Digital pixel test structures implemented in a 65 nm CMOS process Aglieri Rinella, Gianluca; Andronic, Anton; Antonelli, Matias ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
11/2023, Letnik:
1056
Journal Article
Recenzirano
Odprti dostop
The ALICE ITS3 (Inner Tracking System 3) upgrade project and the CERN EP R&D on monolithic pixel sensors are investigating the feasibility of the Tower Partners Semiconductor Co. 65nm process for use ...in the next generation of vertex detectors. The ITS3 aims to employ wafer-scale Monolithic Active Pixel Sensors thinned down to 20–40µm and bent to form truly cylindrical half barrels. Among the first critical steps towards the realisation of this detector is to validate the sensor technology through extensive characterisation both in the laboratory and with in-beam measurements. The Digital Pixel Test Structure (DPTS) is one of the prototypes produced in the first sensor submission in this technology and has undergone a systematic measurement campaign whose details are presented in this article.
The results confirm the goals of detection efficiency and non-ionising and ionising radiation hardness up to the expected levels for ALICE ITS3 and also demonstrate operation at ＋20°C and a detection efficiency of 99% for a DPTS irradiated with a dose of 10151MeV neq cm-2. Furthermore, spatial, timing and energy resolutions were measured at various settings and irradiation levels.
The repair of osteochondral defects with chondrocytes genetically modified to express desired growth factors promises great potential in orthopaedic therapy. Controlled expression of the transgenes ...is required in many instances. The objective of the present study was to demonstrate the inducibility of tetracycline-responsive transgene expression in osteochondral defects in the knee joint filled with genetically modified chondrocyte implants.
An expression plasmid containing the lacZ gene under the control of the minimal CMV promoter fused to the Tet-responsible element (TRE) as well as the reverse transactivator (rtTA2
s
-M2) was constructed and used to transfect isolated articular chondrocytes from New Zealand white rabbits. rtTA2
s
-M2 binds to the TRE in the presence of tetracycline and leads to the transcription of the transgene. Different concentrations of DNA and various DNA:lipid ratios were tested to determine best transfection conditions. Transfection efficiency and inducibility were analysed by histochemical analysis and flow-cytometry. To evaluate the system
in vivo, collagen-sponges were seeded with transfected autologous chondrocytes and implanted in osteochondral defects in the knees of NZW-rabbits. Gene expression was induced by doxycycline and 3 weeks later, LacZ-expression in isolated knee joints was evaluated in histological sections by X-gal staining.
In vitro 13.5% (±1.32) of induced primary chondrocytes were LacZ-positive, while non-induced controls showed a background-staining in 0.6% (±0.2).
In vivo, upon doxycycline treatment, induction of lacZ-gene-expression could be demonstrated in chondrocytes in 3-week-old, well-integrated implants.
For the first time, tetracycline-inducible gene expression is demonstrated to work in the treatment of osteochondral defects. This demonstrates the feasibility for a gene therapy-assisted approach using controlled expression of therapeutic growth factors from transplanted genetically modified chondrocytes.
Zusammenfassung
EINLEITUNG: Bei Schwangeren über 35 Jahre muss in Deutschland die Möglichkeit zur Durchführung einer invasiven genetischen Diagnostik besprochen werden. Alternativ wird zunehmend das ...kombinierte Ersttrimesterscreening (ETS) nach Nicolaides eingesetzt. Ziel dieser Arbeit war es, die Testperformance des ETS gegenüber dem Altersindikations-Screening (AIS) zu untersuchen und welche ökonomischen Konsequenzen daraus resultieren. MATERIAL UND METHODEN: An der Medizinischen Hochschule Hannover wurden 2743 kombinierte ETS durchgeführt. Hierzu wurde das Computerprogramm PIA Fetal Database verwendet. Alle Messungen wurden mit dem NT-Modul der JOY-Software nachberechnet. Bei auffälligem Test wurde die Möglichkeit einer invasiven Diagnostik besprochen. Auf der Basis der so ermittelten Testleistungsparameter wurde eine Kostenanalyse durchgeführt. ERGEBNISSE: Beide ETS-Methoden erreichten mit einer Sensitivität von 85,7 % und einer Falsch-Negativ-Rate (FNR) von 14,3 % eine deutlich verbesserte Performance gegenüber dem AIS (Sensitivität: 42,9 %, FNR: 57,1 %). Mit einer Spezifität von 97,6 % und einer Falsch-Positiv-Rate (FPR) von 2,5 % zeigte sich JOY gegenüber PIA (Spezifität 96,5 %, FPR 3,5 %) und dem AIS (Spezifität 76,4 %, FPR 23,6 %) überlegen (p < 0,001). Die bundesweiten Gesamtkosten würden sich bei alleiniger Umsetzung des AIS auf etwa 385 Mio. Euro belaufen. Bei Anwendung von PIA würden die Aufwendungen bei 196 Mio. Euro liegen und mit JOY müssten etwa 178 Mio. Euro veranschlagt werden. DISKUSSION: Die Anwendung des AIS ist nicht mehr zeitgemäß und wurde in der Praxis bereits durch effektivere Screeningmethoden ergänzt. Im direkten Vergleich schnitt die Risikokalkulationssoftware JOY in dieser Studie am besten ab. Eine Aufnahme in die Mutterschaftsrichtlinien sollte diskutiert werden.
The ALICE ITS3 (Inner Tracking System 3) upgrade project and the CERN EP R&D on monolithic pixel sensors are investigating the feasibility of the Tower Partners Semiconductor Co. 65 nm process for ...use in the next generation of vertex detectors. The ITS3 aims to employ wafer-scale Monolithic Active Pixel Sensors thinned down to 20 to 40 um and bent to form truly cylindrical half barrels. Among the first critical steps towards the realisation of this detector is to validate the sensor technology through extensive characterisation both in the laboratory and with in-beam measurements. The Digital Pixel Test Structure (DPTS) is one of the prototypes produced in the first sensor submission in this technology and has undergone a systematic measurement campaign whose details are presented in this article. The results confirm the goals of detection efficiency and non-ionising and ionising radiation hardness up to the expected levels for ALICE ITS3 and also demonstrate operation at +20 C and a detection efficiency of 99% for a DPTS irradiated with a dose of \(10^{15}\) 1 MeV n\(_{\mathrm{eq}}/\)cm\(^2\). Furthermore, spatial, timing and energy resolutions were measured at various settings and irradiation levels.
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