Clean Room Research Articles

Monitoring of Trace Molecular Impurities in Clean-Room Air

A new measurement system has been introduced to perform real-time measurements of molecular air contaminants at different location in a clean room down to a concentration of approximately 0.1 ppb. The system consists of an air sampling unit coupled to a proton transfer mass spectrometer and a Cavity Ring-Down Spectrometer. The measurements show that the time average concentrations of more than 10 different volatile impurity molecules exceed 1 ppb.

Evaluation of the Impact of a New Cooling Cell Processor System on Islet Cell Isolation Facility.

Standard cell therapy equipment, including the gold standard cell processor to purify human islets for clinical transplantation, is rarely refrigerated, potentially exposing cells to elevated temperatures during the centrifugation step. Custom cooling systems have a direct benefit on human islet viability and function. The current study was designed to test the effectiveness of a newly developed, readily available cooled cell processor system requiring minimal modifications and to evaluate its impact on human cell viability and the GMP cleanroom environment.The cooler system, a mechanically refrigerated heat exchanger set at -30 °C was used to deliver cooled medical grade dry air to the cell processor bowl through a hole drilled in the centrifuge cover. With the limited availability of pancreas donors in Qatar, system validation was done with continuous density gradient purification of pooled human bone marrow buffy coat. Sterility, turbulence, and particle count were measured in class C and class B clean room environments. No turbulence developed around the cooled cell processor, and no excess 0.5 µm and 5 µm airborne particulates were generated as per cleanroom GMP standards. At the beginning and end of the collection steps, the temperature rose respectively to 21.50 °C ± 0.34 °C and 21.93 °C ± 0.20 °C in the non-cooled cell processor and to only 10.9 °C ± 0.17 °C and 11.16 °C ± 0.35 °C in the cooled- cell processor (p <0.05). The cooled cell processor led to both improved recovery (98%) of the mononuclear cell fraction and viability (100% ± 2%) post-processing. The new cooling system effectively reduces the heat produced by the cell processor while having no particulate impact on the GMP clean room environment. The cooled cell processor described here is an inexpensive ($16,000 without including taxes, customs clearance, and transportation) and minimally invasive method to provide robust cooling. Currently, this technology in the GMP cell therapy facilityis being applied to human islet cell isolation and transplantation for the clinical program.

Investigation of Acinetobacter baumannii Outbreak in a Burn Unit Revealed a Surprising Environmental Source.

We describe an outbreak of Acinetobacter baumannii in a 15-bed regional burn unit in an academic tertiary care medical center, and the investigations and control measures used to halt the outbreak are described.Nine cases of A. baumannii were reported in our burn unit in a one-year period, which was higher than our expected number of two-three cases per year. Our burn unit director requested an outbreak investigation, and our hospital's infection control department investigated thoroughly and found a source for that outbreak, which was never reported as a source in the previous literature. We identified table fans as the source of this outbreak. We then developed a strict fan policy, and after implementation of the policy, and terminal cleaning of rooms, only two cases per year of A. baumannii were reported in the next three-year period. We concluded that the table fans were colonized with A. baumannii and since they were used interchangeably in all patient rooms, caused this outbreak. There are no specific joint commission guidelines for the use of fans in hospitals. While fans can be used for the comfort of the patient, we should be cautious not to spread infections.

Microplastics analytics: why we should not underestimate the importance of blank controls

Recent years have seen considerable scientific attention devoted towards documenting the presence of microplastics (MPs) in environmental samples. Due to omnipresence of environmental microplastics, however, disentangling environmental MPs from sample contamination is a challenge. Hence, the environmental (collection site and laboratory) microplastics contamination of samples during processing is a reality that we must address, in order to generate reproducible and reliable data. Here we investigated published literature and have found that around 1/5 of studies failed to use blank controls in their experiments. Additionally, only 34% of the studies used a controlled air environment for their sample processing (laminar flow, fume hood, closed laboratory, clean room, etc.). In that regard, we have also shown that preparing samples in the fume hood, leads to more microplastics > 1 μm) contamination than preparing it in the laboratory bench and the laminar flow. Although it did not completely prevent microplastics contamination, the processing of sample inside the laminar flow is the best option to reduce sample contamination during processing. Overall, we showed that blank controls are a must in microplastics sample preparation, but it is often overlooked by researchers.Graphical

Psychosocial factors predicting symptoms of depression and anxiety in allogeneic hematopoietic stem cell transplant recipients in Japan.

