1

Dipartimento di Scienze Molecolari Applicate ai BiosistemiVia Trentacoste 2 - Milano

Alessandro Lascialfari

Francesco Orsini (tecnico)

Paolo Arosio (post-doc)

Dipartimento di Chimica ed ElettrochimicaMarco Scavini

Serena Cappelli (tecnico)

Unità Università degli studi di Milano

Altri partecipanti alla ricerca– Dipartimento di Fisica “A. Volta” - Università degli studi di Pavia

Maurizio Corti

Evrim Umut (dottorando)

Andrea Capozzi (laureando, da fine aprile)

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DISMAB - Via Trentacoste 2

Atomic force microscopy (AFM)Atomic force microscopy (AFM)* Atomic Force Microscopy / Scanning Tunneling Microscopy / Magnetic Force Microscopy - Autoprobe

CP Research System - Veeco. Working temperature range 0-60°C. Cell for liquids, measurements in solution.

* AFM Microscope with force spectroscopy facility, Nanoscope IIIA-Multimode, Veeco

Wide-band Nuclear Magnetic Resonance (NMR)Wide-band Nuclear Magnetic Resonance (NMR)* Fourier transform Stelar Spinmaster spectrometer for NMR (also relaxometry), working in the range

5-70 MHz (with electromagnet , magnetic field 0-1.5 Tesla) and flux cryostat (3.8 < T < 350K)• SMARTracer relaxometer by Stelar for NMR-Fast Field Cycling. Frequencies : 10 KHz < f < 10

MHz. Temperature : 150 < T < 300 K.

Muon Spin Rotation Muon Spin Rotation International facilities PSI-Switzerland and ISIS-Didcot(UK) International facilities PSI-Switzerland and ISIS-Didcot(UK)

Experimental apparatusesExperimental apparatuses

In strict collaboration, Dept. of Physics, Pavia

Wide-band Nuclear Magnetic Resonance (NMR)* Fourier transform Tecmag and Bruker spectrometers for NMR f-range 5-400 MHz (SC magnet-electromagnets 0-9

Tesla)* Cryostats for T-range 1.5<T<1000K, pressure chambers to reach 15 kbar

MagnetometryMagnetometry* SQUID magnetometer for susceptibility and magnetization measurements in the range 0-7 Tesla and 1.8-800K. 

Magnetic Resonance Imaging (MRI)• Esaote MRI-Imager ARTOSCANfor in-vitro imaging acquisition sequences at low magnetic field 0.2 Tesla

Adiabatic and non-adiabatic calorimeters, Non-conventional Electron Paramagnetic Resonance (EPR)

Dipartimento di Chimica Fisica ed Elettrochimica : slides MARCO SCAVINI

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Atomic Force Microscopy techniqueAtomic Force Microscopy techniqueAtomic Force Microscopy techniqueAtomic Force Microscopy technique

Multimode - Nanoscope 3d AFM (Veeco). Working temperature range 0-60 °C. Liquid cell for measurements in solution. PicoForce modulus for force spectroscopy measurements

Multimode - Nanoscope 3d AFM (Veeco). Working temperature range 0-60 °C. Liquid cell for measurements in solution. PicoForce modulus for force spectroscopy measurements

AutoProbe CP Research AFM (Veeco). Working temperature range 0-60 °C. Liquid cell for measurements in solution.

AutoProbe CP Research AFM (Veeco). Working temperature range 0-60 °C. Liquid cell for measurements in solution.

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Nuclear Magnetic Resonance (NMR) techniqueNuclear Magnetic Resonance (NMR) techniqueNuclear Magnetic Resonance (NMR) techniqueNuclear Magnetic Resonance (NMR) technique

Smartracer relaxometer10 kHz<f<10 MHz

(H=0.000235-0.235 Tesla)

Smartracer relaxometer10 kHz<f<10 MHz

(H=0.000235-0.235 Tesla)

