Vent Filter Research Articles

Hollow-fibre infection model: adaptations for the culture and assessment of fastidious organisms.

The hollow-fibre infection model (HFIM) is a valuable in vitro platform for emulating antimicrobial drug pharmacokinetic profiles. Despite its potential, standardized protocols for HFIM operation, especially concerning fastidious organisms, are lacking. This study addresses this gap by examining challenges in culturing Pasteurella multocida and Actinobacillus pleuropneumoniae, two fastidious organisms, in the HFIM. Our findings reveal effective strategies to prevent system clogging, involving multiple freeze-thaw cycles of horse blood, centrifugation and cell straining to enhance the clarity of the Mueller-Hinton fastidious medium defined by the European Committee on Antimicrobial Susceptibility Testing and Clinical and Laboratory Standards Institute. Additionally, we propose that the provision of a CO2 atmosphere, along with the utilization of gas-permeable tubing and gas vent filters, significantly facilitates the growth of fastidious organisms. Remarkably, both P. multocida and A. pleuropneumoniae were sustained for a period of up to 10 days under these optimized conditions. This study provides crucial insights into the modifications necessary to successfully culture fastidious organisms in the HFIM, paving the way for more accurate and representative in vitro models for antimicrobial drug testing. These advancements hold promise for advancing research in the field of antimicrobial pharmacokinetics and efficacy against challenging pathogens.

Pore Forming Agent–Assisted Fabrication of Porous Platinum Vent Frits and Their Suitability Evaluation for Radioisotope Power Sources

Disc-shaped porous platinum sintered frits were fabricated employing a pore forming agent (PFA) via a powder-metallurgical process. Porous vent frits using several platinum-PFA compositions were prepared after characterizing the starting materials (platinum and PFA powders) for particle size (D50) and distribution (D10 to D90), morphology, Brunauer-Emmet-Teller surface area, density (apparent and tap), etc. The sintered platinum vent frits were extensively characterized to evaluate their suitability for application in terms of surface microstructure analysis by scanning electron microscopy, helium/air permeability parameters, and particulate filtration characteristics. This paper reports for the first time on the measurement of retention efficiency of vent frits for particulate sizes 0.3, 0.5, and 1 µm. The platinum frits made using 10 and 20 vol % PFA were found to be suitable as a vent hole filter for radioisotope power sources.

Development of a transportable single-use biomanufacturing system for therapeutic phage preparations

Background: The worldwide antibiotic crisis has led to a renewed interest in phage therapy. Lytic phages against bacterial pathogens can be isolated from the environment or selected from a collection in a matter of days. Product discovery costs are very low, but conventional biopharmaceutical production of phages is lengthy, complex and costly. In addition, phage treatment in low-income countries with poor infrastructure, battlefields, healthcare emergency situations (e.g. the 2012 foodborne E. coli 0104:H4 outbreak in Germany) demands a fast, global and decentralized access to phages. To address this demand, we developed a single-use, pre-sterilised, portable and closed biomanufacturing platform for therapeutic phage preparations. Methods & Materials: The basic components of this platform are as follows: a stacked bioreactor vessel with an adaptable number of chambers, in which the host bacterial strain, phage seed, culture medium (soft agar overlay technique) and extraction buffer are injected, is connected to (a) a cascade of clarification, purification and sterilisation filters, (b) phage vent filters, (c) tubings and connectors and (d) a filling system to dispense the final phage suspension into recipients. The following devices are necessary: a peristaltic pump, a fridge, a shaker and an incubator. Twenty-four different prototype assemblies for the production of Pseudomonas aeruginosa phages were tested. The following parameters were measured: pressure in function of volumetric throughput, phage yield and titre, endotoxin level, pH and assembly integrity (leaks). Results: The most suitable of the 24 tested prototype assemblies (presented at the conference) allowed for the production of 1-200 L (per bioreactor chamber) of phage suspension at a concentration of 107 pfu/ml with endotoxin levels and pH compatible with intravenous (IV) application, and this in 24 to 36 h. Conclusion: We developed a small-scale, portable and disposable biomanufacturing platform that allows for bacterial infection treatment at point-of-care, in short time frames, and at low cost, especially useful in remote locations with limited infrastructure since it does not necessarily require a cleanroom environment. MM and HVR contributed equally to this work. Funding: Grant HFM 15-5 of the Royal Higher Institute for Defense.

