The emerging field of bioelectronic medicine seeks methods for deciphering and modulating electrophysiological activity in the body to attain therapeutic effects at target organs. Current approaches to interfacing with peripheral nerves and muscles rely heavily on wires, creating problems for chronic use, while emerging wireless approaches lack the size scalability necessary to interrogate small-diameter nerves. Furthermore, conventional electrode-based technologies lack the capability to record from nerves with high spatial resolution or to record independently from many discrete sites within a nerve bundle. Here, we demonstrate neural dust, a wireless and scalable ultrasonic backscatter system for powering and communicating with implanted bioelectronics. We show that ultrasound is effective at delivering power to mm-scale devices in tissue; likewise, passive, battery-less communication using backscatter enables high-fidelity transmission of electromyogram (EMG) and electroneurogram (ENG) signals from anesthetized rats. These results highlight the potential for an ultrasound-based neural interface system for advancing future bioelectronics-based therapies.

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When placed on a temperature gradient, a Drosophila larva navigates away from excessive cold or heat by regulating the size, frequency, and direction of reorientation maneuvers between successive periods of forward movement. Forward movement is driven by peristalsis waves that travel from tail to head. During each reorientation maneuver, the larva pauses and sweeps its head from side to side until it picks a new direction for forward movement. Here, we characterized the motor programs that underlie the initiation, execution, and completion of reorientation maneuvers by measuring body segment dynamics of freely moving larvae with fluorescent muscle fibers as they were exposed to temporal changes in temperature. We find that reorientation maneuvers are characterized by highly stereotyped spatiotemporal patterns of segment dynamics. Reorientation maneuvers are initiated with head sweeping movement driven by asymmetric contraction of a portion of anterior body segments. The larva attains a new direction for forward movement after head sweeping movement by using peristalsis waves that gradually push posterior body segments out of alignment with the tail (i.e., the previous direction of forward movement) into alignment with the head. Thus, reorientation maneuvers during thermotaxis are carried out by two alternating motor programs: (1) peristalsis for driving forward movement and (2) asymmetric contraction of anterior body segments for driving head sweeping movement.

Miniature fluorescence microscopes are a standard tool in systems biology. However, widefield miniature microscopes capture only 2D information, and modifications that enable 3D capabilities increase the size and weight and have poor resolution outside a narrow depth range. Here, we achieve the 3D capability by replacing the tube lens of a conventional 2D Miniscope with an optimized multifocal phase mask at the objective’s aperture stop. Placing the phase mask at the aperture stop significantly reduces the size of the device, and varying the focal lengths enables a uniform resolution across a wide depth range. The phase mask encodes the 3D fluorescence intensity into a single 2D measurement, and the 3D volume is recovered by solving a sparsity-constrained inverse problem. We provide methods for designing and fabricating the phase mask and an efficient forward model that accounts for the field-varying aberrations in miniature objectives. We demonstrate a prototype that is 17 mm tall and weighs 2.5 grams, achieving 2.76 μm lateral, and 15 μm axial resolution across most of the 900 × 700 × 390 μm3 volume at 40 volumes per second. The performance is validated experimentally on resolution targets, dynamic biological samples, and mouse brain tissue. Compared with existing miniature single-shot volume-capture implementations, our system is smaller and lighter and achieves a more than 2× better lateral and axial resolution throughout a 10× larger usable depth range. Our microscope design provides single-shot 3D imaging for applications where a compact platform matters, such as volumetric neural imaging in freely moving animals and 3D motion studies of dynamic samples in incubators and lab-on-a-chip devices.

A 0.8 mm 3 wireless, ultrasonically powered, freefloating neural recording implant is presented. The device is comprised only of a 0.25 mm 2 recording IC and a single piezoceramic resonator that is used for both power harvesting and data transmission. Uplink data transmission is performed by analog amplitude modulation of the ultrasound echo. Using a 1.78 MHz main carrier, >35 kbps/mote equivalent uplink data rate is achieved. A technique to linearize the echo amplitude modulation is introduced, resulting in <1.2% static nonlinearity of the received signal over a ±10 mV input range. The IC dissipates 37.7 µW, while the neural recording front-end consumes 4 µW and achieves a noise floor of 5.3 µVrms in a 5 kHz bandwidth. This work improves sub-mm recording mote depth by >2.5x, resulting in the highest measured depth/volume ratio by ∼3x. Orthogonal subcarrier modulation enables simultaneous operation of multiple implants, using a single-element ultrasound external transducer. Dual-mote simultaneous power up and data transmission is demonstrated at a rate of 7 kS/s at the depth of 50 mm.

We present a 6.5mm 3 , 10mg, wireless peripheral nerve stimulator. The stimulator is powered and controlled through ultrasound from an external transducer and utilizes a single 750x750x750µm 3 piezocrystal for downlink communication, powering, and readout, reducing implant volume and mass. An IC with 0.06mm 2 active circuit area, designed in TSMC 65nm LPCMOS process, converts harvested ultrasound to stimulation charge with a peak efficiency of 82%. A custom wireless protocol that does not require a clock or memory circuits reduces on-chip power to 4µW when not stimulating. The encapsulated stimulator was cuffed to the sciatic nerve of an anesthetized rodent and demonstrated full-scale nerve activation in vivo. We achieve a highly efficient and temporally precise wireless peripheral nerve stimulator that is the smallest and lightest to our knowledge.

The lifetime of neural implants is strongly dependent on packaging due to the aqueous and biochemically aggressive nature of the body. Over the last decade, there has been a drive towards neuromodulatory implants which are wireless and approaching millimeter-scales with increasing electrode count. A so-far unrealized goal for these new types of devices is an in-vivo lifetime comparable to a sizable fraction of a healthy patient’s lifetime (>10–20 years). Existing, approved medical implants commonly encapsulate components in metal enclosures (e.g. titanium) with brazed ceramic inserts for electrode feedthrough. It is unclear how amenable the traditional approach is to the simultaneous goals of miniaturization, increased channel count, and wireless communication. Ceramic materials have also played a significant role in traditional medical implants due to their dielectric properties, corrosion resistance, biocompatibility, and high strength, but are not as commonly used for housing materials due to their brittleness and the difficulty they present in creating complex housing geometries. However, thin-film technology has opened new opportunities for ceramics processing. Thin films derived largely from the semiconductor industry can be deposited and patterned in new ways, have conductivities which can be altered during manufacturing to provide conductors as well as insulators, and can be used to fabricate flexible substrates. In this review, we give an overview of packaging for neural implants, with an emphasis on how ceramic materials have been utilized in medical device packaging, as well as how ceramic thin-film micromachining and processing may be further developed to create truly reliable, miniaturized, neural implants.

Miniaturization of implantable neural recording systems to micron-scale volumes will enable minimally invasive implantation and alleviate cortical scarring, gliosis, and resulting signal degradation. Ultrasound (US) power transmission has been demonstrated to have high efficiency and low tissue attenuation for mm-scale implants at depth in tissue [1,2,3], but has not been demonstrated with precision recording circuitry. We present an US implantable wireless neural recording system scaled to 0.8mm 3 , verified to safely operate at 5cm depth with state of the art neural recording performance an average circuit power dissipation of 13μW, and 28.8μW including power conversion efficiency. Sub-mm scale is achieved through single-link power and communication on a single piezocrystal (Lead Zirconate Titanate, PZT) utilizing linear analog backscattering, small die area, and eliminating all other off-chip components.