Relation between hematocrit partitioning and red blood cell lingering in a microfluidic network.

Despite increased interest in the effect of lingering red blood cells (LRBCs) on the heterogeneous hematocrit distribution in the microcirculation, quantitative data on LRBCs before and after the lingering event are still limited. The aim of the study was to investigate the relation between red blood cell (RBC) lingering and hematocrit partitioning in a microfluidic model of a microvascular bifurcation in the limit of low hematocrit conditions (tube hematocrit <10%). To this end, the classification of LRBCs was performed based on timing, position, and velocity of the RBCs. The investigation provided statistical information on the velocity, shape, and orientation of LRBCs as well as on their lateral distribution in the parent and daughter vessels. LRBCs traveled predominantly close to the centerline of the parent vessel, but they marginated close to the distal wall in the daughter vessels. Differently than the RBC flow observed in the smallest vessels, no influence of lingering events on the local hematocrit partitioning was observed in our experiments. However, importantly, we found that LRBCs flowing in the daughter vessel after lingering may be connected to reverse hematocrit partitioning in downstream bifurcations by influencing the skewness of the hematocrit distribution in the daughter vessel, which relates to the so-called network history effect.

Evaluation of extra-corporeal membrane oxygenator cannulae in pulsatile and non-pulsatile pediatric mock circuits.

BACKGROUND: This study evaluated the hemodynamic performance of arterial and venous cannulae in a compliant pediatric extracorporeal membrane oxygenation (ECMO) mock circuit in pulsatile and non-pulsatile flow conditions. METHODS: The ECMO setup consisted of an oxygenator, diagonal pump, and standardized-length arterial/venous tubing with pressure transducers. A validated left-heart mock loop was adapted to simulate pediatric conditions. The pulsatile flow was driven by a computer-controlled piston pump set at 120 bpm. A roller pump was used for non-pulsatile conditions. The circuit was primed with 40% glycerol-based solution. The cardiac output was set to 1 L/min and the aortic pressure to 40-50 mmHg. Four arterial cannulae (8Fr, 10Fr, 12Fr, 14Fr) and five venous cannulae (12Fr, 14Fr, 16Fr, 18Fr, 20Fr) (Medtronic, Inc., Minneapolis, MN, USA) were tested at increasing flow rate in 12 combinations. RESULTS: The pulsatile condition required lower ECMO pump speeds for all cannulae combinations at a given flow rate, inducing a significantly smaller increase of flow in the mock loop. Under non-pulsatile conditions, the aortic and arterial pressures in the cannulae were higher (p < 0.01) while no significant differences in pressure drop and pressure-flow characteristics (M-number) were observed. The total hemodynamic energy was higher in case of non-pulsatile flow (p < 0.01). CONCLUSION: Under non-pulsatile conditions, the system was characterized by overall higher pressures, resulting in higher support to the patient. The consequent increase of potential energy compensates for increases of kinetic energy, leading to a higher total hemodynamic energy. Pressure gradients and M number are independent of the testing conditions. Pulsatile testing conditions led to more physiological testing conditions, and it is recommended for ECMO testing.

The impact of roller pump-assisted cardiotomy suction unit on hemolysis.

Hemolysis in cardiac surgery is often related to the contact of blood with air or artificial surfaces. Variations of negative pressure in the suction cannulas may represent an additional factor. Limited data exist on the contribution of a roller pump-assisted (RPA) cardiotomy suction unit to hemolysis. Elevation of free hemoglobin (fHb) following air suction (AS) or suction tip occlusion (STO) events of a pump-assisted cardiotomy suction unit was investigated in a mock circuit filled with blood from slaughtered domestic pigs. AS-associated hemolysis was measured over 240 minutes with 2 minutes of AS occurring every 10 minutes. STO-associated hemolysis was analyzed over 80-minute periods: configuration 1 (c1) comprised a cycle of 20 minutes (min) occlusion and 60 minutes RPA flow (20/60 minutes); c2 comprised 20 cycles of 1/3 minutes; c3 comprised 40 cycles of 0.5/1.5 minutes; and c4 comprised 80 cycles of 0.25/0.75 minutes. The AS setup did not lead to significant hemolysis after 2 (P = .97), 3 (P = .40) or 4 (P = .11) hours. The STO setup showed the greatest hemolysis (ΔfHb of 30 mg/dL) in c1 after 20 minutes. ΔfHb was different in c1 from all other configurations at 20 minutes (P < .0001) and 80 minutes (P < .05). Ex vivo generation of large negative pressures by STO events is the main cause of cardiotomy suction-associated hemolysis. The clinical relevance of this mechanism needs further investigations.

