Good design practices for an integrated containment and production system for advanced therapies.

Advances in molecular biology and the possibility of differentiating stem cells have opened up new scenarios in therapies that use progenitor or variously differentiated cells. Regardless of the choice of the system, designing a plant for producing advanced therapies requires a clear understanding of the final objective (the product), taking into account all the regulatory, environment, process, risk assessment, asepsis, and validation aspects involved until its implementation. Good Manufacturing Practice (GMP) compliant procedures are a prerequisite for cell production in clinical application, and clean rooms are zones for producing cell therapies. Clean rooms for clinical application require high running and maintenance costs and need trained operators and strict procedures to prepare the rooms and the people involved in the processes. While today production mainly occurs in open systems (clean rooms), there is evidence of processes in closed systems (isolators). The isolator is a Grade A aseptic closed system that requires a controlled environment and at least a Grade D environment in the case of sterile productions (A in D closed system). The use of isolators can ensure a very high level of protection against the risk of product contamination and, at the same time, provide the operators with a very safe working environment. Furthermore, working with closed systems can optimize and facilitate the production of Advanced Therapy Medical Products in GMP environments, by providing an easily reproducible working tool even for large-scale production, with generally lower costs compared to a classical clean room approach. In conclusion, the isolator workstation as a possible alternative to the classic clean room, due to its small size and the simplification of the working and maintenance operational procedures, may represent an interesting solution in the perspective of the increasingly more stringent requests for cost reductions of GMP in clinical application.

A new advanced packaging system for extending the shelf life of refrigerated farmed fish fillets.

BACKGROUND: An innovative pilot-plant packaging was developed and evaluated for applying oregano essential oil (OEO) vapours in conditions of high vacuum for exploring the antimicrobial effect of essential oil vapours applied immediately before packaging of fish fillets. Farmed sea bream (Sparus aurata) fresh fillets have been used as a model for validating this new technology. These fillets, as a refrigerated product under modified atmosphere packaging (MAP), have a relatively short shelf life (12-14 days) mainly due to the fast microbial growth. The effects of conventional OEO dippings [pretreatment dipping (0.1% of OEO) of whole fish (T1) and filleted sea bream (T2)] were compared with the OEO application in vapour phase (67 µL L-1 ) under vacuum (5-10 hPa) immediately before MAP fillet packaging (T3). RESULTS: T3/T2 samples showed the lowest microbial growth after 28 days at 4 °C, with loads up to 1/2.6 log units for Enterobacteria/lactic acid bacteria compared to untreated samples. The initial trimethylamine nitrogen (TMA-N) content (2.6 mg kg-1 ) increased in T1 and T2/T3 samples by 9.6 and 6/7 units, respectively, after 28 days. Quality Index Method (QIM) better reflected the fish fillets shelf life than texture and colour measurements. The shelf life of T3/T2 samples was established in at least 28 days (4 °C), while the QIM threshold (6) was exceeded after 7/21 days in untreated/T1 fillets. CONCLUSION: The fish shelf life was extended with vapour OEO treatment using this new technology, similarly to OEO dipping treatment, according to QIM, corroborated by the microbial quality and TMA-N contents. © 2020 Society of Chemical Industry.

[Study on purification effect of formaldehyde in cleanroom by new return air device].

Objective: To effectively reduce the concentration of poisons in cleanroom, protect the health of workers, realize the optimization and automatic control of the new return air device. And the influence of initial concentration, air volume, temperature and relative humidity of formaldehyde on the purification effect of the new return air device was explored. Methods: The purification effect of the new return air device installed with the activated carbon and the photocatalyst purification net or ordinary activated carbon purification network was tested in a 60 m(3) simulated cleanroom. The concentration of formaldehyde was determined by solution absorption-phenol reagent spectrophotometry. Based on the single factor experiment to determine the combination of two purification nets. The effects of air volume, initial formaldehyde concentration, temperature and relative humidity on the purification effect of the new return air device were investigated by orthogonal test. Then, the performance parameters of the return air device to purify formaldehyde were determined. Results: The formaldehyde purification efficiency of the two types of purification nets in the new return air device was higher than that of the ordinary activated carbon purification network (P<0.05) . The combination of activated carbon and photocatalyst purification net has no effect on the formaldehyde purification efficiency of the return air device (P>0.05) . According to the direct analysis and variance analysis, air volume was the most sensitive factor (F value is 18.894, P<0.05) , followed by initial concentration (F value is 16.128, P<0.05) , while temperature and relative humidity have little effect (F value is 0.041 and 0.599, respectively, P>0.05) . LSD analysis showed that there was no significant difference in the purification efficiency of formaldehyde between 475 m(3)/h and 626 m(3)/h (P>0.05) . From the perspective of formaldehyde purification efficiency and energy saving, when the air volume is set to 475 m(3)/h, the new return air device has higher purification efficiency for high concentration of formaldehyde. Conclusion: The new return air device consisting of activated carbon and photocatalyst purification net can play a good purification role in cleanroom with different temperatures and different humidity. Its formaldehyde purification efficiency is affected by air volume and initial concentration.

