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resources:p2:start [2014/01/13 17:15] – mouradaresources:p2:start [2014/01/15 19:13] – egz
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 ====== BBB ====== ====== BBB ======
  Delivery of SPMNMs to CNS of rodents with artificially provoked epileptic seizures   Delivery of SPMNMs to CNS of rodents with artificially provoked epileptic seizures 
- 
- 
  
 I. Introduction I. Introduction
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 **5. Magnetohydrodynamic effect** **5. Magnetohydrodynamic effect**
  
 +MICRO MAGNETOHYDRODYNAMICS
  
-====== Epilepsy ======+ 
 +Key words: water molecule, cyclic water molecule, superparamagnetic nanoparticles (SPMNPs),  microfluidics, SPMNPs internalization by cells. 
 + 
 +Application:  
 +1. Explaining why a static external magnetic field (from permanent magnet) will help SPMNs cross the Blood Brain Barrier (others use ultrasound to disrupt BBB, very dangerous) 
 +2. No one has explained the internalization of SPMNPs by biological cells. In our case, SPMNPs should be internalized by cells because epileptic magnetic fields are produced by intracellular component of the electric field. The extra-cellular is of no use for trapping the SPMNs. 
 +Hypothesis  
 + 
 +Water molecules bond to each other and form cyclic water under the effect of weak and time varying magnetic (or strong but not both) fields. Cyclic water exhibits super-fluidity, this is why water present in all sorts of cells (everywhere) in the body to transport nutrients and wastes in and out of every body cell. Now, when in presence of SPMNPs, water that surrounds a NP becomes ordered and confers the NP with its super fluidity properties, thus internalization of the magnetic NP by cells is facilitated. It is as if, the right magnetic excitation of the SPMNs creates a natural biocompatible coating that confers the particle with a sort of stealth behaviour, long sought by scientists, and by doing so enhances the NPs bio-distribution. 
 + 
 +Experimental setting 
 +In microfluidic chanels where SPMNPs are positioned permannatly, depending on the presence or absence of the excitatory external magnetic field, water flux will change according to whether or not SPMNPs are magnetized or not. If theey are then microfluid (water) will spend less time between inlet and outlet of the apparatus, this will prove that water becomes superfluid around the NP (changes molecular conformation) and theus encounters lss and less resistance in the chanel. 
 + 
 + {{:resources:p2:magnetohydro.jpg|}} 
 + 
 +Figure 1. (a) Effect of supperfluidity of water around spherical sperparamagnetic NPs.(b) fluid properties in absence of magnetic effects 
 + 
 + 
 +**Nanopore** 
 + 
 +Set-up ( which nanoseconds membrane? size of hole? monitoring? , ? (background: Physics? Coil? calculation?) chemical protocol?  
 + 
 + 
 + 
 +====== Epilepsy ====== 
  