Stelar Spimaster 5<f<70 MHz(H=0.1175-1.5 Tesla

Stelar Spimaster 5<f<70 MHz(H=0.1175-1.5 Tesla

WIDE BAND NMRnot high resolution

WIDE BAND NMRnot high resolution

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Nuclear Magnetic ResonanceNuclear Magnetic ResonanceNuclear Magnetic ResonanceNuclear Magnetic Resonance

NMR is a spectroscopic technique :

ResonantResonant (0 = B0 e B1 << B0) Microscopic i.e. local probeMicroscopic i.e. local probe (it studies the magnetic/electrical

interactions between nuclei, atoms and molecules) At radiofrequencyradiofrequency (0.01-1000 MHz) It’s widely used in solid and liquid state Physics, Chemistry, solid and liquid state Physics, Chemistry,

pharmacological and bio-medical worldpharmacological and bio-medical world From 1975 it is an laternative to TAC; now also better for many

applications It does not use ionizing radiationsdoes not use ionizing radiations

NMR is a spectroscopic technique :

ResonantResonant (0 = B0 e B1 << B0) Microscopic i.e. local probeMicroscopic i.e. local probe (it studies the magnetic/electrical

interactions between nuclei, atoms and molecules) At radiofrequencyradiofrequency (0.01-1000 MHz) It’s widely used in solid and liquid state Physics, Chemistry, solid and liquid state Physics, Chemistry,

pharmacological and bio-medical worldpharmacological and bio-medical world From 1975 it is an laternative to TAC; now also better for many

applications It does not use ionizing radiationsdoes not use ionizing radiations

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Nuclear Magnetic ResonanceNuclear Magnetic ResonanceNuclear Magnetic ResonanceNuclear Magnetic Resonance

APPARATUS A static magnetic field

A rf magnetic field

Electronics

Cryogenics

EXPERIMENTAL PARAMETERS3 main parameters:

spectrum

nuclear spin-spin relaxation time T2

nuclear spin-lattice relaxation time T1

LOCAL PROBE Nuclei are local probes sensitive to local hyperfine interactions

Local spin dynamics (mainly T1 and T2) and spin distribution (mainly spectra) can

be studied

In MRI and relaxometry, sensitivity to spin dynamics and molecular “motion”

APPARATUS A static magnetic field

A rf magnetic field

Electronics

Cryogenics

EXPERIMENTAL PARAMETERS3 main parameters:

spectrum

nuclear spin-spin relaxation time T2

nuclear spin-lattice relaxation time T1

LOCAL PROBE Nuclei are local probes sensitive to local hyperfine interactions

Local spin dynamics (mainly T1 and T2) and spin distribution (mainly spectra) can

be studied

In MRI and relaxometry, sensitivity to spin dynamics and molecular “motion”

Nuclei (T2n)

Electrons(T2e)

Phonons(lattice)

T1n

T1n

T1e

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Nuclear Magnetic Resonance : statics i.e. spectraNuclear Magnetic Resonance : statics i.e. spectraNuclear Magnetic Resonance : statics i.e. spectraNuclear Magnetic Resonance : statics i.e. spectra

ExamplesExamples

4.0 4.4 4.8 5.2

0

1

2

3

4

5

1H NMR

Fe8

L=197.9MHz

12K

5.5K

3K

4.2K

1.8KE

cho

inte

nsi

ty (

a.u

.)

H ( T )High-resolution NMR(not our group)

High-resolution NMR(not our group)

Wide-band NMRWide-band NMR

NMR spectra : sensitive to local magnetic field i.e. useful to estimate local field created by e.g. electrons

NMR spectra : sensitive to local magnetic field i.e. useful to estimate local field created by e.g. electrons

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NMR : spin dynamics i.e. relaxation ratesNMR : spin dynamics i.e. relaxation ratesNMR : spin dynamics i.e. relaxation ratesNMR : spin dynamics i.e. relaxation rates

0.01 0.1 1 10 100

0

5

10

15

20

25

30

35

40

Fe3O4

Au-Fe3O4 dimer

Au-Fe3O4 coreshell

Endorem

r 1 (s-1

.mM

-1)

Larmor frequency (MHz)