Automation of cellular therapy product manufacturing: results of a split validation comparing CD34 selection of peripheral blood stem cell apheresis product with a semi-manual vs. an automatic procedure.

BACKGROUND: Automation of cell therapy manufacturing promises higher productivity of cell factories, more economical use of highly-trained (and costly) manufacturing staff, facilitation of processes requiring manufacturing steps at inconvenient hours, improved consistency of processing steps and other benefits. One of the most broadly disseminated engineered cell therapy products is immunomagnetically selected CD34+ hematopoietic "stem" cells (HSCs). METHODS: As the clinical GMP-compliant automat CliniMACS Prodigy is being programmed to perform ever more complex sequential manufacturing steps, we developed a CD34+ selection module for comparison with the standard semi-automatic CD34 "normal scale" selection process on CliniMACS Plus, applicable for 600 × 10(6) target cells out of 60 × 10(9) total cells. Three split-validation processings with healthy donor G-CSF-mobilized apheresis products were performed; feasibility, time consumption and product quality were assessed. RESULTS: All processes proceeded uneventfully. Prodigy runs took about 1 h longer than CliniMACS Plus runs, albeit with markedly less hands-on operator time and therefore also suitable for less experienced operators. Recovery of target cells was the same for both technologies. Although impurities, specifically T- and B-cells, were 5 ± 1.6-fold and 4 ± 0.4-fold higher in the Prodigy products (p = ns and p = 0.013 for T and B cell depletion, respectively), T cell contents per kg of a virtual recipient receiving 4 × 10(6) CD34+ cells/kg was below 10 × 10(3)/kg even in the worst Prodigy product and thus more than fivefold below the specification of CD34+ selected mismatched-donor stem cell products. The products' theoretical clinical usability is thus confirmed. CONCLUSIONS: This split validation exercise of a relatively short and simple process exemplifies the potential of automatic cell manufacturing. Automation will further gain in attractiveness when applied to more complex processes, requiring frequent interventions or handling at unfavourable working hours, such as re-targeting of T-cells.

Cryopreservation in Closed Bag Systems as an Alternative to Clean Rooms for Preparations of Peripheral Blood Stem Cells.

Autologous and allogeneic stem cell transplantation (SCT) represents a therapeutic option widely used for hematopoietic malignancies. One important milestone in the development of this treatment strategy was the development of effective cryopreservation technologies resulting in a high quality with respect to cell viability as well as lack of contamination of the graft.Stem cell preparations have been initially performed within standard laboratories as it is routinely still the case in many countries. With the emergence of cleanrooms, manufacturing of stem cell preparations within these facilities has become a new standard mandatory in Europe. However, due to high costs and laborious procedures, novel developments recently emerged using closed bag systems as reliable alternatives to conventional cleanrooms. Several hurdles needed to be overcome including the addition of the cryoprotectant dimethylsulfoxide (DMSO) as a relevant manipulation. As a result of the development, closed bag systems proved to be comparable in terms of product quality and patient outcome to cleanroom products. They also comply with the strict regulations of good manufacturing practice.With closed systems being available, costs and efforts of a cleanroom facility may be substantially reduced in the future. The process can be easily extended for other cell preparations requiring minor modifications as donor lymphocyte preparations. Moreover, novel developments may provide solutions for the production of advanced-therapy medicinal products in closed systems.

Conception, realization and qualification of a radioactive clean room lab facility dedicated to the synthesis of radiolabeled API for human ADME studies.

