Novel functionalities in magnetic domain wall devices on-chip for biology and nanomedicine

The work of this doctoral thesis deals with the study, design and implementation of novel functionalities in domain wall (DW) based magnetic devices for application in the field of biology and nanomedicine. The devices allow for the manipulation of magnetic particles at the micro- and nano-scale through the coupling with externally controlled magnetic domain walls. This recent manipulation method has attracted a growing interest in biology and medicine as functionalized magnetic particles are commonly used as molecular and cellular carriers or markers. Until now the functionalities and the applications are still limited to linear transport of biomolecules or cells in non–microfluidic environments. The aim of this research activity is twofold: on the one hand adding new features to DW magnetic micro- and nanostructures and on the other their implementation in lab-on-a-chip systems to test medical nanoplatforms for the controlled release of anti-tumor drugs. DW based magnetic structures hold the potential to improve existing lab-on-chip applications and methodologies, like the transport and sorting of biomolecules, paving the way to microfluidic tools able to select and synthetize a large number of single biological entities. Moreover the degree of complexity of these structures is much lower than other technique for the single particle manipulation on-chip and they can be easily integrated in miniaturized systems. Magnetic domain walls in confined magnetic structures form the fundamental core of the devices here presented. At the submicrometer scale the DW spin configuration starts to be dominated by the geometry rather than by the intrinsic properties of the material. In this framework the DWs behaves as “quasi-particles”, being sources of magnetic field that can be precisely manipulated by external magnetic fields. The design of the device is thus fundamental for the realization of additional features with respect to the traditional molecular or cellular conveyors. It has been recently demonstrated how micro- and nanofabricated, planar stripes made by Permalloy (Ni80Fe20) constitute excellent conduits where the DWs can be nucleated and moved between adjacent geometrical constriction, like corners or curves, under the action of external magnetic fields. Methods for evaluating both computationally and experimentally the magnetic force on a superparamagnetic bead generated by DWs confined in Permalloy nano- and microcorners are initially presented. Attractive forces in the tens of pN range are obtained for a 1 µm bead, with a spatial extension of few microns in the case of microcorners which makes them suitable for trapping cells or large polymeric aggregates. Starting from these structures microfluidic devices, mimicking the conditions of the capillaries, have been successfully implemented with switchable DWs trapping sites, in order to study the controlled release of an anti-tumor drug from magnetic thermo-responsive nanocarriers. As a major results of this PhD activity we studied the dynamics of the thermo-actuated release of Doxorubicin drug under different flow rate conditions and as a function of the thermo-responsive polymer shell of the nanocarrier. In the second part of the experimental activity two novel functionalities in DW based nanostructures have been demonstrated. Bifurcated conduits, which combine zigzag shaped structures and curvilinear sections, have been designed and fabricated allowing for the creation of innovative single magnetic particles de-multiplexer. The single particle sorting of magnetic beads of different size (1 µm and 2.8 µm) on the same structure geometry was obtained. Furthermore, by adding another DW injector pad to a zigzag shaped conveyor it was possible to trap couples of single particles and bring them in contact in a reproducible way. A compatible microfluidic device which permits the magnetically controlled meeting of two magnetic particles is illustrated and currently under test. All the above described magnetic conduits allow the motion only along a predefined path. Once the magnetic bead is trapped, it can be manipulated only along the direction imposed by the patterned structure. A major achievement of this Ph.D. activity is represented by the demonstration of the “free” 2-dimensional manipulation on-chip based on DWs. Arrays of Permalloy rings allow the external user to trap and move magnetic particles “without any predetermined paths”, thanks to appropriate magnetic fields sequences. Preliminary tests are reported in the chapter 7, in which 1 µm magnetic beads have been successfully handled along linear or pseudorandom paths. Furthermore by transferring the magnetic rings pattern on the top of a PDMS microfluidic bifurcated channel, 1 µm magnetic beads have been trapped in the middle of the bifurcation and magnetically sorted to one of the two branches in fluid static condition. The coupling of a magnetic particle with a single domain wall in Permalloy micro- and nanostructures has proven to be a tunable and efficient way to study and manipulate biological entities at the nano-scale in microfluidic environments. This technological platform provides novel tools for biology and nanomedicine and holds the potential for single molecule biophysics applications.

Il lavoro di questa tesi di dottorato comprende lo studio, la progettazione e realizzazione di nuove funzionalità in dispositivi magnetici a singole pareti di dominio e la loro applicazione nell’ambito della nano – medicina. I dispositivi permettono di manipolare alla nano scala particelle magnetiche mediante accoppiamento con pareti di dominio magnetiche controllate in remoto. Questa nuova tecnica, ideata nel 2009, ha trovato subito un notevole e crescente interesse nell’ambito biologico e medico poiché particelle magnetiche funzionalizzate sono comunemente usate come vettori o marker molecolari e cellulari. Fino ad ora le funzionalità e le applicazioni si sono, però, limitate al trasporto lineare di molecole o cellule in ambienti non microfludici. Lo scopo di questa attività di ricerca è duplice: da un lato aggiungere nuove funzionalità ai nano dispositivi magnetici e dall’altro implementarli in un sistema integrabile lab-on-chip per testare nuove nano-piattaforme per il rilascio controllato di farmaci anti-tumorali. Essi hanno, infatti, le potenzialità per migliorare applicazioni esistenti, come il trasporto e la selezione di molecole biologiche, aprendo la strada a strumenti microfluidici in grado di selezionare e sintetizzare un elevato numero di singole entità biologiche. Inoltre il grado di complessità di queste strutture è notevolmente più basso di altre tecniche per la manipolazione di singole particelle su chip e possono essere facilmente integrati in strumenti miniaturizzati. Le pareti di dominio magnetiche in strutture confinate alla nano–scala sono il nucleo fondamentale dei dispositivi studiati. In essi la struttura di spin della parete inizia ad essere dominata dalla geometria piuttosto che dalle proprietà intrinseche del materiale. In tale contesto le pareti di dominio si comportano come “quasi-particelle” che possono essere precisamente manipolate tramite campi magnetici esterni o correnti polarizzate in spin. Il design delle nanostrutture è dunque determinante per la realizzazione di funzionalità aggiuntive rispetto alle tradizionali linee di trasporto molecolari o cellulari. Strisce planari, nano-fabbricate, di Permalloy (NiFe) sono eccellenti condotti dove le pareti di dominio possono essere nucleate e spostate tra vincoli geometrici adiacenti come angoli e curve, sotto l’azione di campi magnetici esterni. Condotti biforcati, che uniscono strutture a zigzag e tratti curvi, permettono di creare innovativi demultiplexer di singole particelle magnetiche. Matrici bidimensionali di condotti magnetici circolari consentono finalmente una manipolazione libera nel piano del chip senza percorsi predeterminati, grazie a opportune sequenze di campi magnetici. Dispositivi microfluidici, mimanti le condizioni di capillari sanguigni, sono stati implementati, con successo, con siti di cattura reversibili a pareti di dominio, per lo studio del rilascio di farmaci anti-tumorali tramite portatori magneto e termo-responsivi.