superparamagnetism and its biological applications

a presentation on superparamagnetism and its biological applications

1. Few subjects are more difficult to understand than magnetism. Encyclopedia Britannica Presented By- R. UDAY KIRAN Superparamagnetism and its Biological Applications

2. Nanotechnology Plays by Different Rules Normal scale Nanoscale

3. 3 Description of magnetic particles

4. MESOSCOPIC MAGNETISM macroscale nanoscale permanent magnets micron particles nanoparticles clusters molecular clusters Individual spins S = 10 23 10 10 10 8 10 6 10 5 10 4 10 3 10 2 10 1 multi - domain single - domain Single molecule nucleation, propagation and annihilation of domain walls uniform rotation quantum tunneling, quantum interference -1 1 -40 -20 20 40 M/M S m H(mT) -1 1 -100 100 M/M S m H(mT) -1 1 -1 1 M/M S m H(T) Fe 8 1K 0.1K 0.7K Mn 12 -ac Ferritin 1 nm 10 nm 100 nm superparamagnetism Classical Quantum size

5. Natural Nanomagnets : Ferritin Man on average has 3-4 g of iron 30 mg per day are exchanged in plasma . Ferritin stores iron in mineral form ; Ferritins are found in animals, vegetables, mushrooms and bacteria The internal core, 7 nm, may contain up to 4,000 iron(III) ions Approximately FeO(OH) Magnetism depends on the number of ions Magnetic measurements provide information on the number of ions in the core Magnetosomes Nanomagnets embedded in cell membranes Magneto tactic bacteria iron core

6. Magnetism in reduced dimensions Intrinsic properties Finite-size effects Surface effects Interparticle interactions Nanomagnetism Size, aspect ratio distribution

7. Magnetism in reduced dimensions Surface effects lower coordination number broken magnetic exchange bonds frustrated magnetic interactions surface spin disorder reduced M in ferri -, antiferro -systems enhanced M in metallic ferro -systems Surface and core magnetic orders spin glass? dead magnetic layer? bulk-like? high-field irreversibilities high saturation fields shifted hysteresis loops

8. 8 Magnetic Moment vs. Cluster Size Figure above from: Billas et al., J. Magn . Magn . Mater. 168 (1997) 64

9. Superparamagnetism Superparamagnetism (SPM) is a type of magnetism that occurs in small ferromagnetic or ferrimagnetic nanoparticles . This implies sizes around a few nanometers to a couple of tenth of nanometers , depending on the material. Additionally, these nanoparticles are single-domain particles. In a simple approximation , the total magnetic moment of the nanoparticle can be regarded as one giant magnetic moment, composed of all the individual magnetic moments of the atoms which form the nanoparticle .

10. Superparamagnetism For a magnetic particle the magnetic energy with uniaxial anisotropy is given by For particles with nanometric dimensions Superparamagnetic relaxation is the spontaneous fluctuations of the magnetization direction such that it alternately is near θ=0 and θ=180 . The superparamagnetic relaxation time τ is given by where τ is of the order of 10 -10 -10 -13 s, k B is the Boltzmann’s constant and T is the temperature.

11. Superparamagnetism (SPM) τ=τ exp(E / ( k B T )) Neel-Arrhenius equation τ – Average length of time that it takes for a ferromagnetic cluster to randomly flip directions as a result of thermal fluctuations τ – Attempt period (characteristic of the material) E – Anisotropic energy which is proportional to V E=KV K is the anisotropy energy density constant

12. Superparamagnetism (SPM) Blocking temperature T b E=KV=25k B T b T>T b τ < < τ Behave like Paramagnetic particle T<T b τ > > τ Magnetic ordering and open loops If V↓ then τ ↓ SPM limit of hard drives REF: IEEE Transaction on Magnetics Vol 33, No. 1(1997)978-983 An upper bound of about 36 Gbit/in.2 τ=τ exp(E / (k B T)) Neel-Arrhenius equation

13. What are the implications of such superparamagnetic states? Without external magnetic field, the net moment is zero. As soon as an external field is applied, the nanoparticles react similar to a paramagnet (hence the “ paramagnetism ” in the name) with the one exception that their magnetic susceptibility is much larger (hence the “super” in the name). A word of clarification: Normally, any ferromagnetic or ferrimagnetic material can behave paramagnetically . This is from a certain temperature on and upwards, the so called Curie temperature Tc However , superparamagnetic behaviour is observed below the Cure temperature and thus has to be explained differently.

14. New Properties of SPM Small size and larger magnetic moment for each particle like Ferromagnetism --Large M S Response to external field like paramagnetic response---No open loop Superparamagnetic relaxation τ=τ exp(E / ( k B T )) Neel-Arrhenius equation

15. Paramagnet, Ferromagnet & Superparamagnet Zero Magnetic Field Magnetic Field Applied Paramagnet Domain moments align randomly—no net moment. Net moment appears; the applied magnetic field helps the domains “find” each other to become coupled. Ferromagnet Domain moments coupled (below Curie temp.) to produce strong, permanent moment. Even higher magnetic moment. Superparamagnet Domain moments that would couple as in Ferromagnet do not do so because of small size—boundary effect. Domains “find” each other and now it generates a moment comparable to Ferromagnet .