10 1000

20

40

60

80

100

120

140

Fe3O

4

Au-Fe3O

4 dimer

Au-Fe3O

4 coreshell

Endorem

r 2 (s-1

.mM

-1)

Larmor frequency (MHz)

NMR relaxation rates : sensitive to local electron spin dynamicsthrough hyperfine nuclei-electron interaction

NMR relaxation rates : sensitive to local electron spin dynamicsthrough hyperfine nuclei-electron interaction

1 10 100

0.000

0.002

0.004

0.006

0.008

0.010

0.012

0.014 3,54 T 1,65 T 0,65 T

1 /

T1 (

ms-1

)

T (K)

0 50 100 150 200 250 300

0

10

20

30

40

50

60

dimer sample

28 MHz70 MHz147 MHz353 MHz

1 /

T2 (

ms-1

)

Temperature (K)

Spin dynamics vs T at different constant fields

Spin dynamics vs T at different constant fields

Spin dynamics vs H at room temperature

Spin dynamics vs H at room temperature

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MUSR : spin dynamics through a different local probeMUSR : spin dynamics through a different local probeMUSR : spin dynamics through a different local probeMUSR : spin dynamics through a different local probe

MUSR relaxation rates : sensitive to local electron spin dynamicsthrough hyperfine muon-electron interaction

MUSR relaxation rates : sensitive to local electron spin dynamicsthrough hyperfine muon-electron interaction

Typical muon polarization behaviourTypical muon polarization behaviour

Polarization can be studied vs T and HPolarization can be studied vs T and H

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Magnetic Resonance ImagingMagnetic Resonance Imaging

MRI Timeline1946 MR phenomenon - Bloch & Purcell 1952 Nobel Prize - Bloch & Purcell 1950-70 NMR developed as analytical tool 1972 Computerized Tomography 1973 Backprojection MRI - Lauterbur 1975 Fourier Imaging - Ernst 1977 Echo-planar imaging - Mansfield 1980 FT MRI demonstrated - Edelstein 1986 Gradient Echo Imaging - NMR Microscope 1987 MR Angiography - Dumoulin 1991 Nobel Prize - Ernst 1992 Functional MRI 1994 Hyperpolarized 129Xe Imaging

2003 Nobel Prize - Lauterbur & Mansfield

Pavia apparatusPavia apparatus

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Magnetic Magnetic NanoNanoparticles in particles in TheranosticsTheranostics:

Research (I) :magnetic nanoparticles in biomedicineResearch (I) :magnetic nanoparticles in biomedicine

Diagnostics : Diagnostics : MRI CAMRI CA, fluorescence, fluorescenceTherapy :Therapy : MagnetothermiaMagnetothermia

AntibodyAntibody

Magnetic nucleusMagnetic nucleus

BiocompatibleBiocompatibleshellshell

Fluorescent Fluorescent moleculemolecule

DrugDrugMolecular Molecular

ImagingImagingMolecular Molecular

ImagingImaging

Research (II) :Molecular nanomagnets

SMM : finite number N of magnetic centers [e.g. Cr(III), Fe(III)], Single molecule behaviour

(very weak intermolecular interaction), AF or F interaction Non magnetic S=0 or low-spin, high-spin ground state

Single Single molecule molecule of Cr7Feof Cr7Fe

Slowly relaxing CoPhOMeSlowly relaxing CoPhOMe

SCM : magnetic chains with weak intrmolecular interactions and metallic/rare-earth

ions alternating to radical groups slow relaxation of M (NANOWIRESNANOWIRES), frustration, peculiar magnetic phases

SIM : single rare-earth ions very diluted in the lattice. Good systems for study

of quantum tunneling of magnetization (electro-nuclear coupled levels)

Crystal structureCrystal structure

pp-NO-NO22.C.C66FF44CNSSNCNSSN

Role in the project

NMR and MUSRSpectra

Relaxation rates

NMR and MUSRSpectra

Relaxation rates

Electron spin dynamics

Electron spin dynamics

Effects of plasmons/magnetoplasmonsMRI Contrast agents efficiency (r1, r2)Effects of plasmons/magnetoplasmonsMRI Contrast agents efficiency (r1, r2)

