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We report a new approach for realizing a flexible photonic crystal (PC) cavity that enables wide-range tuning of its resonance frequency. Our PC cavity consists of a regular array of silicon nanowires embedded in a polydimethylsiloxane (PDMS) matrix and exhibits a cavity resonance in the telecommunication band that can be reversibly tuned over 60 nm via mechanical stretching—a record for two-dimensional (2D) PC structures. These mechanically reconfigurable devices could find potential applications in integrated photonics, sensing in biological systems, and smart materials., Chemistry and Chemical Biology

Wireless communication technologies for bioelectronic implants enable remote monitoring for diagnosis and adaptive therapeutic intervention without the constraints of wired connections. However, wireless data uplink from millimeter-scale devices deep in the body struggles to achieve low power consumption while maintaining large misalignment tolerances. Here, we report a passive wireless backscatter communication system based on magnetoelectric transducers that consumes less than 0.3 pJ/bit and achieves less than 1E-6 bit error rate at a distance of 55 mm while tolerating a misalignment of 10 mm. Using this robust data uplink, we designed a wireless cardiac sensing node that can transmit electrocardiogram signals from the beating heart surface of a porcine model to a custom external transceiver using the magnetoelectric backscatter uplink. This reliable, near-zero-power communication method provides opportunities for next-generation bioelectronics to feature real-time physiological monitoring and closed-loop therapies while maintaining a small form factor and low power consumption., Competing Interests: Conflict of interest F.A., J.E.W., K.Y., and J.T.R. receive monetary and/or equity compensation from Motif Neurotech. The terms of these arrangements have been reviewed and approved by Rice University in accordance with their policies on conflict of interest in research.

Miniature bioelectronic implants promise revolutionary therapies for cardiovascular and neurological disorders. Wireless power transfer (WPT) is a significant method for miniaturization, eliminating the need for bulky batteries in devices. Despite successful demonstrations of millimetric battery free implants in animal models, the robustness and efficiency of WPT are known to degrade significantly under misalignment incurred by body movements, respiration, heart beating, and limited control of implant orientation during surgery. This article presents an omnidirectional WPT platform for millimetric bioelectronic implants, employing the emerging magnetoelectric (ME) WPT modality, and magnetic field steering technique based on multiple transmitter (TX) coils. To accurately sense the weak coupling in a miniature implant and adaptively control the multicoil TX array in a closed loop, we develop an active echo (AE) scheme using a tiny coil on the implant. Our prototype comprises a fully integrated 14.2 mm3 implantable stimulator embedding a custom low power system on chip (SoC) powered by an ME film, a TX with a custom three channel AE RX chip, and a multicoil TX array with mutual inductance cancellation. The AE RX achieves negative 161 dBm per Hz input referred noise with 64 dB gain tuning range to reliably sense the AE signal, and offers fast polarity detection for driver control. AE simultaneously enhances the robustness, efficiency, and charging range of ME WPT. Under 90 degree rotation from the ideal position, our omnidirectional WPT system achieves 6.8x higher power transfer efficiency (PTE) than a single coil baseline. The tracking error of AE negligibly degrades the PTE by less than 2 percent from using ideal control.

