Ultrasonic imaging front-end design for CMUT: A 3-level 30Vpp pulse-shaping pulser with improved efficiency and a noise-optimized receiver

A four-channel analog front-end (AFE) transceiver chip for medical ultrasound imaging is demonstrated. The high voltage transmitter uses a 3-level pulse-shaping technique to deliver over 50% more acoustic power for the same power dissipation, compared to traditional methods. The design requires minimum off-chip components and is scalable for more channels. The receiver is implemented with a transimpedance amplifier (TIA) topology and is optimized for noise, bandwidth and power dissipation. Based on both acoustic and electrical measurements, we demonstrate the Transmitter (Tx) efficiency improvement, Tx beamformation and the pulse-echo response, revealing the system's full functionality.Semiconductor Research Corporation. Focus Center for Circuit and System Solutions (C2S2

Ultrasonic Imaging Transceiver Design for CMUT: A Three-Level 30-Vpp Pulse-Shaping Pulser With Improved Efficiency and a Noise-Optimized Receiver

This paper demonstrates a four-channel transceiver chip for medical ultrasonic imaging, interfacing to the capacitive micromachined ultrasonic transducers (CMUTs). The high-voltage transmitter (Tx) uses a three-level pulse-shaping technique with charge recycling to improve the power efficiency. The design requires minimum off-chip components and is scalable for more channels. The receiver is implemented with a transimpedance amplifier (TIA) topology and is optimized for tradeoffs between noise, bandwidth, and power dissipation. The test chip is characterized with both acoustic and electrical measurements. Comparing the three-level pulser against traditional two-level pulsers, the measured Tx efficiency shows 56%, 50%, and 43% more acoustic power delivery with the same total power dissipation at 2.5, 3.3, and 5.0 MHz, respectively. The CMUT receiver achieves the lowest noise efficiency factor compared with that of the literature (2.1 compared to a previously reported lowest of 3.6, in units of mPA ·√(mW/Hz). In addition, the transceiver chip is tested as a complete system for medical ultrasound imaging applications, in experiments including Tx beamformation, pulse-echo channel response characterization, and ultrasonic Doppler flow rate detection.Semiconductor Research Corporation. Focus Center for Circuit and System Solutions (C2S2

Hematopoietic Cell Transplantation in Patients With Primary Immune Regulatory Disorders (PIRD): A Primary Immune Deficiency Treatment Consortium (PIDTC) Survey.

Primary Immune Regulatory Disorders (PIRD) are an expanding group of diseases caused by gene defects in several different immune pathways, such as regulatory T cell function. Patients with PIRD develop clinical manifestations associated with diminished and exaggerated immune responses. Management of these patients is complicated; oftentimes immunosuppressive therapies are insufficient, and patients may require hematopoietic cell transplant (HCT) for treatment. Analysis of HCT data in PIRD patients have previously focused on a single gene defect. This study surveyed transplanted patients with a phenotypic clinical picture consistent with PIRD treated in 33 Primary Immune Deficiency Treatment Consortium centers and European centers. Our data showed that PIRD patients often had immunodeficient and autoimmune features affecting multiple organ systems. Transplantation resulted in resolution of disease manifestations in more than half of the patients with an overall 5-years survival of 67%. This study, the first to encompass disorders across the PIRD spectrum, highlights the need for further research in PIRD management

Energy extraction from the biologic battery in the inner ear

Endocochlear potential (EP) is a battery-like electrochemical gradient found in and actively maintained by the inner ear [superscript 1, 2]. Here we demonstrate that the mammalian EP can be used as a power source for electronic devices. We achieved this by designing an anatomically sized, ultra-low quiescent-power energy harvester chip integrated with a wireless sensor capable of monitoring the EP itself. Although other forms of in vivo energy harvesting have been described in lower organisms [superscript 3, 4, 5], and thermoelectric [superscript 6], piezoelectric [superscript 7] and biofuel [superscript 8, 9] devices are promising for mammalian applications, there have been few, if any, in vivo demonstrations in the vicinity of the ear, eye and brain. In this work, the chip extracted a minimum of 1.12 nW from the EP of a guinea pig for up to 5 h, enabling a 2.4 GHz radio to transmit measurement of the EP every 40–360 s. With future optimization of electrode design, we envision using the biologic battery in the inner ear to power chemical and molecular sensors, or drug-delivery actuators for diagnosis and therapy of hearing loss and other disorders.Focus Center Research Program. Focus Center for Circuit & System Solutions. Semiconductor Research Corporation. Interconnect Focus CenterNational Institutes of Health (U.S.) (Grant K08 DC010419)National Institutes of Health (U.S.) (Grant T32 DC00038)Bertarelli Foundatio