The human absorption, distribution, metabolism and elimination study administering radiolabeled drugs to human volunteers is an important clinical study in the development program of new drug candidates. The manufacture of radiolabeled Active Pharmaceutical Ingredients is covered by national drug laws and may come within the scope of regulatory GMP requirements. Additionally, authorities may request an appropriate environmental zoning to minimize the risk of microbiological contaminations particularly during the synthesis of radiolabeled Active Pharmaceutical Ingredients intended for parenteral application. Thus, a radioactive clean room lab facility in line with both GMP and radiation safety regulations was installed and the environmental zoning validated by appropriate testing of technical parameters and microbial and particle monitoring. The considerations detailed in this paper cover only GMP aspects related to the synthesis of radioactive drug substance. The subsequent, final formulation step in the overall process for manufacturing of radioactive drug product for any kind of administration is not within the scope of this paper. Under these qualified and controlled environmental conditions, we are now in a position to provide radiolabeled drug substances for all kinds of drug administration including both po and iv.

Automated CD34+ cell isolation of peripheral blood stem cell apheresis product.

BACKGROUND AIMS: Immunomagnetic enrichment of CD34+ hematopoietic "stem" cells (HSCs) using paramagnetic nanobead coupled CD34 antibody and immunomagnetic extraction with the CliniMACS plus system is the standard approach to generating T-cell-depleted stem cell grafts. Their clinical beneficence in selected indications is established. Even though CD34+ selected grafts are typically given in the context of a severely immunosuppressive conditioning with anti-thymocyte globulin or similar, the degree of T-cell depletion appears to affect clinical outcomes and thus in addition to CD34 cell recovery, the degree of T-cell depletion critically describes process quality. An automatic immunomagnetic cell processing system, CliniMACS Prodigy, including a protocol for fully automatic CD34+ cell selection from apheresis products, was recently developed. We performed a formal process validation to support submission of the protocol for CE release, a prerequisite for clinical use of Prodigy CD34+ products. METHODS: Granulocyte-colony stimulating factor-mobilized healthy-donor apheresis products were subjected to CD34+ cell selection using Prodigy with clinical reagents and consumables and advanced beta versions of the CD34 selection software. Target and non-target cells were enumerated using sensitive flow cytometry platforms. RESULTS: Nine successful clinical-scale CD34+ cell selections were performed. Beyond setup, no operator intervention was required. Prodigy recovered 74 ± 13% of target cells with a viability of 99.9 ± 0.05%. Per 5 × 10E6 CD34+ cells, which we consider a per-kilogram dose of HSCs, products contained 17 ± 3 × 10E3 T cells and 78 ± 22 × 10E3 B cells. CONCLUSIONS: The process for CD34 selection with Prodigy is robust and labor-saving but not time-saving. Compared with clinical CD34+ selected products concurrently generated with the predecessor technology, product properties, importantly including CD34+ cell recovery and T-cell contents, were not significantly different. The automatic system is suitable for routine clinical application.

Occupational hazards control of hazardous substances in clean room of semiconductor manufacturing plant using CFD analysis.

The manufacturing processes in chip industries are complex, and many kinds of raw materials and solvents of different nature are used, most of which are highly toxic and dangerous. During the machine preventive maintenance period, these toxic and harmful substances will escape from the sealed reaction chamber to the clean workshop environment and endanger the health of the workers on-site, resulting in occupational diseases. From the perspective of prevention, the spread and prediction of hydrochloric acid (HCl) that escaped from the metal-etching chamber during maintenance were studied in this article. The computational fluid dynamics technology was used for a three-dimensional numerical simulation of the indoor air velocity field and the HCl concentration field, and the simulation results were then compared with the on-site monitoring data to verify the correctness and feasibility. The occupational hazards and control measures were analyzed based on the numerical simulation, and the optimal control measure was obtained. In this article, using the method of ambient air to analyze the occupational exposure can provide a new idea to the field of occupational health research in the integrated circuit industry and had theoretical and practical significance.

Bacterial diversity in the indoor air of pharmaceutical environment.

AIMS: To monitor bacterial diversity of ISO Class 8 pharmaceutical clean room environment using conventional culture-based methods and pyrosequencing analysis. METHODS AND RESULTS: Bacterial isolates were obtained through viable particulate air monitoring, passive air monitoring and surface-monitoring procedures. A total of 157 bacterial isolates were obtained and assigned to four different phyla, Actinobacteria, Firmicutes, Proteobacteria and Deinococcus-Thermus, encompassing 52 species of 24 genera based on 16S rRNA gene sequence analysis. The genera Micrococcus and Staphylococcus were found as the main bacterial groups among the isolates. However, a big discrepancy was found between the culture based and pyrosequencing results. A total of 11 409 quality reads were obtained from the pyrosequencing analysis, and the subsequent phylogenetic analysis indicated that Proteobacteria was the most abundant group at phylum level, followed by Actinobacteria and Firmicutes. Bacillus, Propionibacterium and Acinetobacter were identified as the most abundant genera by the pyrosequencing analysis. CONCLUSIONS: The culture-based results were in line with previous reports on the airborne bacterial composition of various environments, but the pyrosequencing analysis revealed a unique diversity of bacteria in this case. No significant pathogens above Riskgroup 2 were found from either culture based or pyrosequencing studies. SIGNIFICANCE AND IMPACT OF THE STUDY: The presence of various bacterial taxa including a number of groups, whose presence in air is previously unknown, was confirmed through this analysis. The main source of bacteria in the indoor air environment of pharmaceutical processes is likely human, but no significant primary pathogens were detected. Culture-based analysis may give limited information on the bacterial diversity of air environment.