We explored whether a patient's psychosocial background before allogeneic hematopoietic stem cell transplantation (allo-HSCT) could predict the occurrence of psychiatric symptoms during treatment and after hospital discharge. Logistic regression analysis was performed using INTERMED, a scale that comprehensively evaluates psychological factors such as psychiatric history, current mental status, and coping skills, and social factors such as social participation status, relationships with others, and living environment, which were used as independent variables. The Center for Epidemiologic Studies Depression Scale was used to measure depression, while the Profile of Mood States was used to measure anxiety and other symptoms. Both measures were used as dependent variables and were administered upon clean room admission, during clean room stay, at clean room discharge, and at 3, 6, and 12months after hospital discharge. Participants included 70 patients (45 males and 25 females, mean age 53.3 ± 12.3years). Thirty-eight patients participated in the program for the entire period, up to 12months after hospital discharge. The total score on the Japanese version of the INTERMED and psychological factor scores assessed at baseline were significant predictors of depressed mood on discharge; however, there were no significant predictors of scores on the Profile of Mood States. A comprehensive pretransplant evaluation of psychosocial background can help predict the appearance of psychiatric symptoms after allo-HSCT. In patients who are expected to develop psychiatric symptoms after allo-HSCT, it is important to consider early intervention by a specialist and close monitoring by a medical team.

Mapping and change information between structural and behavioural domain – Behaviour prediction framework

During product development it is very important to do research in comparing the system functionality throughout its working operation and when unexpected parameters occur. In modelling of the system behaviour, the uncertain effects of the system due to the influence of the changing working environment was also considered here. The observed system was presented with its two models: structure model and behavioural model. The system structure model was represented in matrix notation with a Design Structure Matrix (DSM). The second domain of the system, i.e. its behaviour, was modelled by the Model Predictive Control (MPC) method and by studying the system stability using the second Lyapunov method. The mutual transfer of information between these two domains allows the creation of system variants suitable for working in uncertain situations. By combining the developed environment (Behaviour Prediction Framework) and its algorithm, and using existing computer tools (©LOOMEO and ©MATLAB), the research results were verified. This was done with a case study of an air handling unit used for air treatment in the food industry and clean rooms. While carrying out the simulation of the behaviour of the air conditioning system, the following facts about influential parameters were established. The most influential parameter for the systems stability was the environment temperature from −40 to −25 °C. The reason was that heat transfer coefficient was then very large. In addition, high air flow rate in range from 3.6 to 7.8 m3/s, was had also a great influence on stability. System instability was happened with smaller geometries (the cross-sectional area – height ×weight) of the air handling unit.

3D Printing‐Assisted Nanoimprint Lithography of Polymers

Fused filament fabrication, commonly referred to as 3D printing, is an additive manufacturing method finding plenty of applications nowadays. In contrast, polymer nanopatterning by nanolithographic techniques plays an important role in obtaining functional surfaces and coatings for applications in different fields including micro‐ and nanoelectronics. In spite of their relevance, additive manufacturing and polymer nanolithography have not found yet a common niche to be developed. Although both approaches are oriented to achieve different types of objects, it is shown that the confluence of both technologies can be desirable and potentially convenient. Herein, it is demonstrated that by employing conventional 3D printing, it is possible to fabricate nanostructured polymer surfaces in a relatively simple way by using similar approaches as those used in nanoimprint lithography but without the need for clean room conditions. To do that, a printed‐assisted nanoimprint lithography concept (3DPrANIL) has been tested for different types of polymer and silicon templates. It is demonstrated that a polymeric nanostructured hydrophilic template can be replicated accurately on another polymer rendering a nanostructured surface with enhanced hydrophobicity. The results support 3DPrANIL as novel method to obtain micro‐ and nanostructured surfaces with different functionalities like iridescence and hydrophobicity.

