A compression transmission device for the evaluation of bonding strength of biocompatible microfluidic and biochip materials and systems.

Bonding of a variety of inorganic and organic polymers as multi-layered structures is one of the main challenges for biochip production even to date, since the chemical nature of these materials often does not allow easy and straight forward bonding and proper sealing. After selection of an appropriate method to bond the chosen materials to form a complex biochip, function and stability of bonding either requires qualitative burst tests or expensive mechanical multi-test stations, that often do not have the right adaptors to clamp biochip slides without destruction. Therefore, we have developed a simple and inexpensive bonding test based on 3D printed transmission elements that translate compressive forces via manual compression, hand press or hydraulic press compression into shear and tensile force. Mechanical stress simulations showed that design of the bonding geometry and size must be considered for bonding tests since the stress distribution thus bonding strength heavily varies with size but also with geometry. We demonstrate the broad applicability of our 3D printed bonding test system by testing the most frequent bonding strategies in combination with the respective most frequently used biochip material in a force-to-failure study. All evaluated materials are biocompatible and used in cell-based biochip devices. This study is evaluating state-of-the-art bonding approaches used for sealing of microfluidic biochips including adhesive bonding, plasma bonding, solvent bonding as well as bonding mediated by amino-silane monolayers or even functional thiol-ene epoxy biochip materials that obviate intermediate adhesive layers.

Characterization of four functional biocompatible pressure-sensitive adhesives for rapid prototyping of cell-based lab-on-a-chip and organ-on-a-chip systems.

In the advent of affordable photo- and soft-lithography using polydimethylsiloxane (PDMS), low cost multi-step microfabrication methods have become available to a broad scientific community today. Although these methods are frequently applied for microfluidic prototype production in academic and industrial settings, fast design iterations and rapid prototyping within a few minutes with a high degree of flexibility are nearly impossible. To reduce microfluidic concept-to-chip time and costs, a number of alternative rapid prototyping techniques have recently been introduced including CNC micromachining, 3D printing and plotting out of numeric CAD designs as well as micro-structuring of thin PDMS sheets and pressure sensitive adhesives. Although micro-structuring of pressure sensitive adhesives promises high design flexibility, rapid fabrication and simple biochip assembly, most adhesives are toxic for living biological systems. Since an appropriate bio-interface and proper biology-material interaction is key for any cell chip and organ-on-a-chip system, only a limited number of medical-grade materials are available for microfluidic prototyping. In this study, we have characterized four functional biomedical-grade pressure sensitive adhesives for rapid prototyping (e.g. less than 1 hour) applications including structuring precision, physical and optical properties as well as biocompatibilities. While similar biocompatibility was found for all four adhesives, significant differences in cutting behavior, bonding strength to glass and polymers as well as gas permeability was observed. Practical applications included stability testing of multilayered, membrane-integrated organ-on-a-chip devices under standard cell culture conditions (e.g. 2-3 weeks at 37 °C and 100% humidity) and a shear-impact up to 5 dynes/cm2. Additionally, time- and shear-dependent uptake of non-toxic fluorescently labelled nanoparticles on human endothelial cells are demonstrated using micro-structured adhesive-bonded devices. Our results show that (a) both simple and complex microdevices can be designed, fabricated and tested in less than 1 hour, (b) these microdevices are stable for weeks even under physiological shear force conditions and (c) can be used to maintain cell monolayers as well as 3D cell culture systems.

[Tracheal bronchus and contralateral pneumonectomy]. / Trachealer Bronchusabgang und kontralaterale Pneumonektomie.

One-lung ventilation is a standard procedure for many types of lung surgery. The anesthesiologist can be challenged if unknown anomalies of the bronchial tree occur. We report a patient with a tracheal bronchus on the right side presenting for left pneumonectomy, and present one possible solution to airway management.

Sensory integration intervention: historical concepts, treatment strategies and clinical experiences in three patients with succinic semialdehyde dehydrogenase (SSADH) deficiency.

This paper is a review of clinical experiences providing developmental therapy services for three boys diagnosed with paediatric neurotransmitter disease. The clinical presentation of paediatric neurotransmitter diseases might parallel other diagnostic characteristics seen in a typical paediatric therapy clinic (i.e. hypotonia, motor and cognitive delays, coordination, expressive speech, and ocular motor difficulties.) From the clinical perspective of the author, sensory integrative function is but one aspect of a thorough evaluation and treatment plan for all patients. The manifestations of sensory integration dysfunction (SID), also known as sensory processing dysfunction (SPD), can occur alone or be concurrent with a variety of known medical, behavioural and neurological diagnoses. These manifestations of SPD can include, but are not limited to: hypotonia, hyperactivity, irritability, distractibility, attention difficulties, learning difficulties, clumsiness and incoordination, instability, poor motor skills, social-emotional difficulties, and behavioural problems. This paper summarizes the theory and practice applications of sensory integration. The author discusses clinical experiences providing occupational therapy services utilizing sensory integration methods and strategies with clients who were eventually diagnosed with SSADH deficiency.

