Electronic, Optical, and Magnetic Neural Interfaces

Mammalian nervous system contains billions of neurons that exchange electrical, chemical and mechanical signals. Our ability to study this complexity is limited by the lack of technologies available for interrogating neural circuits across their diverse signaling modalities without inducing a foreign-body reaction. My talk will describe neural interface strategies pursued in my group aimed at mimicking the materials properties and transduction mechanisms of the nervous system. Specifically, I will discuss (1) Fiber-based probes for multifunctional interfaces with the brain and spinal cord circuits; (2) Magnetic nanotransducers for minimally invasive neural stimulation; and (3) Active scaffolds for neural tissue engineering and interrogation. Fiber-drawing methods can be applied to create multifunctional polymer-based probes capable of simultaneous electrical, optical, and chemical probing of neural tissues in freely moving subjects[1]. Similar engineering principles enable ultra-flexible miniature fiber-probes with geometries inspired by nerves, which permit simultaneous optical excitation and recording of neural activity in the spinal cord allowing for optical control of lower limb movement[2]. Furthermore, fiber-based fabrication can be extended to design of scaffolds that direct neural growth[3] and activity[4] facilitating repair of damaged nerves. Molecular mechanisms of action potential firing inspire the development of materials-based strategies for direct manipulation of ion transport across neuronal membranes. For example, hysteretic heat dissipation by magnetic nanomaterials can be used to remotely trigger activity of neurons expressing heat-sensitive ion channels. Since the alternating magnetic fields in the low radiofrequency range interact minimally with the biological tissues, the magnetic nanoparticles injected into the brain can act as transducers of wireless magnetothermal deep brain stimulation[5, 6]. Similarly, local hysteretic heating allows magnetic nanoparticles to disrupt protein aggregates associated with neurodegenerative disorders[7]. 1. Canales, A., Jia, X., Froriep, U.P., Koppes, R.A., Tringides, C.M., Selvidge, J., Hou, C., Wei, L., Fink, Y., Anikeeva, P., Multifunctional fibers for simultaneous optical, electrical and chemical interrogation of neural circuits in vivo. Nature Biotechnology, 2015. 33(3): p. 277-284. 2. Lu, C., Froriep, U.P., Canales, A., Koppes, R.A., Caggiano, V., Selvidge, J., Bizzi, E., Anikeeva, P., Polymer fiber probes enable optical control of spinal cord and muscle function in vivo. Advanced Functional Materials, 2014. 24(42): p. 6594-6600. 3. Koppes, R.A., Park, S., Hood, T., Jia, X., Poorheravi, N.A., Achyuta, A.K.H., Fink, Y. Anikeeva, P., Thermally drawn fibers as nerve guidance scaffolds. Biomaterials, 2016. 81: p. 27-35. 4. Park, S., Koppes, R. A., Froriep, U. P., Jia, X., Achyuta, A. K. H., McLaughlin, B. L., Anikeeva, P., Optogenetic control of nerve growth. Scientific Reports, 2015. 5. 5. Chen, R., Romero, G., Christiansen, M.G., Mohr, A., Anikeeva, P., Wireless magnetothermal deep brain stimulation. Science, 2015. 347(6229): p. 1477-1480. 6. Romero, G., Christiansen, M.G., Stocche Barbosa, L., Garcia, F., Anikeeva, P., Localized Excitation of Neural Activity via Rapid Magnetothermal Drug Release. Advanced Functional Materials, 2016. 7. Loynachan, C.N., Romero, G., Christiansen, M.G., Chen, R., Ellison, R., O\u27Malley, T.T., Froriep, U.P., Walsh, D.M., Anikeeva, P., Targeted Magnetic Nanoparticles for Remote Magnetothermal Disruption of Amyloid-β Aggregates. Advanced Healthcare Materials, 2015. 4(14): p. 2100-2109