The Presence of Aromatic Substances in Incense: Determining Indoor Air Quality and Its Impact on Human Health

Indoor air quality has become a topic of great concern. Burning incense has recently been identified as one of the primary sources of volatile organic compounds, specifically benzene, in an indoor setting. The current paper aims to evaluate volatile organic compound (VOC) emissions, particularly benzene, within indoor environments through the utilization of an experimental clean room. Experimental findings showed that 10 types of incense sticks emitted benzene in concentrations between 11.1 and 66.5 μg m−3, which were 2.5 lower than the limit suggested for non-occupation indoor exposure (160 μg m−3), identified by the American Association of Industrial Hygienists (ACGIH). Furthermore, a correlation between the dimensions (diameter and length) of the combustible parts in an incense stick was investigated and indicated a slight influence on the release of benzene. Taking into consideration the substantial influence benzene has on human health, coupled with a lack of precise legislation regarding indoor air quality in residential settings, this research serves as an initial investigation into the noteworthy effects of burning incense in private and public indoor settings.

Design, development, fabrication and evaluation of the dynamics of a graphene based underwater acoustic vector sensor: A simulation and experimental study

In the last decade, the usage of underwater vector sensor has gained a lot of importance in the detection of low frequency underwater acoustic signals, as the noise level radiated by the submarine has been drastically reduced. Acoustic sensor based on Micro Electro Mechanical Systems (MEMS) technology is the recent advancement in the area of underwater acoustic vector sensors. We are reporting the design, fabrication, preliminary characterization and evaluation of the dynamics of a two-dimensional underwater acoustic vector sensor by simulation and experimental study. The vector sensor is realized using Reduced Graphene Oxide (rGO) as sensing element and Kapton as flexible substrate, to yield better sensitivity compared to the conventional acoustic vector sensor. Design of vector sensor is inspired by the biological sensing system of fish. The application of piezoresistive transduction principle and MEMS technology helps in miniaturisation and low frequency acoustic signal detection. The fabrication process is made simple, scalable and cost minimum by using the method of drop casting for the deposition of rGO on flexible substrate kapton, thereby eliminating the requirement of clean room. COMSOL Multiphysics 5.5 version is used to simulate acoustic vector sensors using polysilicon and rGO on substrates, silicon and flexible kapton respectively. The simulation results indicate that the sensitivity of rGO based acoustic vector sensor is −149.47 dB which is better in comparison with the sensitivity of −173.37 dB of conventional polysilicon vector sensor. By simulation, the natural frequency of the sensor is found to be 46.62 Hz, which closely matches with the theoretical value 41.06 Hz of the device as per the design criteria and hence, it could detect the low frequency acoustic signals. The displacement sensitivity of the fabricated sensor is found to be 0.0264 V/mm and 0.0276 V/mm for applied displacements in axial and radial directions respectively. The device is tested for its performance parameters i.e., sensitivity and directivity, by performing an acoustic test in the presence of an elastic medium, water. This test results infer that, the device is able to detect and give smooth output response for the acoustic signals in the low frequency range. The Y and X-channel receiving sensitivity exhibited by the sensor is found to be −128.04 dB to −134.93 dB and −130.61 dB to −136.78 dB respectively. Directivity pattern of the sensor is found to be in the shape of 8 with symmetry. As the device is a vector sensor, in addition to the scalar pressure measurement, it should be able to provide additional incentives such as acoustic particle displacement and acoustic particle velocity at any point in the acoustic field. In this paper, an experimental setup is made to generate deep and intermediate water waves, thereby attempting to simulate ocean conditions in the laboratory. Subsequently the numerical evaluation of the wave kinematics, i.e., fluid particle displacement and fluid particle velocity are performed by applying Airy's theory. An effort is also made to analyse the wave kinematics for various water depths, varying from Surface Water Level (SWL) till the sea bed. In this study, wave kinematics are analysed numerically by using experimental data and also by modelling Fluid-Structure Interactions in COMSOL Multiphysics environment. Our results show that the fluid flow of velocity 0.31 m/s results in fluid particle velocity of 0.125 m/s at time 0.215 s (around f = 5 Hz) by both the methods and fluid particle displacement is found to be 19.66 μm. The experimental test setup and videos are made publicly available1: 1https://sites.google.com/view/smithapaib/downloads

