Clean Room Research Articles

Characterization of new silicon carbide neutron detectors with thermal and fast neutrons

The aim of this work is to present a characterization of a new silicon carbide (SiC) neutron detector fabricated at the Institute of Microelectronics of Barcelona (IMB-CNM-CSIC). The device is based on a 50μm thick p-n diode built in a 4H-SiC wafer. Performance studies were carried out under different neutron energy spectra, including thermal and quasi-monoenergetic fast neutrons at the CNA HiSPANoS facility. We implemented a method for the fabrication of enriched LiF conversion layers to use for the detection of thermal neutrons. The detector was proven to be capable of being used for thermal neutron detection with conversion layers of 10B and LiF. A detection efficiency of 6 ± 1% was achieved with a 25μm thick LiF conversion layer. It was also confirmed that the device can be employed for the detection of recoil nuclei and protons produced by fast neutrons. The spectra obtained experimentally were compared with PHITS simulations. This work represents the first step towards the design and fabrication of new SiC neutron detectors in the IMB-CNM-CSIC clean room with potential applications in various scientific and technological fields.

The environmental microbial retrieving assessment of cell-processing facilities for cell therapy in a hospital laboratory.

Cell therapy represents a promising treatment modality. A critical component in the production of cell therapy products is maintaining the sterility of cell therapy clean rooms (CTCRs). This study aimed to evaluate the environmental microbial load within CTCRs. We systematically monitored microbial load in CTCRs, following established guidelines. Cultured microbial samples underwent metagenomic sequencing, and alpha and beta diversity analyses, functional annotation, and resistance gene profiling were performed using various bioinformatics tools to assess microbial diversity and function. From November 2023 to January 2024, we collected 42 environmental microbial colony samples from various sources within the CTCR and performed metagenomic sequencing on 39 samples. Alpha diversity analysis revealed no significant differences among surface, settle_plate, and airborne categories, but significant disparities within surface subgroups were revealed. Beta diversity analysis showed notable differences between surface and airborne categories and among surface subgroups. Species distribution analysis identified Bacillus as the predominant genus on surfaces. Functional annotation and resistance gene analysis indicated distinct resistance patterns, with significant variations between subgroups, such as microscopes and transfer windows, and hands and other Grade_B environments. Resistance to hydrogen peroxide was notably higher in the transfer window group. These findings highlight the importance of stringent disinfection protocols and enhanced hand hygiene to maintain sterility in CTCRs. These findings provide valuable insights for implementing effective measures to maintain cleanliness throughout CTCRs. The annotation and study of resistance genes can help rapidly identify methods to control cellular contamination under circumstances of environmental microbial pollution.IMPORTANCEMaintaining the sterility of cell therapy clean rooms (CTCRs) is crucial for the production of safe and effective cell therapy products. Our study systematically evaluated the environmental microbial load within CTCRs, revealing significant microbial diversity and distinct resistance patterns to disinfection methods. These findings underscore the need for stringent disinfection protocols and enhanced hand hygiene practices to ensure CTCR sterility. By identifying key microbial species and their resistance genes, our research provides essential insights into controlling contamination and safeguarding the production environment, ultimately contributing to the reliability and success of cell therapy treatments.

A customised novel hybrid post-treatment process achieved excellent mechanical properties in additively manufactured Haynes 230 alloy

ABSTRACT It is challenging to maintain decent plasticity while increasing strength in laser powder bed fusion (LPBF) manufactured Haynes 230 alloy. The fundamental issue of both inadequate affected depth and deteriorated plasticity exists for laser shock peening (LSP). To address this problem, the treatment method of heat treatment plus laser shock peening (HT-LSP) was proposed. After heat treatment, dispersive M23C6 carbides were precipitated, and dislocation was predominately decreased inside grains but increased at grain boundaries. The junction of three imperfect dislocations was identified at M23C6 after HT-LSP treatment, indicating the novel phenomenon of twin formation via the polar-axis mechanism of dislocation proliferation, given the inhibition of intergranular transfer of dislocations and adequate clean rooms without dislocation clusters inside grains. Grain rotation occurred after HT-LSP derived from dynamic recrystallisation and twin distortion. The hardness along depth direction of the sample demonstrated the increased effective affected depth of LSP from 900 to 1400 μm after heat treatment. The shear strength of the HT-LSP sample was increased to 662 MPa. The elongation of the sample reaching 13.4% was also higher than that with LSP. The mechanical performance improvement was mainly due to the gradient twin layer, carbides’ precipitation and high-density dislocation.