Networks of miniature bioelectronic implants would enable precise measurement and manipulation of the complex and distributed physiological systems in the body. For example, sensing and stimulation nodes throughout the heart, brain, or peripheral nervous system would more accurately track and treat disease or support prosthetic technologies with many degrees of freedom. A main challenge to creating this type of in-body bioelectronic network is the fact that wireless power and data transfer are often inefficient when communicating through biological tissues. This challenge is typically compounded as one increases the number of implants within the network. Here, we show that magnetoelectric wireless data and power transfer enable a network of millimeter-sized bioelectronic implants where the power transfer efficiency of the system improves as the number of implanted devices increases. Using this property, we demonstrate networks of wireless battery-free bioelectronics ranging from 1 to 6 implants where the wireless power transfer efficiency for the system increases from 0.2% to 1.3%, with each node in the network receiving 2.2 mW at a distance of 1 cm. We use this system for efficient and robust wireless data and power transfer to demonstrate proof-of-concept networks of miniature spinal cord stimulators and cardiac pacing devices in large animals. The scalability of this network architecture enabled by magnetoelectric wireless power transfer provides a platform for building wireless closed-loop networks of bioelectronic implants for next-generation electronic medicine., Competing Interests: Competing interests J.T.R., F.A., and J.E.W. receive monetary and/or equity compensation from Motif Neurotech. A.F. is a consultant for Medtronic, Inc. and Abbott, Inc. M.R. receives monetary and/or equity compensation from Maxwell Biomedical, Rhythio, XNHealth, consults for Ziopatch, and is the medical director for IRhythm. The terms of these arrangements have been reviewed and approved by Rice University, the Houston Methodist Research Institute, Baylor College of Medicine, and The Texas Heart Institute in accordance with their policies on conflict of interest in research. The other authors declare no competing interests.

To maximize the capabilities of minimally invasive implantable bioelectronic devices, we must deliver large amounts of power to small implants; however, as devices are made smaller, it becomes more difficult to transfer large amounts of power without a wired connection. Indeed, recent work has explored creative wireless power transfer (WPT) approaches to maximize power density (the amount of power transferred divided by receiver footprint area (length × width)). Here, we analyzed a model for WPT using magnetoelectric (ME) materials that convert an alternating magnetic field into an alternating voltage. With this model, we identify the parameters that impact WPT efficiency and optimize the power density. We find that improvements in adhesion between the laminated ME layers, clamping, and selection of material thicknesses lead to a power density of 3.1 mW/mm 2 , which is over 4 times larger than previously reported for mm-sized wireless bioelectronic implants at a depth of 1 cm or more in tissue. This improved power density allows us to deliver 31 mW and 56 mW to 10-mm 2 and 27-mm 2 ME receivers, respectively. This total power delivery is over 5 times larger than similarly sized bioelectronic devices powered by radiofrequency electromagnetic waves, inductive coupling, ultrasound, light, capacitive coupling, or previously reported magnetoelectrics. This increased power density opens the door to more power-intensive bioelectronic applications that have previously been inaccessible using mm-sized battery-free devices.

A major challenge for miniature bioelectronics is wireless power delivery deep inside the body. Electromagnetic or ultrasound waves suffer from absorption and impedance mismatches at biological interfaces. On the other hand, magnetic fields do not suffer these losses, which has led to magnetically powered bioelectronic implants based on induction or magnetothermal effects. However, these approaches have yet to produce a miniature stimulator that operates at clinically relevant high frequencies. Here, we show that an alternative wireless power method based on magnetoelectric (ME) materials enables miniature magnetically powered neural stimulators that operate up to clinically relevant frequencies in excess of 100 Hz. We demonstrate that wireless ME stimulators provide therapeutic deep brain stimulation in a freely moving rodent model for Parkinson's disease and that these devices can be miniaturized to millimeter-scale and fully implanted. These results suggest that ME materials are an excellent candidate to enable miniature bioelectronics for clinical and research applications., Competing Interests: Declaration of Interests This work relates to patent PCT/US2020/026688., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Advances in microfabrication technologies and biomaterials have enabled a growing class of electronic devices that can stimulate and record bioelectronic signals. Many of these devices have been developed for humans or vertebrate animals, where miniaturization allows for implantation within the body. There are, however, another class of bioelectronic interfaces that exploit microfabrication and nanoelectronics to record signals from tiny, millimeter-sized organisms. In these cases, rather than implanting a device inside an animal, animals themselves are loaded in large numbers into bioelectronic devices for neural circuit and behavioral interrogation. These scalable interfaces provide platforms to develop new therapeutics as well as better understand basic principles of bioelectronic communication, neuroscience, and behavior. Here we review recent progress in these bioelectronic technologies and describe how they can complement on-chip optical, mechanical, and chemical interrogation methods to achieve high-throughput, multimodal studies of millimeter-sized small animals., Competing Interests: Declaration of Interests J.T.R, D.L.G., and B.W.A. are inventors on a patent for suspended nano-electrodes for on-chip electrophysiology filed by Rice University. All other authors declare no competing interests., (Copyright © 2020. Published by Elsevier Inc.)