Correlation with magnetic and plasmonic propertiesCorrelation with magnetic and plasmonic properties

Requests for samples

NMR Possibly 150/200 mg or more of powders

NMR-MRI Solution with known magnetic ion concentration

Ideal concentration : 0.1-3 mg/ml of magn. center

MUSR500 mg or more of powders

NMR Possibly 150/200 mg or more of powders

NMR-MRI Solution with known magnetic ion concentration

Ideal concentration : 0.1-3 mg/ml of magn. center

MUSR500 mg or more of powders

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Projects (others : C. Lenardi, F. Orsini)Projects (others : C. Lenardi, F. Orsini)FIRB “Investigation of protein structure and function by AFM and physiological studies” (ending)EU FP7 - NANOTHER “Integration of novel NANOparticle based technology for THERapeutics and diagnosis of

different types of cancer”EU FP6 - MAGMANet “Molecular Approach to Nanomagnets and Multifunctional Materials ” (ending)Fondazione Cariplo “Processi di funzionalizzazione di polimeri per la modifica della biocompatibilità e

dell’adesione di proteine ” (ending)Fondazione Cariplo “Progettazione di nuovi biosensori magnetici per l'applicazione in scienze della salute e

ambientali ” (ending)

Main collaborations and projects

CurrentCurrently actively active main collaborations main collaborations (others : C. Lenardi, F. (others : C. Lenardi, F. Orsini)Orsini)

LOCAL, LOCAL, NATIONALNATIONAL, INTERNATIONAL, INDUSTRIES, INTERNATIONAL, INDUSTRIES• DISMAB, University of Milano (Italy), Prof. V.F. Sacchi, Dr. P. Perego, Dr. M. Castagna• Dept. Pharmacological Sciences, University of Milano, Prof. R. Paoletti, Prof. E.Tremoli, Dr.U.Guerrini, Dr.G.Sironi• Dept. Chem. And Electrochem., University of Milano, Dr. M. Scavini • S3 CNR-INFM, Modena (Italy) – AFFILIATIONAFFILIATION – Prof. M. Affronte• Dept. Physics “A. Volta” – University of Pavia (Italy) – F. Borsa, M. Corti, P. Carretta, A. Rigamonti, S. Sanna• Dept. Chemistry – University of Firenze (Italy) – D. Gatteschi, A. Caneschi, C. Sangregorio, R. Sessoli• Dept. Chemistry – University of Cagliari (Italy) – M.F. Casula• Dept. Physics, University of Parma (Italy), Dr. L. Romano’, Prof. G. Amoretti, Prof. P. Santini, Dr. S. Carretta• National Nanotechnology Laboratory, CNR-INFM, Lecce (Italy), Dr. T. Pellegrino• Dept. Physics – University of Firenze, Firenze (Italy) – Prof. A. Rettori• Dept. Physics, University of Milano Bicocca, Milano (Italy), gruppo prof. C. Riccardi • Dept. Chemistry, Manchester University (UK), prof. R. Winpenny• Dept. Physics, University of Zaragoza (Spain), Prof. F. Palacio e Dr. A. Millan• Dept. Chemistry, University of Valencia (Spain), prof. E. Coronado• Department of Physics, Boston College (USA), Prof. M. J. Graf• Inorganic Chemistry Department, University of Bucarest (Romania), prof. M. Andruh• CNRS and University of Montpellier (France), Dr. J. Larionova, Dr. Y. Guari• Centro Ricerche Colorobbia, Vinci (FI) (Italia), Dr. G. Baldi, Dr. D. Bonacchi

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MAGNETISMMAGNETISM:Scientific fields of interest

MAGNETISMMAGNETISM:Scientific fields of interest

MAGMANet (Nanother)MAGMANet (Nanother)

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Core (FeCore (Fe33OO44+Fe+Fe22OO33))

Coating (dextran...)Coating (dextran...)

