Amplifier Module for 260-GHz Band Using Quartz Waveguide Transitions

Packaging of MMIC LNA (monolithic microwave integrated circuit low-noise amplifier) chips at frequencies over 200 GHz has always been problematic due to the high loss in the transition between the MMIC chip and the waveguide medium in which the chip will typically be used. In addition, above 200 GHz, wire-bond inductance between the LNA and the waveguide can severely limit the RF matching and bandwidth of the final waveguide amplifier module. This work resulted in the development of a low-loss quartz waveguide transition that includes a capacitive transmission line between the MMIC and the waveguide probe element. This capacitive transmission line tunes out the wirebond inductance (where the wire-bond is required to bond between the MMIC and the probe element). This inductance can severely limit the RF matching and bandwidth of the final waveguide amplifier module. The amplifier module consists of a quartz E-plane waveguide probe transition, a short capacitive tuning element, a short wire-bond to the MMIC, and the MMIC LNA. The output structure is similar, with a short wire-bond at the output of the MMIC, a quartz E-plane waveguide probe transition, and the output waveguide. The quartz probe element is made of 3-mil quartz, which is the thinnest commercially available material. The waveguide band used is WR4, from 170 to 260 GHz. This new transition and block design is an improvement over prior art because it provides for better RF matching, and will likely yield lower loss and better noise figure. The development of high-performance, low-noise amplifiers in the 180-to- 700-GHz range has applications for future earth science and planetary instruments with low power and volume, and astrophysics array instruments for molecular spectroscopy. This frequency band, while suitable for homeland security and commercial applications (such as millimeter-wave imaging, hidden weapons detection, crowd scanning, airport security, and communications), also has applications to future NASA missions. The Global Atmospheric Composition Mission (GACM) in the NRC Decadel Survey will need low-noise amplifiers with extremely low noise temperatures, either at room temperature or for cryogenic applications, for atmospheric remote sensing

474 Phase 1 study of SEA-TGT, a human, nonfucosylated anti-TIGIT monoclonal antibody with enhanced immune-effector function, in patients with advanced malignancies (SGNTGT-001, trial in progress)