Non-Equilibrium Phonon Transport Across Nanoscale Interfaces

Despite the ubiquity of applications of heat transport across nanoscale interfaces, including integrated circuits, thermoelectrics, and nanotheranostics, an accurate description of phonon transport in these systems remains elusive. Here we present a theoretical and computational framework to describe phonon transport with position, momentum and scattering event resolution. We apply this framework to a single material spherical nanoparticle for which the multidimensional resolution offers insight into the physical origin of phonon thermalization, and length-scale dependent anisotropy of steady-state phonon distributions. We extend the formalism to handle interfaces explicitly and investigate the specific case of semi-coherent materials interfaces by computing the coupling between phonons and interfacial strain resulting from aperiodic array of misfit dislocations. Our framework quantitatively describes the thermal interface resistance within the technologically relevant Si-Ge heterostructures. In future, this formalism could provide new insight into coherent and driven phonon effects in nanoscale materials increasingly accessible via ultrafast, THz and near-field spectroscopies.Comment: 6 pages, 3 figure

Physical properties and design of light-emitting devices based on organic materials and nanoparticles

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2009.Includes bibliographical references (p. 201-213).This thesis presents the detailed experimental and theoretical characterization of light-emitting devices (LEDs) based on organic semiconductors and colloidal quantum dots (QDs). This hybrid material system has several advantages over crystalline semiconductor technology; first, it is compatible with inexpensive fabrication methods such as solution processing and roll-to-roll deposition; second, hybrid devices can be fabricated on flexible plastic substrates and glass, avoiding expensive crystalline wafers; third, this technology is compatible with patterning methods, allowing multicolor light sources to be fabricated on the same substrate by simply changing the emissive colloidal QD layer. While the fabrication methods for QD-LEDs have been extensively investigated, the basic physical processes governing the performance of QD-LEDs remained unclear. In this thesis we use electronic and optical measurements combined with morphological analysis to understand the origins of QD-LED operation. We investigate charge transport and exciton energy transfer between organic materials and colloidal QDs and use our findings as guidelines for the device design and material choices. We fabricate hybrid QD-LEDs with efficiencies exceeding those of previously reported devices by 50-300%. Novel deposition methods allow us to fabricate QD-LEDs of controlled and tunable color by simply changing the emissive QD layer without altering the structure of organic charge transport layers. For example, we fabricate white light sources with tunable color temperature and color rendering index close to that of sunlight, inaccessible by crystalline semiconductor based lighting or fluorescent sources. Our physical modeling of hybrid QD-LEDs provides insights on carrier transport and exciton generation in hybrid organic-QD devices that are in agreement with our experimental data. The general nature of our experimental and theoretical findings makes them applicable to a variety of hybrid organic-QD optoelectronic devices such as LEDs, solar cells, photodetectors and chemical sensors.by Polina Olegovna Anikeeva.Ph.D

Flexible fiber-based optoelectronics for neural interfaces

Neurological and psychiatric conditions pose an increasing socioeconomic burden on our aging society. Our ability to understand and treat these conditions relies on the development of reliable tools to study the dynamics of the underlying neural circuits. Despite significant progress in approaches and devices to sense and modulate neural activity, further refinement is required on the spatiotemporal resolution, cell-type selectivity, and longterm stability of neural interfaces. Guided by the principles of neural transduction and by the materials properties of the neural tissue, recent advances in neural interrogation approaches rely on flexible and multifunctional devices. Among these approaches, multimaterial fibers have emerged as integrated tools for sensing and delivering of multiple signals to and from the neural tissue. Fiber-based neural probes are produced by thermal drawing process, which is the manufacturing approach used in optical fiber fabrication. This technology allows straightforward incorporation of multiple functional components into microstructured fibers at the level of their macroscale models, preforms, with a wide range of geometries. Here we will introduce the multimaterial fiber technology, its applications in engineering fields, and its adoption for the design of multifunctional and flexible neural interfaces. We will discuss examples of fiber-based neural probes tailored to the electrophysiological recording, optical neuromodulation, and delivery of drugs and genes into the rodent brain and spinal cord, as well as their emerging use for studies of nerve growth and repair.United States. National Institute of Neurological Disorders and Stroke (Grant 5R01NS086804)United States. National Science Foundation. Division of Materials Research (Grant DMR-1419807)United States. National Science Foundation. Division of Engineering Education & Centers (Grant EEC-1028725)McGovern Institute for Brain Research at MI