Nutrient balances as indicators for sustainability of broiler production systems.

1. Flock balances of nitrogen, phosphorus, zinc and copper (N, P, Zn, Cu) were calculated in order to evaluate environmental effects of three different broiler production systems (intensive indoor, free range and organic). 2. Nutrient gain in birds per unit nutrient intake (retention) in intensive indoor production was higher than in free range and organic production. 3. Nutrient surplus relative to nutrient retention was higher in organic production than in free range and intensive indoor production. 4. The main reasons for differences in nutrient efficiency between intensive indoor, free range and organic production were duration of growth period, strain of broilers and feeding strategy. 5. The calculation of whole farm indicators (livestock density, N and P excretions per hectare of farmland) demonstrates how defining system boundaries affects the outcome of an evaluation: organic farms had the smallest livestock densities and the lowest N and P excretions per hectare of farmland. 6. In the efforts to reach a more holistic evaluation of agricultural production systems, the definition of adequate system boundaries must be discussed. In addition to nutrient balances, further indicators of sustainability, such as human and ecological toxicity, should be considered.

Comparison of the effects of IL-1 alpha and TNF-alpha on phagocyte accumulation and murine antibacterial immunity.

IL-1 and TNF both are reported to increase host antibacterial resistance. To directly compare their effects on tissue phagocyte accumulation and antibacterial activity, we infused recombinant human IL-1 alpha and TNF-alpha into C3H/HeJ mice. Although IL-1, at a dose of 1 microgram/day, did not significantly elevate blood neutrophil concentrations, it increased the number of PMNs within the spleen three to fourfold within 2 days. Similar neutrophil accumulation also occurred in the lungs, bone marrow, and liver of treated animals without detectable changes in macrophage numbers. IL-1 also increased myelopoiesis in the spleen by Days 3-4 of infusions. The capacity of splenocytes from IL-1-treated animals to kill Listeria monocytogenes in vitro and to suppress listeria proliferation in vivo after the intravenous infusion of bacteria both rose in parallel with PMN accumulation. Comparable doses of TNF also enhanced listeria killing in vivo but in contrast to IL-1, it significantly depressed peripheral blood neutrophil counts, and inhibited splenic neutrophil accumulation and in vitro listericidal activity in listeria-infected mice. Our results suggest that IL-1 enhances host resistance to infection by increasing tissue neutrophil accumulation while TNF protects by a different mechanism, despite a net inhibitory effect on neutrophil accumulation.

Characterization of the pattern of inflammatory cell influx and cytokine production during the murine host response to Listeria monocytogenes.

To examine the physiologic mechanisms responsible for enhanced antibacterial activity during infection with Listeria monocytogenes (LM), we developed an in vitro assay for quantifying leukocyte anti-listerial activity (LAA) in spleen and bone marrow. When LAA was serially measured in C57B1/6 (B6) mice infected i.v. with LM, two distinct phases of response were observed. Splenic LAA increased four- to fivefold during the first 2 days after i.v. infusion of LM (from 2.4 +/- 1.8 U/spleen before infection to 11.8 +/- 2.4, p less than 0.01), dropped significantly on days 3 to 4, and increased again to similar levels from days 5 to 7. A fall in bone marrow activity from the 3.5 +/- 1.5 to 1.6 +/- 0.7 U/mouse (two femurs) coincided with the initial rise in splenocyte activity, and was followed by a gradual return to base line. Bacterial containment in vivo correlated well with splenic LAA in vitro. Carbonyl iron pretreatment of cells from both normal and LM-infected animals ablated LAA, suggesting the effectors were phagocytic. LAA in normal spleens was unaffected by 400 rad; LAA of normal marrow as well as splenocyte and marrow cell suspensions obtained 2 days after LM infection was markedly reduced by this dose of irradiation. Quantitative studies of spleen composition revealed a 10-fold increase in polymorphonuclear neutrophils between day 0 and day 2 followed by a marked decrease on day 3; this pattern closely resembled the changes in LAA observed during the same period. In contrast, splenic macrophage number did not increase from base line until after day 3. To look for evidence of changes in the efficiency of bacterial killing by phagocytes during infection, we calculated LAA/splenic phagocyte. The efficiency of killing increased threefold over base line within 1 day after LM infusion but we detected no additional increases later in infection. Because cytokines may have mediated some or all of the changes observed, we measured the capacity of splenocytes obtained at various times after infection to produce IL-2, TNF, and IFN-gamma in vitro. TNF activity increased in parallel with the first and second LAA peaks, whereas increases in IL-2 and IFN-gamma activity were associated only with the second.(ABSTRACT TRUNCATED AT 400 WORDS)