BackgroundT-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory domains (TIGIT), and costimulatory receptor CD226 competitively bind 2 ligands, CD155 and CD112, which are expressed by tumor cells and antigen-presenting cells in the tumor microenvironment.1 2 Dual TIGIT/programmed cell death protein-1 (PD-1) blockade increased tumor antigen-specific CD8+ T-cell expansion and function in vitro and promoted potent antitumor response in vivo.3 4 TIGIT/PD-1 dual blockade using a TIGIT monoclonal antibody (mAb) with intact Fc produced clinical responses in advanced cancer.5 SEA-TGT is an investigational, human, nonfucosylated mAb directed against TIGIT. SEA-TGT binds to TIGIT, blocking inhibitory checkpoint signals directed at T cells. SEA-TGT enhances binding to activating FcγRIIIa and decreases binding to inhibitory FcγRIIb; this depletes immunosuppressive regulatory T cells and amplifies naive and memory T cells, potentially augmenting PD-1 inhibition effects. Preclinically, at suboptimal doses, SEA-TGT plus anti-PD-1 mAbs had superior antitumor activity than either agent alone.6MethodsSafety and antitumor activity of SEA TGT in ~377 adults (≥18 years) will be evaluated in this phase 1, multicenter, open-label, dose-escalation/expansion study. Part A will assess the safety/tolerability of SEA TGT to determine maximum tolerated and recommended doses. Part B will assess the safety and antitumor activity of the recommended dose in disease-specific expansion cohorts. Part C will assess SEA-TGT plus sasanlimab in dose-expansion cohorts after an initial safety run-in. Patients with histologically/cytologically confirmed relapsed/refractory/progressive metastatic solid tumors including non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), gastric/gastroesophageal junction carcinoma, cutaneous melanoma, bladder, cervical, ovarian or triple-negative breast cancer, or selected lymphomas will be eligible for Parts A and B. Part C will enroll patients with histologically confirmed advanced NSCLC (high [tumor proportion score (TPS) ≥50%] and low [TPS=1–49%] PD ligand 1 [PD-L1] expression), cutaneous melanoma, and HNSCC without previous anti–PD-1/PD-L1 therapy exposure. SEA TGT will be administered on Day 1 of 21-day cycles.Laboratory abnormalities, adverse events, dose-limiting toxicities, and dose-level safety and activity are primary endpoints. Secondary endpoints are objective response (OR) and complete response (CR) rates, duration of OR/CR, progression-free survival, overall survival, pharmacokinetics (PK), and antidrug antibodies. Exploratory analysis will include pharmacodynamics (PD), PK/PD relationships, biomarkers, and resistance to SEA-TGT. This trial is recruiting in Europe and North America.Trial RegistrationNCT04254107ReferencesBlake SJ, Dougall WC, Miles JJ, et al. Molecular pathways: Targeting CD96 and TIGIT for cancer immunotherapy. Clin Cancer Res 2016;22(21):5183–5188.Chauvin JM, Zarour HM. TIGIT in cancer immunotherapy. J ImmunoTher Cancer 2020;8:e000957.Johnston RJ, Comps-Agrar L, Hackney J, et al. The immunoreceptor TIGIT regulates antitumor and antiviral CD8+ T cell effector function. Cancer Cell 2014;26(6):923–937.Chauvin JM, Pagliano O, Fourcade J, et al. TIGIT and PD-1 impair tumor antigen-specific CD8+ T cells in melanoma patients. J Clin Invest 2015;125(5):2046–2058.Rodriguez-Abreu D, Johnson ML, Hussein MA, et al. Primary analysis of a randomized, double-blind, phase 2 study of the anti-TIGIT antibody tiragolumab (tira) plus atezolizumab (atezo) versus placebo plus atezo as first-line (1L) treatment in patients with PD-L1-selected NSCLC (CITYSCAPE). J Clin Oncol 2020;38(15 suppl):9503.Smith A, Zeng W, Lucas S, et al. Poster 1583. SEA-TGT is an empowered anti-TIGIT antibody that displays superior combinatorial activity with several therapeutic agents. Presented at: American Association for Cancer Research Annual Meeting; April 9–14, 2021; Virtual Meeting.Ethics ApprovalInstitutional review boards or independent ethics committees of participating sites approved the trial, which will be conducted in compliance with the Declaration of Helsinki and International Conference on Harmonisation Guidelines for Good Clinical Practice. All patients will provide written informed consent

Acute mountain sickness.

Acute mountain sickness (AMS) is a clinical syndrome occurring in otherwise healthy normal individuals who ascend rapidly to high altitude. Symptoms develop over a period ofa few hours or days. The usual symptoms include headache, anorexia, nausea, vomiting, lethargy, unsteadiness of gait, undue dyspnoea on moderate exertion and interrupted sleep. AMS is unrelated to physical fitness, sex or age except that young children over two years of age are unduly susceptible. One of the striking features ofAMS is the wide variation in individual susceptibility which is to some extent consistent. Some subjects never experience symptoms at any altitude while others have repeated attacks on ascending to quite modest altitudes. Rapid ascent to altitudes of 2500 to 3000m will produce symptoms in some subjects while after ascent over 23 days to 5000m most subjects will be affected, some to a marked degree. In general, the more rapid the ascent, the higher the altitude reached and the greater the physical exertion involved, the more severe AMS will be. Ifthe subjects stay at the altitude reached there is a tendency for acclimatization to occur and symptoms to remit over 1-7 days

Noise Measurements of Discrete HEMT Transistors and Application to Wideband Very Low-Noise Amplifiers

