Superparamagnetic nanoparticles (SPMNPs) have attracted interest for various biomedical applications due to their unique magnetic behavior, excellent biocompatibility, easy surface modification, and low cost. Their unique magnetic properties, superparamagnetism, and magnetophoretic mobility have led to their inclusion in immunoassays to enhance biosensor sensitivity and allow for rapid detection of various analytes. In this review, we describe SPMNP characteristics valuable for incorporation into biosensors, including the use of SPMNPs to increase detection capabilities of surface plasmon resonance and giant magneto-resistive biosensors. The current status of SPMNP-based immunoassays to improve the sensitivity of rapid diagnostic tests is reviewed, and suggested strategies for the successful adoption of SPMNPs for immunoassays are presented.

Liquid crystalline (LC) organic radicals were expected to show a novel non-linear magnetic response to external magnetic and electric fields due to their coherent collective molecular motion. We have found that a series of chiral and achiral all-organic LC radicals having one or two five-membered cyclic nitroxide radical (PROXYL) units in the core position and, thereby, with a negative dielectric anisotropy exhibit spin glass (SG)-like superparamagnetic features, such as a magnetic hysteresis (referred to as ‘positive magneto-LC effect’), and thermal and impurity effects during a heating and cooling cycle in weak magnetic fields. Furthermore, for the first time, a nonlinear magneto-electric (ME) effect has been detected with respect to one of the LC radicals showing a ferroelectric (chiral Smectic C) phase. The mechanism of the positive magneto-LC effect is proposed and discussed by comparison of our experimental results with the well-known magnetic properties of SG materials and on the basis of the experimental results of a nonlinear ME effect. A recent theoretical study by means of molecular dynamic simulation and density functional theory calculations suggesting the high possibility of conservation of the memory of spin-spin interactions between magnetic moments owing to the ceaseless molecular contacts in the LC and isotropic states is briefly mentioned as well.

The cancer therapy with the lowest possible toxicity is today an issue that raises major difficulties in treating malignant tumors because chemo- and radiotherapy currently used in this field have a high degree of toxicity and in many cases are ineffective. Therefore, alternative solutions are rapidly being sought in cancer therapy, in order to increase efficacy and a reduce or even eliminate toxicity to the body. One of the alternative methods that researchers believe may be the method of the future in cancer therapy is superparamagnetic hyperthermia (SPMHT), because it can be effective in completely destroying tumors while maintaining low toxicity or even without toxicity on the healthy tissues. Superparamagnetic hyperthermia uses the natural thermal effect in the destruction of cancer cells, obtained as a result of the phenomenon of superparamagnetic relaxation of the magnetic nanoparticles (SPMNPs) introduced into the tumor; SPMNPs can heat the cancer cells to 42–43 °C under the action of an external alternating magnetic field with frequency in the range of hundreds of kHz. However, the effectiveness of this alternative method depends very much on finding the optimal conditions in which this method must be applied during the treatment of cancer. In addition to the type of magnetic nanoparticles and the biocompatibility with the biological tissue or nanoparticles biofunctionalization that must be appropriate for the intended purpose a key parameter is the size of the nanoparticles. Also, establishing the appropriate parameters for the external alternating magnetic field (AMF), respectively the amplitude and frequency of the magnetic field are very important in the efficiency and effectiveness of the magnetic hyperthermia method. This paper presents a 3D computational study on specific loss power (Ps) and heating temperature (ΔT) which allows establishing the optimal conditions that lead to efficient heating of Fe3O4 nanoparticles, which were found to be the most suitable for use in superparamagnetic hyperthermia (SPMHT), as a non-invasive and alternative technique to chemo- and radiotherapy. The size (diameter) of the nanoparticles (D), the amplitude of the magnetic field (H) and the frequency (f) of AMF were established in order to obtain maximum efficiency in SPMHT and rapid heating of magnetic nanoparticles at the required temperature of 42–43 °C for irreversible destruction of tumors, without affecting healthy tissues. Also, an analysis on the amplitude of the AMF is presented, and how its amplitude influences the power loss and, implicitly, the heating temperature, observables necessary in SPMHT for the efficient destruction of tumor cells. Following our 3D study, we found for Fe3O4 nanoparticles the optimal diameter of ~16 nm, the optimal range for the amplitude of the magnetic field of 10–25 kA/m and the optimal frequency within the biologically permissible limit in the range of 200–500 kHz. Under the optimal conditions determined for the nanoparticle diameter of 16.3 nm, the magnetic field of 15 kA/m and the frequency of 334 kHz, the magnetite nanoparticles can be quickly heated to obtain the maximum hyperthermic effect on the tumor cells: in only 4.1–4.3 s the temperature reaches 42–43 °C, required in magnetic hyperthermia, with major benefits in practical application in vitro and in vivo, and later in clinical trials.