Predicting transient particle transport in enclosed environments with the combined computational fluid dynamics and Markov chain method.

To quickly obtain information about airborne infectious disease transmission in enclosed environments is critical in reducing the infection risk to the occupants. This study developed a combined computational fluid dynamics (CFD) and Markov chain method for quickly predicting transient particle transport in enclosed environments. The method first calculated a transition probability matrix using CFD simulations. Next, the Markov chain technique was applied to calculate the transient particle concentration distributions. This investigation used three cases, particle transport in an isothermal clean room, an office with an underfloor air distribution system, and the first-class cabin of an MD-82 airliner, to validate the combined CFD and Markov chain method. The general trends of the particle concentrations vs. time predicted by the Markov chain method agreed with the CFD simulations for these cases. The proposed Markov chain method can provide faster-than-real-time information about particle transport in enclosed environments. Furthermore, for a fixed airflow field, when the source location is changed, the Markov chain method can be used to avoid recalculation of the particle transport equation and thus reduce computing costs.

Blueprint for the design, construction, and validation of a plastic and phthalate-minimised laboratory.

Micro and nanosized plastics (MNPs), and a range of associated additive chemicals, have become pervasive contaminants that humans and the environment are exposed to everyday. However, one of the principal challenges in their analysis is adequate strategies to minimise background contamination. Here a blueprint for a specialised plastics and additive-minimised clean room laboratory built for this purpose is presented. Common laboratory construction materials (n = 23) were tested, including acoustic baffles, ceiling materials, floor materials, glazing rubber, and silicone sealant. The % polymer content ranged from 2-76% w/w while the sum concentration of six phthalates ranged from 0.81 (0.73-0.86) to 21000 (15000-27000) mg/kg, assigning many of these materials as inappropriate for use in a clean room environment. The final design of the laboratory consisted of three interconnected rooms, operated under positive pressure with the inner rooms constructed almost entirely of stainless steel. Background concentrations of MNPs and phthalates in the new laboratory were compared to two Physical Containment Level 2 (PC2) laboratory environments, with concentrations of MNPs reduced by > 100 times and phthalates reduced by up to 120 times. This study reports the first known clean room of its kind and provides a blueprint for reference and use by future plastics research.

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.

Case Study on the design optimization of the positive pressure operating room.

Ventilation systems of operating rooms (ORs) are significantly important in preventing postoperative wound infections that can cause morbidity and mortality after surgery in or out of the hospital. This study aims to identify the optimum overpressure for efficient operation while reducing the risk of surgical site infections (SSIs) based on the actual OR with the help of computational fluid dynamics. The species transport model, Lagrangian discrete phase model, and turbulent standard k- ε model are mainly used for the transient numerical study to improve the performance of the OR and reduce SSI cases. Four OR schemes were initially calculated for the best location of the patient on the surgical table. The results revealed that the modified position 90˚ is the best location with the minimum CO2 and BCP concentrations. The investigated operating room could host up to ten surgical members with the optimum overpressure of 5.89 Pa and 0.56 m/s of supply velocity under the standard cleanliness level. Modifying the supply surface area will enhance the performance of the operating room by providing a cleaner zone and maintaining the desired room pressure, even with a low airflow rate. This optimization scheme could guide practical applications in all positively pressurized operating rooms to address issues related to overpressure effects.

Assessment of microbial contamination in laser materials processing laboratories used for prototyping of biomedical devices.