The noise models of InP and GaAs HEMTs are compared with measurements at both 300 and 20 K. The critical parameter, T_(drain), in the Pospieszalski noise model is determined as a function of drain current by measurements of the 1-GHz noise of discrete transistors with 50-Ω generator impedance. The dc I-V for the transistors under test are presented and effects of impact-ionization are noted. InP devices with both 100% and 75% indium mole fraction in channel are included. Examples of the design and measurement of very wideband low-noise amplifiers (LNAs) using the tested transistors are presented. At 20-K physical temperature the GaAs LNA achieves <10-K noise over the 0.7-16-GHz range with 16 mW of power and an InP LNA measures <20-K noise over the 6-50-GHz range with 30 mW of power

On-wafer measurements of S-MMIC amplifiers from 400–500 GHz

In this paper, we describe the design, simulation, and on-wafer measurements of Submillimeter-wave Monolithic Integrated Circuit (S-MMIC) amplifiers having gain in the 400-500 GHz range. A single-stage amplifier and two three-stage amplifiers with similar topology are presented, and have been fabricated in Northrop Grumman Corporation's (NGC) 35-nm InP high electron mobility transistor (HEMT) process. The circuits were fabricated using different indium channel compositions on different wafers, and comparison of the results based on the indium content will be presented. We have performed on-wafer S-parameter calibration and measurements using newly developed WR2.2 waveguide wafer probes from 325-508 GHz. We measured approximately 5 dB of gain for the single stage amplifier at 437 GHz, and approximately 10 dB of gain at 474 GHz for a three-stage amplifier, with over 9 dB of gain at 490 GHz

COMP6235 L2

Indium Phosphide MMIC LNAs are enabling new capabilities in instrument development. The development of arrays of hundreds of cryogenically-cooled millimeter wave receivers has previously been challenging, but is now achievable with highly repeatable MMIC processes and advances in cryogenic on-wafer testing of LNAs. We have developed InP HEMT LNA MMICs for the 67–90 GHz frequency band that is the last missing receiver system from the ALMA. These MMICs provided average performance of less than 22.5 K noise temperature over the frequency band and minimum noise temperature of 17.5 K at 72 GHz. These LNAs achieve NT=220K (NF=2.4dB) at 90 GHz for Earth remote sensing instrument on Sentinel-6. Our HRMR (High Resolution Microwave Radiometer) achieves NEDT < 0.05K enabling Sentinel-6 to measure coastal ocean topography at 3 km resolution with better than 1 cm accuracy

Miniature Packaging Concept for LNAs in the 200-300 GHz Range

In this work, we describe new miniaturized low noise amplifier modules which we developed for incorporation in small-scale satellites or Cubesats, and which exhibit similar or better performance compared to previously reported LNAs in the literature. We have targeted the WR4 (170-260 GHz) and WR3 (220-325 GHz) waveguide bands for the module development. The modules include two different methods of E-plane probes which have been developed for low loss, and stability at high frequencies. MMIC LNAs were also developed for these frequency ranges and fabricated in Northrop Grumman Corporation's 35 nm InP HEMT technology, and we have experimentally verified that noise performance is lower than reported in prior work. The best results include a miniature LNA module with 550K noise at 224 GHz, and a wideband LNA module with 15 dB gain from 230-280 GHz

Cryogenic low noise MMIC amplifiers for U-Band (40–60 GHz)

In this work, we describe monolithic millimeter-wave integrated circuit (MMIC) Low Noise Amplifier (LNA) and mixer designs for U-Band, also known as the WR19 waveguide band (40–60 GHz). The LNAs were fabricated in NGC's 35 nm InP HEMT MMIC process. The MMICs were packaged in WR19 waveguide housings and tested for noise, both at room temperature and cryogenically. We present the results, including a comparison to the state-of-the-art, and discuss applications for amplifiers in this frequency range. To date, these are the first cryogenic 35 nm InP MMIC results covering the 40–60 GHz range. We achieved a noise temperature less than 30 K over the 40–60 GHz range, when the amplifiers were cryogenically cooled. These results are comparable with other results in the literature, and we believe are the lowest reported for MMICs in the 50–60 GHz range