Noninvasive Clean Room Free Printed Piezoresistive Breath Sensor for Point of Care Application

Respiratory rate and pattern evaluation are vital parameters for clinical examination and overall assessment of the health status of an individual. Wearable and flexible real-time breath monitoring sensors are promising and advantageous tools that can help in early and quick diagnosis. This work is a single-step cost-effective, stretchable, and comfortable breath sensor with easy fabrication. The developed Laser-Induced Graphene (LIG)-based Wearable Sensor (LIG-WS) is a kirigami-structured piezoresistive-based respiratory sensor for evaluating variations in breathing patterns. This sensor utilizes the hygroscopic nature of LIG to analyze the breathing pattern and the respiratory rate. The flexible breath sensor can be attached to a surgical mask, helping to recognize various diseases, including sleep apnea, asthma, and cardiac arrest. The fabricated sensor has been tested for sensing different types of breathing patterns, such as usual, slow, shallow, and labored. A quick response time of 2.2 s is observed, and the sensitivity has been analyzed at different humidity, temperature, and touch responses. The stability of the sensor is evaluated over 30 days which demonstrated appreciable stability. The sensor has relevance in wearable breath monitoring and medical diagnostics.

Prediction of Clean-room Air-conditioning Defects Using Deep Learning and a Differential Pressure Sensor

A clean room is used for adjusting the concentration of suspended particles using an air-conditioner. It has a fan-filter unit combining a centrifugal fan and a high-efficiency particulate air filter that purifies the outside air and directly affects its cleanliness. Defects in these systems are typically detected using special sensors for each fault, which can be costly. Therefore, this paper proposes a system for diagnosing defects in the fan-filter unit using a single differential sensor and deep learning. The fan-filter unit is part of the air-conditioning system, and it is usually defective in bearings, filters, and motors. These faults include ball wear, internal bearing contamination, filter contamination, and motor speed changes. Each defect was artificially induced in experiments, and the differential pressure data of each defect was learned using a long short-term memory (LSTM) deep learning algorithm. The results of deep learning experiments generated by randomly mixing data five times were presented using a confusion matrix, and the results showed an accuracy of 87.2±2.60%. Therefore, the possibility of diagnosing defects in the fan-filter unit using a single sensor was confirmed.

COVID-19 outbreak in an acute psychiatric unit—Unique challenges and creative solutions

Background: We describe the management of a major COVID-19 outbreak in January 2022 during the SARS-CoV-2 omicron-variant winter surge involving the only inpatient psychiatric facility of Santa Clara County, California, which serves a population of 1.9 million. Methods: On January 14, 2022, infection prevention staff were notified of a symptomatic COVID-19 case in our locked inpatient psychiatric unit who had been admitted since October 2021. The index patient had no visitors or transfers outside the unit. The patients in this unit were noncompliant with masking and mingled with each other during meals. Initial testing identified 23 positive cases among 47 patients and 12 staff cases. Mitigating actions included closing the unit to new admissions, creating alternate care areas in the emergency psychiatric unit, and separating patients into “exposed but negative” and “infected” cohorts and housing them in “red,” and “yellow” zones, respectively. A “green” zone was created by clearance of positive cases. For the cohort exposed to COVID-19, masking was enforced by supervision, dining was scheduled in batches, and daily symptom screening and antigen testing were performed in addition to standard postexposure RT-PCR testing on day 4 and day 7. Mandatory N95 respirators and eye protection were implemented for staff on unit entry. Exposed staff followed employee health protocols for postexposure testing. Enhanced environmental control measures included terminal cleaning and UV-C disinfection of common areas and patient rooms and a thorough investigation of airflow. Discharged patients were contacted if they were residing in congregate facilities. Results: Of 47 patients, 39 (83%) tested positive for COVID-19. However, 8 patients remained negative; all 8 had received at least their primary vaccine series (Table 1). In total, 16 HCWs were SARS-CoV-2 positive in this outbreak. The outbreak officially ended 25 days after the first case. All SARS-CoV-2–positive patients had mild illness, not requiring treatment or hospitalization. We identified vaccine immune escape, staff presenteeism, patient noncompliance with masking, and comingling as major causes of transmission. We determined through contact tracing and temporality that the outbreak likely started from a positive staff member or visitor because most patients had been long-term residents. Conclusions: This outbreak was challenging due to the specialized behavioral needs of the involved patients. It was imperative to reopen this unit quickly and safely to provide psychiatric care to our county’s most vulnerable patients. Ongoing PPE education, repeated reinforcement, engagement in staff wellness to combat pandemic fatigue, and aggressive vaccination are all crucial to minimizing the impact of future outbreaks.Disclosures: None