 MRI imaging of superparamagnetic particles and rods aggregates in the brain MRI imaging of superparamagnetic particles and rods aggregates in the brain
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 • Evidence of an off-resonance effect of SPMNPs on proton resonance • Evidence of an off-resonance effect of SPMNPs on proton resonance
 • translation of diffusion coefficients into surgical coordinates. • translation of diffusion coefficients into surgical coordinates.
-• Correlation with histopathological findings and intended epilepsy triggering zones  +• Correlation with histopathological findings and intended epilepsy triggering zones  
 + 
 +** Micro-coil and usu=sage of MRI + Injection of nano-particles in rat/mouse**  
 + 
 +======III.  Magnetophoresis & Simulation ====== 
 +Simulation of superparamagnetic nanomaterial interacting with epileptic seizure-like driven uT magnetic fields 
 + 
 +I. Introduction 
 +It is much more efficient to model the system before starting any in-vivo or in-vitro protocol. This will reduce the cost and help develop an efficient design tool, either for the imaging protols (size and morphology of the aggregates) or for the superparamagnetic materials to be used. Computer Simulation provides a means to virtually test the the interaction of the sad SPMNMs with neuronal bundles of different degrees of anisotropy (Fig. 1).  It is Obvious that the isotropic configuration results in an overall magnetic  
 +field that is null, hence the impossibility of measuring it at a distance, like its the case in MEG. As a mater of fact, MEG detects magnetic fiels developed by highly anisotropic configurations inherent to temporal and hypocampal regions of the brain. The aggregation of superparamagnetic  nanomateriarls will thus, address the tow configurations identically, since the SPMNMs are assumed to be omnipresent in the brain at the ictal and interictal periods of time. So close they will be from the sources of the electrical currents propagating in the pyramidal cells, that they will be under the influence of 1) pico-Tesla fields in the isotropic case and 2) micro-Tesla fields in the anisotropic one. 
 + 
 + 
 + 
 + 
 + 
 + 
 +{{:resources:p2:neurons.jpg|}} 
 + 
 + 
 + 
 + 
 + 
 + 
 + 
 +Figure 1. Tow different magnetic fields configurations 
 +II. Time independent analysis 
 +we will start with a modeling approach based on finite element modeling FEM to model SPMNMs absence of motion in presence of hydrodynamic forces and naturally occurring magnetic fields like the ones found in an epileptic seizure focus. An epileptic focus can be likened to a trap for the nanoparticles that eventually one has to asses its trapping efficiency. To do so, the neuronal network configurations will be considered independently from the particles and their motion. Using a static simulation that takes into account, magnetophoretic and hydrodinamic forces in their analytical forms, one can easily identify the spacial coordinates of regions where the forces add up to zero [1]. this simulaion work could be carried out on simulation platforms combining Matlab or ANSYS. 
 + 
 +III. Time dependent analysis 
 + 
 +Conventional simulation tools like ANSYS and COMSOL are not adapted to our application since they excel in modeling cases where applied fields are strong and thus, they consider their propagation unaffected by particles shapes and varying magnetic moments. In case of weak magnetic applied fields, the propagation of the magnetic field will be sparse and transient non uniform field are created within the particle itself, let alone at  inter-sources distances. Consequently, particles shapes and magnetic moments are critical to this effect, and redefining the propagation of the magnetic fields  is mandatory, using a whole new technique that combines MATLAB to calculate and define the time varying proprieties of nanoparticles and insert them in the ANSYS geometric model, to iterate on the magnetic and hydrodynamic constraints. The derived transient forces from iteration step J, will be used to calculate the spacial position/and/or angular rotation for iteration step J+1. The magnetophoretic and hydrodynamic loads for the next iterations are recalculated and forces are derived for the new simulation step.    
 +IV. Theoretical considerations 
 +The paramagnetic particle (aspect ratio L/D) subjected to a magnetic field   has a magnetic moment   m proportional to its magnetic susceptibility tensor   
 +where   is the magnetic volume of the particle. Projecting  along its main axes  and  with   , it writes : 
 +  
 +If we replace the anisotropy of susceptibility of the rod by  and if the magnetic field  rotates (abruptly or at a pulsation  ) in the plane , the rod experiences a magnetic torque:  
 +  
 +and a viscous torque  [1]: 
 +  
 +Where   is the coefficient of hydrodynamic drag experienced by the rod and  the instantaneous angular velocity of the rod, n, the viscosity of the fluid carrier, L the length and D the diameter of the nanoparticle respectively.  
 +References 
 + 
 +[2] A. Anguelouch, R. L. Leheny, and D. H. Reich, "Application of ferromagnetic nano-wires to interfacial microrheology," Appl. Phys. Lett. 89, 111914 (2006). 
 + 
 + 
 + 
 +**Sandwich**  
 +Literature? math? figures..... set-up? 
 + 
 + 
 + 
  
  
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 This paper presents the design, optimization and optical characterization of an array electrostatic actuators based MEMS to be used as an adaptive optics component of a portable retinal imaging device. The proposed wave-front corrector is implemented in (CMC) polymump technology and  features an array of cantilevers on which planar reflective gold thin films were deposited for characterization purposes.  The cantilevers relative deflections will be set based on the output of a wave-front analyzer to correct higher order optical aberrations. For the sake of achieving precise wave front correction, three cantilever sizes were implemented on the chip for a total of 64 cantilevers that will serve as actuators of a deformable mirror in future work.  Array of actuators are hindered by the off-plane initial misalignment phenomenon caused by thin films deposition process and mismatches between the cantilevers displacement due to size nonuniformities introduced by the fabrication process. The device total surface is XXX × XXX mm2. The COMSOL simulation of the modeled Large, medium and small size cantilevers predicted maximum deflections of 6, 4 and 2 um respectively at maximum DC voltages of XXX, XXX and XXX respectively. These values are verified by laser interferometry and shown that they can be considerably augmented by omitting the gold deposited layer in future versions of the device.  This paper presents the design, optimization and optical characterization of an array electrostatic actuators based MEMS to be used as an adaptive optics component of a portable retinal imaging device. The proposed wave-front corrector is implemented in (CMC) polymump technology and  features an array of cantilevers on which planar reflective gold thin films were deposited for characterization purposes.  The cantilevers relative deflections will be set based on the output of a wave-front analyzer to correct higher order optical aberrations. For the sake of achieving precise wave front correction, three cantilever sizes were implemented on the chip for a total of 64 cantilevers that will serve as actuators of a deformable mirror in future work.  Array of actuators are hindered by the off-plane initial misalignment phenomenon caused by thin films deposition process and mismatches between the cantilevers displacement due to size nonuniformities introduced by the fabrication process. The device total surface is XXX × XXX mm2. The COMSOL simulation of the modeled Large, medium and small size cantilevers predicted maximum deflections of 6, 4 and 2 um respectively at maximum DC voltages of XXX, XXX and XXX respectively. These values are verified by laser interferometry and shown that they can be considerably augmented by omitting the gold deposited layer in future versions of the device. 
 +
 +**Diagram and description of set-up**
  
