Fiber drawing enables scalable fabrication of multifunctional flexible fibers that integrate electrical, optical, and microfluidic modalities to record and modulate neural activity. Constraints on thermomechanical properties of materials, however, have prevented integrated drawing of metal electrodes with low‐loss polymer waveguides for concurrent electrical recording and optical neuromodulation. Here, two fabrication approaches are introduced: 1) an iterative thermal drawing with a soft, low melting temperature (Tm) metal indium, and 2) a metal convergence drawing with traditionally non‐drawable high Tm metal tungsten. Both approaches deliver multifunctional flexible neural interfaces with low‐impedance metallic electrodes and low‐loss waveguides, capable of recording optically‐evoked and spontaneous neural activity in mice over several weeks. These fibers are coupled with a light‐weight mechanical microdrive (1 g) that enables depth‐specific interrogation of neural circuits in mice following chronic implantation. Finally, the compatibility of these fibers with magnetic resonance imaging is demonstrated and they are applied to visualize the delivery of chemical payloads through the integrated channels in real time. Together, these advances expand the domains of application of the fiber‐based neural probes in neuroscience and neuroengineering.
To reversibly manipulate neural circuits with increased spatial and temporal control, photoswitchable ligands can add an optical switch to a target receptor or signaling cascade. This approach, termed photopharmacology, has been enabling to molecular neuroscience, however, its application to behavioral experiments has been impeded by a lack of integrated hardware capable of delivering both light and compounds to deep brain regions in moving subjects. Here, we devise a hybrid photochemical genetic approach to target neurons using a photoswitchable agonist of capsaicin receptor (TRPV1), red-AzCA-4. Using the thermal drawing process we created multifunctional fibers that can deliver viruses, photoswitchable ligands, and light to deep brain regions in awake, freely moving mice. We implanted our fibers into the ventral tegmental area (VTA), a midbrain hub of the mesolimbic pathway, and used them to deliver a transgene coding for TRPV1. This sensitized excitatory VTA neurons to red-AzCA-4, and allowed us to optically control conditioned place preference using a mammalian ion-channel, thus extending applications of photopharmacology to behavioral experiments. Applied to endogenous receptors, our approach may accelerate studies of molecular mechanisms underlying animal behavior. AUTHOR CONTRIBUTIONS JAF and PA conceived and coordinated the study. DBK synthesized the photoswitchable compounds. JAF and GR carried out imaging experiments in cultured neurons. JAF, MJA, and IG fabricated and characterized the multifunctional fibers. YF aided in fiber design. PC and FK produced lentiviral vectors. JAF, MJA, PC, AC, and IG performed immunohistochemical experiments. JAF and MJA performed the behavioral experiments. PC, AC, MJA, and JAF wrote scripts for data analysis. JAF, MJA, and PA wrote the manuscript with input from all co-authors.
Due to supply chain disruption, the COVID-19 pandemic has caused severe shortages in personal protective equipment (PPE) for health care professionals. Local fabrication based on 3D printing is one way to address this challenge, particularly in the case of simple products such as protective face shields. As a consequence, many public domain designs for face shields have become available. No clear path exists, however, for introducing a locally fabricated and unapproved product into a clinical setting. In a US health care setting, face shields are regulated by the Food and Drug Administration (FDA); similar policies exist in other countries. We describe a research protocol under which rapid iteration on an existing design, coupled with clinical feedback and real-world testing in an emergency department, allowed a face shield to be implemented by the members of the incident command team at a major academic medical center. We describe our design and testing process and provide an overview of regulatory considerations associated with fabrication and testing of face shields and related products. All designs, materials used, testing protocols, and survey results are reported in full to facilitate the execution of similar face shield efforts in other clinical settings. Our work serves as a case study for development of a robust local response to pandemics and other health care emergencies, with implications for healthcare professionals, hospital administrators, regulatory agencies and concerned citizens.
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