Dimensinal metrology for nanometre-scale science and engineering: Towards sub-nanometre accurate encodders

Abstract Metrology is the science and engineering of measurement. It has played a crucial role in the industrial revolution at the milli-inch length scale and in the semiconductor revolution at the micrometre length scale. It is often proclaimed that we are standing at the threshold of another industrial revolution, brought by the advent and maturing of nanotechnology. We argue that for nanotechnology to have a similarly revolutionary effect a metrology infrastructure at and below the nanometre scale is instrumental and has yet to be developed. This paper focuses on dimensional metrology, which concerns itself with the measurement of lengths and its applications such as pattern placement and feature size control. We describe our efforts to develop grating-and grid-based scales with sub-nanometre accuracy over 300 mm dimensions using the nanoruler-a scanning-beam interference lithography tool

Follow-Up of Cancer Patients Receiving Anti-PD-(L)1 Therapy Using an Electronic Patient-Reported Outcomes Tool (KISS): Prospective Feasibility Cohort Study

Background: Immune checkpoint inhibitors (ICIs) have become a standard of care for various tumor types. Their unique spectrum of side effects demands continuous and long-lasting assessment of symptoms. Electronic patient-reported outcome (ePRO) follow-up has been shown to improve survival and quality of life of cancer patients treated with chemotherapy.Objective: This study aimed to investigate whether ePRO follow-up of cancer patients treated with ICIs is feasible. The study analyzed (1) the variety of patient reported symptoms, (2) etiology of alerts, (3) symptom correlations, and (4) patient compliance.Methods: In this prospective, one-arm, multi-institutional study, we recruited adult cancer patients whose advanced cancer was treated with anti-programmed cell death protein 1 (PD)-ligand (L)1 agents in outpatient settings. The ePRO tool consisted of a weekly questionnaire evaluating the presence of typical side effects, with an algorithm assessing the severity of the symptom according to National Cancer Institute Common Terminology Criteria for Adverse Events and an urgency algorithm sending alerts to the care team. A patient experience survey was conducted monthly. The patients were followed up to 6 months or until disease progression.Results: A total of 889 symptom questionnaires was completed by 37 patients (lung cancer, n=15; melanoma, n=9; genitourinary cancer, n=9; head and neck cancer, n=4). Patients showed good adherence to ePRO follow-up. The most common grade 1 symptoms were fatigue (28%) and itching (13%), grade 2 symptoms were loss of appetite (12%) and nausea (12%), and grade 3-4 symptoms were cough (6%) and loss of appetite (4%). The most common reasons for alerts were loss of appetite and shortness of breath. In the treatment benefit analysis, positive correlations were seen between clinical benefit and itching as well as progressive disease and chest pain.Conclusions: According to the results, ePRO follow-up of cancer patients receiving ICIs is feasible. ePROs capture a wide range of symptoms. Some symptoms correlate to treatment benefit, suggesting that individual prediction models could be generated

Relativistic corrections in displacement measuring interferometry

Displacement measuring interferometry is based on measuring the Doppler frequency shift that a beam of radiation undergoes upon reflection off a mirror connected to a moving stage. Usually the velocity of the reflecting stage is very small compared to the speed of light and is therefore deduced using the classical expression for the Doppler shift. We calculate relativistic corrections to the Doppler frequency shift, considering arbitrary stage motion in two dimensions and multiple passes through the moving interferometer arm. Changes in optical path lengths due to the varying stage displacement are explicitly taken into account. For stage velocities on the order of only 1 m/s the resulting corrections to the classically derived stage displacement can amount to nanometers. We discuss model velocity profiles similar to those currently employed in industrial step-and-scan systems for integrated circuit manufacturing, and for recently proposed scanning-beam interference lithography schemes. Expected future increases in stage speed and wafer sizes will necessitate the inclusion of relativistic corrections to the Doppler shift to maintain pattern placement accuracy at the nanometer level

Nanometer-level repeatable metrology using the nanoruler

We report on the measurement of the fringe-to-substrate phase error in our Nanoruler system. This system utilizes scanning beam interference lithography to pattern and measure large-area, nanometer-accuracy gratings that are appropriate for semiconductor and integrated opto-electronic metrology. We present the Nanonruler's metrology system that is based on digital frequency synthesizers, acousto-optics, and heterodyne phase sensing. It is used to assess the fringe-to-substrate placement stability and the accuracy of the feedback signals. The metrology system can perform measurements in real time, on the fly, and at arbitrary locations on the substrate. Experimental measurements are presented that demonstrate the nanometer-level repeatability of the system. Dominant error sources are highlighted