16. Types of Magnetism

17. Application of Magnetic Nanoparticles in Biomedicine Their size is comparable to the targeted entities. Nanoparticles can be magnetic. An external magnetic field gradient can be applied to influence their movement . This way, they can either deliver certain drugs or tag certain entities. Nanoparticles may also be resonantly excited. This allows heat transfer to the surrounding tissue.

18. Radionuclide and Gene Delivery Radionuclide Delivery: An advantage of radionuclide therapy is that the radionuclides do not have to decouple from the magnetic carriers. The magnetic carriers can transport the radionuclides to the target area where they can destroy the cancerous tissue. After the desired result has been achieved, both the carriers and the radionuclides can be directed out of the circulatory system. Gene Therapy: In gene therapies, the magnetic carriers are coated with the therapeutical gene and transported to the target area . Thanks to the possibilitiy of holding the gene and carrier at the target for an extended time, the chances rise that the gene can get transfected . Applications in this field of study are only in their beginning

19. Ferrofluids : Suppose some particles do have magnetic moments. N S N S N S N S They will chain together! The chain causes high viscosity.  Magnetorheological effect .

20. Magnetorheological Effect

21. A magnetic fluid.

22. Just pretty.

23. Hyperthermia: Hyperthermia is usually an unwanted overheating of the body not to be confused with common fever. In a hyperthermic state, the body absorbes or produces more heat than it can dissipate . However, hyperthermia can also be a wanted effect in order to destroy tumorous cells and hence is sometimes created artificially. The magnetic particles first have to be brought to the target area, where they can be caused to heat up by an AC magnetic field of sufficient strength and frequency. The heat should exceed the threshold of 42 degree Celsius and last for about 30 minutes in order to properly destroy the tumour.

24. Mechanism of heating process for MNPs Hyperthermia 1. Hysteresis loss Hysteresis loss at different temp. Applied field H(T) Magnetization (emu/g) T c T 2 T 1 2. Neel mechanism Rotation of the magnetization vector within the particles. 3. Brownian Mechanism Mechanical rotation of the magnetic particle Intrinsic superparamagnetism (the particle magnetic moments aligns with external field) Extrinsic superparamagnetism (the particle itself aligns with field) H

25. H=0 H ≠ 0 H=0 Ne ́ el relaxation H = 0 Brownian relaxation Magnetic relaxation mechanisms

26. Drug Delivery The advantages of targeted drug delivery seem numerous: Most drugs are non-specific , i.e. they get distributed over the whole body as soon as they get administered intravenously. Targeted delivery can ensure that only specific areas get influenced by the (otherwise harmful) drugs and as little as possible of the drug needs to be administered. This method seems especially applicable, when the drug is very damaging to healthy tissue. Fields of application: • Chemotherapy, • radionuclide therapy, • arthritis or • gene therapy.

27. Gene Delivery Att tillföra en ny gen i en cell FeOfection is a solution of nanoparticles with an iron oxide core. The core is stable and the magnetic properties can be used e.g. in tracking of cells with MRI. The surface of the particles are modified to promote binding of DNA to the particles and facilitate transport of the resulting particle/DNA complexes into cells. FeOfection can be used for both transient (temporary expression) and stable (incorporated in the genome) transfection .

28. Imaging using magnetic nanoparticles Marknaden drivs av ett medicinskt behov av effektivare och känsligare diagnostik

29. Iron Oxide NH 2 Phospholipid Amino-PEG NHS-Alexa 647 Iron Oxide NH 2 U-2 OS cell incubated with Alexa-647 magnetic nanoparticles for 1 hour FeOdots incubated with cells and exposed to a magnetic field NH 2 NH 2

30. Imaging - Regenerative medicine Stamceller märks med Genovis magnetiska nanopartiklar ex vivo och injeceras i mus T2* Map Prussian blue positive cells at edge of tumor C6 glioma FeOlabeled cells were injected i.v. in C6 glioma in mouse flank 14 days prior to 3T MRI Cells labeled with FeOlabel can easily be visualised with MRI. Mesenchymal stem cells were labeled with FeOlabel and then injected into a mouse with a C6 glioma. After 14 days the cells are visible with MRI. Particles can also be visualised by Prussian Blue iron staining.

31. Challenges in Nanomagnetism 100% spin- polarized materials Magnetic logic Instant boot-up computer Spin-transistor with gain RT magnetic semiconductors Nano-bio Mag-sensors Ultra-strong Permanent Magnets Ultra High density media Opportunities in Nanomagnetism

32. Superparamagnetism Superparamagnetism paramagnetism below Curie’s temperature large susceptibility superparamagnetism limit Origin of superparamagnetism magnetism: result of spin alignment thermal excitation, ferromagnetism <-> paramagnetism small scale, below Tc: thermal excitation destroys the ordering between the clusters thermal excitation cannot upset alignment within the cluster ferro~ inside & para~ outside => treated as a large spin as a whole Experiment results stepped hysteresis can be found below certain temperature. frequency dependent AC susceptibility

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36. Thank You.

37. QUESTIONS???