A novel encryption protocol for facilitating de-identification of genomics health data

The exponential growth and affordability of genomics sequencing in the clinical landscape in recent years have intensified a challenge facing privacy experts. They grapple with how to evaluate and mitigate the significant risk of genomics data being used to re-identify individuals. The lack of clear genomics guidance in HIPAA has invited a wide spectrum of expert opinion from advocating for conservative limitations to be placed on genomics data sharing to ‘security’-based arguments that carefully calibrated technical, administrative, and legal safeguards may provide adequate protection in many cases. The need to weigh privacy concerns against the extraordinary value that genomics data offers to cancer and rare disease clinical research is compounded by the reality that conventional data modifications, such as redaction, aggregation, and perturbation, often critically undermine these important use cases. We present an innovative solution for de-identifying genomics data according to a conservative interpretation of HIPAA while still preserving maximal utility for clinical purposes. Our solution rejects the notion that privacy can be achieved directly via security. Instead, we introduce a reversible encryption protocol designed to be applied to specific combinations of genetic variants and their locations on the genome. The encrypted genomic data is fully de-identified, allowing researchers to perform analyses on the encrypted data in a secure Clean Room environment. The environment host is then able to decrypt and deliver variant-level summary statistics and aggregated outputs from the analysis to the recipient. As information in this format no longer links to patient-level data the solution remains de-identified end-to-end.

Multiplexed Microfluidic Platform for Parallel Bacterial Chemotaxis Assays.

The sensing of and response to ambient chemical gradients by microorganisms via chemotaxis regulates many microbial processes fundamental to ecosystem function, human health, and disease. Microfluidics has emerged as an indispensable tool for the study of microbial chemotaxis, enabling precise, robust, and reproducible control of spatiotemporal chemical conditions. Previous techniques include combining laminar flow patterning and stop-flow diffusion to produce quasi-steady chemical gradients to directly probe single-cell responses or loading micro-wells to entice and ensnare chemotactic bacteria in quasi-steady chemical conditions. Such microfluidic approaches exemplify a trade-off between high spatiotemporal resolution of cell behavior and high-throughput screening of concentration-specific chemotactic responses. However, both aspects are necessary to disentangle how a diverse range of chemical compounds and concentrations mediate microbial processes such as nutrient uptake, reproduction, and chemorepulsion from toxins. Here, we present a protocol for the multiplexed chemotaxis device (MCD), a parallelized microfluidic platform for efficient, high-throughput, and high-resolution chemotaxis screening of swimming microbes across a range of chemical concentrations. The first layer of the two-layer polydimethylsiloxane (PDMS) device comprises a serial dilution network designed to produce five logarithmically diluted chemostimulus concentrations plus a control from a single chemical solution input. Laminar flow in the second device layer brings a cell suspension and buffer solution into contact with the chemostimuli solutions in each of six separate chemotaxis assays, in which microbial responses are imaged simultaneously over time. The MCD is produced via standard photography and soft lithography techniques and provides robust,repeatable chemostimulus concentrations across each assay in the device. This microfluidic platform provides a chemotaxis assay that blends high-throughput screening approaches with single-cell resolution to achieve a more comprehensive understanding of chemotaxis-mediated microbial processes. Key features • Microchannel master molds are fabricated using photolithography techniques in a clean room with a mask aligner to fabricate multilevel feature heights. • The microfluidic device is fabricated from PDMS using standard soft lithography replica molding from the master molds. • The resulting microchannel requires a one-time calibration of the driving inlet pressures, after which devices from the same master molds have robust performance. • The microfluidic platform is optimized and tested for measuring chemotaxis of swimming prokaryotes.