Microbial contamination of medical devices during pilot production can be a significant barrier as the laboratory environment is a source of contamination. There is limited information on microbial contaminants in laser laboratories and environments involved in the pilot production of medical devices. This study aimed to determine the bioburden and microbial contaminants present in three laser laboratories - an ISO class 7 clean room, a pilot line facility and a standard laser laboratory. Microbiological air sampling was by passive air sampling using settle plates and the identity of isolates was confirmed by DNA sequencing. Particulate matter was analysed using a portable optical particle counter. Twenty bacterial and 16 fungal genera were isolated, with the genera Staphylococcus and Micrococcus being predominant. Most isolates are associated with skin, mouth, or upper respiratory tract. There was no significant correlation between microbial count and PM2.5 concentration in the three laboratories. There were low levels but diverse microbial population in the laser-processing environments. Pathogenic bacteria such as Acinetobacter baumannii and Candida parapsilosis were isolated in those environments. These results provide data that will be useful for developing a contamination control plan for controlling microbial contamination and facilitating advanced manufacturing of laser-based pilot production of medical devices.

Evaluation of safety and efficacy of allogeneic adipose tissue-derived mesenchymal stem cells in pediatric bronchiolitis obliterans syndrome (BoS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

BACKGROUND: Allo-HSCT is a definite approach for the management of a wide variety of lethal and debilitating malignant and non-malignant disorders. However, its two main complications, acute and chronic graft-versus-host disease (GVHD), exert significant morbidities and mortalities. BoS, as a manifestation of chronic lung GVHD, is a gruesome complication of allo-HSCT, and for those with steroid-refractory disease, no approved second-line therapies exist. Mesenchymal stem cells (MSCs) exert anti-inflammatory and growth-promoting effects, and their administration against a wide range of inflammatory and neurologic disorders, as well as GVHD, has been associated with promising outcomes. However, literature on the safety and effectiveness of MSC therapy for BoS and pediatric cGVHD is scarce. METHODS: We designed a single-arm trial to administer adipose tissue (AT)-derived MSCs to pediatric patients with refractory BoS after allo-HSCT. AT-MSCs from obese, otherwise healthy donors were cultured in an ISO class 1 clean room and injected into the antecubital vein of eligible patients with a dose of 1 × 106/kg. The primary endpoints included a complete or partial response to therapy [in terms of increased forced expiratory volume in one second (FEV1) values and steroid dose reduction] and its safety profile. RESULTS: Four eligible patients with a median age of 6.5 years were enrolled in the study. Steroid-induced osteoporosis and myopathy were present in three cases. A partial response was evident in three cases after a single injection of AT-MSCs. The treatment was safe and tolerable, and no treatment-related adverse events were noted. Two patients developed manageable COVID-19 infections one and 4 months after AT-MSC injection. After a median follow-up duration of 19 months, all cases are still alive and have had no indications for lung transplantation. CONCLUSIONS: AT-MSCs could be safely administered to our pediatric cases with BoS post-allo-HSCT. Considering their advanced stage of disease, their sub-optimal functional capacity due to steroid-induced complications, and COVID-19 infection post-treatment, we believe that AT-MSC therapy can have possible efficacy in the management of pediatric BoS. The conduction of further studies with larger sample sizes and more frequent injections is prudent for further optimization of AT-MSC therapy against BoS. Trial registration Iranian Registry of Clinical Trials (IRCT), IRCT20201202049568N2. Registered 22 February 2021, https://en.irct.ir/trial/53143 .

Processing Adipose Tissue Samples in a GMP Environment Standardizes the Use of SVF in Cell Therapy Treatments: Data on 302 Patients.

Stromal vascular fraction (SVF) cells, together with adipose-derived mesenchymal stem cells, are becoming the tool of choice for many clinical applications. Currently, nearly 200 clinical trials are running worldwide to prove the efficacy of this cell type in treating many diseases and pathological conditions. To reach the goals of cell therapies and produce ATMPs as drugs for regenerative medicine, it is necessary to properly standardize GMP processes and, thus, collection methods, transportation strategies, extraction protocols, and characterization procedures, without forgetting that all the tissues of the human body are characterized by a wide inter-individual variability which is genetically determined and acquired during life. Here, we compare 302 samples processed under GMP rules to exclude the influence of the operator and of the anatomical site of collection. The influence of variability in the ages and genders of patients, along with laboratory parameters such as total cell number, cell viability, stem cell number, and other stromal vascular fraction cell subpopulations, has been compared. The results show that when the laboratory protocol is standardized, the variability of quantifiable cell parameters is widely statistically non-significant, meaning that we can take a further step toward standardized advanced cell therapy products.

Relationship between biochemical, environmental, and microbiological changes with the success rate of fertilization techniques.

