magnetic matter and can be used for many

    applications including the processing of clays, iron ores, rare earths and industrial

    minerals. In addition to the strongly magnetic minerals of Fe, Co, and Ni, a vast number

    of weakly magnetic minerals, which are not normally treatable by ordinary magnetic

    separators, may be processed by High Gradient Magnetic Separators. Metso HGMS

    separators are able to remove even weakly paramagnetic materials. (From Metso

    Minerals)

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    Figure 3. Kaolin decolorizes to white after magnetic separation . Courtesy of

    R.Weller/Cochise College and U.S. Geological Survey.

    b. Steel production

    Conventional methods for cleaning steel mill waste and process waters include

    sedimentation, flocculation followed by sedimentation, and fixed bed filtration.

    Sedimentation methods require large areas for settling tanks and clarifiers (Oberteuffer

    1975). Table 2 lists some of the contaminants generated in a steel production process. On

    average 1 ton of steel needs 151 tons of water for cooling, cleaning purposes. Apparently,

    the process generates many magnetic particulates. Those particles, especially the ones in

    the gas and hot water streams, need vast space and heavy machinery for removal by

    regular methods, filtration, flocculation, etc. Magnetic separation, instead, offers great

    time, space and cost savings (Oberteuffer 1975, Harland 1976, Gerber 1983 p133). In a

    sample treatment at Kawasaki Steel Corporation of Japan, a 3 kOe field strength, 2.1 m

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    diameter magnetic filter removes 80% of contaminants from the cooling wastewater of

    vacuum degassing process (Hirschbein 1982).

    Sources Contaminants

    Coke production Non-magnetic particles, dissolved organics, oil

    Iron making Magnetic particles, dissolved organics

    Steel making Magnetic particles

    Hot forming Magnetic particles, oil, acids

    Cold finishing Magnetic particles, oil

    Table 2. Sources of contaminants in a steel production process (Oberteuffer 1975).

    Power plants (both conventional and nuclear) with wastewater, steam and cooling

    systems often requires filtering off the ferromagnetic or paramagnetic particulates

    clumping on the thermal, process streams (Berger 1983 book page).

    Fly ash from coal power plants has 18% iron oxides. Magnetic filtration is capable of

    saving 15% of fly ash and recycling it. Estimates show that this can replace some of the

    magnetite used in industry (Hirschbein 1982). Figure 4 shows an example of a ball mill

    separator used in these operations.

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    Figure 4. A ball mill separator from Eriez. Separation of ball mill grinding ball segments

    from the discharge.

    c. Enrichment of ores Mineral Beneficiation

    Treatment of ores with magnetic separation carried out mostly for 2 purposes:

    Enrichment of iron ores or cleaning non-iron ores from iron species. The very similar

    density of transition metal minerals makes it challenging to use conventional methods of

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    separation. The magnetic nature of iron species, therefore, plays a crucial role in the

    beneficiation of the ores.

    Among the iron ores taconite leads for the need of magnetic beneficiation. From a

    taconite ore (33% iron) kelland (kelland 1973) was able to recover iron at 95% on a 5

    cm/sec flow rate. Today, Metso Minerals, Inc. (formerly Sala International AB) offers

    magnetic separators that can separate iron from ores up to 100% (depending on the

    particulate sizes, magnetic field and flow rate). Figure 5 shows a successful continuous

    HGMS separator.

    Figure 5. Continuous High Gradient Magnetic Separation for many low susceptibility

    minerals that are associated with other minerals or have extra Fe in the crystals, and are

    hence often possible to separate. (From Metso Minerals)

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    Magnetic separation of pyrite (FeS2) from coal for desulfurization is also very much

    practiced by industrial means (Maxwell 1978). The weakly magnetic nature of pyrite,

    however, led to pretreatments for better removal. The most useful procedure was found to

    be the thermal conversion of pyrite (FeS2, Ms=0.3 emu/g) to pyrrohite (Fe7S8, Ms=22

    emu/g). Up to 91% removal of sulfur from coal was achieved by microwave heating

    followed by a magnetic separation (Uslu 2003). Figure 6 shows a picture of Eugene Hise

    testing magnetic separation on pulverized coal. Figure 7 has an industrial scale drum

    separator used in large scale applications.

