A 1.1 nW Energy-Harvesting System with 544 pW Quiescent Power for Next-Generation Implants

This paper presents a nW power management unit (PMU) for an autonomous wireless sensor that sustains itself by harvesting energy from the endocochlear potential (EP), the 70-100 mV electrochemical bio-potential inside the mammalian ear. Due to the anatomical constraints inside the inner ear, the total extractable power from the EP is limited close to 1.1-6.25 nW. A nW boost converter is used to increase the input voltage (30-55 mV) to a higher voltage (0.8-1.1 V) usable by CMOS circuits in the sensor. A pW charge pump circuit is used to minimize the leakage in the boost converter. Furthermore, ultralow-power control circuits consisting of digital implementations of input impedance adjustment circuits and zero current switching circuits along with Timer and Reference circuits keep the quiescent power of the PMU down to 544 pW. The designed boost converter achieves a peak power conversion efficiency of 56%. The PMU can sustain itself, and a duty-cyled ultralow-power load while extracting power from the EP of a live guinea pig. The PMU circuits have been implemented on a 0.18- μm CMOS process.Semiconductor Research Corporation. Focus Center for Circuit and System Solutions (C2S2)Interconnect Focus Center (United States. Defense Advanced Research Projects Agency and Semiconductor Research Corporation)National Institutes of Health (U.S.) (Grant K08 DC010419)National Institutes of Health (U.S.) (Grant T32 DC00038)Bertarelli Foundatio

A Sub-nW 2.4 GHz Transmitter for Low Data-Rate Sensing Applications

This paper presents the design of a narrowband transmitter and antenna system that achieves an average power consumption of 78 pW when operating at a duty-cycled data rate of 1 bps. Fabricated in a 0.18 μm CMOS process, the transmitter employs a direct-RF power oscillator topology where a loop antenna acts as a both a radiative and resonant element. The low-complexity single-stage architecture, in combination with aggressive power gating techniques and sizing optimizations, limited the standby power of the transmitter to only 39.7 pW at 0.8 V. Supporting both OOK and FSK modulations at 2.4 GHz, the transmitter consumed as low as 38 pJ/bit at an active-mode data rate of 5 Mbps. The loop antenna and integrated diodes were also used as part of a wireless power transfer receiver in order to kick-start the system power supply prior to energy harvesting operation.Semiconductor Research Corporation. Interconnect Focus CenterSemiconductor Research Corporation. C2S2 Focus CenterNational Institutes of Health (U.S.) (Grant K08 DC010419)National Institutes of Health (U.S.) (Grant T32 DC00038)Bertarelli Foundatio

Characterization of cochlear transcription, translation and energy extraction in aging and noise-induced pathology

Thesis: Ph. D., Harvard-MIT Program in Health Sciences and Technology, 2014.Cataloged from PDF version of thesis.Includes bibliographical references (pages 147-163).Success in otologic practice is currently limited by the diagnostic tools and treatment options available to address an individual's specific presentation of hearing loss. This limitation results from insufficient characterization of the inner ear's biochemical environment as well as physical hurdles associated with accessing inner ear tissues. The encapsulation of the hearing organ within a bony shell and delicate nature of its tissues make standard tissue biopsy techniques impossible and leave many imaging methods impractical. This thesis sought to approach these clinical limitations in two ways: (1) performing novel transcriptional and translational characterizations of inner ear tissues and (2) development of a novel technique to access and communicate diagnostic information from within the inner ear. The first part of this thesis employs whole transcriptome shotgun sequencing to study murine inner ear transcriptional activity in young, healthy animals as well as changes associated with organ aging and noise-induced auditory neuropathy, an important mechanism of hearing impairment in humans. Knowledge of the inner ear's transcriptional behavior (Part I) is coupled with novel translational insights provided by high-throughput tandem mass-spectrometry (Part III) studies of human inner ear fluids obtained from healthy and pathologic populations. These studies illuminate homeostatic mechanisms employed by the highly specialized inner ear tissues, providing a critical knowledge-base for inner ear scientists and pharmacologists, and identify important expression-level changes which occur during the onset and progression of inner ear pathologies. While these high-throughput studies offer the powerful ability to gain a wealth of knowledge into which genes are active within the inner ear, functional assessment of the specific role these genes play must be assessed in a more focused manner. Phenotypic characterization of mice with specific genetic mutations (Part II) has been performed to provide critical insight into the specific role Fgf23 plays in development and maintenance of the auditory system. The second arm of this thesis seeks to provide clinical practicality to the above work by developing a method to safely access the inner ear environment to gather and communicate diagnostic information (Part IV). A guinea pig model was utilized to develop an approach to insert microelectrodes into the fluid spaces of the inner ear in order to harness and monitor the natural electrochemical gradient of the organ. The useful energy extracted from this "biological battery" was used to power a combined microchip/radio transmitter capable of performing voltage-sensing operations within endolymph and wirelessly relaying this information to an external receiver. This study was the first to utilize a mammalian electrochemical potential to power an electronic device. By performing this task while preserving the integrity of the hearing organ this work provides the first, critical proof-of-concept demonstration toward clinically-applicable sensing and therapeutic devices powered by the inner ear. Further refinement of this technique into a long-term, fully-implantable device will enable previously impossible longitudinal studies of organ behavior in awake, behaving subjects and the incorporation of sensing modalities into current inner ear prostheses to monitor biochemical changes and maximize patient benefits.by Andrew Christopher Lysaght.Ph. D