Risk factors for the transmission of Clostridioides difficile or methicillin-resistant Staphylococcus aureus in acute care

Background: Some hospitals continue to struggle with nosocomial transmission of Clostridioides difficile infection (CDI) and methicillin-resistant Staphylococcus aureus (MRSA) despite years of infection control efforts. We investigated the relationship between unit infrastructural–organizational risk factors and nosocomial transmission of CDI and MRSA. Methods: This retrospective observational study included 100 eligible acute-care inpatient units from 12 hospitals in British Columbia, Canada, from April 1, 2020, to September 16, 2021. The outcome variables included whether a unit was on the CDI or MRSA vulnerable unit list (ie, defined as having ≥5 CDI cases or ≥6 MRSA cases being attributed to the unit in the last 6 fiscal periods), the average CDI/MRSA rate, as well as the average CDI/MRSA standardized infection ratio (SIR). Independent variables included, but were not limited to, infection control factors (eg hand hygiene rate), infrastructural factors (eg, unit age, total beds on unit), and organizational factors (eg, hallway bed utilization, nursing overtime). Multivariable regression was performed to identify statistically significant risk factors using SAS, R Studio, and Stata software. Results: For CDI, older units were associated with higher odds of being on the CDI vulnerable unit list (aOR, 1.086; 95% CI, 1.024–1.175), higher CDI rate (adjusted relative risk [aRR], 0.012; 95% CI, 0.004–0.020), and higher CDI SIR (aRR, 0.011; 95% CI, 0.003–0.020). Larger unit size was associated with higher odds of being on the CDI vulnerable unit list (aOR, 1.210; 95% CI, 1.095–1.400) and higher CDI SIR (aRR, 0.013; 95% CI, 0.001–0.026). For MRSA, an increase in hand hygiene rate was associated with lower odds of being on the MRSA vulnerable unit list (aOR, 0.71; 95% CI, 0.53–0.897), lower MRSA rate (aRR, −0.035; 95% CI, −0.063 to −0.008), and lower MRSA SIR (aRR, −0.039; 95% CI, −0.069 to −0.008). Higher MRSA bioburden was associated with higher odds of being on the MRSA vulnerable unit list (aOR, &gt;999; 95% CI, &gt;999 to &gt;999), higher MRSA rate (aRR, 9.008; 95% CI, 5.586–12.429), and higher MRSA SIR (aRR, 4.964; 95% CI, 1.971–7.958). Additionally, higher MRSA rates were associated 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 having a clean supply room with the door consistently closed (aRR, −0.283; 95% CI, −0.536 to −0.03). Conclusions: Several infrastructural and organizational factors were associated with nosocomial transmissions of CDI and MRSA. Further research is needed to investigate the mechanisms by which these factors are associated.Disclosures: None

The “LED‐version” of the electron gun

SummaryWe report on our progress to develop and optimize electron sources for practical applications. A simple fabrication process is introduced based on a wafer dicing saw and a wet chemical etch step without the need for a clean room. Due to the formation of crystal facets the samples show a homogeneous geometry throughout the array. Characterization techniques are developed to systematically compare various arrays. A very defined measurement procedure based on current controlled IV‐sweeps as well as lifetime measurements at various currents is proposed. To investigate the current distribution in the array a commercial CMOS detector is used and shows the potential for in depth analysis of the arrays. Finally, a compact hermetically sealed housing is presented enabling electron generation in atmospheric pressure environments.