A multi-scale model of gas transport in the lung to study heterogeneous lung ventilation during the multiple-breath washout test.

The multiple-breath washout (MBW) is a lung function test that measures the degree of ventilation inhomogeneity (VI). The test is used to identify small airway impairment in patients with lung diseases like cystic fibrosis. However, the physical and physiological factors that influence the test outcomes and differentiate health from disease are not well understood. Computational models have been used to better understand the interaction between anatomical structure and physiological properties of the lung, but none of them has dealt in depth with the tracer gas washout test in a whole. Thus, our aim was to create a lung model that simulates the entire MBW and investigate the role of lung morphology and tissue mechanics on the tracer gas washout procedure. To this end, we developed a multi-scale lung model to simulate the inert gas transport in airways of all size. We then applied systematically different modifications to geometrical and mechanical properties of the lung model (compliance, residual airway volume and flow resistance) which have been associated with VI. The modifications were applied to distinct parts of the model, and their effects on the gas distribution within the lung and on the gas concentration profile were assessed. We found that variability in compliance and residual volume of the airways, as well as the spatial distribution of this variability in the lung had a direct influence on gas distribution among airways and on the MBW pattern (washout duration, characteristic concentration profile during each expiration), while the effects of variable flow resistance were negligible. Based on these findings, it is possible to classify different types of inhomogeneities in the lung and relate them to specific features of the MBW pattern, which builds the basis for a more detailed association of lung function and structure.

Red blood cells stabilize flow in brain microvascular networks.

Capillaries are the prime location for oxygen and nutrient exchange in all tissues. Despite their fundamental role, our knowledge of perfusion and flow regulation in cortical capillary beds is still limited. Here, we use in vivo measurements and blood flow simulations in anatomically accurate microvascular network to investigate the impact of red blood cells (RBCs) on microvascular flow. Based on these in vivo and in silico experiments, we show that the impact of RBCs leads to a bias toward equating the values of the outflow velocities at divergent capillary bifurcations, for which we coin the term "well-balanced bifurcations". Our simulation results further reveal that hematocrit heterogeneity is directly caused by the RBC dynamics, i.e. by their unequal partitioning at bifurcations and their effect on vessel resistance. These results provide the first in vivo evidence of the impact of RBC dynamics on the flow field in the cortical microvasculature. By structural and functional analyses of our blood flow simulations we show that capillary diameter changes locally alter flow and RBC distribution. A dilation of 10% along a vessel length of 100 µm increases the flow on average by 21% in the dilated vessel downstream a well-balanced bifurcation. The number of RBCs rises on average by 27%. Importantly, RBC up-regulation proves to be more effective the more balanced the outflow velocities at the upstream bifurcation are. Taken together, we conclude that diameter changes at capillary level bear potential to locally change the flow field and the RBC distribution. Moreover, our results suggest that the balancing of outflow velocities contributes to the robustness of perfusion. Based on our in silico results, we anticipate that the bi-phasic nature of blood and small-scale regulations are essential for a well-adjusted oxygen and energy substrate supply.

Portal hyperperfusion after major liver resection and associated sinusoidal damage is a therapeutic target to protect the remnant liver.

