Comparative evaluation of analogue front-end designs for the CMS Inner Tracker at the High Luminosity LHC

The CMS Inner Tracker, made of silicon pixel modules, will be entirely replaced prior to the start of the High Luminosity LHC period. One of the crucial components of the new Inner Tracker system is the readout chip, being developed by the RD53 Collaboration, and in particular its analogue front-end, which receives the signal from the sensor and digitizes it. Three different analogue front-ends (Synchronous, Linear, and Differential) were designed and implemented in the RD53A demonstrator chip. A dedicated evaluation program was carried out to select the most suitable design to build a radiation tolerant pixel detector able to sustain high particle rates with high efficiency and a small fraction of spurious pixel hits. The test results showed that all three analogue front-ends presented strong points, but also limitations. The Differential front-end demonstrated very low noise, but the threshold tuning became problematic after irradiation. Moreover, a saturation in the preamplifier feedback loop affected the return of the signal to baseline and thus increased the dead time. The Synchronous front-end showed very good timing performance, but also higher noise. For the Linear front-end all of the parameters were within specification, although this design had the largest time walk. This limitation was addressed and mitigated in an improved design. The analysis of the advantages and disadvantages of the three front-ends in the context of the CMS Inner Tracker operation requirements led to the selection of the improved design Linear front-end for integration in the final CMS readout chip.

Characterization of FBK 3D pixel sensor modules based on RD53A readout chip for the ATLAS ITk

CERN is planning to upgrade its Large Hadron Collider to the High Luminosity phase (HL-LHC), pushing detector technologies to cope with unprecedently demanding performance in terms of particle rate and radiation hardness. The ATLAS experiment decided to equip the innermost layer (L0) of its Inner Tracker (ITk) with small-pitch 3D pixels of two different geometries, i.e., 25 µm × 100 µm for the central barrel and 50 µm × 50 µm for the lateral rings. A new generation of 3D pixels featuring these small-pitch dimensions and reduced active thickness (∼150 µm) has been developed to this purpose within a collaboration of INFN and FBK since 2014. Recently, the R&D activities have been focused on the characterization of modules based on sensors compatible with the RD53A readout chip, which were tested in laboratory and at beam lines. In this paper, we report on the characterization of modules irradiated with protons up to a fluence of 1 × 1016 neq/cm2, including threshold tuning and noise measurements, and results from beam tests performed at DESY. Moreover, we will discuss about the electrical characteristics at wafer level and at module level before and after irradiation.

Protease-controlled secretion and display of intercellular signals

To program intercellular communication for biomedicine, it is crucial to regulate the secretion and surface display of signaling proteins. If such regulations are at the protein level, there are additional advantages, including compact delivery and direct interactions with endogenous signalling pathways. We created a modular, generalizable design called Retained Endoplasmic Cleavable Secretion (RELEASE), with engineered proteins retained in the endoplasmic reticulum and displayed/secreted in response to specific proteases. The design allows functional regulation of multiple synthetic and natural proteins by synthetic protease circuits to realize diverse signal processing capabilities, including logic operation and threshold tuning. By linking RELEASE to additional novel sensing and processing circuits, we were able to achieve elevated protein secretion in response to undruggable oncogene KRAS mutants. RELEASE should enable the local, programmable delivery of intercellular cues for a broad variety of fields such as neurobiology, cancer immunotherapy and cell transplantation.

Point-of-care serodiagnostic test for early-stage Lyme disease using a multiplexed paper-based immunoassay and machine learning

ABSTRACTCaused by the tick-borne spirochete, Borrelia burgdorferi, Lyme disease (LD) is the most common vector-borne infectious disease in North America and Europe. Though timely diagnosis and treatment are effective in preventing disease progression, current tests are insensitive in early-stage LD, with a sensitivity <50%. Additionally, the serological testing currently recommended by the US Center for Disease Control has high costs (>$400/test) and extended sample-to-answer timelines (>24 hours). To address these challenges, we created a cost-effective and rapid point-of-care (POC) test for early-stage LD that assays for antibodies specific to seven Borrelia antigens and a synthetic peptide in a paper-based multiplexed vertical flow assay (xVFA). We trained a deep learning-based diagnostic algorithm to select an optimal subset of antigen/peptide targets, and then blindly-tested our xVFA using human samples (N(+) = 42, N(−)= 54), achieving an area-under-the-curve (AUC), sensitivity, and specificity of 0.950, 90.5%, and 87.0% respectively, outperforming previous LD POC tests. With batch-specific standardization and threshold tuning, the specificity of our blind-testing performance improved to 96.3%, with an AUC and sensitivity of 0.963 and 85.7%, respectively.