Self-assembled ultraflexible probes for long-term neural recordings and neuromodulation.

Ultraflexible microelectrode arrays (MEAs) that can stably record from a large number of neurons after their chronic implantation offer opportunities for understanding neural circuit mechanisms and developing next-generation brain-computer interfaces. The implementation of ultraflexible MEAs requires their reliable implantation into deep brain tissues in a minimally invasive manner, as well as their precise integration with optogenetic tools to enable the simultaneous recording of neural activity and neuromodulation. Here, we describe the process for the preparation of elastocapillary self-assembled ultraflexible MEAs, their use in combination with adeno-associated virus vectors carrying opsin genes and promoters to form an optrode probe and their in vivo experimental use in the brains of rodents, enabling electrophysiological recordings and optical modulation of neuronal activity over long periods of time (on the order of weeks to months). The procedures, including device fabrication, probe assembly and implantation, can be completed within 3 weeks. The protocol is intended to facilitate the applications of ultraflexible MEAs for long-term neuronal activity recording and combined electrophysiology and optogenetics. The protocol requires users with expertise in clean room facilities for the fabrication of ultraflexible MEAs.

Evaluation of a tabletop UV-LED device for disinfection of smart devices and tools

Smart devices and tools, which are transferred into clean rooms, have a risk of surface contamination. Chemical disinfection can harm such devices and the process is prone to error due to the manual procedure. Therefore, a UVC-LED based disinfection device was developed, which can inactivate almost all kind of pathogens. The disinfection efficiency was investigated on 3 test surfaces (stainless steel, plastic, glass), each with 5 different types of pathogens (S. aureus, P. aeruginosa, A. brasiliensis-spores, B. subtilis-spores, Pae. glucanolyticus-spores). The tabletop device is capable of significant inactivation rates between 2 and 8 log10 depending on the type of pathogen in less than 10 min. For the first time, we report that Pae. glucanolyticus-spores can be inactivated with UV-LEDs. Furthermore, we report that the type of surface material does have an impact on the disinfection performance. We assume that it is related to the surface roughness of the different materials combined in conjunction with the size of the microorganisms. The novel UV-LED disinfection device has the potential to become a routine device for bringing tablets and other electronical devices into cleanrooms.

Effects of light-guided nudges on health care workers' hand hygiene behavior

Hospital-acquired infectionsare the most frequent adverse events in health care and can be reduced by improving thehand hygiene compliance (HHC) of health care workers (HCWs). We aimed to investigate the effect of nudging with sensor lights on HCWs' HHC. An 11-month intervention study was conducted in 2 inpatient departments at a university hospital. An automated monitoring system (Sani NudgeTM) measured theHHC. Reminder and feedback nudges with lights were displayed on alcohol-based hand rub dispensers. We compared the baseline HHC with HHC during periods of nudging and usedthefollow-up data to establishif a sustained effect had been achieved. A total of 91 physicians, 135 nurses, and 15 cleaning staff were enrolled in the study. The system registered 274,085 hand hygiene opportunities in patient rooms, staff restrooms, clean rooms, and unclean rooms. Overall, a significant, sustained effect was achieved by nudging with lights in relation to contact with patients and patient-near surroundings for both nurses and physicians. Furthermore, a significant effect was observed on nurses' HHC in restrooms and clean rooms. No significant effect was found for the cleaning staff. Reminder or feedback nudges with light improved and sustained physicians' and nurses' HHC, and constitute a new way of changing HCWs' hand hygiene behavior.