Extended liver resection results in loss of a large fraction of the hepatic vascular bed, thereby causing abrupt alterations in perfusion of the remnant liver. Mechanisms of hemodynamic adaptation and associated changes in oxygen metabolism after liver resection and the effect of mechanical portal blood flow reduction were assessed. A pig model (n = 16) of extended partial hepatectomy was established that included continuous observation for 24 h under general anesthesia. Pigs were randomly separated into two groups, one with a portal flow reduction of 70% compared with preoperative values, and the other as a control (n = 8, each). In controls, portal flow [mean (SD)] increased from 74 (8) mL·min-1·100 g-1 preoperatively to 240 (48) mL·min-1·100 g-1 at 6 h after resection (P < 0.001). Hepatic arterial buffer response was abolished after resection. Oxygen uptake per unit liver mass increased from 4.0 (1.1) mL·min-1·100 g-1 preoperatively to 7.7 (1.7) mL·min-1·100 g-1 8 h after resection (P = 0.004). Despite this increase in relative oxygen uptake, total hepatic oxygen consumption (V̇o2) was not maintained, and markers of hypoxia and anaerobic metabolism were significantly increased in hepatocytes after resection. Reduced postoperative portal flow was associated with significantly decreased levels of aspartate aminotransferase and bilirubin and increased hepatic clearance of indocyanine green. In conclusion, major liver resection was associated with persistent portal hyperperfusion, loss of the hepatic arterial buffer response, decreased total hepatic V̇o2 and with increased anaerobic metabolism. Portal flow modulation by partial portal vein occlusion attenuated liver injury after extended liver resection.NEW & NOTEWORTHY Because of continuous monitoring, the experiments allow precise observation of the influence of liver resection on systemic and local abdominal hemodynamic alterations and oxygen metabolism. Major liver resection is associated with significant and persistent portal hyperperfusion and loss of hepatic arterial buffer response. The correlation of portal hyperperfusion and parameters of liver injury and dysfunction offers a novel therapeutic option to attenuate liver injury after extended liver resection.

Cardiac electrophysiology catheters for electrophysiological assessments of the lower urinary tract-A proof of concept ex vivo study in viable ureters.

AIMS: To explore the feasibility of minimally invasive catheter-based electrophysiology studies in the urinary tract. This is a well-known method used in cardiology to investigate and treat arrhythmias. METHODS: We developed an experimental platform which allows electrophysiological recordings with cardiac catheters and conventional needle electrodes in ex vivo pig ureters. The action potential was triggered by a stimulating electrode. We considered 13 porcine ureters (freshly collected and harvested in organ bath), 7 of which were used to optimize the setup and define the stimulation parameters; we performed the recordings in the remaining six ureters. The electrical propagation of the generated action potential was tracked with multiple sensing electrodes, from which propagation directions, velocities, refractory periods, and pacing thresholds were extracted. RESULTS: We recorded propagating electrical activity in four ureters using needle electrodes and in two ureters using cardiac catheters. Propagation velocities for forward direction (from kidney to bladder) derived by the two methods were similar (15.1 ± 2.6 mm/s for cardiac catheters, 15.6 ± 2.3 mm/s for needle recordings). Pacing thresholds, activation patters, and refractory times were provided for the ureteric smooth muscle. Retrograde propagations and corresponding velocities were also observed and measured. CONCLUSIONS: This study is a proof-of-concept showing that electrical activity can be measured "from the inside" of urinary cavities using catheters and that obtained results are comparable with the more invasive needle recordings. Catheter-based electrophysiology may allow, in the clinical setting, for: i) a more differentiated understanding of urological disorders such as overactive bladder and ii) new therapeutic approaches (e.g., targeted tissue ablation).

Packaging Technology for an Implantable Inner Ear MEMS Microphone.

Current cochlear implant (CI) systems provide substantial benefits for patients with severe hearing loss. However, they do not allow for 24/7 hearing, mainly due to the external parts that cannot be worn in all everyday situations. One of the key missing parts for a totally implantable CI (TICI) is the microphone, which thus far has not been implantable. The goal of the current project was to develop a concept for a packaging technology for state-of-the-art microelectromechanical systems (MEMS) microphones that record the liquid-borne sound inside the inner ear (cochlea) as a microphone signal input for a TICI. The packaging concept incorporates requirements, such as biocompatibility, long-term hermeticity, a high sensing performance and a form factor that allows sensing inside the human cochlea and full integration into the existing CI electrode array. The present paper (1) describes the sensor packaging concept and the corresponding numerical and experimental design verification process and (2) gives insight into new engineering solutions for sensor packaging. Overall, a packaging concept was developed that enables MEMS microphone technology to be used for a TICI system.

Detection and quantification of overactive bladder activity in patients: Can we make it better and automatic?

