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Invited Talk

Invited Talk. National Conference on ‘Materials for Electrical, Electronic & Magnetic Applications: Characterization & Measurements (MEEMA-2005) September 2-3,2005, DMRL-Hyderabad. Certain Characteristics of Nanomagnetic Particles with

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Invited Talk

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  1. Invited Talk • National Conference on • ‘Materials for Electrical, Electronic & Magnetic Applications: Characterization & Measurements (MEEMA-2005) • September 2-3,2005, DMRL-Hyderabad

  2. Certain Characteristics of Nanomagnetic Particles with Special reference to Biomagnetic Applications R V Mehta, R V Upadhyay,Rucha Desai CSIR-Emeritus Scientist, Department of Physics, Bhavnagar University, Bhavnagar Acknowledgement Council of Scientific and Industrial Research, Department of Science & Technology and Gujarat Council Of Science and Technology

  3. In this talk certain biomedical applications of fine ferro (ferri) magnetic particles in general and ferrofluid in particular will be described. The talk is divided into the four sections. • Background • Novel phenomena exhibited by a ferrofluid • Preparation • Physics behind the use of FF in BMD • Biomedical Applications

  4. (I) Background (a) What is a ferrofluid? (b) What is its composition? (c) Brief History (d) Science of ferrofluid (e) Potential Application of ferrofluid

  5. (II) Novel Phenomena (a) Liquid magnet (b) Defying gravity (C) Levitation of non magnetic object (d) Self levitation (e) Generation of fluid motion without any mechanical means (f) Ability to conduct magnetic flux (g) Spontaneous formation of stable liquid spikes in presence of critical magnetic field. These and several other properties are well explained on basis of Rosensweig model of Ferrohydrodynamics. Certain additional properties like viscosity and asymmetric flow are batter explained on Shliomis model which takes into account spin of the particles. A ferrifluid appears and behaves like any normal black liquid. But as soon as one applies a magentic field - particularly a gradient magnetic field, its fascinating properties are revealod.

  6. (III) Preparation (a) Ball milling (b) Co-precipitation (c) Decomposition of metal carbonyl (d) Reduction of metal salt (e) Electrolytic process (f) Evaporation technique

  7. 1. Why Nanomagnetic particles ? (i) Size is smaller than a cell, a gene & a protein (ii) They can be coated with biomolecules. 2. What should be their characteristics. (i) Low toxicity (ii) High magnetization (iii) Narrow size distribution 3. Surface Modification. (i) For stability (ii) Producing Functional groups for binding (iii) Avoid immediate uptake by the Reticulendothelial System (RES)

  8. (IV) Physics behind the use of FF in BMA 1. Size of FF particle is 4-10 nm Cell size : 10 to 100 m Virus : 20 to 450 nm Protein : 5 - 50 nm gene : 2 nm wide and 10 to 100 nm long 2. A fine magnetic particle can be coated with a biomolecule e.g. protein, silane starch etc. This facillate to interact it with or bound to a biological entity. Thus a biomolecule of interest can be “tagged” or “labeled”.

  9. 3. Due to Columbian interaction one can position or immobilize it with the help of an external magnetic field. It shall be remarked here that a magnetic field can penetrate a living tissue. Hence one can transport – say an anticancer drug to a targetted region of a body – say a tumour by magnetic means. Moreover nanomagnets can be made to resonantly respond to a time varying magnetic field. This may lead to transfer of energy from the exciting field to the nanoparticle resulting in the heating of the particle. This phenomenon can be used in cancer treatment by hyperaemia.

  10. One question may occur that when we introduced magnetic particles in a human body and apply an external magnetic field whether this field has effects other biocomponents of body e.g. blood, tissues bones etc? We know that tissues and bones are diamagnetic while blood is paramagnetic. To find whether the magnetic response of these materials has any effect on net response of the magnetic particles subject to an external field, one has to study response of all type of particles. B = 0 ( H + M) M = m / V M =  H  is dimensionaless in SI system and M & H are in A / m Diamagnet d :~ -10-6 to 10-3 Paramagnet p :~ 10-6 to 10-1 Ferromagnet f :~ 1 f depends on T as well as H

  11. Notes: - (1) FM gives rise to hysteresis loop which is due to irreversibility of magnetization process that is related to pinning of domain walls at imurities or grain boundaries as well as due to intrinsic effects such as the magnet crystalline anisotropy. (2) Area of the loop depend upon size of the particles. Multi-domain (large - particle) needs little energy for wall movement. Hence loop is narrow - while single Domain ground state leads to broad loop. Still smaller size ( ~ 10 nm) gives rise to SPM. Here particle moments is free to rotate in response to thermal energy while the individual atomic moment maintains their ordered state with respect to each other. This leads to anisotropic but still sigmoidal shape.