    Figure 6. Eugene Hise pours crushed coal into a magnetic separator designed to remove

    contaminants from pulverized coal. (Courtesy of Oak Ridge National Laboratory

    (ORNL). Ref: ORNL Review 1992 Vol 25 (3-4) Chapter 7)

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    Figure 7. An industrial scale drum separator used in large scale applications. From Eriez

    manual.

    d. Food industry

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    General use of magnetic separation in food industry is removing rare earth elements

    from food ingredients. Similar to the ore beneficiation or desulfurization, the target

    substances are weakly magnetic and need high magnetic fields applied to a continous

    process of food production line.

    Bunting Magnetics Co. offers magnetic metal separators and metal detectors for the

    quality of food and extended service life of the processing equipment, especially for

    cheese processing, chocolate plants, pet food processing, flour mills, spice plants,

    vegetable processing. Removal of both ferrous and nonferrous tramp metals is achieved

    by their line of food safety products for the food processing industry (For more

    information visit www.buntingmagnetics.com). Figure 8, 9 and 10 show case studies

    from Greenwood Magnetics Ltd. (For more information visit

    www.greenwoodmagnetics.com).

    Figure 8. A single row easy-clean grid box was supplied to a major international food

    producer. Manufactured to specification, the grid was fitted with a perspex inspection

    http://www.buntingmagnetics.com/http://www.greenwoodmagnetics.com/http://www.greenwoodmagnetics.com/http://www.buntingmagnetics.com/
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    window and safety switches. The high-density rare earth easy-clean magnetic tubes

    filter loose tea with a flow rate of 5tph. Internally the welds were fully laid, ground

    smooth and crack and crevice free to food industry standards.

    Figure 9. The Bullet magnet was specified by a leading flour producer. Flour flows

    upwards through the 5 pipe and any ferrous contamination is removed by the high

    intensity rare earth bullet magnet (8500 gauss min). This particular customer specified a

    bolted flat door, so that the magnet could be completely removed when required.

    Figure 10. A water-jacketed pipeline magnet was supplied to Foxs Biscuits.

    Manufactured to suit a 4 pipeline pressure resistant up to 10bar, nine high intensity rare

    earth magnets (11500 gauss) filter liquid chocolate flowing at 300l/minute. The

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    pressurised heated water-jacket maintains the temperature of the chocolate. All 316

    stainless steel, and manufactured to food industry standards.

    e. Arsenic removal Water treatment (JT)

    [in progress]

    D. Biotechnological (Batch) Applications

    The ability to control remotely inspired many biotechnologists and medical scientists to

    investigate magnetic solutions for several biochemical processes, such as protein and cell

    separations and purifications, magnetic drug targeting and delivery, and enzyme based

    bio-catalysis. Unlike industrial applications, in-lab or batch applications require tailor-

    made magnetic materials but remain fine with steady, not continuous, bench-top or batch,

    process solutions. First, we will give key components of a magnetic material to be used in

    vivo and then review some of the biological applications of magnetic separation.

    a. Materials requirement

    In vivo applications of magnetic materials require biocompatibility. Thus, biochemists

    tend to use naturally existing minerals, such as magnetic iron oxides (magnetite, Fe3O4

    and maghemite, -Fe2O3), due to their biologically safe nature i.e. in the ferrofluids

    (Tartaj 2003 J of Phy).

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    A summary of key requirements for a bio-magnetic separation material is as follows (also

    depicted in Figure 8):

    1. Biocompatibility

    2. Suitable linkers

    3. Functional layers on magnetic core

    4. Protective layer

    5. Antigen detection

    6. Shape recognition

    7. Fluorescent signaling

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    Figure 11. On a single particle, several necessary sections of a magnetic material that

    could be used in biological systems is summarized. (from ref. [Salata 2004 Review] with

    permission)

    b. Protein purification

    Magnetic separation of biological entities proven to be rapid and more effective for over

    30 years now (Robinson 1973 Biotech, Lilly 1974 Biotech, Guesdon 1977

    Immunochem, Hirschbein 1982 ApplBiochem, Hubbuch 2001). Proper coating and

    labeling of the magnetic particles and the target species would yield hassle-free and

    time-saver purifications with reduced costs (Setchell 1985, Safarik 2004

    BiomagResTech). Although very effective, magnetic affinity separations need to be

    very specific. Immobilization of ligands on the magnetic adsorbents for the capture of

    the target species is crucial and perhaps because of this, though standard liquid column

    chromatography is currently the most often used technique, magnetic separations will

    prevail with significant research in magnetic affinity separations and biochemical

    analysis (Safarik 2004 BiomagResTEch). Recent studies on magnetic materials for

    protein separations involve silica coated magnetite with amino functionality for salmon

    sperm DNA elution (Bruce 2005 Langmuir), phospholipid coated magnetite for

    myoglobin recovery (Bucak 2003 BiotechnolProg), polyethylenimine coated magnetite

    for purification of plasmid DNA from bacterial cells (Chiang 2005 J ChromatogB),

    magnetic separation of erbium (III) attached biological particles (Evans 1981 Science),

    magnetic polyacrylamide-agarose beads for measuring rabbit antibody (Guesdon 1977),