SSmall mall PParticle of article of IIron ron OOxidexide( >20 nm )( >20 nm )

SPIOSPIO

Core (FeCore (Fe33OO44+Fe+Fe22OO33))

USPIOUSPIO UUltraltraSSmall mall PParticle of article of IIron ron OOxidexide

( < 15 nm )( < 15 nm )

Superparamagnetic MRI-contrast agents : Superparamagnetic MRI-contrast agents : a schemea scheme

Coating (dextran...)Coating (dextran...)

Problems : low reproducibility, unknown mixing of ferrites, not-controlled microscopic chemico-physical

properties no real control on the efficacyno real control on the efficacy

Problems : low reproducibility, unknown mixing of ferrites, not-controlled microscopic chemico-physical

properties no real control on the efficacyno real control on the efficacy

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Magnetic field biosensorsMagnetic field biosensors

IgG

BSA

AbIgG-c-Biotin

Streptavidin

Fe2O3-c-PMA-c-Biotin

ppAA

• Plasma Deposited Poly Acrylic Acid (ppAA) [1]

• Adsorption of human IgG

• Blocking of the unreacted surface groups by BSA

• Reaction with biotinated Ab-IgG molecules at different concentrations

• Absorption of streptavidin

• Absorption of biotinated modified γ-Fe2O3 superparamagnetic nanoparticles [2]

• Plasma Deposited Poly Acrylic Acid (ppAA) [1]

• Adsorption of human IgG

• Blocking of the unreacted surface groups by BSA

• Reaction with biotinated Ab-IgG molecules at different concentrations

• Absorption of streptavidin

• Absorption of biotinated modified γ-Fe2O3 superparamagnetic nanoparticles [2]

Technique of detection : SQUID. It uses the presence of magnetic nanoparticles and the labelling of biosensors

Technique of detection : SQUID. It uses the presence of magnetic nanoparticles and the labelling of biosensors

They detect protein-”anti”protein interaction

They detect protein-”anti”protein interaction

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Magnetic field biosensorsMagnetic field biosensors

• Hydrogel of Agarose (1%) directly prepared in the glass tube for NMR measurements

• Diffusion of biotinated modified γ-Fe2O3 superparamagnetic nanoparticles with mild shaking

• Diffusion of streptavidin <= WORK IN PROGRESS!!!

• Hydrogel of Agarose (1%) directly prepared in the glass tube for NMR measurements

• Diffusion of biotinated modified γ-Fe2O3 superparamagnetic nanoparticles with mild shaking

• Diffusion of streptavidin <= WORK IN PROGRESS!!!

Technique of detection : NMR. It uses the presence of magnetic nanoparticles and the labelling of biosensors

Technique of detection : NMR. It uses the presence of magnetic nanoparticles and the labelling of biosensors

They detect protein-”anti”protein interaction

They detect protein-”anti”protein interaction

Agarose

Fe2O3-c-PMA-c-Biotin

Very recent studies

SMMSMM :Cr7Fe (NMR, ) – heterometallic ring ST=1/2 distribution of magnetic moment, distribution of magnetic moment,

correlation functioncorrelation function

Dimers (NMR, ) basic exchange interactionsbasic exchange interactions

Ni10 (NMR, ) resonant resonant phonon trappingphonon trappingFeCu6, CoCu6 (NMR, ) - ST=1/2 system singlesingle molecule molecule paramagnetparamagnetFe4 (MUSR, ) - high-spin system ST=5 transitions to higher Stransitions to higher STT states states

SCMSCM :Gd-based chains (NMR) Gd-based chains (NMR) peculiar phase transitions peculiar phase transitions

(Villain’s conjecture)(Villain’s conjecture)Co or Dy-based chains (NMR, MUSR) – slowly relaxing two mechanisms of relaxation, two mechanisms of relaxation,

size effectssize effects

SIMSIM : LiYF4:Ho (MUSR) spin spin dynamics dynamics and and tunnelingtunneling

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SUPERCONDUCTORSSUPERCONDUCTORS

Cables, wires

Magnets (MRI !!)