  12. SPM : - Activation law for relaxation time of the net magnetization  = 0 exp ( E / kB T ) E is the energy barrier to moment reversal and kB T is the thermal energy For non - interacting particles 0 in range of10-10 to 10-12 sec and weakly dependent on temperature. E arises due to (I) Magneto crystalline anisotropy and / or (II) Shape anisotropy. For uniaxial form E = KV where K is the anisotropy energy density and V is a particle volume. Since E  V, For small particles, the thermal activation due to kB T causes the flipping of the net moment direction which results in SPM for ferro / ferri magnetic particles. NOTE : - SPM depends also on meas

  13. (I) meas <<  the flipping is slow and quasi static properties are observed called “blocked” state. (II) meas >>  the flipping is prominent compared to the experimental time and particles “appear” paramagnetic at the same temperature and same size. Blocking temprature is  = meas DC magnetization time scale : 102 S AC susceptibility : ~ 10-1 to 10-5 S Mössbauer or ESR : ~ 10-7 to 10-9 S

  14. From above we conclude (I) Signal (magnetic response) due to magnetic particle is far larger than bio-materials of the body. (II) Energy is required to overcome the barrier to domain wall motion imposed by the intrinsic anisotropy or impurities and grain boundaries in the materials. This energy is supplied by external field under suitable condition for a time varying magnetic field. There will be continuous flow of energy from field to the material which may be transferred into heat. This is the physical basis of hyperthermia. (III)For SP particles also energy transfer arises due to the requirement of energy to coherently align the moments to achieve the saturation state.

  15. Force on Nanomagnets: - For targeted drug delivery or magnetic separation of bio-molecules translatory motion of nanomagnets by application of magnetic field is required. Now uniform field will give rise to torque but not translatory motion while gradient field on a dipole will give such motion [Ref. D. J. Griffiths, Intro to ED, p. 162]. Assuming a nanomagnet as a point like dipole, the drag force will be given by Fm = ( m . ) B Geometrical interpretation – differentiation with respect to the direction m. If m = (0,0,mz) then ( m . ) = mz ( / z). Hence force will exist only if the gradient field in B is in the Z – direction. When a nanomagnet is suspended in a weakly dielectric medium like water the total moment on the particle m = Vm . M where Vmis the volume of the particle and M is the volumetric magnetization given by M =  . H where  = m - wis the effective susceptibility of particle related to water.

  16. If the suspension is dilute then overall response of the particle will be B = 0 . H and Fm = Vm ( 0 ) ( B .  ) B If there will no time varying field or current in the medium then using ( x B ) = 0 to the vector identity  ( B . B ) = 2B x ( x B ) + 2 ( B .  ) B = 2 ( B .  ) B Fm = Vm (  )  (B2 / 2) = Vm (  )  ( (B . H) / 2 ) If  = 0 the magnetic force acts in the direction of stepest ascent of the energy density scalar held. Application: - • Separation • Drug targeting • Hyperthermia • MRI contrast enhancement • Biosensing • Eye surgery • Tissue engineering

  17. Magnetic separation: - • Enrichment of certain biomolecues e.g. RBC or DNA in a sample is useful in biomedicine. • These molecules are tagged or labeled using fine biocompatible magnetic particles and then separated out using a magnetic separator. • Biocompatible magnetic particles are prepared by coating biomolecules e.g. starch dextran, silane, PVA, etc. on magnetic particles. • This provides a link between the particle and the target site on a cell. Also increases colloidal stability of the fluid system. • Specific binding sites on the cell are targeted by antibodies or other biological molecules e.g. hormones. • Antibodies specifically bound to their matching antigen thus the cell is labeled. • RBC, lung cancer cells, bacteria, urological cancer cells are successfully labeled in this way.