Ligand-based targeting of c-kit using engineered γδ T cells as a strategy for treating acute myeloid leukemia

The application of immunotherapies such as chimeric antigen receptor (CAR) T therapy or bi-specific T cell engager (BiTE) therapy to manage myeloid malignancies has proven more challenging than for B-cell malignancies. This is attributed to a shortage of leukemia-specific cell-surface antigens that distinguish healthy from malignant myeloid populations, and the inability to manage myeloid depletion unlike B-cell aplasia. Therefore, the development of targeted therapeutics for myeloid malignancies, such as acute myeloid leukemia (AML), requires new approaches. Herein, we developed a ligand-based CAR and secreted bi-specific T cell engager (sBite) to target c-kit using its cognate ligand, stem cell factor (SCF). c-kit is highly expressed on AML blasts and correlates with resistance to chemotherapy and poor prognosis, making it an ideal candidate for which to develop targeted therapeutics. We utilize γδ T cells as a cytotoxic alternative to αβ T cells and a transient transfection system as both a safety precaution and switch to remove alloreactive modified cells that may hinder successful transplant. Additionally, the use of γδ T cells permits its use as an allogeneic, off-the-shelf therapeutic. To this end, we show mSCF CAR- and hSCF sBite-modified γδ T cells are proficient in killing c-kit+ AML cell lines and sca-1+ murine bone marrow cells in vitro. In vivo, hSCF sBite-modified γδ T cells moderately extend survival of NSG mice engrafted with disseminated AML, but therapeutic efficacy is limited by lack of γδ T-cell homing to murine bone marrow. Together, these data demonstrate preclinical efficacy and support further investigation of SCF-based γδ T-cell therapeutics for the treatment of myeloid malignancies

Custom Integrated Circuits

Contains table of contents for Part III, table of contents for Section 1 and reports on eleven research projects.IBM CorporationMIT School of EngineeringNational Science Foundation Grant MIP 94-23221Defense Advanced Research Projects Agency/U.S. Army Intelligence Center Contract DABT63-94-C-0053Mitsubishi CorporationNational Science Foundation Young Investigator Award Fellowship MIP 92-58376Joint Industry Program on Offshore Structure AnalysisAnalog DevicesDefense Advanced Research Projects AgencyCadence Design SystemsMAFET ConsortiumConsortium for Superconducting ElectronicsNational Defense Science and Engineering Graduate FellowshipDigital Equipment CorporationMIT Lincoln LaboratorySemiconductor Research CorporationMultiuniversity Research IntiativeNational Science Foundatio

Nanostructures, Technology, Research, and Applications

Contains reports on twenty research projects and a list of publications.Joint Services Electronics Program Grant DAAH04-95-1-0038National Science Foundation Grant ECS-94-07078Semiconductor Research CorporationU.S. Army Research Office Grant DAAH04-95-1-0564Defense Advanced Research Projects Agency/Naval Air Systems Command Contract N00019-95-K-0131National Aeronautics and Space Administration Contract NAS8-38249National Aeronautics and Space Administration Grant NAGW-2003IBM Corporation Contract 1622National Science Foundation Graduate FellowshipU.S. Navy - Office of Naval Research Grant N00014-95-1-1297U.S. Army Research Office Contract DAAH04-94-G-0377U.S. Air Force - Office of Scientific Research Grant F49620-92-J-0064U.S. Air Force - Office of Scientific Research Grant F49620-95-1-0311National Science Foundation Contract DMR 94-0034U.S. Air Force - Office of Scientific Research Contract F49620-96-0126Harvard-Smithsonian Astrophysical Observatory Contract SV630304National Aeronautics and Space Administration Grant NAG5-5105Los Alamos National Laboratory Contract E57800017-9