Fuzzy Evaluation Model for Operational Performance of Air Cleaning Equipment

Global warming has led to the continuous deterioration of the living environment, in which air quality directly affects human health. In addition, the severity of the COVID-19 pandemic has further increased the attention to indoor air quality. Indoor clean air quality is not only related to human health but also related to the quality of the manufacturing environment of clean rooms for numerous high-tech processes, such as semiconductors and packaging. This paper proposes a comprehensive model for evaluating, analyzing, and improving the operational performance of air cleaning equipment. Firstly, three operational performance evaluation indexes, such as the number of dust particles, the number of colonies, and microorganisms, were established. Secondly, the 100(1− α)% upper confidence limits of these three operational performance evaluation indexes were deduced to construct a fuzzy testing model. Meanwhile, the accumulated value of ϕ was used to derive the evaluation decision-making value. The proposed model can help companies identify the key quality characteristics that need to be improved. Furthermore, the competitiveness of cooperative enterprises towards smart manufacturing can be strengthened, so that enterprises can not only fulfill their social responsibilities while developing the economy but also take into account the sustainable development of enterprises and the environment.

Airflow and aerosol transport in the hospital isolation zone based on dynamic scenarios

To contain the leakage of viral aerosols, buffer rooms are usually provided in front of isolation wards. However, dynamic events of door movement and healthcare worker (HCW) walking will result in highly concentrated aerosols intruding into the buffer room from the ward, challenging the control of virus transmission risk. In this work, airflow exchange and bioaerosol particle transport between the negative-pressure isolation ward and the buffer room under dynamic scenarios were studied by transient computational fluid mechanics (CFD) simulation, thereby the fate of particles was divided into invasion stage and decay stage. The effects of ventilation pattern and HCW location on the concentration level and attenuation trend of particles were quantitatively analyzed. The results showed that increasing the HCW walking distance could increase the peak particle concentration within the buffer room by 4.5 % during the invasion stage. The effect of the buffer room ventilation layout on air exchange and particle transport was more pronounced than the HCW stay position. In the decay stage, the two more effective ventilation layouts could decrease the complete clearance time of particles and the particle concentration in the breathing zone by 31 % and 42 %, respectively. To reduce the infection risk, bioaerosol levels need to be reduced both in the buffer room and in the HCW breathing zone.

NUOVA OFFICINA ASSERGI: a novel infrastructure for the production of cryogenic and radiopure Si-based photodetectors

The NUOVA OFFICINA ASSERGI (NOA) is a new facility for the production and integration of large-area silicon photodetectors operating at cryogenic temperatures. Silicon photomultipliers are proving to be a promising technology for next-generation experiments searching for rare events in underground laboratories. New photosensor technology with high performance at cryogenic temperature has been developed by Fondazione Bruno Kessler (FBK) and integrated at Laboratori Nazionali del Gran Sasso (LNGS) into large-area optical units, thus opening the frontiers toward the realization of scalable liquid argon experiments probing dark matter. The massive production of such detectors is now feasible in NOA, a clean room of 421 m2 designed to operate in a radon-free mode. NOA, commissioned and operational at LNGS, hosts the most advanced packaging machines and electronic test facilities for the integration of silicon devices in a dust-controlled environment. The infrastructure layout is split into two experimental areas: one for the production of electronic devices and cryogenic temperature tests and the other for operating with large detector installations. The NOA facility can be operated with a radon abatement system, making it a unique facility for packaging and testing SiPM-based photosensors and for assembling detector components in a radon-free environment. Therefore, NOA supports the deployment of underground experiments at LNGS and the development of new technologies for the search of rare events, such as dark matter and neutrinoless double-beta decay.

Facile SILAR deposited SnS/NiS vertical heterojunction for high performance flexible broadband photodetector