Evidence is accumulating to support the hypothesis that some animals use light-induced radical pairs to detect the direction of the Earth's magnetic field. Cryptochrome proteins seem to be involved in the sensory pathway but it is not yet clear if they are the magnetic sensors: they could, instead, …

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Birds can use two kinds of information from the geomagnetic field for navigation: the direction of the field lines as a compass and probably magnetic intensity as a component of the navigational ‘map’. The direction of the magnetic field appears to be ...

Magnetic Resonance Imaging (MRI) is a popular imaging modality due to its ability to provide excellent soft tissue contrast without exposure to ionizing radiation. It can be used for temperature monitoring (thermometry) as well as for assessing the biochemistry in vivo (MRS). This dissertation focuses separately on the development, application and quantitation issues of these two aspects of MRI. Radiofrequency (RF)-induced tissue heating is a concern in MRI. The dosimetric quantity for monitoring RF heating is the Specific Absorption Rate (SAR) defined as the RF power absorbed per unit mass of tissue. A novel approach for imaging SAR from absolute temperature images obtained using a paramagnetic lanthanide complex-Thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis (methylene phosphonate) (TmDOTP5-) was developed. The effects of a bare-ended, insulated conductor in a phantom were investigated by 3D SAR imaging. 3D SAR maps were also generated using a high SAR sequence while varying the pulse duration. The high spatial resolution SAR maps correctly identified the local SAR rise near the wire end and also revealed increasing SAR with increasing pulse duration in the high SAR sequence, as expected. These results demonstrate the potential of MR thermometry with paramagnetic lanthanide complexes for evaluating safety of implants, medical devices as well as different pulse sequences. The second part of the thesis is dedicated to the technique of measuring in vivo levels of the neurotransmitter γ-aminobutyric acid (GABA) using MRS. GABA is an inhibitory neurotransmitter in the brain which is involved in the control of fine movement and balance. GABA MRS with spectral editing was performed and GABA was quantified using custom fitting parameters in the tool LCModel to measure changes in movement disorders - particularly Parkinson's disease (PD) and sleep bruxism. Higher levels of thalamic GABA were detected in PD with correlation to disease severity indicating the possibility to use GABA MRS as a biomarker for PD progression. On the other hand, in the bruxers, lower levels of GABA correlating with higher levels of glutamate in the dorso-lateral prefrontal cortex were detected indicating disturbances in the GABAergic and glutamatergic pathways. Lastly, since GABA quantification is a much discussed topic in literature with no one, clear and best approach, an effort was made to compare some popular fitting approaches in LCModel. Semi-synthetic simulated GABA spectra were used to test the accuracy, sensitivity and specificity of methods, all of which handled the baseline and macromolecules in the GABA spectra differently. Overall, the approaches using

This thesis presents sodium magnetic resonance as an in vivo means for non-invasively visualizing the changes in cell sodium ion homeostasis that occur in ischemic tissue during acute stroke. Single quantum sodium magnetic resonance imaging (MRI) was used to determine the time course of tissue sodium concentration (TSC) in a non-human primate model of reversible focal brain ischemia. In each animal, TSC increased slowly and linearly as a function of time after the onset of focal brain ischemia. Changes in the TSC accumulation were seen upon reperfusion. The results demonstrate that the increase in TSC in ischemic tissue is readily measurable using sodium MRI at clinical magnetic field strengths (3.0 T) in acceptable imaging times (5 minutes). The results also indicate that sodium MRI could predict the stroke onset time in patients that are unsure when their symptoms began, potentially extending the use of thrombolytic therapy to patients that would otherwise not receive treatment. Many studies have hypothesized that the best means for the in vivo study of the changes in cell sodium ion homeostasis that occur during brain ischemia is to use imaging schemes that isolate the sodium NMR signal from the intracellular compartment. This thesis investigates the contribution of the extracellular sodium pool to the brain's triple quantum (TQ) sodium MR signal in the rat using the thulium shift reagent, TmDOTP5-. Within the SNR of the experiment, there was no evidence of any contribution to the TQ sodium MR signal from the sodium in the extracellular brain, vascular, and muscle spaces in the head. Finally, TQ sodium MR images in the in vivo non-human primate are presented for the first time. Moreover, these images were obtained in clinically acceptable 18 minute data acquisition times. TQ sodium MRI during non-human primate focal brain ischemia identified large changes in the ischemic region as early as 34 minutes after the onset of ischemia. The increase in the TQ sodium MRI signal intensity observed in the ischemic hemisphere is hypothesized to be due to an increase in the intracellular sodium concentration as a result of impaired ion homeostasis during evolving brain ischemia.