Follow-up of cancer patients receiving anti-PD-(L)1 therapy using an electronic patient-reported outcomes tool (KISS):prospective feasibility cohort study

Abstract Background: Immune checkpoint inhibitors (ICIs) have become a standard of care for various tumor types. Their unique spectrum of side effects demands continuous and long-lasting assessment of symptoms. Electronic patient-reported outcome (ePRO) follow-up has been shown to improve survival and quality of life of cancer patients treated with chemotherapy. Objective: This study aimed to investigate whether ePRO follow-up of cancer patients treated with ICIs is feasible. The study analyzed (1) the variety of patient reported symptoms, (2) etiology of alerts, (3) symptom correlations, and (4) patient compliance. Methods: In this prospective, one-arm, multi-institutional study, we recruited adult cancer patients whose advanced cancer was treated with anti-programmed cell death protein 1 (PD)- ligand (L)1 agents in outpatient settings. The ePRO tool consisted of a weekly questionnaire evaluating the presence of typical side effects, with an algorithm assessing the severity of the symptom according to National Cancer Institute Common Terminology Criteria for Adverse Events and an urgency algorithm sending alerts to the care team. A patient experience survey was conducted monthly. The patients were followed up to 6 months or until disease progression. Results: A total of 889 symptom questionnaires was completed by 37 patients (lung cancer, n=15; melanoma, n=9; genitourinary cancer, n=9; head and neck cancer, n=4). Patients showed good adherence to ePRO follow-up. The most common grade 1 symptoms were fatigue (28%) and itching (13%), grade 2 symptoms were loss of appetite (12%) and nausea (12%), and grade 3-4 symptoms were cough (6%) and loss of appetite (4%). The most common reasons for alerts were loss of appetite and shortness of breath. In the treatment benefit analysis, positive correlations were seen between clinical benefit and itching as well as progressive disease and chest pain. Conclusions: According to the results, ePRO follow-up of cancer patients receiving ICIs is feasible. ePROs capture a wide range of symptoms. Some symptoms correlate to treatment benefit, suggesting that individual prediction models could be generated. Trial Registration: Clinical Trials Register, NCT3928938; https://clinicaltrials.gov/ct2/show/NCT0392893

ePROs in the follow-up of cancer patients treated with immune checkpoint inhibitors:a retrospective study

Abstract Purpose: Patient-reported outcome (PRO) follow-up has been shown to improve quality of life (QoL) and survival of cancer patients receiving chemotherapy. Kaiku Health application is a web-based electronic PRO (ePRO) tool which is designed for follow-up of cancer patients receiving immune checkpoint inhibitors (ICI). Purpose of the current study is to investigate whether symptoms collected by Kaiku Health ePRO tool on cancer patients receiving immune checkpoint inhibitors (ICI) follows to symptoms reported in clinical trials and whether coupling of specific symptoms does occur. Methods: We retrospectively collected data on symptom timing and severity, and QoL of patients followed with Kaiku Health IO module in two Finnish cancer centers between 2017 and 2018. Kaiku Health IO module consists of 18 adaptive questions, which assess the presence and severity of symptoms. Patients were requested (via e-mail) to fill online symptom questionnaires with 3–7 day interval and QoL questionnaires (QLQ-C30) with 1–2 month interval. Results: The IO module was used to follow 37 patients who had filled in total 559 symptom questionnaires. There was good adherence to ePRO follow-up with a median of 11 questionnaires filled per patient. The reported symptoms and their severity follow closely what has been seen in clinical trials investigating ICIs. Correlation analysis of the symptoms showed the strongest positive correlations between itching and rash; nausea and vomiting, decreased appetite, or stomach pain; cough and shortness of breath. Conclusions: The results of the current study suggest that real-world symptom data collected through the ePRO application on cancer patients receiving ICI therapy aligns with the data from clinical trials. Correlations between different symptoms occur, which might reflect therapeutic efficiency, side effects, or tumor progression. These correlations should be further investigated with data coupled to clinical outcomes

A generalized scanning beam interference lithography system for patterning gratings with variable period progressions,” submitted to

We demonstrate a versatile interference lithography system that can continuously vary the pattern period and orientation during fabrication of general periodic structures in one or two dimensions. Initial experimental results, using closed-loop beam steering control and double exposures on a stationary substrate, are obtained in order to illustrate its principle of operation. A fringe-locking scheme for phase control is also demonstrated including discussion of issues related to future system developments