Repulsion of Repulsion of

magnetic magnetic

fieldfield : Meissner effect

““Zero” Zero”

resistivityresistivity below

a critical T=Tc

Magnetic Levitation train

““High-THigh-Tcc“ SC“ SC

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Superconducting “fluctuations”

T

dia

Tc(0)Tc(H)

[ Theory with eexact solution xact solution : Prange (1970), but no field quenching of fluctuating pairs ]

H

T >> TC

T TC

Mdia

dia

H1/2

…..and magnetization curves

First experiments ( Gollub, Tinkham et al.) in metals evidence the

breakdown of a description which neglects the effect of the field in

suppressing the fluctuating pairs, but only from M(T) curves.

Susceptibility (already subtracted of Pauli term)………..

SF

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SOME RECENT PUBLICATIONSSOME RECENT PUBLICATIONSCACA

A.Figuerola, A. Fiore, R. Di Corato, A. Falqui, C. Giannini, E. Micotti,A.Lascialfari, M. Corti, R. Cingolani, T. Pellegrino,

P. D. Cozzoli and L.Manna. J. Am. Chem. Soc. 130, 1477 (2008)M. Corti, A. Lascialfari, M. Marinone, A. Masotti, E. Micotti, F. Orsini, G. Ortaggi, G. Poletti, C. Innocenti,

C. Sangregorio, J. Magn. Magn. Mater. 320 , e316 (2008)M. Corti, A. Lascialfari, E. Micotti, A. Castellano, M. Donativi, A. Quarta, P.D. Cozzoli, L. Manna, T. Pellegrino,

C. Sangregorio, J. Magn. Magn. Mater. 320, e320 (2008)A Boni, M Marinone, C Innocenti, C Sangregorio, M Corti, A Lascialfari, M Mariani, F Orsini,

G Poletti and M F Casula, J. Phys. D: Appl. Phys. 41, 134021 (2008)Y. Guari, J. Larionova, M. Corti, A. Lascialfari, M. Marinone, G. Poletti, K. Molvinger and C. Guérin,

Dalton Trans. 28, 3658 (2008), DOI: 10.1039/b808221a 2)A.Masotti, A. Pitta, G. Ortaggi, M. Corti, C. Innocenti, A. Lascialfari, M. Marinone, P. Marzola, A. Daducci, A.

Sbarbati, E. Micotti, F. Orsini, G. Poletti, C. Sangregorio, Magn Reson Mater Phy 22, 77 (2009)

P. Sánchez, E. Valero, N.Gálvez, J. M. Domínguez-Vera, M. Marinone, G. Poletti, M. Corti and A. Lascialfari, Dalton Transactions, 800-804 (2009)

L. Lartigue, K. Oumzil, Y. Guari, J. Larionova, C. GueLrin, J.-L. Montero, V. Barragan-Montero, C. Sangregorio, A. Caneschi,

C. Innocenti, T. Kalaivani, P. Arosio and A. Lascialfari, Organic Letters 11, 2992 (2009)

SCSCE. Bernardi, A. Lascialfari, A. Rigamonti, and L. Romanó, Phys. Rev. B 77, 064502 (2008) S. Cagliero, A. Agostino, M. Mizanur Rahman Khan, M. Truccato, F. Orsini, M. Marinone,

G. Poletti, A. Lascialfari, Appl Phys A 95, 479 (2009)A. Lascialfari, A. Rigamonti, E. Bernardi, M. Corti, A. Gauzzi, and J. C. Villegier, Phys. Rev. B 80, 104505 (2009)

MNMMNMF. Cinti, A. Rettori, M. G. Pini, M. Mariani, E. Micotti, A. Lascialfari, N. Papinutto, A. Amato, A. Caneschi,

D. Gatteschi, and M. Affronte, Phys. Rev. Lett. 100, 057203 (2008)F. Borsa, Y. Furukawa, A. Lascialfari, Inorg. Chim. Acta 361, 3777 (2008)

M.Belesi, E.Micotti, M. Mariani, F.Borsa, A. Lascialfari, S. Carretta, P. Santini, G. Amoretti, E. J. L. Mcinnes, I. S. Tidmarsh, J. Hawkett, Phys. Rev. Lett. 102, 177201 (2009)

CACAA.Figuerola, A. Fiore, R. Di Corato, A. Falqui, C. Giannini, E. Micotti,A.Lascialfari, M. Corti, R. Cingolani, T.