Snorkelers in mangrove forest waters inhabited by the upside-down jellyfish Cassiopea xamachana report discomfort due to a sensation known as stinging water, the cause of which is unknown. Using a combination of histology, microscopy, microfluidics, videography, molecular biology, and mass spectrometry-based proteomics, we describe C. xamachana stinging-cell structures that we term cassiosomes. These structures are released within C. xamachana mucus and are capable of killing prey. Cassiosomes consist of an outer epithelial layer mainly composed of nematocytes surrounding a core filled by endosymbiotic dinoflagellates hosted within amoebocytes and presumptive mesoglea. Furthermore, we report cassiosome structures in four additional jellyfish species in the same taxonomic group as C. xamachana (Class Scyphozoa; Order Rhizostomeae), categorized as either motile (ciliated) or nonmotile types. This inaugural study provides a qualitative assessment of the stinging contents of C. xamachana mucus and implicates mucus containing cassiosomes and free intact nematocytes as the cause of stinging water.

Developing a mechanistic understanding of protein dynamics and conformational changes at polymer interfaces is critical for a range of processes including industrial protein separations. Salting out is one example of a procedure that is ubiquitous in protein separations yet is optimized empirically because there is no mechanistic description of the underlying interactions that would allow predictive modeling. Here, we investigate peak narrowing in a model transferrin-nylon system under salting out conditions using a combination of single-molecule tracking and ensemble separations. Distinct surface transport modes and protein conformational changes at the negatively charged nylon interface are quantified as a function of salt concentration. Single-molecule kinetics relate macroscale improvements in chromatographic peak broadening with microscale distributions of surface interaction mechanisms such as continuous-time random walks and simple adsorption-desorption. Monte Carlo simulations underpinned by the stochastic theory of chromatography are performed using kinetic data extracted from single-molecule observations. Simulations agree with experiment, revealing a decrease in peak broadening as the salt concentration increases. The results suggest that chemical modifications to membranes that decrease the probability of surface random walks could reduce peak broadening in full-scale protein separations. More broadly, this work represents a proof of concept for combining single-molecule experiments and a mechanistic theory to improve costly and time-consuming empirical methods of optimization., Competing Interests: The authors declare no competing interest.

An important feature of animal behavior is the ability to switch rapidly between activity states, however, how the brain regulates these spontaneous transitions based on the animal's perceived environment is not well understood. Here we show a C. elegans sleep-like state on a scalable platform that enables simultaneous control of multiple environmental factors including temperature, mechanical stress, and food availability. This brief quiescent state, which we refer to as microfluidic-induced sleep, occurs spontaneously in microfluidic chambers, which allows us to track animal movement and perform whole-brain imaging. With these capabilities, we establish that microfluidic-induced sleep meets the behavioral requirements of C. elegans sleep and depends on multiple factors, such as satiety and temperature. Additionally, we show that C. elegans sleep can be induced through mechanosensory pathways. Together, these results establish a model system for studying how animals process multiple sensory pathways to regulate behavioral states.

