Micro simulated moving bed chromatography-mass spectrometry as a continuous on-line process analytical tool

Continuous manufacturing is becoming increasingly important in the (bio-)pharmaceutical industry, as more product can be produced in less time and at lower costs. In this context, there is a need for powerful continuous analytical tools. Many established off-line analytical methods, such as mass spectrometry (MS), are hardly considered for process analytical technology (PAT) applications in biopharmaceutical processes, as they are limited to at-line analysis due to the required sample preparation and the associated complexity, although they would provide a suitable technique for the assessment of a wide range of quality attributes. In this study, we investigated the applicability of a recently developed micro simulated moving bed chromatography system (µSMB) for continuous on-line sample preparation for MS. As a test case, we demonstrate the continuous on-line MS measurement of a protein solution (myoglobin) containing Tris buffer, which interferes with ESI-MS measurements, by continuously exchanging this buffer with a volatile ammonium acetate buffer suitable for MS measurements. The integration of the µSMB significantly increases MS sensitivity by removing over 98% of the buffer substances. Thus, this study demonstrates the feasibility of on-line µSMB-MS, providing a versatile PAT tool by combining the detection power of MS for various product attributes with all the advantages of continuous on-line analytics

Influence of Auditory Cues on the Neuronal Response to Naturalistic Visual Stimuli in a Virtual Reality Setting

Virtual reality environments offer great opportunities to study the performance of brain-computer interfaces (BCIs) in real-world contexts. As real-world stimuli are typically multimodal, their neuronal integration elicits complex response patterns. To investigate the effect of additional auditory cues on the processing of visual information, we used virtual reality to mimic safety-related events in an industrial environment while we concomitantly recorded electroencephalography (EEG) signals. We simulated a box traveling on a conveyor belt system where two types of stimuli – an exploding and a burning box – interrupt regular operation. The recordings from 16 subjects were divided into two subsets, a visual-only and an audio-visual experiment. In the visual-only experiment, the response patterns for both stimuli elicited a similar pattern – a visual evoked potential (VEP) followed by an event-related potential (ERP) over the occipital-parietal lobe. Moreover, we found the perceived severity of the event to be reflected in the signal amplitude. Interestingly, the additional auditory cues had a twofold effect on the previous findings: The P1 component was significantly suppressed in the case of the exploding box stimulus, whereas the N2c showed an enhancement for the burning box stimulus. This result highlights the impact of multisensory integration on the performance of realistic BCI applications. Indeed, we observed alterations in the offline classification accuracy for a detection task based on a mixed feature extraction (variance, power spectral density, and discrete wavelet transform) and a support vector machine classifier. In the case of the explosion, the accuracy slightly decreased by –1.64% p. in an audio-visual experiment compared to the visual-only. Contrarily, the classification accuracy for the burning box increased by 5.58% p. when additional auditory cues were present. Hence, we conclude, that especially in challenging detection tasks, it is favorable to consider the potential of multisensory integration when BCIs are supposed to operate under (multimodal) real-world conditions

A simplified model for structural stiffness and crashworthiness optimisation of composite fuselages

In this paper, a multi-objective optimisation for the initial design of crashworthy composite structures is proposed. The focus is on the optimisation model with its minimisation of inhomogeneous deformation capability. It promotes homogeneous contribution of all crash elements, as a representative of structural crashworthiness. For the first time, homogeneous contribution has been identified as a metric for crashworthiness of composite structures and been transferred into a mathematical expression. The structural model uses discrete elements for very efficient computation in combination with the genetic algorithm NSGA-II. Clustering as a machine learning technique is applied to the Pareto set of solutions in order to identify representative structural solutions. The approach uses positioning of elements and the shape of the spring characteristic of these elements as variables. The method enables the simultaneous consideration of static and crash loads, which is demonstrated by a case study featuring a composite aircraft fuselage substructure. So far, static and crash loads have been only considered separately, but never at the same time. The novelty of this approach is in the combination of an appropriate simplified modelling technique and a new formulation of the optimisation model. The proposed optimisation is beneficial in improving the crashworthiness of composites, as optimisation of the geometry and material behaviour enables a non-linear response to be obtained in an otherwise brittle material

Initial Design of Crashworthy Composite Structures

At the initial phase of the design process, only static and equivalent static loads are considered in the structural layout of an aircraft composite fuselage.Therefore, the dynamic structural behaviour of a composite fuselage under crash load conditions is an inappropriate result of static structural layout. This thesis provides a novel method based on the intelligent application of structural modelling and optimization techniques to overcome this lacking feature in the design process. Therein, the key innovation is to consider static and crash loads simultaneously at the initial phase of composite design. The novel method is based on evolutionary computation techniques applied on structural simulation in order to include energy absorption or deformation work characteristics immanent to composite materials and composite design within a multi-objective optimization approach foran overall system response. The proposed method includes the systematic transfer of design information from the intitial design phase to the preliminary design. Based on the systematic transfer, the prototypical development of an adaptive deformation element for the purpose of deformation control and energy absoprtion is conducted

Experimental investigation on the deformation of CFRP cylinders using piezo-actuators

In this paper, the deformation of cylindrical composite structures employing piezoelectric actuators is investigated. It specifically addresses radial deformations of a composite cylinder generated by macro fibre composites (MFC). The purpose is to experimentally characterise the shape as well as the magnitude of the composite cylinder’s deformation using an optical full-field 3D measurement system. Besides cylinder expansion and contraction under operating conditions, shell bending appeared to contribute significantly to the overall deformation behaviour. With the data provided the development of an adaptive primary aircraft structure is conceivable