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    magnetic polymer latexes for isolation of trypsin from pancreatic extract (Khng 1998),

    ProtA-immobilized magnetic immunomicrospheres for immunoaffinity purification of

    antibodies IgG2a from mouse ascites (Liu 2004 JApplPolS), silica coated magnetite

    with iminodiacetic acid functionality for bovine hemoglobin (BHb) and bovine serum

    albumin (BSA) (Ma 2006 Coll), streptavidin-functionalized magnetic nanoparticles for

    stimulant biotoxin (Mertz 2005 JMMM), magnetite and nickel particles for the

    immobilization of a-chymotrypsin (Munro 1975 IEEE), Nickel-NiO-BSA-chymotrypsin

    for casein hydrolysis (Munro 1981 BiotechBioeng), magnetic affinity support for

    adsorption of lysozyme (Tong 2001 BiotechProg), streptavidin-biotin coated magnetic

    beads for DNA-RNA isolation (Uhlen 1989 Nature), polyethyleneimine coated

    magnetite for virus capture (Veyret 2005 AnalBiochem), carboxyl-modified magnetic

    nanobeads for the isolation of genomic DNA from human whole blood (Xie 2004

    JMMM), TeNT-linked iron oxide nanobeads with dextran coating for explaining the

    relative capacity of the specific compartments of a cell resulting from endocytosis

    through different receptors that promote antigen presentation and immune (Perrin-

    Cocon 2001 JMMM). Figure 8 describes a standard setup for a bench-top magnetic

    separation (Tartaj 2003 Review). Figure 9 shows a summary of the available magnetic

    separators (Safarik 2004 BiomagResTech).

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    Figure 12. A simple, standard representation of a bio-magnetic separation. (From Tartaj

    2003)

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    Figure 13. Examples of batch magnetic separators applicable for magnetic separation of

    proteins and peptides. A: Dynal MPC -S for six microtubes (Dynal, Norway); B: Dynal

    MPC 1 for one test tube (Dynal, Norway); C: Dynal MPC L for six test tubes

    (Dynal, Norway); D: magnetic separator for six Eppendorf tubes (New England

    BioLabs, USA); E: MagneSphere Technology Magnetic Separation Stand, two position

    (Promega, USA); F: MagnaBot Large Volume Magnetic Separation Device (Promega,

    USA); G: MagneSphere Technology Magnetic Separation Stand, twelve-position

    (Promega, USA); H: Dynal MPC 96 S for 96-well microtitre plates (Dynal, Norway);

    I: MagnaBot 96 Magnetic Separation Device for 96-well microtitre plates (Promega,

    USA); J: BioMag Solo-Sep Microcentrifuge Tube Separator (Polysciences, USA); K:

    BioMag Flask Separator (Polysciences, USA); L: MagneSil Magnetic Separation Unit

    (Promega, USA); M: MCB 1200 processing system for 12 microtubes based on MixSep

    process (Sigris Research, USA); N: PickPen magnetic tool (Bio-Nobile, Finland).

    Reproduced with the permission of the above mentioned companies; the photos were

    taken from their www pages. (REF: Safarik 2004 Protein Review)

    In an excellent review, Safarik and Safarikova discuss advantages and the equipment for

    a successful protein purification via magnetic means with a full scan of magnetic

    separation applications in isolation of enzymes, antibodies and proteins (Safarik 2004

    Biomag Res Tech). The efforts for the industrial scale applications are noteworthy and

    can be applied for a few biological molecules (Hubbuch 2002 BiotechBioeng, Safarik

    2001 BiotechLett).

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    Magnetic separation based protein analysis and detection systems on chips are of great

    interest for early diagnosis for fatal infections. Biobarcoded magnetic beads (Nam 2003

    Science), microfluidic biochemical detection system (Choi 2002 LabOnaChip),

    micromachined magnetic particle separator (Ahn 1996) are prominent examples of this

    field.