  18. Principle of Separator: - The fluid mixture containing the labeled material is passed through a region having proper field gradient. The later immobilize the labeled material via the magnetic force eqn. described above. This force should overcome the hydrodynamic drag force given by Fd = 6 Rmv viscosity, Rm – radius of the magnetic particle, v – vm - vw is the difference in velocities of the cell and the water. Buoyancy force which depend on the difference between the Density of the cell and water being small – may be neglected. Taking Vm = 4 / 3  Rm3 and equating the two forces, we get v = (( Rm2  ) / gn ) .( B2 ) or v = ( 0 ) .( B2 ) - magnetophoretic mobility (MPM) . (MPM)FM > (MPM)SPM

  19. Seperators: - (a) Simple Disadvantage: - slow accumulation rate Unwanted Labled (b) Column seperator Unwanted (c) Magnets in Quadrature (a) Longitudional section (b) Crossectional view Non mettalic column Disadvantage: - Through faster settling and absorption of labeled particle on metric.

  20. Drug Delivery Physical Principle: - The usual chemotherapy being non-specific the drug attack on normal as well as the target cells. This may cause side effects. Hence localized treatment is preferred. Further dosage also will be reduced. In magnetically targeted therapy, a cytotoxic drug is attached to biocompatible magnetic nanoparticle carrier. These drug / carrier complexes – form biocompatible ferrofluid are injected into patient via circulatory system. External high gradient magnetic fields are used to concentrate the complax at a specific target site within the body. Then the drug can be released either via enzymatic activity or changing either pH, temperature, osmolatity etc. Physical principle are same as in magnetic separator and derived from the force exerted on a SPM particle by a field gradient.

  21. Parameter: - H, dH / dq, Vm, M Hydrodynamic parameters like blood flow rate, ferrofluid concentration infusion rate, circulation time Physiological parameters like tissue depth ( which decide distance of field source ) reversibility and strength of drug / cancer system tumour volume.

  22. Hyperthermia: - The procedure involves dispersing magnetic particles throughout the the target tissue and then applying an AC magnetic field of sufficient strength and frequency to cause the particle to heat. This heat conducts into the immediately surrounding diseased tissue where by if the temperature can be maintained around than therapeutic threshold of 42 0c for 30 min. or move the cancer is destroyed. The other hyperthermia devices suffers from the drawback due to coincidental heating of healthy tissue, the magnetic particle Hyperthermia is attractive because here only desired tissue gets heated.

  23. Problems: - Enough heat must be generated by the magnetic particle to sustain tissue temperature of at least 42 0c for 30 min. But blood flow and tissue perfusion – which cool the tissue complicates the heat deposition rate. Further both the above parameters vary significantly as tissue is heated. [Rule of thumb – the deposition rate of 100 mWcm-3]. The frequency and strength of the externally applied field HFMF adversely affects the physiological responses viz. stimulation of peripheral and skeltal muscles, cardiac stimulation and non – specific inductive heating of tissue. Useable range f : 0.05 – 1.2 MHz H : 0 – 15 kA / m empirical rule : Hf > 4.85 X 108 A / ms

  24. Amount of magnetic material Depends on method of administration. (I) Direct – large dose (II) Intravascular or antibody targetting usual range S = 10 mg / cc of tumor tissue. (4) Choice of particle – Fe3O4 / Fe2O3

  25. Heating mechanisms: - (A) Large FM particles: Heat generated per unit volume PFM = 0 f (Ignore eddy current and FMR heating) Even with strong anisotropic magnets like Sm - Co or Nd-Fe-B saturation field for loops is hardly attained. Minor loops heating reduces level of heating. 25% is ideal maximum. (B) Mfluid hyperthermia or SPM particle In fluid state, SPM state occurs due to intrinsic Neel relaxation and Brownian relaxation losses due to Brownian rotation are maximum at a lower frequency than due to Neel relaxation for a given size.

  26. Rosensweig using Debye model explained the Physics behind heating of SPM particles by AC magnetic field BSPM = 0f”H2 Measurement of the heat generation form magnetic particles are in terms of SAR in W / g. SAR x Density of particle = PFm or Pspm FM requires field :~ 100 kA / m SPM requires field  20 kA / m Example: - At 14 kA / m and 300 kHz (SAR)SPM = 209 W /g and (SAR)FM = 75 W /g

  27. Thank You

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