AIMS: To explore the use of time-frequency analysis as an analytical tool to automatically detect pattern changes in bladder pressure recordings of patients with overactive bladder (OAB). To provide quantitative data on the bladder's non-voiding activity which could improve the current diagnosis and potentially the treatment of OAB. METHODS: We developed an algorithm, based on time-frequency analysis, to analyze bladder pressure during the filling phase of urodynamic studies. The algorithm was used to generate a bladder overactivity index (BOI) for a quantitative estimation of the average bladder non-voiding-activity. We tested the algorithm with one control group and two groups of patients with OAB symptoms: one group with detrusor overactivity (DO), assessed by an experienced urologist (OAB-with-DO group), and another group for which detrusor overactivity was not diagnosed (OAB-without-DO group). RESULTS: The algorithm identified diagnostically significant data on the bladder non-voiding activity in a specified frequency range. BOI was significantly higher for both OAB groups compared to the control group: the median value of BOI was twice as big in OAB-without-DO and more than four times higher in OAB-with-DO compared to control group. Moreover the algorithm was successfully tested to detect episodes of detrusor overactivity. CONCLUSIONS: We have shown that a simple algorithm, based on time-frequency analysis of bladder pressure, may be a promising tool in the clinical setting. The algorithm can provide quantitative data on non-voiding bladder activity in patients and quantify the changes according to phenotype. Moreover the algorithm can detect DO, showing potential for triggering conditional bladder stimulation.

Proof of Concept for an Intracochlear Acoustic Receiver for Use in Acute Large Animal Experiments.

(1) Background: The measurement of intracochlear sound pressure (ICSP) is relevant to obtain better understanding of the biomechanics of hearing. The goal of this work was a proof of concept of a partially implantable intracochlear acoustic receiver (ICAR) fulfilling all requirements for acute ICSP measurements in a large animal. The ICAR was designed not only to be used in chronic animal experiments but also as a microphone for totally implantable cochlear implants (TICI). (2) Methods: The ICAR concept was based on a commercial MEMS condenser microphone customized with a protective diaphragm that provided a seal and optimized geometry for accessing the cochlea. The ICAR was validated under laboratory conditions and using in-vivo experiments in sheep. (3) Results: For the first time acute ICSP measurements were successfully performed in a live specimen that is representative of the anatomy and physiology of the human. Data obtained are in agreement with published data from cadavers. The surgeons reported high levels of ease of use and satisfaction with the system design. (4) Conclusions: Our results confirm that the developed ICAR can be used to measure ICSP in acute experiments. The next generation of the ICAR will be used in chronic sheep experiments and in TICI.

Comparison of Hemodynamic Performance, Three-Dimensional Flow Fields, and Turbulence Levels for Three Different Heart Valves at Three Different Hemodynamic Conditions.

The hemodynamic performance of different prosthetic heart valves is difficult to compare among studies due to a variety of test conditions and experimental techniques. Existing studies are typically limited to one family of valves (biological or mechanical) and testing conditions of 5l/min and often lack sufficient spatial resolution. To address these limitations, a pulse duplicator with a multi-view imaging system (Tomo-PIV) was employed to investigate the three-dimensional flow field in the aortic root of three different valves: a tri-leaflet mechanical heart valve (TRIFLO, Novostia), a bi-leaflet mechanical heart valve (On-X, Artivion), and a biological heart valve (Perimount, Edwards Lifesciences). The valves were tested at low (3 l/min), normal (5 l/min), and elevated (7 l/min) cardiac output ( C O ) under hypotensive (40/60mmHg), normotensive (80/120mmHg), and moderate hypertensive (105/170mmHg) pressure conditions, respectively. Compared to the Perimount, peak mean velocity was - 33%, - 24%, - 18% for the TRIFLO and - 32%, - 20%, - 11% for the On-X at low, moderate, and elevated CO , respectively. Corresponding peak TKE values decreased by - 66%, - 57%, - 44% (TRIFLO) and - 60%, - 50%, - 36% (On-X). At low CO , EOA was lower for Perimount (1.07cm2) than for TRIFLO (1.47cm2) and On-X (1.52cm2), while it increased for elevated CO to 2.75cm2 (TRIFLO) and 2.16cm2 (Perimount and On-X). For all valves, increasing CO led to increased flow velocities, higher E O A , and higher levels of turbulence, and the spatial influence of the valve on the flow field in the ascending aorta was extended. TKE peaked closer to the STJ than for TRIFLO and Perimount.

On the role of aortic valve architecture for physiological hemodynamics and valve replacement, Part I: Flow configuration and vortex dynamics.