    Recently, nanorods of Ni with Au edges were successfully used to remove His-tagged

    proteins with 90% recovery (Lee 2004 Angewandte).

    c. Cell separation

    Similar to protein purifications, magnetic separations offer rapid quantification, high

    cell recovery when compared to the conventional methods, i.e. centrifugation (Chang

    2005 J Ind Microbiol). As early as 1977, 99% recovery of neuroblasioma cells was

    obtained in a matter of minutes (Kronick 1977 Science). Same year, magnetic separation

    of red blood cells and lymphoid cells were also introduced (Molday 1977 Nature).

    Magnetic separation of cells is advantageous over the conventional methods mainly

    because it lets target cells to be isolated directly from the medium, i.e. blood, bone

    marrow, tissue homogenates, stool, cultivation, media, food, water, soil etc (Safarik

    1999 JChromB).

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    Labeled cells, i.e. neural progenitor cells (Lewin 2000 Nature Biotech), red blood cells

    (Haukanes 1993 Nature Biotech, Takayasu 2000, Zborowski 2003 BiophysicalJ, Seesod

    1997 Am J Trop Med Hyg), tumor cells (Wang 2004 NanoLett), malarial parasites

    (Melville 1981 IEEE), bakers yeast (Azevedo 2003 IEEE), can be targeted to magnetic

    beads which can therefore be separated (Pankhurst 2003). Magnetic moment or giant

    magnetoresistance of the magnetic particle-cell assembly can tell us about the location

    and even the count of the cells that are present (Pankhurst 2003).

    With efforts to take magnetic cell separation to industrial level, Berger and coworkers

    were able to develop a micro cell separator (Berger 2001 Electrophoresis), Haik

    introduced a magnetic device for continuous separation of red blood cells (Haik 1999

    JMMM) and Zborowski applied a magnetic quadrupole flow sorter on a model cell

    system of human peripheral lymphocytes targeted with commercial monoclonal

    antibodies and iron-dextran colloid (Zborowski 1999 JMMM). Figure 14 and 15 shows

    two examples of magnetic devices for cell separations.

    Recently, magnetic nanowires were experimented with cell separation techniques and

    found to be four times better in purity (80 %) and recovery (85%) yields (Hultgren 2004

    IEEE).

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    Figure 14. Magnetically labeled cells can be separated on a gravity feed through a high

    gradient magnetic separator (HGMS). From ref (Berger 2001 Electrophoresis)

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    Figure 15. A magnetic device for separation of red blood cells. (from ref [Haik 1999

    JMMM])

    d. Drug Delivery

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    Bio-distribution of pharmaceuticals always faces a big challenge: Unspecific, evenly

    distribution of the drugs all over the body. This requires a large amount of the dose

    to get enough of it to the target which also brings a side effect of the non-specific

    toxicity in healthy sectors. Among other drug targeting methods, magnetic targeting

    offers one of the most viable solutions to the targeting problem (Torchilin 2000

    Europ J Pharm). To our knowledge, first applications in magnetic drug targeting

    date back to late 1970s (Mosbach 1979 and Senyei 1978, Widder 1978).

    For a successful delivery, a carrier must also be fully controllable. Aggregation,

    clogging or intrinsic, permanent magnetic behavior is completely unacceptable.

    Superparamagnetic iron oxides, therefore, offer both requirements for being an

    excellent shuttle for a successful drug delivery. Figure 12 explains how a

    magnetically targeted carrier would work.

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    Figure 16. Magnetic Targeted Carriers (MTC) offer a target oriented drug delivery.

    (Courtesy of FeRx Inc. from Saiyed 2003)

    Researchers at FeRx Inc. were able to craft iron particles with activated carbon (1-2

    m) and attach Doxorubicin, an anti-cancer drug (Wilson 2004 Radiology). They

    used the magnetic particle drug assembly to cure cancer tumor in a reversible drug

    release fashion (Saiyed 2003, http://www.magneticsmagazine.com/e-

    prints/ReRx.pdf). Sadly, FeRx, Inc. is now out of business and laid off most of its

    employees (For more information visit

    http://www.biotechcareercenter.com/FeRx.html,

    http://www.9news.com/acm_news.aspx?OSGNAME=KUSA&IKOBJECTID=c17c

    7125-0abe-421a-00b3-c79476c2f9f1&TEMPLATEID=0c76dce6-ac1f-02d8-0047-

    c589c01ca7bf).