A 78 pW 1 [b over s] 2.4 GHz radio transmitter for near-zero-power sensing applications

This paper presents an ultra-low-standby-power radio transmitter that was designed for applications with extreme energy storage and/or energy harvesting constraints. By utilizing aggressive power gating techniques within a low-complexity architecture featuring only a single RF stage, the transmitter achieved a standby power consumption of 39.7 pW. The architecture employed a direct-RF power oscillator that featured an on-board loop antenna that functioned as both the resonant and radiative element. Supporting both OOK and FSK modulations, the transmitter consumed 38 [pJ over bit] at an instantaneous data rate of 5 [Mb over s]. After duty-cycling down to an average data rate of 1 [b over s], the transmitter consumed an average power of 78 pW.National Institutes of Health (U.S.) (Grant K08 DC010419)National Institutes of Health (U.S.) (Grant T32 DC00038)Bertarelli FoundationFocus Center Research Program. Focus Center for Circuit & System SolutionsSemiconductor Research Corporation. Interconnect Focus Cente

Quantitative polarized light microscopy of unstained mammalian cochlear sections

Hearing loss is the most common sensory deficit in the world, and most frequently it originates in the inner ear. Yet, the inner ear has been difficult to access for diagnosis because of its small size, delicate nature, complex three-dimensional anatomy, and encasement in the densest bone in the body. Evolving optical methods are promising to afford cellular diagnosis of pathologic changes in the inner ear. To appropriately interpret results from these emerging technologies, it is important to characterize optical properties of cochlear tissues. Here, we focus on that characterization using quantitative polarized light microscopy (qPLM) applied to unstained cochlear sections of the mouse, a common animal model of human hearing loss. We find that the most birefringent cochlear materials are collagen fibrils and myelin. Retardance of the otic capsule, the spiral ligament, and the basilar membrane are substantially higher than that of other cochlear structures. Retardance of the spiral ligament and the basilar membrane decrease from the cochlear base to the apex, compared with the more uniform retardance of other structures. The intricate structural details revealed by qPLM of unstained cochlear sections ex vivo strongly motivate future application of polarization-sensitive optical coherence tomography to human cochlea in vivo.United States. National Institute for Deafness and other Communicative Disorders (Grant K08 DC010419)United States. National Institute for Deafness and other Communicative Disorders (Grant United States. National Institute for Deafness and other Communicative Disorders (Grant K08 DC010419))NASA Microgravity Fluid Sciences (Grant NNX09AV99G

Deep immune profiling of patients treated with lenalidomide and dexamethasone with or without daratumumab

CD38-targeted antibody, daratumumab, is approved for the treatment of multiple myeloma (MM). Phase 1/2 studies GEN501/SIRIUS revealed a novel immunomodulatory mechanism of action (MOA) of daratumumab that enhanced the immune response, reducing natural killer (NK) cells without affecting efficacy or safety. We further evaluated daratumumab’s effects on immune cells in whole blood samples of relapsed/refractory MM patients from both treatment arms of the phase 3 POLLUX study (lenalidomide/dexamethasone [Rd] or daratumumab plus Rd [D-Rd]) at baseline (D-Rd, 40; Rd, 45) and after 2 months on treatment (D-Rd, 31; Rd, 33) using cytometry by time-of-flight. We confirmed previous reports of NK cell reduction with D-Rd. Persisting NK cells were phenotypically distinct, with increased expression of HLA-DR, CD69, CD127, and CD27. The proportion of T cells increased preferentially in deep responders to D-Rd, with a higher proportion of CD8+ versus CD4+ T cells. The expansion of CD8+ T cells correlated with clonality, indicating generation of adaptive immune response with D-Rd. D-Rd resulted in a higher proportion of effector memory T cells versus Rd. D-Rd reduced immunosuppressive CD38+ regulatory T cells. This study confirms daratumumab’s immunomodulatory MOA in combination with immunomodulatory drugs and provides further insight into immune cell changes and activation status following daratumumab-based therapy