Low-cost, flexible broadband photodetectors fabricated from two-dimensional transition metal chalcogenides have garnered attention because of their excellent absorption coefficient and photoconductivity. Likewise, vertical heterojunctions fabricated from two two-dimensional (2D) transition metal chalcogenides (TMCs) also have drawn major curiosity lately owing to their superior optical performance. This work reports a p-p type II vertical Van der Waal's heterojunction structure by depositing thin film of NiS over SnS on a flexible paper substrate. Morphological and structural characterization confirms presence of a rhombohedral β-NiS crystal structure along with traces of Ni(OH)2 on orthorhombic SnS nanoparticles. The device fabrication method made use of the inexpensive, clean room free SILAR (Successive Ionic Layer Adsorption and Reaction) technique. A purposeful modification of narrow bandgap property of NiS is done by depositing it in an alkaline environment. The fabricated device records optical responsivity of 0.92 mA/W under UV illumination, 5.32 mA/W under Visible illumination, and 0.8 mA/W under NIR illumination. A maximum EQE of 1.3 % is observed along with superior response times of 0.114 s (UV),0.103 s (Visible) and 1.34 s (NIR). The acquired photo response is due to superior absorption property of NiS in UV region and SnS in the visible and NIR region. The difference in fermi level between two materials causes efficient separation of the charge carriers that results in junctional electric field upon light illumination. The device underwent flexibility testing and shown exceptional resistance to bending force making it suitable for numerous applications like wearable healthcare monitoring, security purposes and flexible image sensors.

Convolution of Analyte-Electrode Interactions over Distinct Time-Scales Leading to Taste Discrimination in Single Response Electroplated Metal Microwires-Based Microfluidic Electronic Tongue

A microfluidic electronic tongue (MET) is demonstrated via analyzing a single equivalent admittance spectrum derived from stainless-steel microwires electroplated with copper, nickel, iron, and zinc, all interconnected in parallel. These microwires were integrated into a microfluidic chip composed of polydimethylsiloxane (PDMS). A single admittance response for taste analytes, passing through micro-channels, was measured by short-circuiting the ends of multi-wire MET chip. The resulting admittance response from the MET was processed via principal component analysis (PCA) for visualization of clustering according to the taste groups. The performance of MET was assessed in terms of cluster analysis and Silhouette coefficient (SC).This analytical method effectively clusters four primary taste samples based on their distinct flavor profiles, showcasing notable differentiation with a Silhouette coefficient surpassing 0.71. The elucidation provided by the biplot reveals that electronic and ionic interaction at analyte-electrode interactions over distinct time scales contribute synergistically towards discrimination of taste in dimensionally reduced 2-D PCA space. Real admittance responses at lower and higher frequency range contribute majorly in the composition of first and second principal components respectively. The equivalent electric circuit (EEC) was fitted to the developed MET to gain better understanding of response mechanism. A capacitor (C) in parallel to a series combination of resistor (R) and inductor (L), is (C[RL]) kind of EEC fitted to the admittance spectra. Interestingly, when relying on fitted equivalent electric circuit data, the taste discriminability of the MET is notably diminished as not all EEC elements are able to capture signature response specific to each taste. This observation critically evaluates the strategy of suitable data selection towards accurate and efficient taste discrimination as the admittance response over complete frequency range are pivotal contributors to the MET's impressive taste discrimination capabilities.A pivotal aspect of the MET's functionality lies in deploying a single admittance response, a convolution of the responses of multiwire configurations integrated into the MET. This approach ensures global selectivity by utilizing copper, nickel, iron, and zinc electrodeposited stainless-steel microwires. These functionalization-free sensing units exhibit the ability to discriminate sweet, sour, bitter, and salty taste groups with remarkable clarity, boasting a Silhouette coefficient value of 0.77.The MET's adaptability is further underscored by its electroplating modification, which is both expandable and enables clean room-free fabrication methods. This capability paves the way for the widespread manufacturing of MET chips featuring readily interchangeable and reusable calibration-free electrodes.Looking ahead, the MET holds promise for future applications in quality control, particularly in the assessment of real food and beverage samples such as milk and soft drinks. The efficiency demonstrated in discriminating between tastes suggests that the MET could offer a cost-efficient and simplified solution for taste and quality assessments across diverse commercial applications. This potential extends to scenarios where clean room facilities are not readily available.In summary, the MET's unique approach, utilizing a single equivalent admittance spectrum from electroplated metal wires in a microfluidic context, showcases robust taste discrimination capabilities. Integrating PDMS microfluidic chips and employing principal component analysis add layers of sophistication to the methodology. The MET's global selectivity, functionalization-free sensing units, and adaptability in manufacturing advocate its potential for revolutionizing taste and quality assessment in various industries, providing a glimpse into a future where simplicity and cost-efficiency are paramount considerations in analytical methodologies.

