Rabinowitz, Jake, Elizabeth Whittier, Zheng Liu, Krishna Jayant, Joachim Frank, Kenneth Shepard. “Nanobubble-controlled nanofluidic transport.” Science Advances 6, no. 46 (2020).

Nanofluidic platforms offering tunable material transport are applicable in biosensing, chemical detection, and filtration. Prior studies have achieved selective and controllable ion transport through electrical, optical, or chemical gating of complex nanostructures. Here, we mechanically control nanofluidic transport using nanobubbles. When plugging nanochannels, nanobubbles rectify and occasionally enhance ionic currents in a geometry-dependent manner. These conductance effects arise from nanobubbles inducing surface-governed ion transport through interfacial electrolyte films residing between nanobubble surfaces and nanopipette walls. The nanobubbles investigated here are mechanically generated, made metastable by surface pinning, and verified with cryogenic transmission electron microscopy. Our findings are relevant to nanofluidic device engineering, three-phase interface properties, and nanopipette-based applications.

Moreaux, Laurent C., Dimitri Yatsenko, Wesley D. Sacher, Jaebin Choi, Changhyuk Lee, Nicole J. Kubat, R. James Cotton, Edward S. Boyden, Michael Z. Lin, Lin Tian, Andreas S. Tolias, Joyce K.S. Poon, Kenneth L. Shepard, and Michael L. Roukes, “Integrated Neurophotonics: Toward Dense Volumetric Interrogation of Brain Circuit Activity—at Depth and in Real Time” Neuron 108, pages 66-92(2020)

We propose a new paradigm for dense functional imaging of brain activity to surmount the limitations of present methodologies. We term this approach ‘‘integrated neurophotonics’’; it combines recent advances in microchip-based integrated photonic and electronic circuitry with those from optogenetics. This approach has the potential to enable lens-less functional imaging from within the brain itself to achieve dense, largescale stimulation and recording of brain activity with cellular resolution at arbitrary depths. We perform a computational study of several prototype 3D architectures for implantable probe-array modules that are designed to provide fast and dense single-cell resolution (e.g., within a 1-mm3 volume of mouse cortex comprising -100,000 neurons). We describe progress toward realizing integrated neurophotonic imaging modules, which can be produced en masse with current semiconductor foundry protocols for chip manufacturing. Implantation of multiple modules can cover extended brain regions.

Sherman, Jeffrey D., Jeffrey Elloian, Jakub Jadwiszczak, and Kenneth L. Shepard, “On the Temperature Dependence of the Piezoelectric Response of Prepoled Poly(vinylidene fluoride) Films” ACS Applied Polymer Materials (2020)

There is growing interest in integrating piezoelectric materials with complementary metal-oxide-semiconductor (CMOS) technology to enable expanded applications. A promising material for ultrasound transducer applications is poly(vinylidene fluoride) (PVDF), a piezoelectric polymer. One of the challenges with PVDF is that its piezoelectric properties can deteriorate when exposed to temperatures in excess of 70 °C for extended periods of
time during fabrication. Here, we report on the effects of both shortening annealing times and providing this heating nonuniformly, as is characteristic of some processing conditions, on the piezoelectric coefficient (d33) of PVDF films for various thicknesses. In this case, no degradation in the d33 was observed at temperatures below 100 °C for anneal times of under 1 min when this heating is applied through one side of the film, making PVDF compatible with many bonding and photolithographic processing steps required for CMOS integration. More surprisingly, for one-sided heating to temperatures between 90 and 110 °C, we observed a transient enhancement of the d33 by nearly 40% that lasted for several hours after these anneals. We attribute this effect to induced strain in these films.

Jaebin Choi, Adriaan J. Taal, William L. Meng, Eric H. Pollmann, John W. Stanton,  Changhyuk Lee, Sajjad Moazeni, Laurent C. Moreaux, Michael L. Roukes, and Kenneth L. Shepard, “Fully Integrated Time-Gated 3D Fluorescence Imager for Deep Neural Imaging,”   IEEE Transactions on Biomedical Circuits and Systems 14, no. 4, pages 636-645 (2020).