Pellegrino, P. D. Cozzoli and L.Manna. J. Am. Chem. Soc. 130, 1477 (2008)

M. Corti, A. Lascialfari, M. Marinone, A. Masotti, E. Micotti, F. Orsini, G. Ortaggi, G. Poletti, C. Innocenti, C. Sangregorio, J. Magn. Magn. Mater. 320 , e316 (2008)

M. Corti, A. Lascialfari, E. Micotti, A. Castellano, M. Donativi, A. Quarta, P.D. Cozzoli, L. Manna, T. Pellegrino, C. Sangregorio, J. Magn. Magn. Mater. 320, e320 (2008)

A Boni, M Marinone, C Innocenti, C Sangregorio, M Corti, A Lascialfari, M Mariani, F Orsini, G Poletti and M F Casula, J. Phys. D: Appl. Phys. 41, 134021 (2008)

Y. Guari, J. Larionova, M. Corti, A. Lascialfari, M. Marinone, G. Poletti, K. Molvinger and C. Guérin, Dalton Trans. 28, 3658 (2008), DOI: 10.1039/b808221a 2)

A.Masotti, A. Pitta, G. Ortaggi, M. Corti, C. Innocenti, A. Lascialfari, M. Marinone, P. Marzola, A. Daducci, A. Sbarbati,

E. Micotti, F. Orsini, G. Poletti, C. Sangregorio, Magn Reson Mater Phy 22, 77 (2009) P. Sánchez, E. Valero, N.Gálvez, J. M. Domínguez-Vera, M. Marinone, G. Poletti, M. Corti and

A. Lascialfari, Dalton Transactions, 800-804 (2009)L. Lartigue, K. Oumzil, Y. Guari, J. Larionova, C. GueLrin, J.-L. Montero, V. Barragan-Montero, C. Sangregorio, A.

Caneschi, C. Innocenti, T. Kalaivani, P. Arosio and A. Lascialfari, Organic Letters 11, 2992 (2009)

SCSCE. Bernardi, A. Lascialfari, A. Rigamonti, and L. Romanó, Phys. Rev. B 77, 064502 (2008) S. Cagliero, A. Agostino, M. Mizanur Rahman Khan, M. Truccato, F. Orsini, M. Marinone,

G. Poletti, A. Lascialfari, Appl Phys A 95, 479 (2009)A. Lascialfari, A. Rigamonti, E. Bernardi, M. Corti, A. Gauzzi, and J. C. Villegier, Phys. Rev. B 80, 104505 (2009)

MNMMNMF. Cinti, A. Rettori, M. G. Pini, M. Mariani, E. Micotti, A. Lascialfari, N. Papinutto, A. Amato, A. Caneschi,

D. Gatteschi, and M. Affronte, Phys. Rev. Lett. 100, 057203 (2008)F. Borsa, Y. Furukawa, A. Lascialfari, Inorg. Chim. Acta 361, 3777 (2008)

M.Belesi, E.Micotti, M. Mariani, F.Borsa, A. Lascialfari, S. Carretta, P. Santini, G. Amoretti, E. J. L. Mcinnes, I. S. Tidmarsh, J. Hawkett, Phys. Rev. Lett. 102, 177201 (2009)

24

Some general considerations about Magnetism in bio-medicineSome general considerations about Magnetism in bio-medicine

TechniquesMagnetic Resonance Imaging Imaging (clinic and research) and NMRMagnetic nanoparticlesMagnetic nanoparticles joint to drug deliverydrug delivery/targeting, markersMagnetic hyperthermiahyperthermiaMagnetic driven transportMagnetic driven transport of particlesMagnetic biosensors’ biosensors’ detectors (NMR, SQUID,....)MagnetoencelographyMagnetoencelography or neuromagnetism (SQUID detection of cerebral activity), MagnetocardiographyMagnetocardiography (by means of SQUIDs)

Materials (nanosized)Paramagnetic systemsFerrites (e.g. hard disk in computers)Superparamagnetic systemsMolecular nano-particles