Aortic valve replacement has become an increasing concern due to the rising prevalence of aortic stenosis in an ageing population. Existing replacement options have limitations, necessitating the development of improved prosthetic aortic valves. In this study, flow characteristics during systole in a stenotic aortic valve case are compared with those downstream of two newly designed surgical bioprosthetic aortic valves (BioAVs). To do so, advanced three-dimensional fluid-structure interaction simulations are conducted and dedicated analysis methods to investigate jet flow configuration and vortex dynamics are developed. Our findings reveal that the stenotic case maintains a high jet flow eccentricity due to a fixed orifice geometry, resulting in flow separation and increased vortex stretching and tilting in the commissural low-flow regions. One BioAV design introduces non-axisymmetric leaflet motion, which reduces the maximum jet velocity and forms more vortical structures. The other BioAV design produces a fixed symmetric triangular jet shape due to non-moving leaflets and exhibits favourable vorticity attenuation, revealed by negative temporally and spatially averaged projected vortex stretching values, and significantly reduced drag. Therefore, this study highlights the benefits of custom-designed aortic valves in the context of their replacement through comprehensive and novel flow analyses. The results emphasise the importance of analysing jet flow, vortical structures, momentum balance and vorticity transport for thoroughly evaluating aortic valve performance.

On the role of aortic valve architecture for physiological hemodynamics and valve replacement, Part II: Spectral analysis and anisotropy.

Severe aortic valve stenosis can lead to heart failure and aortic valve replacement (AVR) is the primary treatment. However, increasing prevalence of aortic stenosis cases reveal limitations in current replacement options, necessitating improved prosthetic aortic valves. We investigate flow disturbances downstream of severe aortic stenosis and two bioprosthetic aortic valve (BioAV) designs using advanced energy-based analyses. Three-dimensional high-fidelity fluid-structure interaction simulations have been conducted and a dedicated and novel spectral analysis has been developed to characterise the kinetic energy (KE) carried by eddies in the wavenumber space. In addition, new field quantities, i.e. modal KE anisotropy intensity as well as normalised helicity intensity, are introduced. Spectral analysis shows kinetic energy (KE) decay variations, with the stenotic case aligning with Kolmogorov's theory, while BioAV cases differing. We explore the impact of flow helicity on KE transfer and decay in BioAVs. Probability distributions of modal KE anisotropy unveil flow asymmetries in the stenotic and one BioAV cases. Moreover, an inverse correlation between temporally averaged modal KE anisotropy and normalised instantaneous helicity intensity is noted, with the coefficient of determination varying among the valve configurations. Leaflet dynamics analysis highlights a stronger correlation between flow and biomechanical KE anisotropy in one BioAV due to higher leaflet displacement magnitude. These findings emphasise the role of valve architecture in aortic turbulence as well as its importance for BioAV performance and energy-based design enhancement.

The relation between aortic morphology and transcatheter aortic heart valve thrombosis: Particle tracing and platelet activation in larger aortic roots with and without neo-sinus.

Transcatheter aortic heart valve thrombosis (THVT) affects long-term valve durability, transvalvular pressure gradient and leaflet mobility. In this study, we conduct high-fidelity fluid-structure interaction simulations to perform Lagrangian particle tracing in a generic model with larger aortic diameters (THVT model) with and without neo-sinus which is compared to a model of unaffected TAVI patients (control model). Platelet activation indices are computed for each particle to assess the risk of thrombus formation induced by high shear stresses followed by flow stagnation. Particle tracing indicates that fewer particles contribute to sinus washout of the THVT model with and without neo-sinus compared to the control model (-34.9%/-34.1%). Stagnating particles in the native sinus of the THVT model show higher platelet activation indices than for the control model (+39.6% without neo-sinus, +45.3% with neo-sinus). Highest activation indices are present for particles stagnating in the neo-sinus of the larger aorta representing THVT patients (+80.2% compared to control). This fluid-structure interaction (FSI) study suggests that larger aortas lead to less efficient sinus washout in combination with higher risk of platelet activation among stagnating particles, especially within the neo-sinus. This could explain (a) a higher occurrence of thrombus formation in transcatheter valves compared to surgical valves without neo-sinus and (b) the neo-sinus as the prevalent region for thrombi in TAV. Pre-procedural identification of larger aortic roots could contribute to better risk assessment of patients and improved selection of a patient-specific anti-coagulation therapy.

Dielectric Elastomer Actuator-Based Valveless Impedance-Driven Pumping for Meso- and Macroscale Applications.

