RESUMEN
Electron beam lithography (EBL) stands out as a powerful direct-write tool offering nanometer-scale patterning capability and is especially useful in low-volume R&D prototyping when coupled with pattern transfer approaches like etching or lift-off. Among pattern transfer approaches, lift-off is preferred particularly in research settings, as it is cost-effective and safe and does not require tailored wet/dry etch chemistries, fume hoods, and/or complex dry etch tools; all-in-all offering convenient, 'undercut-free' pattern transfer rendering it useful, especially for metallic layers and unique alloys with unknown etchant compatibility or low etch selectivity. Despite the widespread use of the lift-off technique and optical/EBL for micron to even sub-micron scales, existing reports in the literature on nanofabrication of metallic structures with critical dimension in the 10-20 nm regime with lift-off-based EBL patterning are either scattered, incomplete, or vary significantly in terms of experimental conditions, which calls for systematic process optimization. To address this issue, beyond what can be found in a typical photoresist datasheet, this paper reports a comprehensive study to calibrate EBL patterning of sub-50 nm metallic nanostructures including gold nanowires and nanogaps based on a lift-off process using bilayer polymethyl-methacrylate as the resist stack. The governing parameters in EBL, including exposure dose, soft-bake temperature, development time, developer solution, substrate type, and proximity effect are experimentally studied through more than 200 EBL runs, and optimal process conditions are determined by field emission scanning electron microscope imaging of the fabricated nanostructures reaching as small as 11 nm feature size.
RESUMEN
BACKGROUND: Amivantamab, an EGFR-MET bispecific antibody, is the first approved targeted therapy for patients with EGFR Ex20ins NSCLC after prior platinum-based chemotherapy-a population with historically poor outcomes before amivantamab approval. As antitumor activity in single-arm studies typically focuses on responders, the evaluation of outcomes in patients with stable disease (SD) as best response is of clinical interest. PATIENTS AND METHODS: Among 114 patients with post-platinum EGFR Ex20ins NSCLC in CHRYSALIS (NCT02609776; data cutoff: March 30, 2021), response was assessed by blinded independent central review via RECIST v1.1. Patients alive and receiving therapy at 12 weeks were grouped by response at this landmark: partial or complete response (PR+), SD, or progressive disease (PD). Progression-free survival (PFS) and overall survival (OS) by response cohort were determined using the Kaplan-Meier method; hazard ratios (HRs) and 95% confidence intervals (CIs) between response cohorts were calculated using Cox proportional hazards regression. RESULTS: Among patients alive and receiving therapy at 12 weeks (n=107), 42 (39%) had PR+, 52 (49%) had SD, and 13 (12%) had PD. Among patients with PR+ and SD, median PFS was 12.2 and 7.0 months, respectively. A corresponding improvement in OS was observed in patients achieving PR+ (median: not reached; HR vs PD=0.21 [95% CI: 0.08-0.54]) and SD (median: 23.0 months; HR vs PD=0.33 [95% CI: 0.14-0.77]), relative to those with PD (median: 14.0 months). CONCLUSION: SD was observed in 49% of patients receiving amivantamab, with corresponding increases in OS that dramatically improved the prognoses of this patient population.