Organizational and infrastructural risk factors for health care–associated Clostridioides difficile infections or methicillin-resistant Staphylococcus aureus in hospitals

This study explores the infrastructural and organizational risk factors for healthcare-associated (HCA) Clostridioides difficile infections (CDIs) and methicillin-resistant Staphylococcus aureus (MRSA) in hospitals. This is a retrospective observational study involving all eligible inpatient units from 12 hospitals in British Columbia, Canada, from April 1, 2020 to September 16, 2021. The outcomes were the average HCA CDI or MRSA rates. Covariates included, but were not limited to, infection control factors (eg, hand hygiene rate), infrastructural factors (eg, unit age), and organizational factors (eg, hallway bed utilization). Multivariable regression was performed to identify statistically significant risk factors. Older units were associated with higher HCA CDI rates (adjusted relative risk [aRR]: 0.012; 95%confidence interval (CI) [0.004, 0.020]). Higher HCA MRSA rates were associated with decreased hand hygiene rate (aRR: -0.035; 95%CI [-0.063, -0.008]), higher MRSA bioburden (aRR: 9.008; 95%CI [5.586, 12.429]), increased utilization of hallway beds (aRR: 0.680; 95%CI [0.094, 1.267]), increased nursing overtime rate (aRR: 5.018; 95%CI [1.210, 8.826]), and not keeping the clean supply room door closed (aRR: -0.283; 95%CI [-0.536, -0.03]). The study confirmed the multifaceted nature of infection prevention and emphasized the importance of interdepartmental collaboration to improve patient safety.

A Study on the Improvement of Safety and Efficiency of Clean Rooms in Semiconductor Factories Through Real Fire Experiments

A Study on the Improvement of Safety and Efficiency of Clean Rooms in Semiconductor Factories Through Real Fire Experiments

Fabrication of microneedles using wire electric discharge machining and improving surface quality by electrochemical polishing

Microneedle (MN) arrays have many applications in biomedical engineering to deliver drugs transdermally or extract biomarkers from the interstitial fluid from the human skin. Several methods have been developed to fabricate different sizes and shapes of MN using polymers, ceramics and metals. However, most of these methods require expensive sophisticated machines and clean room facilities. So, it is difficult to fabricate microneedle arrays in large quantities at a reasonable cost. This study reports the fabrication of a high-quality stainless steel master pattern for an MN array using a wire-cut electric discharge machining process followed by electrochemical polishing (ECP). Different densities of a 5 × 5 array of microneedles with pyramidal shapes were fabricated by machining channels onto the workpiece surface in a criss-cross pattern. A systematic experimental study was carried out with reference to the offset between the two consecutive channel faces and the depth of channels. The output parameters are MN height (MNH), MN base (MNBW) and tip width (MNTW). The average needle tip width, base width, and height of microneedles were found to be 55.3 ± 5 µm, 679.8 ± 10 µm, and 914.7 ± 19 µm. Finally, the sharpness of the MN tips and the overall surface finish of the MN array were improved with ECP. The reductions in MNH, MNBW, and MNTW were reported to be −18.3%, −9.7%, and −95.4%, respectively, with a final tip width of 2.55 ± 1.62 µm. The MNs’ tip angle was reported to be 32.52° ± 1.56.

Development and optimization of large-scale integration of 2D material in memristors

Two-dimensional (2D) materials like transition metal dichalcogenides (TMD) have proved to be serious candidates to replace silicon in several technologies with enhanced performances. In this respect, the two remaining challenges are the wafer scale growth of TMDs and their integration into operational devices using clean room compatible processes. In this work, two different CMOS-compatible protocols are developed for the fabrication of MoS2-based memristors, and the resulting performances are compared. The quality of MoS2 at each stage of the process is characterized by Raman spectroscopy and x-ray photoemission spectroscopy. In the first protocol, the structure of MoS2 is preserved during transfer and patterning processes. However, a polymer layer with a minimum thickness of 3 nm remains at the surface of MoS2 limiting the electrical switching performances. In the second protocol, the contamination layer is completely removed resulting in improved electrical switching performances and reproducibility. Based on physico-chemical and electrical results, the switching mechanism is discussed in terms of conduction through grain boundaries.