The success rate for the evaluation of the results of techniques of Assisted Human Reproduction implies the occurrence of pregnancy with a live, healthy child. There are reports of the association between chemical and unhealthy environmental air conditions (bacteria, dust, particulates and volatile compounds) and reducing the success rate of embryo production and the occurrence of pregnancy. This paper reviews available information about the interference of biochemical, environmental and microbiological changes with the success of the assisted reproductive technique.

Airborne Toluene Detection Using Metal-Organic Frameworks.

The pollution of indoor air is a major worldwide concern in our modern society for people's comfort, health, and safety. In particular, toluene, present in many substances including paints, thinners, candles, leathers, cosmetics, inks, and glues, affects the human health even at very low concentrations throughout its action on the central nervous system. Its prevalence in many workplace environments can fluctuate considerably, which led to firm regulation with exposure limits varying between 50 and 400 ppm depending on exposure time. This therefore requires the development of technologies for an accurate detection of this contaminant. Metal-organic frameworks have been proposed as promising candidates to detect and monitor a series of molecules at even extremely low concentrations owing to the high tunability of their functionality. Herein, a high-throughput Monte Carlo screening approach was devised to identify the best MOFs from the computation-ready, experimental (CoRE) metal-organic framework (MOF) density-derived electrostatic and chemical (DDEC) database for the selective capture of toluene from air at room temperature, with the consideration of a ternary mixture composed of extremely low-level concentration of toluene (10 ppm) in oxygen and nitrogen to mimic the composition of air. An aluminum MOF, DUT-4, with channel-like micropores was identified as an excellent candidate for the selective adsorption of toluene from air with a predicted adsorption uptake of 0.5 g/g at 10 ppm concentration and room temperature. The toluene adsorption behavior of DUT-4 at low equivalent concentrations, alongside its sensing performance, was further experimentally investigated by its incorporation in a quartz crystal microbalance sensor, confirming the promises of DUT-4. Decisively, the resulting high sensitivity and fast kinetics of our developed sensor highlight the applicability of this hand-in-hand computational-experimental methodology to porous material screening for sensing applications.

Multicellular Cell Seeding on a Chip: New Design and Optimization towards Commercialization.

This paper shows both experimental and in-depth theoretical studies (including simulations and analytical solutions) on a microfluidic platform to optimize its design and use for 3D multicellular co-culture applications, e.g., creating a tissue-on-chip model for investigating diseases such as pulmonary arterial hypertension (PAH). A tissue microfluidic chip usually has more than two channels to seed cells and supply media. These channels are often separated by barriers made of micro-posts. The optimization for the structures of these micro-posts and their spacing distances is not considered previously, especially for the aspects of rapid and cost-efficient fabrication toward scaling up and commercialization. Our experimental and theoretical (COMSOL simulations and analytical solutions) results showed the followings: (i) The cell seeding was performed successfully for this platform when the pressure drops across the two posts were significantly larger than those across the channel width. The circular posts can be used in the position of hexagonal or other shapes. (ii) In this work, circular posts are fabricated and used for the first time. They offer an excellent barrier effect, i.e., prevent the liquid and gel from migrating from one channel to another. (iii) As for rapid and cost-efficient production, our computer-aided manufacturing (CAM) simulation confirms that circular-post fabrication is much easier and more rapid than hexagonal posts when utilizing micro-machining techniques, e.g., micro-milling for creating the master mold, i.e., the shim for polymer injection molding. The findings open up a possibility for rapid, cost-efficient, large-scale fabrication of the tissue chips using micro-milling instead of expensive clean-room (soft) lithography techniques, hence enhancing the production of biochips via thermoplastic polymer injection molding and realizing commercialization.

Improvement of Polytetrafluoroethylene Membrane High-Efficiency Particulate Air Filter Performance with Melt-Blown Media.

Polytetrafluoroethylene (PTFE) membrane filters are widely used in low-load application areas, such as industrial cleanrooms, due to their low initial pressure drop. In this study, melt-blown (MB) nonwoven was introduced as a pre-filtration layer at the front end of a high-efficiency particulate air (HEPA) filter to improve the filter performance of the PTFE membrane. Pre-filtration reduces the average particle size, which reaches the PTFE membrane and reduces the dust load on the HEPA filters. A comparative analysis of the HEPA filters by composite MB and PTFE was conducted. Regarding the MB composite on the PTFE, low-weight and high-weight MB composites were effective in increasing dust filtration efficiency, and the dust loading capacity of the PTFE composite with high-weight MB increased by approximately three times that of the PTFE membrane. In addition, the filter was installed on an external air conditioner in an actual use environment and showed a high efficiency of 99.984% without a change in differential pressure after 120 days.