25

Aims of the work on MRI contrast agentsAims of the work on MRI contrast agentsAims of the work on MRI contrast agentsAims of the work on MRI contrast agents To obtain MRI contrast agents based on superparamagnetic cores coated in different

ways Samples with controllable size, shape, kind of magnetic ion of the core – narrow

distributions of sizes – and coating/functionalization

MOTIVATION

a) reproducilibity of physical properties/performances ;

b) optimization of the chemico-physical characteristics ;

c) feedback to synthetic process to optimize the performances / study role of different parameters

d) Systematic study of nuclear relaxivitySystematic study of nuclear relaxivity (the efficiency) as a function of the core dimensions, shape, coating, bulk anisotropy, kind of magnetic ion

e) ModelModel for the dependence of the nuclear relaxivities of novel contrast agents on anisotropy and molecular reorientation

f) Multifunctionality Multifunctionality (molecular targeting, hyperthermia, fluorescence....)

g) Low toxicity of Fe-oxides

To obtain MRI contrast agents based on superparamagnetic cores coated in different ways

Samples with controllable size, shape, kind of magnetic ion of the core – narrow distributions of sizes – and coating/functionalization

MOTIVATION

a) reproducilibity of physical properties/performances ;

b) optimization of the chemico-physical characteristics ;

c) feedback to synthetic process to optimize the performances / study role of different parameters

d) Systematic study of nuclear relaxivitySystematic study of nuclear relaxivity (the efficiency) as a function of the core dimensions, shape, coating, bulk anisotropy, kind of magnetic ion

e) ModelModel for the dependence of the nuclear relaxivities of novel contrast agents on anisotropy and molecular reorientation

f) Multifunctionality Multifunctionality (molecular targeting, hyperthermia, fluorescence....)

g) Low toxicity of Fe-oxides

26

Highly-sensitive magnetic field biosensors (MFB)Highly-sensitive magnetic field biosensors (MFB)Highly-sensitive magnetic field biosensors (MFB)Highly-sensitive magnetic field biosensors (MFB) The scheme of MFB , molecular result of steps I + II :

I) biomolecular probe attached to a (nanostructured and functionalized) surfaceII) complementary biomolecule labelled with a magnetic nanoparticle

Examples : antibody-antigene, protein-protein, DNA-DNA, enzyme reactions, etc.

APPLICATIONS Labelling to “in vivo” molecular interactions (imaging) Reagents in miniaturized microfluidic systems Affinity ligands for rapid and high-throughput magnetic readouts of arrays probes for Magnetic Force Microscopy

Scientific/technological related problems, to be optimized :a) Nanostructuring (regular) of surfaceb) Functionalization of surfacec) Magnetic labelling of biomolecule (choice of magnetic NP) (surface characteristics

of NP allow covalent and stoichiomteris attachment of oligonucleotides, nucleic acids, small molecules, peptides, receptor ligands, proteins, antibodies,.....)

d) Choice of system of magnetic detection (Hall s., NMR/MRI, SQUID,....)e) Development for applications

The scheme of MFB , molecular result of steps I + II : I) biomolecular probe attached to a (nanostructured and functionalized) surfaceII) complementary biomolecule labelled with a magnetic nanoparticle

Examples : antibody-antigene, protein-protein, DNA-DNA, enzyme reactions, etc.

APPLICATIONS Labelling to “in vivo” molecular interactions (imaging) Reagents in miniaturized microfluidic systems Affinity ligands for rapid and high-throughput magnetic readouts of arrays probes for Magnetic Force Microscopy

Scientific/technological related problems, to be optimized :a) Nanostructuring (regular) of surfaceb) Functionalization of surfacec) Magnetic labelling of biomolecule (choice of magnetic NP) (surface characteristics

of NP allow covalent and stoichiomteris attachment of oligonucleotides, nucleic acids, small molecules, peptides, receptor ligands, proteins, antibodies,.....)

d) Choice of system of magnetic detection (Hall s., NMR/MRI, SQUID,....)e) Development for applications