The classic approach to measure the spiking response of neurons involves the use of metal electrodes to record extracellular potentials. Starting over 60 years ago with a single recording site, this technology now extends to ever larger numbers and densities of sites. We argue, based on the mechanical and electrical properties of existing materials, estimates of signal-to-noise ratios, assumptions regarding extracellular space in the brain, and estimates of heat generation by the electronic interface, that it should be possible to fabricate rigid electrodes to concurrently record from essentially every neuron in the cortical mantle. This will involve fabrication with existing yet nontraditional materials and procedures. We further emphasize the need to advance materials for improved flexible electrodes as an essential advance to record from neurons in brainstem and spinal cord in moving animals., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Understanding factors affecting the susceptibility of organisms to thermal stress is of enormous interest in light of our rapidly changing climate. When adaptation is limited, thermal acclimation and deacclimation abilities of organisms are critical for population persistence through a period of thermal stress. Holobionts (hosts plus associated symbionts) are key components of various ecosystems, such as coral reefs, yet the contributions of their two partners to holobiont thermal plasticity are poorly understood. Here, we tested thermal plasticity of the freshwater cnidarian Hydra viridissima (green hydra) using individual behavior and population responses. We found that algal presence initially reduced hydra thermal tolerance. Hydra with algae (symbiotic hydra) had comparable acclimation rates, deacclimation rates, and thermal tolerance after acclimation to those without algae (aposymbiotic hydra) but they had higher acclimation capacity. Acclimation of the host (hydra) and/or symbiont (algae) to elevated temperatures increased holobiont thermal tolerance and these effects persisted for multiple asexual generations. In addition, acclimated algae presence enhanced hydra fitness under prolonged sublethal thermal stress, especially when food was limited. Our study indicates while less intense but sublethal stress may favor symbiotic organisms by allowing them to acclimate, sudden large, potentially lethal fluctuations in climate stress likely favor aposymbiotic organisms. It also suggests that thermally stressed colonies of holobionts could disperse acclimated hosts and/or symbionts to other colonies, thereby reducing their vulnerability to climate change.

Magnetically sensitive ion channels would allow researchers to better study how specific brain cells affect behavior in freely moving animals; however, recent reports of "magnetogenetic" ion channels based on biogenic ferritin nanoparticles have been questioned because known biophysical mechanisms cannot explain experimental observations. Here, we reproduce a weak magnetically mediated calcium response in HEK cells expressing a previously published TRPV4-ferritin fusion protein. We find that this magnetic sensitivity is attenuated when we reduce the temperature sensitivity of the channel but not when we reduce the mechanical sensitivity of the channel, suggesting that the magnetic sensitivity of this channel is thermally mediated. As a potential mechanism for this thermally mediated magnetic response, we propose that changes in the magnetic entropy of the ferritin particle can generate heat via the magnetocaloric effect and consequently gate the associated temperature-sensitive ion channel. Unlike other forms of magnetic heating, the magnetocaloric mechanism can cool magnetic particles during demagnetization. To test this prediction, we constructed a magnetogenetic channel based on the cold-sensitive TRPM8 channel. Our observation of a magnetic response in cold-gated channels is consistent with the magnetocaloric hypothesis. Together, these new data and our proposed mechanism of action provide additional resources for understanding how ion channels could be activated by low-frequency magnetic fields., (Copyright © 2019 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

A generalized platform for introducing a diverse range of biomolecules into living cells in high-throughput could transform how complex cellular processes are probed and analyzed. Here, we demonstrate spatially localized, efficient, and universal delivery of biomolecules into immortalized and primary mammalian cells using surface-modified vertical silicon nanowires. The method relies on the ability of the silicon nanowires to penetrate a cell's membrane and subsequently release surface-bound molecules directly into the cell's cytosol, thus allowing highly efficient delivery of biomolecules without chemical modification or viral packaging. This modality enables one to assess the phenotypic consequences of introducing a broad range of biological effectors (DNAs, RNAs, peptides, proteins, and small molecules) into almost any cell type. We show that this platform can be used to guide neuronal progenitor growth with small molecules, knock down transcript levels by delivering siRNAs, inhibit apoptosis using peptides, and introduce targeted proteins to specific organelles. We further demonstrate codelivery of siRNAs and proteins on a single substrate in a microarray format, highlighting this technology's potential as a robust, monolithic platform for high-throughput, miniaturized bioassays.