Revisiting the question of endolymphatic therapy

Lymphotropic therapy was the first step in the development of endolymphatic therapy. Lymphotropic therapy was carried out by creating a subcutaneous depot of a contrast agent or injecting the drug directly into the lymph node. The next step was the introduction of the drug into the lymphatic system by a single puncture of the peripheral lymphatic vessel. After G. V. Bondar put his idea into action by making a special tool, it became possible to do long-term endolymphatic infusion.&#x0D; Lymphatic catheterization is performed in a clean operating room. Catheterization of the thigh lymphatic vessels is the most common technique. A network of superficial lymphatic vessels extends from the medial edge of the sartorius muscle into the subcutaneous fat, reaching the lower superficial inguinal lymph nodes. The deep lymphatic vessels of the thigh are adjacent to the femoral vein. The use of a longitudinal or longitudinal-oblique skin incision is preferable. The benefits of this access are that lymphatic vessels can be catheterized more than once during chemotherapy and wounds heal faster because the skin is cut along the fibers instead of across them.&#x0D; When comparing endolymphatic and intravenous methods of administration of platinum group chemotherapy drugs in combination with fluorouracil or methotrexate in 289 patients with T3N0-1 M0-1 ovarian cancer, the vast majority of whom had serous adenocarcinomas (85.62±2.77 and 84.93±3.17), a significantly higher frequency of complete and partial regressions was registered (59.63±3.87%) with the endolymphatic technique than with intravenous administration (32.03±4.14%).&#x0D; Endolymphatic chemotherapy with fluorouracil 700–800 m g/m daily for 5 days in combination with intravenous administration of doxorubicin 40 mg/m in the treatment of patients with advanced, inoperable gastric cancer (n=33) increased overall efficacy to 39.4%±8.5% when compared to patients (n=32) who received the same drugs intravenously (12.5%±5.84%). The compared groups had significantly different median survival (35 and 19 weeks) and life expectancy (41.3±4.4 and 23.8±3.4 weeks).&#x0D; The endolymphatic administration of cytostatics, which demonstrates less toxicity compared to the intravenous one, has the right to exist and the potential to further develop improved techniques of administration.

Predictive stability, novel HPLC-MS analysis and semi-automatic compounding process for the emergency implementation of a production line of pancuronium in injectable solution.

During the early months of the COVID-19 pandemic, the international medical product supply chain was tight, causing breaks in the availability of neuromuscular blocking agents essential for the treatment of patients in intensive care units. The present study describes the pharmaceutical development of an injectable 2 mg/mL solution of pancuronium bromide (PC) in a very short lapse of time. The sterile solution was compounded into a good manufacturing practice grade A clean room, filtered (0.2 µm) and filled into 10 mL type I glass, manually sealed with bromobutyl rubber stoppers. A novel HPLC-MS stability indicating method for pancuronium quantification and its degradation product was developed and validated. This fast, sensitive and straightforward method was used to study the stability of the formulation using a semi-predictive method, enabling a very fast attribution of a temporary shelf-life, which was confirmed by a classic prospective stability study. The production line and the analytical tools set-up were performed in six weeks and the semi-predictive stability study was conducted in 90 days, allowing us to predict a shelf life, which was successfully confirmed by prospective study. In conclusion, using innovative methods, we were able to rapidly overcome the shortage of a critical drug.

Microfluidics based bioimaging with cost-efficient fabrication of multi-level micrometer-sized trenches.

Microfluidic devices, through their vast applicability as tools for miniaturized experimental setups, have become indispensable for cutting edge research and diagnostics. However, the high operational cost and the requirement of sophisticated equipment and clean room facility for the fabrication of these devices make their use unfeasible for many research laboratories in resource limited settings. Therefore, with the aim of increasing accessibility, in this article, we report a novel, cost-effective micro-fabrication technique for fabricating multi-layer microfluidic devices using only common wet-lab facilities, thereby significantly lowering the cost. Our proposed process-flow-design eliminates the need for a mastermold, does not require any sophisticated lithography tools, and can be executed successfully outside a clean room. In this work, we also optimized the critical steps (such as spin coating and wet etching) of our fabrication process and validated the process flow and the device by trapping and imaging Caenorhabditis elegans. The fabricated devices are effective in conducting lifetime assays and flushing out larvae, which are, in general, manually picked from Petri dishes or separated using sieves. Our technique is not only cost effective but also scalable, as it can be used to fabricate devices with multiple layers of confinements ranging from 0.6 to more than 50 m, thus enabling the study of unicellular and multicellular organisms. This technique, therefore, has the potential to be adopted widely by many research laboratories for a variety of applications.