Opening the Blood Brain Barrier with an Electropermanent Magnet System.

Opening the blood brain barrier (BBB) under imaging guidance may be useful for the treatment of many brain disorders. Rapidly applied magnetic fields have the potential to generate electric fields in brain tissue that, if properly timed, may enable safe and effective BBB opening. By tuning magnetic pulses generated by a novel electropermanent magnet (EPM) array, we demonstrate the opening of tight junctions in a BBB model culture in vitro, and show that induced monophasic electrical pulses are more effective than biphasic ones. We confirmed, with in vivo contrast-enhanced MRI, that the BBB can be opened with monophasic pulses. As electropermanent magnets have demonstrated efficacy at tuning B0 fields for magnetic resonance imaging studies, our results suggest the possibility of implementing an EPM-based hybrid theragnostic device that could both image the brain and enhance drug transport across the BBB in a single sitting.

A polymer index-matched to water enables diverse applications in fluorescence microscopy.

We demonstrate diffraction-limited and super-resolution imaging through thick layers (tens-hundreds of microns) of BIO-133, a biocompatible, UV-curable, commercially available polymer with a refractive index (RI) matched to water. We show that cells can be directly grown on BIO-133 substrates without the need for surface passivation and use this capability to perform extended time-lapse volumetric imaging of cellular dynamics 1) at isotropic resolution using dual-view light-sheet microscopy, and 2) at super-resolution using instant structured illumination microscopy. BIO-133 also enables immobilization of 1) Drosophila tissue, allowing us to track membrane puncta in pioneer neurons, and 2) Caenorhabditis elegans, which allows us to image and inspect fine neural structure and to track pan-neuronal calcium activity over hundreds of volumes. Finally, BIO-133 is compatible with other microfluidic materials, enabling optical and chemical perturbation of immobilized samples, as we demonstrate by performing drug and optogenetic stimulation on cells and C. elegans.

Magnetic Microdevices for MRI-Based Detection of SARS-CoV-2 Viruses.

GOAL: To develop a micron-scale device that can operate as an MRI-based reporter for the presence of SARS-CoV-2 virus. METHODS: Iron rod microdevices were constructed via template-guided synthesis and suspended in phosphate buffered saline (PBS). Heat-inactivated SARS-CoV-2 viruses were added to the samples and imaged with low-field MRI. RESULTS: MRI of microdevices and viruses showed decreased signal intensity at low concentrations of viruses that recovered at higher concentrations. Electron micrographs suggest that reduced MRI intensity may be due to concentration-dependent shielding of water protons from local magnetic inhomogeneities caused by the iron microdevices. CONCLUSIONS: The preliminary results presented in this letter provide justification for further studies exploring the potential diagnostic role of magnetic microdevices in assessing the presence and concentration of SARS-CoV-2 viruses.

Electrokinetic tweezing: three-dimensional manipulation of microparticles by real-time imaging and flow control.

Electrokinetic tweezing in three dimensions is achieved for the first time using a multi-layer microfluidic device, a model-based control algorithm, and a 3D imaging algorithm connected in a feedback loop. Here we demonstrate steering of microparticles along 3D trajectories and trapping in all three dimensions with accuracy as good as 1 µm.

Increasing the oscillation frequency of strong magnetic fields above 101 kHz significantly raises peripheral nerve excitation thresholds.

PURPOSE: A time-varying magnetic field can cause unpleasant peripheral nerve stimulation (PNS) when the maximum excursion of the magnetic field (ΔB) is above a frequency-dependent threshold level [P. Mansfield and P. R. Harvey, Magn. Reson. Med. 29, 746-758 (1993)]. Clinical and research magnetic resonance imaging (MRI) gradient systems have been designed to avoid such bioeffects by adhering to regulations and guidelines established on the basis of clinical trials. Those trials, generally employing sinusoidal waveforms, tested human responses to magnetic fields at frequencies between 0.5 and 10 kHz [W. Irnich and F. Schmitt, Magn. Reson. Med. 33, 619-623 (1995), T. F. Budinger et al., J. Comput. Assist. Tomogr. 15, 909-914 (1991), and D. J. Schaefer et al., J. Magn. Reson. Imaging 12, 20-29 (2000)]. PNS thresholds for frequencies higher than 10 kHz had been extrapolated, using physiological models [J. P. Reilly et al., IEEE Trans. Biomed. Eng. BME-32(12), 1001-1011 (1985)]. The present study provides experimental data on human PNS thresholds to oscillating magnetic field stimulation from 2 to 183 kHz. Sinusoidal waveforms were employed for several reasons: (1) to facilitate comparison with earlier reports that used sine waves, (2) because prior designers of fast gradient hardware for generalized waveforms (e.g., including trapezoidal pulses) have employed quarter-sine-wave resonant circuits to reduce the rise- and fall-times of pulse waveforms, and (3) because sinusoids are often used in fast pulse sequences (e.g., spiral scans) [S. Nowak, U.S. patent 5,245,287 (14 September 1993) and K. F. King and D. J. Schaefer, J. Magn. Reson. Imaging 12, 164-170 (2000)]. METHODS: An IRB-approved prospective clinical trial was performed, involving 26 adults, in which one wrist was exposed to decaying sinusoidal magnetic field pulses at frequencies from 2 to 183 kHz and amplitudes up to 0.4 T. Sham exposures (i.e., with no magnetic fields) were applied to all subjects. RESULTS: For 0.4 T pulses at 2, 25, 59, 101, and 183 kHz, stimulation was reported by 22 (84.6%), 24 (92.3%), 15 (57.7%), 2 (7.7%), and 1 (3.8%) subjects, respectively. CONCLUSIONS: The probability of PNS due to brief biphasic time-varying sinusoidal magnetic fields with magnetic excursions up to 0.4 T is shown to decrease significantly at and above 101 kHz. This phenomenon may have particular uses in dynamic scenarios (e.g., cardiac imaging) and in studying processes with short decay times (e.g., electron paramagnetic resonance imaging, bone and solids imaging). The study suggests the possibility of new designs for human and preclinical MRI systems that may be useful in clinical practice and scientific research.

Positioning and immobilization of individual quantum dots with nanoscale precision.

We demonstrate a technique for the precise immobilization of nanoscale objects at accurate positions on two-dimensional surfaces. We have developed a water-based photoresist that causes nanostructures such as colloidal quantum dots to segregate to a thin layer at surfaces. By combining this material with electroosmotic feedback control, we demonstrate the ability to position selected, individual quantum dots at specific locations and to immobilize them with 130 nm precision via localized UV exposure.

Manipulating quantum dots to nanometer precision by control of flow.

We present a method for manipulating preselected quantum dots (QDs) with nanometer precision by flow control. The accuracy of this approach scales more favorably with particle size than optical trapping, enabling more precise positioning of nanoscopic particles. We demonstrate the ability to position a single QD in a 100 microm working region to 45 nm accuracy for holding times exceeding one hour and the ability to take active quantum measurements on the dynamically manipulated QD.