Effect of Buffer Room Configuration on Isolation of Bacteriophage phi6 and Micrococcus Luteus Emissions

Effect of Buffer Room Configuration on Isolation of Bacteriophage phi6 and Micrococcus Luteus Emissions

OP19 Addressing RWE Challenges in Real-Time: The ‘Clean Room Committee’ Approach Works to Handle Research Hurdles without Bias

OP19 Addressing RWE Challenges in Real-Time: The ‘Clean Room Committee’ Approach Works to Handle Research Hurdles without Bias

Monitoring of CO2 using MWCNTs functionalized clay porous composite for clean room facility

In this current work, a vastly sensitive, selective, and cost-effective CO2 gas sensor was developed by utilizing MWCNTs doped clay ceramics, for the developments in clean room facilities or pharmaceutical purposes. Herein, MWCNTs functionalized clay composites (CTsX; X = 0, 5, 10, and 15) were prepared by a bottom up approach i.e. solid-state reaction method and characterized by SEM with EDAX, XPS, XRD, FTIR, UV–visible spectroscopy, BET, and sensing. SEM micrographs revealed the created pores and grown nanotubes within the base material. XPS demonstrated some sites of Oads deficiencies, attributed to the expediting of sensing phenomena. Further, MWCNTs are well functionalized with clay as confirmed via XRD phases such as SiO2 (trigonal), AlKSi3O8 (monoclinic), Al2CaSi2O8 (triclinic) and C2Ca5Si2O13 (monoclinic). Furthermore, BET established the mesoporous nature of CTs15 composite having mean pore size ∼ 3.82 nm, also CO2 gas (200–1000 ppm) was tested at ambient temperature. Moreover, CTs15 composite showed maximum sensor response (S.R.) 5.31 at 1000 ppm of CO2 gas, whereas minimum response/recovery time (Tres./Trec.) 10.87/8.93 s were noticed at 200 ppm while operated at 28℃ (ambient condition). Additionally, LOD assured 217 ppm, which suggests that fabricated sensor is highly sensitive and selective for CO2, and may be used for clean room services. Therefore, this cost effective and eco-friendly composite is suitable for monitoring of CO2 gas for indoor and outdoor environments within a few seconds of Tres. and Trec..

Low-air-pressure clean room system: A flexible, high-quality model for assisted reproduction laboratories

Low-air-pressure clean room system: A flexible, high-quality model for assisted reproduction laboratories

HVAC Design Optimization for Pharmaceutical Facilities with BIM and CFD

Building Information Modeling (BIM) has been widely used in the past decade to enhance the design quality of Heating, Ventilation, and Air Conditioning (HVAC) systems. However, in specialized areas such as pharmaceutical facilities, HVAC design has traditionally relied on Computer-Aided Design (CAD) drawings. This conventional approach does not allow for the simulation of temperature distribution or the verification of system efficiency, which may lead to design failures. To address these challenges in pharmaceutical facilities, this study proposed a BIM-based approach for optimizing HVAC design with Computational Fluid Dynamics (CFD). By employing CFD to simulate the dynamic airflow conditions of pharmaceutical clean rooms, the effectiveness of HVAC systems can be verified. A case study of a clean room HVAC design is presented to demonstrate the workflow. The results of the case study indicated that the pharmaceutical temperature requirements were met within 1 °C during the design optimization simulation, and there was a 95% match in the 72 h temperature mapping test during site validation. The results confirmed that using CFD with BIM not only successfully simulates the design intentions of indoor air quality but also suggests HVAC system optimization for the required clean room design. The findings of this paper contribute to the body of knowledge on overcoming the limitations of the traditional CAD-based HVAC design process and provide valuable insights on optimizing HVAC design with BIM and CFD technologies.

A generalized disjunctive graph model for a complex production problem

This work focuses on the modeling of the features of a real-world pharmaceutical production problem, where several limited resources must be gathered and scheduled in order to mix and process active substances. The problem can be modelled as a generalization of the job-shop scheduling problem, in which each job corresponds to an order. Besides the standard precedence and capacity constraints of a classical job-shop scheduling problem, release, no-wait and time interval production constraints are added. Furthermore, the processing of each job task must be assisted by an appropriate number of operators and performed by a specific machine, out of a set of feasible machines, that is temporarily installed in a compatible clean room. An innovative generalized disjunctive graph that models all the constraints and the resource conflicts is presented.