  
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 Figure 1. Schematic of  tumor detection unite Figure 1. Schematic of  tumor detection unite
 +
 +
 +
 +====== Magneto-accoustic effect for breast surgery ======
 +II. Breast surgery
 +
 +The therapeutic effect of focused ultrasound was known for quite a century now. Long ago, before MRI systems where made possible, there was absolutely no way to benefit from the therapeutic effect of focused  ultrasounds, for there was no  physical  way to monitor the shifts in the position of focal points of acoustic fields, especially in a human body where, waves, on there way to the target, propagate through paths of different acoustic impedance (fat, muscle, veins and glands ). The spacial shift of focal points coordinates is counterproductive and could prove lethal in cases like tumor ablation. MRI systems allow the visualization and monitoring of focal points and hence, in case of a noticeable  shift  in the coordinates, corrections of the targeting could be carried out.
 +
 +2.1 MRI free focused ultrasound surgery breast carcinoma
 + A totally acoustic imaging and ablation system as mentioned formerly is quiet impossible. Unless, one resorts to contrast agents to highlight tumors under an acoustic field, tumors will remain invisible for contemporary sonographs. Ultrasound contrast agents consist mainly of gas entrapping, polymeric micro capsules that reflect ultrasonic waves in a different way that differs from tissues. But gas bubbles are highly soluble in blood, conferring to the capsules, a very shot period of life within the body and  making them unsuitable for ablation applications. The development of a new technique of visualization and ablation of tumors using acoustic field exclusively is eminent and calls for a new generation of tumor markers for ultrasound imaging and new technique of focusing acoustic energy in homogeneous media, in a way that is independent of human observation and correction.           
 +
 +
 +2.2 All ultrasonic detection and ablation system  of breast tumors
 +
 +Heterogeneity of propagation media has been studied by the navy in order to overcome the problem of object identification by sonars, in troubled waters. Phase conjugation, imported from optics (holography) allows an acoustic echo to be sent back to the source (tumor) and be focused exactly inside it, with an unprecedented resolution (smaller size of the focal points and sharper temperature profiles). The conjugation is carried out simply by recording the imaging signals (By 360 degrees matrix of piezoelectric elements), recording the echos in RAMs (digital memory) and reading it backward to create high power ultrasound waves, meant to be sent back to the tumor. The time reversal of the waves is at the core of this phase conjugation technique. Time reversal is the mere fact of reading the RAM in a reversed manner. This way, we can create a low cost, MRI free targeting system, that is portable reliable. Further more in the development phase of this system, results should be compared with the targeting power given by an MRI system. At Sait-Luc Hospital, Temperature maps (T-maps) are already running on MRI systems, a powerful tool that allowed systems developed by GE (Exablate 2000) to visualize sonication points in the breast in order to correct for the shifts introduced by inhomogeneities. T-maps are MRI sequences based on echo-planar imaging EPI, that can detect a temperature gradient of 0.01 degrees Celsius. Figure. 2, depicts the all ultrasound detection and ablation of breast tumors.
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 +{{:resources:p2:breast_surgery.jpg|}}
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 +
 +Figure. 2, All ultrasound detection and ablation of breast tumors
 +
 +
 +
 +
 +**Magnetic stimulation of nano-particles to generate ultrasonic waves?** 
 +
 +====== Preferences: ======
 +
 +
 +1. BBB: Complete the text and information in above section.
 +2. Sandwich: Complete the text and discussions.
 +3. Interferometry: Experiment
 +4. Cantilever : Design cantilever.
 +
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