The in vitro and in vivo investigation of a novel small chamber dry powder inhalation delivery system for preclinical dosing to rats

Purpose: This research describes a novel “minitower” dry powder delivery system for nose-only delivery of dry powder aerosols to spontaneously breathing rats.Methods: The minitower system forces pressurized air through pre-filled capsules to deliver aerosolized drug to four nose ports; three of which house spontaneously breathing rats, with the fourth used as a control. Within each port are vent filters which capture drug that was not inhaled for further quantitation. These vent filters along with a novel control system referred to as the “artificial rat lung”, allow for the theoretical amount of drug delivered and subsequently inhaled by each rat to be calculated.Results: In vitro and in vivo studies have demonstrated this system’s ability to deliver aerosolized drug to rats. The in vitro study showed that ∼30% of the starting dose reached the 4 ports and was available for inhalation. During in-vivo studies, rats inhaled ∼34% of the delivered dose. Of the estimated inhaled dose, 12–18% was detectable in the various tissue samples, with over 30% of the recovered dose found in the rat’s lungs.Conclusion: Results show that this system is capable of reproducibly delivering drug to the lungs of spontaneously breathing rats. Advantages over current delivery methods include being amenable to the administration of multiple doses and using less (milligram) amount of starting material. In addition, this technique avoids anesthesia which is typically required for instillation or insufflation, and thus has the potential as an efficient and noninvasive aerosol delivery method for preclinical drug development.

Cigarette Design Features in Low-, Middle-, and High-Income Countries

Previous studies have shown that country income grouping is correlated with cigarette engineering. Cigarettes (N = 111 brands) were purchased during 2008–2010 from 11 low-, middle-, and high-income countries to assess physical dimensions and an array of cigarette design features. Mean ventilation varied significantly across low- (7.5%), middle- (15.3%), and high-income (26.2%) countries (P ≤ 0.001). Differences across income groups were also seen in cigarette length (P = 0.001), length of the tipping paper (P = 0.01), filter weight (P = 0.017), number of vent rows (P = 0.003), per-cigarette tobacco weight (P = 0.04), and paper porosity (P = 0.008). Stepwise linear regression showed ventilation and tobacco length as major predictors of ISO tar yields in low-income countries (P = 0.909, 0.047), while tipping paper (P < 0.001), filter length (P < 0.001), number of vent rows (P = 0.014), and per-cigarette weight (P = 0.015) were predictors of tar yields in middle-income countries. Ventilation (P < 0.001), number of vent rows (P = 0.009), per-cigarette weight (P < 0.001), and filter diameter (P = 0.004) predicted tar yields in high-income countries. Health officials must be cognizant of cigarette design issues to provide effective regulation of tobacco products.

(Invited) Integrated Perfusion Culture Microchamber Array Chip for High-Throughput Drug Dose Response Assay

We report a perfusion culture microchamber array chip for high throughput drug dose response assays. The microchamber array chip was equipped with a serial dilution microfluidic network for generating a logarithmic concentration profile. Cell suspension, drug solution and media were introduced into the liquid reservoir with a micropipette. The dose response assay was carried out by applying the appropriate pressure through the air vent filters. The dose response of a model anti cancer drug, paclitaxel, on HeLa cells were successfully evaluated by the fluorescent image analysis in the microchamber array chip. Also, the accuracy of our microchamber array chip was confirmed to be equivalent to conventional assay plates in dose response assays. The perfusion culture microchamber array chip, with its simple interface and well-designed microfluidic network, will likely become an advantageous platform for future cell-based assay on microchips.