This paper reports an implantable 3D imager for time-gated fluorescence imaging in the deep brain. Fluorescence excitation is provided by dual ns-pulsed blue micro-light-emitting diodes (μLED), and fluorescence emission is collected by an 8-by64 single-photon avalanche diode (SPAD) array, together packaged to a width of 420 μm to allow deep insertion through a cannula. Each SPAD is masked by a repeating pattern of Talbot gratings that give each pixel a different angular sensitivity, allowing three-dimensional image reconstruction to a resolution of ~20 μm. The integrated imager is able to monitor fluorescent targets across a field of view of 1000 μm by 600 μm by 500 μm at arbitrary tissue depths.

William Cole Cornell, Yihan Zhang, Anastasia Bendebury, Andreas J.W. Hartel, Kenneth L. Shepard, Lars E.P. Dietrich. “Phenazine oxidation by a distal electrode modulates biofilm morphogenesis.” Biofilm 2 (2020) 100025.

Microbes living in biofilms, dense assemblages of cells, experience limitation for resources such as oxygen when cellular consumption outpaces diffusion. The pathogenic bacterium Pseudomonas aeruginosa has strategies for coping with hypoxia that support cellular redox balancing in biofilms; these include (1) increasing access to oxygen by forming wrinkles in the biofilm surface and (2) electrochemically reducing endogenous compounds called phenazines, which can shuttle electrons to oxidants available at a distance. Phenazine-mediated extra-cellular electron transfer (EET) has been shown to support survival for P. aeruginosa cells in anoxic liquid cultures, but the physiological relevance of EET over a distance for P. aeruginosa biofilms has remained unconfirmed. Here, we use a custom-built electrochemistry setup to show that phenazine-mediated electron transfer at a distance inhibits wrinkle formation in P. aeruginosa biofilms. This result demonstrates that phenazine-dependent EET to a distal oxidant affects biofilm morphogenesis.

Chia-Han Chiang, Sang Min Won, Amy L. Orsborn, Ki Jun Yu, Michael Trumpis, Brinnae Bent, Charles Wang, Yeguang Xue, Seunghwan Min, Virginia Woods, Chunxiu Yu, Bong Hoon Kim, Sung Bong Kim, Rizwan Huq, Jinghua Li, Kyung Jin Seo, Flavia Vitale, Andrew Richardson, Hui Fang, Yonggang Huang, Kenneth Shepard, Bijan Pesaran, John A. Rogers, Jonathan Viventi. “Development of a neural interface for high-definition, long-term recording in rodents and nonhuman primates.” Science translational medicine 12, no. 538 (2020).

Long-lasting, high-resolution neural interfaces that are ultrathin and flexible are essential for precise brain mapping and high-performance neuroprosthetic systems. Scaling to sample thousands of sites across large brain regions requires integrating powered electronics to multiplex many electrodes to a few external wires. However, existing multiplexed electrode arrays rely on encapsulation strategies that have limited implant lifetimes. Here, we developed a flexible, multiplexed electrode array, called “Neural Matrix,” that provides stable in vivo neural recordings in rodents and nonhuman primates. Neural Matrix lasts over a year and samples a centimeter-scale brain region using over a thousand channels. The long-lasting encapsulation (projected to last at least 6 years), scalable device design, and iterative in vivo optimization described here are essential components to overcoming current hurdles facing next-generation neural technologies.

Thimot, Jordan, Kukjoo Kim, Chen Shi, and Kenneth L. Shepard. “A 27-Mbps, 0.08-mm3 CMOS Transceiver with Simultaneous Near-field Power Transmission and Data Telemetry for Implantable Systems.” In 2020 IEEE Custom Integrated Circuits Conference (CICC), pp. 1-4. IEEE, 2020.

