Jeannette Ingabire

Real-time temperature monitoring with high accuracy and spatiotemporal resolution is critical for many biological applications, including disease diagnosis, drug delivery, and biomedical research. However, traditional methods for measuring temperature in biological systems present difficulties for a variety of reasons, such as slow response time, limited spatial resolution, low amplitude, and susceptibility to electromagnetic interference. Most importantly, in many cases, the thermal mass of temperature probes limits the accuracy and speed of measurement significantly. Here, we show that photonic microring resonators (MRRs) can be used for sensitive, precise, and high spatiotemporal resolution measurement of temperature in the biological milieu. The high refractive index of Si MRR and negligible thermal mass enable sensitive, ultrafast, and accurate temperature transients. By using a double resonator circuit, we demonstrate that MRR sensors can measure temperature with a 1 mm spatial resolution. We then show that MRR yields more accurate results than fiber optic probes for measuring temperature transients. Finally, we demonstrate the localized temperature measurement capability of MRRs in mouse brain tissue heated by superparamagnetic nanoparticles in an alternating magnetic field. This compact, lab-on-chip photonic temperature sensing platform holds great promise for continuous monitoring of temperature in critical biological and biomedical applications.

This comparative effectiveness study evaluates aerosol particle leak and standard surgical mask fit with 3 elastomeric harness designs tested on mannequin heads and human participants using US Occupational Safety and Health Administration N95 fit factor requirements.

INTRODUCTION: Brain stimulation techniques are critical for unraveling the innerworkings of complex neuronal pathways governing both normal physiological function and pathologic states in neurological disorders. Focused ultrasound (FUS) is an emerging technique poised to significantly alter central nervous system (CNS) drug delivery and neuroscience research through non-invasive means. Magnetogenetics is a brain stimulation technique which may benefit from FUS technology in that alternating magnetic fields (AMF), like FUS, can pass through the skull without requiring surgery. METHODOLOGY: Magnetogenetics involves the deposition of superparamagnetic iron-oxide nanoparticles (SPIONs) and overexpression of thermoreceptor transmembrane proteins (e.g. TRPV1 and TRPA1) in the brain. When an external AMF is applied, SPIONs generate local heating, which can activate thermoreceptors, depolarize the cell membrane and trigger action potentials in neurons. Monitoring neuronal activation by a magnetogenetics approach can be facilitated by the co-expression of genetically-encoded voltage indicators (GEVI), which enable fluorescence-based detection of membrane depolarization. However, traditional surgical methods used to introduce these components into the brain are invasive and highly focal, precluding investigation of brain-wide neuronal pathways. RESULTS: Here, we demonstrate that our recently developed, flexible configuration for FUS therapy and ultrasound imaging, called theranostic ultrasound (ThUS), can transiently open the blood-brain barrier (BBB) and facilitate the non-invasive delivery of SPION and viral vectors encoding thermoreceptors and GEVI, to enable remote magnetogenetic modulation. We also report significant advances in ThUS pulse sequence design, where we developed a novel multi-target opening volume expansion (MOVE) pulse sequence to maximize BBB opening volume within a single ThUS treatment. ThUS MOVE yielded increased gene delivery commensurate with the number of targeted focal zones and achieved brain-wide expression of GEVI. CONCLUSION: The results presented herein not only demonstrate the feasibility for ThUS to facilitate a non-invasive brain stimulation approach, but also showcase a method for eliciting larger volumes of BBB opening within a single sonication which could dramatically improve gene delivery procedures for both preclinical research and therapeutic purposes in the future.

Objective: Several novel methods, including magnetogenetics and magnetoelectric stimulation, use high frequency alternating magnetic fields to precisely manipulate neural activity. To quantify the behavioral effects of such interventions in a freely moving mouse, we developed a dual-channel magnetic chamber, specifically designed for rate-sensitive magnetothermal-genetic stimulation, and adaptable for other uses of alternating magnetic fields. Approach: chamber suitable for mouse studies. The two channels have nominal frequencies of 50 and 550 kHz with peak magnetic field strengths of 88 and 12.5 mT, achieved with resonant coil drives having peak voltages of 1.6 and 1.8 kV and currents of 1.0 and 0.26 kA, respectively. Additionally, a liquid cooling system enables magnetic field generation for second-level durations, and an observation port and camera allow video capture of the animal's behavior within the chamber. Main Results: The system generates high-amplitude magnetic fields across two widely separated frequency channels with negligible interference (< 1%). Relatively uniform magnetic field distribution (±10% across 94% of the chamber volume) is maintained throughout the chamber, and temperature increase of the inner side of the coil enclosure during the operation is limited to < 0.35 °C/s to ensure in vivo safety. Using cobalt-doped and undoped iron oxide nanoparticles, we demonstrate channel-specific heating rates of 3.5 °C/s and 1.5 °C/s, respectively, validating frequency-selectivity. Both channels can run continuously for 4 seconds stably. Significance: We present a novel magnetic stimulation platform that combines high-frequency, high-power capability with two independently-controlled channels generating different frequencies, along with a real-time behavioral observation system for freely moving animals. The system supports frequency-multiplexed stimulation strategies for precise modulation of neural activity, making it a versatile tool for advancing magnetogenetics, neural circuit interrogation, and noninvasive stimulation approaches in neuroscience and bioengineering.

Abstract Objective. Several novel methods, including magnetogenetics and magnetoelectric stimulation, use high frequency alternating magnetic fields to precisely manipulate neural activity. To quantify the behavioral effects of such interventions in a freely moving mouse, we developed a dual-channel magnetic chamber, specifically designed for rate-sensitive magnetothermal-genetic stimulation, and adaptable for other uses of alternating magnetic fields. Approach. Through an optimized coil design, the system allows independent control of two spatially orthogonal uniform magnetic fields delivered at different frequencies within a 10 × 10 × 6 cm 3 chamber suitable for mouse studies. The two channels have nominal frequencies of 50 and 550 kHz with peak magnetic field strengths of 88 and 12.5 mT, achieved with resonant coil drives having peak voltages of 1.6 and 1.8 kV and currents of 1.0 and 0.26 kA, respectively. Additionally, a liquid cooling system enables magnetic field generation for second-level durations, and an observation port and camera allow video capture of the animal’s behavior within the chamber. Main results. The system generates high-amplitude magnetic fields across two widely separated frequency channels with negligible interference (&lt;1%). Relatively uniform magnetic field distribution (±10% across 94% of the chamber volume) is maintained throughout the chamber, and temperature increase of the inner side of the coil enclosure during the operation is limited to &lt;0.35 °C s −1 to ensure in vivo safety. Using cobalt-doped and undoped iron oxide nanoparticles, we demonstrate channel-specific heating rates of 3.5 °C s −1 and 1.5 °C s −1 , respectively, validating frequency-selectivity. Both channels can run continuously for 4 s stably. Significance. We present a novel magnetic stimulation platform that combines high-frequency, high-power capability with two independently-controlled channels generating different frequencies, along with a real-time behavioral observation system for freely moving animals. The system supports frequency-multiplexed stimulation strategies for precise modulation of neural activity, making it a versatile tool for advancing magnetogenetics, neural circuit interrogation, and noninvasive stimulation approaches in neuroscience and bioengineering.