Engineering intracellular biomineralization and biosensing by a magnetic protein

Remote measurement and manipulation of biological systems can be achieved using magnetic techniques, but a missing link is the availability of highly magnetic handles on cellular or molecular function. Here we address this need by using high-throughput genetic screening in yeast to select variants of the iron storage ferritin (Ft) that display enhanced iron accumulation under physiological conditions. Expression of Ft mutants selected from a library of 10[superscript 7] variants induces threefold greater cellular iron loading than mammalian heavy chain Ft, over fivefold higher contrast in magnetic resonance imaging, and robust retention on magnetic separation columns. Mechanistic studies of mutant Ft proteins indicate that improved magnetism arises in part from increased iron oxide nucleation efficiency. Molecular-level iron loading in engineered Ft enables detection of individual particles inside cells and facilitates creation of Ft-based intracellular magnetic devices. We demonstrate construction of a magnetic sensor actuated by gene expression in yeast.National Institutes of Health (U.S.) (Grant DP2-OD002114)National Institutes of Health (U.S.) (Grant R01-NS076462)National Institutes of Health (U.S.) (Grant R01-MH103160)Thomas and Stacey Siebel Foundation (Fellowship)McGovern Institute for Brain Research at MIT (Friends of the McGovern Institute Fellowship

Wireless Magnetothermal Deep Brain Stimulation

Wireless deep brain stimulation of well-defined neuronal populations could facilitate the study of intact brain circuits and the treatment of neurological disorders. Here we demonstrate minimally-invasive and remote neural excitation through the activation of the heat-sensitive capsaicin receptor TRPV1 by magnetic nanoparticles. When exposed to alternating magnetic fields, the nanoparticles dissipate heat generated by hysteresis, triggering widespread and reversible firing of TRPV1+ neurons. Wireless magnetothermal stimulation in the ventral tegmental area of mice evoked excitation in subpopulations of neurons in the targeted brain region and in structures receiving excitatory projections. The nanoparticles persisted in the brain for over a month, allowing for chronic stimulation without the need for implants and connectors.United States. Defense Advanced Research Projects Agency (Young Faculty Award D13AP00043)McGovern Institute for Brain Research at MITNational Science Foundation (U.S.) (CAREER Award CBET-1253890)National Science Foundation (U.S.). Graduate Research FellowshipAmerican Society for Engineering Education. National Defense Science and Engineering Graduate Fellowshi

Magnetically Actuated Protease Sensors for in Vivo Tumor Profiling

Targeted cancer therapies require a precise determination of the underlying biological processes driving tumorigenesis within the complex tumor microenvironment. Therefore, new diagnostic tools that capture the molecular activity at the disease site in vivo are needed to better understand tumor behavior and ultimately maximize therapeutic responses. Matrix metalloproteinases (MMPs) drive multiple aspects of tumorigenesis, and their activity can be monitored using engineered peptide substrates as protease-specific probes. To identify tumor specific activity profiles, local sampling of the tumor microenvironment is necessary, such as through remote control of probes, which are only activated at the tumor site. Alternating magnetic fields (AMFs) provide an attractive option to remotely apply local triggering signals because they penetrate deep into the body and are not likely to interfere with biological processes due to the weak magnetic properties of tissue. Here, we report the design and evaluation of a protease-activity nanosensor that can be remotely activated at the site of disease via an AMF at 515 kHz and 15 kA/m. Our nanosensor was composed of thermosensitive liposomes containing functionalized protease substrates that were unveiled at the target site by remotely triggered heat dissipation of coencapsulated magnetic nanoparticles (MNPs). This nanosensor was combined with a unique detection assay to quantify the amount of cleaved substrates in the urine. We applied this spatiotemporally controlled system to determine tumor protease activity in vivo and identified differences in substrate cleavage profiles between two mouse models of human colorectal cancer.National Cancer Institute (U.S.) (Grant P30-CA14051)National Institute of Environmental Health Sciences (Grant P30-ES002109)United States. Defense Advanced Research Projects Agency (Award HR0011-15-C-0155

Voices in methods development

To mark the 15th anniversary of Nature Methods, we asked scientists from across diverse fields of basic biology research for their views on the most exciting and essential methodological challenges that their communities are poised to tackle in the near future