Identification of Device Malfunction in Patients Supported With the HeartMate XVE Left Ventricular Assist System

Predicting end-of-life for left ventricular assist devices is important to determine timing of device removal. A retrospective analysis was performed on 46 patients undergoing implantation of the latest HeartMate XVE from July 1, 2003, through March 31, 2006. Devices were assessed by analysis of motor current waveforms and quantification of the titanium or copper particles within dust localized to the driveline vent filter by optical, polarized light, scanning electron microscopy, and energy dispersive x-ray spectroscopy. Assessments were performed monthly for patients supported > or =330 days or for unexpected device alarms. Thirty-one (67%) patients were supported for <330 days and 15 (33%) were supported for > or =330 days. No malfunctions occurred in patients supported <330 days. For patients supported > or =330 days, five had abnormal current waveforms or copper and titanium dust localized to the vent filter. One underwent urgent transplantation, three underwent device replacement (one death; two ongoing), and one is with ongoing support. Of the remaining 10 patients, seven underwent transplantation; two remain on device; and one died while on left ventricular assist device support. There were no unexpected device failures. Bearing wear of the HeartMate XVE is predictable by analysis of current waveforms or titanium and copper dust within the vent filter.

HeartMate XVE malfunction caused by fluid aspiration into the vent port

therapy in patients with advanced heart failure. 1 Malfunction of the LVAD, however, might significantly reduce the survival benefit it incurs. Seven of 41 deaths in patients with LVADs in the REMATCH trial (Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure) were attributed to device malfunction. 1 We present the case of a patient who had an unusual device complication. Fluid was aspirated into the vent port, resulting in the malfunction of the device and a clinical emergency. A treatment algorithm for this challenging problem is described. Clinical Summary A 55-year-old man (6'5, 183 lb) with idiopathic dilated cardiomyopathy had a HeartMate XVE (Thoratec Corp, Pleasanton, Calif) LVAD system implanted. He was convalescing on a stepdown ward 3 weeks postoperatively, with stable LVAD flows of between 5 and 6 L/min. The patient was incontinent of urine at 5 AM on the day of the event. Urine was aspirated into the LVAD vent port. The low flow and power limit advisory alarms of the LVAD activated. The low flow persisted, and the patient became hemodynamically unstable. The vent filter was immediately removed, and the patient was placed on his right side, enabling fluid drainage from the vent port. A dry towel was also used to absorb the remaining fluid at the vent port. After several minutes in this position, the alarms stopped, and the LVAD flow returned to previous levels. A new vent filter was placed, and the patient’ s condition remained stable. The patient experienced the same malfunction again at 9 AM. The device then stopped, and hand pumping was initiated. Electrical activation was not possible. The patient was systemically anticoagulated. He was transferred to the intensive care unit, and arterial line and pulmonary artery catheters were placed for monitoring. The system controller and power source were removed, and the LVAD was successfully activated with the older pneumatic HeartMate driver. This driver was used with a pressurelimiting device on the pneumatic driveline to avoid injury to the electric pump, as recommended by the company. The pneumatic driver rate was increased to 90 beats/min. The patient, however, remained in shock, and respiratory distress ensued. He was mechanically ventilated, and inotropic infusions were initiated to enhance native ventricular function. Despite these maneuvers, the patient was hypotensive, with a central venous pressure of 22 mm Hg and a cardiac output of 2.3 L/min, as measured with the pulmonary artery catheter and the thermodilution method. Metabolic acidosis was present on the arterial blood gases. The arterial pressure tracing suggested poor LVAD stroke volume, and native ventricular ejection confirmed incomplete ventricular unloading by the pneumatically driven HeartMate LVAD. A decision was made to replace the LVAD surgically at 11 AM given the patient’ s persistent shock state. At this point, a final attempt was made to reactivate the pump electrically. Fortunately, the pump could be electrically activated and subsequently functioned without alarms. The patient’ s hemodynamics rapidly normalized: central venous pressure was 8 mm Hg, and cardiac output increased to 5.3 L/min. The need to surgically replace the pump was averted. The device continued to function electrically without