    As can be clearly seen in FeRx example, physical (magnetic properties to drug

    binding capacity) and physiological (target position to body weight) limitations for

    the in vivo studies resulted unsuccessful clinical trials which only encouraged more

    in depth research (Dobson 2006 DDT). For this reason, using epirubicin, an

    anticancer drug, Lubbe and coworkers identified the potential of ferrofluids (Lubbe

    1999 JMMM). More theoretical studies followed: a mathematical model for

    magnetic targeted drug delivery (Grief 2005 JMMM), a hypothetical magnetic drug

    targeting system using FEMLAB simulations with the high gradient magnetic

    separation (HGMS) principles (Ritter 2004 JMMM), a two-step targeted drug

    http://www.biotechcareercenter.com/FeRx.htmlhttp://www.9news.com/acm_news.aspx?OSGNAME=KUSA&IKOBJECTID=c17c7125-0abe-421a-00b3-c79476c2f9f1&TEMPLATEID=0c76dce6-ac1f-02d8-0047-c589c01ca7bfhttp://www.9news.com/acm_news.aspx?OSGNAME=KUSA&IKOBJECTID=c17c7125-0abe-421a-00b3-c79476c2f9f1&TEMPLATEID=0c76dce6-ac1f-02d8-0047-c589c01ca7bfhttp://www.9news.com/acm_news.aspx?OSGNAME=KUSA&IKOBJECTID=c17c7125-0abe-421a-00b3-c79476c2f9f1&TEMPLATEID=0c76dce6-ac1f-02d8-0047-c589c01ca7bfhttp://www.9news.com/acm_news.aspx?OSGNAME=KUSA&IKOBJECTID=c17c7125-0abe-421a-00b3-c79476c2f9f1&TEMPLATEID=0c76dce6-ac1f-02d8-0047-c589c01ca7bfhttp://www.9news.com/acm_news.aspx?OSGNAME=KUSA&IKOBJECTID=c17c7125-0abe-421a-00b3-c79476c2f9f1&TEMPLATEID=0c76dce6-ac1f-02d8-0047-c589c01ca7bfhttp://www.9news.com/acm_news.aspx?OSGNAME=KUSA&IKOBJECTID=c17c7125-0abe-421a-00b3-c79476c2f9f1&TEMPLATEID=0c76dce6-ac1f-02d8-0047-c589c01ca7bfhttp://www.biotechcareercenter.com/FeRx.html
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    delivery system (Rosengart 2005 JMMM), and a new method for locally targeted

    drug delivery with magnetic implants in the cardiovascular system (Yellen 2005

    JMMM). Regardless, anti-cancer drug delivery via magnetic carriers increases drug

    concentration at the tumor site and limits the systemic drug concentration, by which

    it enhances the drug activity to multiples of magnitude (Neuberger 2005 JMMM).

    Recent treatments with magnetic drug targeting involved using of MTCs (Magnetic

    Targeted Carriers) in liver and lung (Goodwin 1999 JMMM), treatment of squamous

    cell carcinoma in rabbits with FFs (ferrofluids) bound to mitoxantrone (FF-MTX)

    that was concentrated with a magnetic field (Alexiou 2000 Cancer Res, Alexiou

    2005 JMMM), preparation of magnetic liposomes containing submicron-sized

    ferromagnetic particles encapsulating the muscle relaxant drugs, diadony or

    diperony, for local anesthesia (Kuznetsov 2001 JMMM), an improved method for

    the physical delivery of rAAV vectors in vivo in which virion particles are

    conjugated to microsphere supports (Mah 2002 Mol Therapy), thrombosis treatment

    using a composition of ferrofluid with fibrinolytic enzyme (Rusetski 1990 JMMM),

    nucleic acid delivery with magnetically labeled non-viral vectors (Schillinger 2005

    JMMM)

    e. Biocatalysis

    This newly developing field is strictly bound to the control of the magnetic beads

    that can immobilize several bio-catalysts, mainly enzymes, such as -lactamase

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    (Gao 2003 ChemComm) and peroxidase (Yang 2004 Anal Chem). Figure 17 shows

    how an enzyme can be immobilized on a nano iron oxide.

    Figure 17. Preparation of enzyme immobilized, silica coated nano iron oxide.

    (courtesy of Gao 2003 CC)

    E. Acknowledgements

    The authors would like to thank the NSF (EEC-0118007) Center of Biological and

    Environmental Nanotechnology and the Robert A. Welch Foundation (C-1349) for

    funding and XYZ for their invaluable help.

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