Lanthanide complexes of the tetraazatetrakis(methylenephosphonate) ligand DOTP8- have been examined by spectrophotometry, potentiometry, osmometry, and 1H, 31P, and 23Na NMR spectroscopy. The LnDOTP5- complexes undergo four protonations between pH 9 and 3, and their stability constants (log KML) range from 27.6 to 29.6 across the lanthanide series. TmDOTP5- acts as a particularly good aqueous shift reagent, inducing paramagnetic shifts in 23Na nuclei of over 400 ppm. 23Na NMR titrations and osmometry measurements indicated that a single Na+ was bound to each TmDOTP5- at low Na+/TmDOTP5- ratios, while three Na+ ions were bound at high Na+/TmDOTP5- ratios.

P. M. Winter, V. Seshan, J. D. Makos, A. D. Sherry, C. R. Malloy, and N. Bansal, (1998) Quantitation of intracellular [Na+] in vivo by using TmDOTP5-as an NMR shift reagent and extracellular marker, J Appl Physiol. 85(5), 1806–12.

Interactions between Li+, Na+, Cs+, Ca2+ and Mg2+ and the shift reagent (SR), TmDOTP5 were studied by 7Li, 6Li, 23Na and 133Cs multinulear NMR spectro…

Evaluation of SAR Using MR Thermometry with Thulium1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(Methylene Phosphonate) (TmDOTP5-) for RF Safety in MRI, LL-PHS-WE3B, 11002408, Shalmali Dharmadhikari,

Solid state NMR is a powerful tool to probe membrane protein structure and motions in native lipid structures. Sample heating, caused by magic angle spinning and radio frequency irradiation in solid state NMR, produces uncertainties in sample temperature and thermal broadening caused by temperature distributions, which can also lead to sample deterioration. To measure the sample temperature in real time, and to quantify thermal gradients and their dependence on radio frequency irradiation or spinning frequency, we use the chemical shift thermometer TmDOTP, a lanthanide complex. Compared to other NMR thermometers (e.g., the proton NMR signal of water), the proton spectrum of TmDOTP exhibits higher thermal sensitivity and resolution. In addition, the H6 proton in TmDOTP has a large chemical shift (−175 ppm at 275 K) and is well resolved from the rest of the proton spectrum. We identified two populations of TmDOTP, with differing temperatures and dependency on the radio frequency irradiation power, within proteoliposome samples. We interpret these populations as arising from the supernatant and the pellet, which is sedimented from the sample spinning. Our results indicate that TmDOTP is an excellent internal standard for monitoring temperatures of biophysically relevant samples without distorting their properties.

Since brain’s microvasculature is compromised in gliomas, intravenous injection of tumor-targeting nanoparticles containing drugs (D-NPs) and superparamagnetic iron oxide (SPIO-NPs) can deliver high payloads of drugs while allowing MRI to track drug distribution. However, therapeutic effect of D-NPs remains poorly investigated because superparamagnetic fields generated by SPIO-NPs perturb conventional MRI readouts. Because extracellular pH () is a tumor hallmark, mapping is critical. Brain is measured by biosensor imaging of redundant deviation in shifts (BIRDS) with lanthanide agents, by detecting paramagnetically shifted resonances of nonexchangeable protons on the agent. To test the hypothesis that BIRDS-based readout remains uncompromised by presence of SPIO-NPs, we mapped in glioma-bearing rats before and after SPIO-NPs infusion. While SPIO-NPs accumulation in the tumor enhanced MRI contrast, the inside and outside the MRI-defined tumor boundary remained unchanged after SPIO-NPs infusion, regardless of the tumor type (9L versus RG2) or agent injection method (renal ligation versus coinfusion with probenecid). These results demonstrate that we can simultaneously and noninvasively image the specific location and the healing efficacy of D-NPs, where MRI contrast from SPIO-NPs can track their distribution and BIRDS-based can map their therapeutic impact.

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