Novacor® LVAS Long-Term Performance

Since the first implant in 1993 of the Novacor wearable left ventricular assist system (LVAS), median implant durations worldwide have increased from 93 days (max 2.2 yrs) to 180 days (max 4.1 yrs) in January 2001. In vitro reliability/durability testing of the Novacor LVAS previously demonstrated a mean time to failure of 4.2 (3.04–5.59) years and revealed a single failure mode - bearing wear - with measurable and gradual symptoms before degradation of pump function. These symptoms, which may allow anticipation of the failure mode in the clinical setting using available noninvasive measures, are: 1) downward trend in position sensor signals; 2) downward drift followed by increase in energy requirement; 3) cyclical variation in sensor tuning; 4) trace metallic particulate deposits on the vent tube filter; and, ultimately, 5) isolated incomplete ejections (premature unlatch or misfire) increasing in frequency with further wear. The clinical experience with long-term implantation is consistent with in vitro reliability/durability tests. The following table compares the clinical experience (observation of two or more of the symptoms) with the results of the in vitro study.TableIn conclusion, the clinical experience parallels that of the in vitro study, showing that the wear mechanism is measurable and gradual.

Autoclave Inactivation of Infectious Radioactive Laboratory Waste Contained Within A Charcoal Filtration System

A model system was developed previously for disposal of solid laboratory waste that is both radioactive and heat sensitive, e.g., HIV. A double polypropylene bag with charcoal vent filter and absorbent was designed to meet requirements for both steam sterilization and disposal as solid radioactive waste. Earlier work demonstrated the effective containment of radioactive gases by the filter and inactivation of organisms as heat sensitive as HIV. We sought to broaden the application of this model to ensure inactivation of microorganisms that are more heat resistant than HIV. The efficacy of steam sterilization using water or solutions of iodophor, hypochlorite, or hydrogen peroxide was studied under constant temperature and time conditions. The systems were monitored with internal probes, physical, chemical, and biological indicators. Biological indicators documented inactivation when bags containing hydrogen peroxide (3%) were autoclaved for 60 min at 121 degrees C. Synergistic activity between hydrogen peroxide and autoclave conditions significantly reduced processing time.

Sterility Test Systems for Product Recovery

When presterilized, closed canister, membrane filter units for sterility testing are validated for process, large volumes of therapeutic products for injection can be tested for sterility, recovered, and added to a subsequent bulk prior to sterile filtration. Intermittent positive pressure, applied to the canisters through the vent filters, makes possible the relatively rapid filtration, with minimal foaming, of viscous solutions such as 25% (w/v) normal serum albumin (human). Canister systems appear to be at least as effective as the standard membrane filter method, and the canisters are particularly suited to the sterility testing of bulks.

Microbiological hazard from the exhaust of a high-vacuum sterilizer.

Data are presented which show the potential for release of viable microorganisms into the atmosphere from high-vacuum steam sterilizers during the evacuation cycle preceding application of steam under pressure. Bacillus subtilis var. niger spores, Serratia marcescens cells, and T1 coliphage disseminated into the sterilizer chamber as small particles from liquid suspensions, and dried spores of B. subtilis var. niger distributed on bulk discard materials were recovered from the atmosphere around pipes venting steam from the steam ejectors used to create chamber vacuum. Evaluation of the hazard involved is discussed, and the design, fabrication, and installation of a valved filter system for preventing release of viable microorganisms are presented. The filtration system utilized an F-700 water-resistant filter and was shown to eliminate the release of viable airborne microorganisms from a high-vacuum sterilizer. A method is presented for determining size requirements for an atmospheric vent filter in relation to the volume of a sterilizer.