This paper describes an inductively powered 27-Mbps, 0.08-mm3 CMOS transceiver with integrated RF receivercoils for simultaneous two-way, near-field data telemetry andpower transmission for implantable systems. A four-coil inductivelink operates at a 27-MHz carrier for power and a 700-MHzcarrier for data telemetry with the antennae taking an area of only2 mm by 2 mm. Amplitude-shift-keying (ASK) modulation is usedfor data downlink at 6.6 kbps and load-shift keying (LSK)backscattering is used for data uplink at 27 Mbps. The transceiverconsumes 2.7 mW and can power a load consuming up to anadditional 1.5 mW. Implemented in a 0.18-um silicon-on-insulator(SOI) technology, post-processing steps are used to decrease chipthickness to approximately 15um, making the chip flexible with atissue-like form factor and removing the effects of the substrate oncoil performance. Power harvesting circuitry, including passiverectifier, voltage regulator, RF limiter, ASK and LSK modulator,clock generator, and digital controller are positioned adjacent tothe coils and limited to an area of 0.5 mm by 2mm. Completetransceiver functionality of the system has been achieved withoverall power transfer efficiency (PTE) of 1.04% through 1 mm oftissue phantom between reader and implant.

Y. Zhang, F. Cadoso, and K. L. Shepard, A 0.72 nW, 1 Sample/s Fully Integrated pH Sensor with 65.8 LSB/pH Sensitivity, Proceedings of the Symposium on VLSI Circuits, 2020.

This paper presents a 0.85 mm 2 fully integrated pH sensor IC utilizing an ion sensitive field effect transistor (ISFET) and reference field effect transistor (REFET) pair in which the native foundry passivation layer is used as an ion sensitive layer. The pH sensor has 10 bit resolution with 65.8 LSB/pH sensitivity, while consuming only 0.72 nW at 1 sample/s, improving an overall figure of merit (FoM) that accounts for power, sampling frequency, and sensitivity by > 4000×.

Shi, Chen, Tiago Costa, Jeffrey Elloian, Yihan Zhang, and Kenneth Shepard. “A 0.065-mm3 Monolithically-integrated Ultrasonic Wireless Sensing Mote for Real-time Physiological Temperature Monitoring.” IEEE Transactions on Biomedical Circuits and Systems (2020).

Accurate monitoring of physiological temperature is important for many biomedical applications, including monitoring of core body temperature, detecting tissue pathologies, and evaluating surgical procedures involving thermal treatment such as hyperthermia therapy and tissue ablation. Many of these applications can benefit from replacing external temperature probes with injectable wireless devices. Here we present such a device for real-time in vivo temperature monitoring that relies on “chip-as-system” integration. With an on-chip piezoelectric transducer and measuring only 380 μm ×× 300 μm × 570 μm, the 0.065-mm3 monolithic device, in the form of a mote, harvests ultrasound energy for power and transmits temperature data through acoustic backscattering. Containing a low-power temperature sensor implemented with a subthreshold oscillator and consuming 0.813 nW at 37 °C, the mote achieves line sensitivity of 0.088 °C/V, temperature error of +0.22/-0.28 °C, and a resolution of 0.0078 °C rms. A long-term measurement with the mote reveals an Allan deviation floor of <138.6 ppm, indicating the feasibility of using the mote for continuous physiological temperature monitoring.

Elloian, Jeffrey, Jeffrey Sherman, Tiago Costa, Chen Shi, and Kenneth Shepard. “Ablation of piezoelectric polyvinylidene fluoride with a 193 nm excimer laser.” Journal of Vacuum Science & Technology A: Vacuum, Surfaces, and Films 38, no. 3 (2020): 033202.

The unique flexible and piezoelectric properties of polyvinylidene fluoride (PVDF) films would allow for new appli-cations for integrated bioelectronic devices. The use of these films has been precluded by the difficulty in machiningit into small, discrete features without damaging the properties of the material. The etching of piezoelectric PVDF bymeans of a 193 nm excimer laser is explored and characterized. Etch rates are shown for common laser fluence values,along with images of the quality of the cuts to provide the reader with an understanding of the compromise betweenetch rate and edge roughness.