Impedance pumps are simple designs that allow the generation or amplification of flow. They are fluid-filled systems based on flexible tubing connected to tubing with different impedances. A periodic off-center compression of the flexible tubing causes the fluid to move and generate flow. Wave reflection at the impedance mismatch is the primary driving mechanism of the flow. In addition to their straightforward design, impedance pumps are bladeless, valveless, and pulsatile. These properties are highly sought after by demanding and challenging applications, such as the biomedical field, as they present less risk of damage, disruption, and obstruction when handling viscous and delicate fluids/matter. In this study, we propose a high-performance impedance-driven pumping concept with embedded actuation based on a multilayered tubular dielectric elastomer. This pumping system is made of three parts, a dielectric elastomer actuator tube, a passive tube, and a rigid ring that binds and decouples the two subsystems. The system is able to generate net fluid flow rates up to 1.35 L/min with an internal pressure of 125 mmHg. The soft simplistic design, self-contained concept, and high performances of these pumping systems could make them disruptive in many challenging meso- and macroscale applications in general and in the biomedical field in particular.

Efficacy of catheter-based drug delivery in a hybrid in vitro model of cardiac microvascular obstruction with porcine microthrombi.

Microvascular obstruction (MVO) often occurs in ST-elevation myocardial infarction (STEMI) patients after percutaneous coronary intervention (PCI). Diagnosis and treatment of MVO lack appropriate and established procedures. This study focused on two major points by using an in vitro multiscale flow model, which comprised an aortic root model with physiological blood flow and a microfluidic model of the microcirculation with vessel diameters down to 50 µm. First, the influence of porcine microthrombi (MT), injected into the fluidic microchip, on perfusion was investigated. We found that only 43% of all injected MT were fully occlusive. Second, it could also be shown that the maximal concentration of a dye (representing therapeutic agent) during intracoronary infusion could be increased on average by 58%, when proximally occluding the coronary artery by a balloon during drug infusion. The obtained results and insights enhance the understanding of perfusion in MVO-affected microcirculation and could lead to improved treatment methods for MVO patients.

Dielectric elastomer actuator-based valveless pump as Fontan failure assist device: introduction and preliminary study.

OBJECTIVES: Fontan failure refers to a condition in which the Fontan circulation, a surgical procedure used to treat certain congenital heart defects, becomes insufficient, leading to compromised cardiac function and potential complications. This in vitro study therefore investigates the feasibility of bladeless impedance-driven cavopulmonary assist device via dielectric elastomer actuator (DEA) as a means to address Fontan failure. METHODS: A cavopulmonary assist device, constructed using DEA technologies and employing the impedance pump concept, is subjected to in vitro testing within a closed-loop setup. This study aims to assess the device's functionality and performance under controlled conditions, providing valuable insights into its potential application as a cavopulmonary assistive technology. RESULTS: The DEA-based pump, measuring 50 mm in length and 30 mm in diameter, is capable of achieving substantial flow rates within a closed-loop setup, reaching up to 1.20 l/min at an activation frequency of 4 Hz. It also provides a broad range of working internal pressures (<10 to >20 mmHg). Lastly, the properties of the flow (direction, magnitude, etc.) can be controlled by adjusting the input signal parameters (frequency, amplitude, etc.). CONCLUSIONS: In summary, the results suggest that the valveless impedance-driven pump utilizing DEA technology is promising in the context of cavopulmonary assist devices. Further research and development in this area may lead to innovative and potentially more effective solutions for assisting the right heart, ultimately benefiting patients with heart-related health issues overall, with a particular focus on those experiencing Fontan failure.

Influence of Roasting Temperature on the Detectability of Potentially Allergenic Lupin by SDS-PAGE, ELISAs, LC-MS/MS, and Real-Time PCR.

Seeds of "sweet lupins" have been playing an increasing role in the food industry. Lupin proteins may be used for producing a variety of foods, including pasta, bread, cookies, dairy products, and coffee substitutes. In a small percentage of the population, lupin consumption may elicit allergic reactions, either due to primary sensitization to lupin or due to cross-allergy with other legumes. Thus, lupin has to be declared on commercial food products according to EU food regulations. In this study, we investigated the influence of roasting seeds of the L. angustifolius cultivar "Boregine" on the detectability of lupin by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), ELISAs, LC-MS/MS, and real-time PCR. Seeds were roasted by fluidized bed roasting, and samples were drawn at seed surface temperatures ranging from 98 °C to 242 °C. With increasing roasting temperature, the extractability of proteins and DNA decreased. In addition, roasting resulted in lower detectability of lupin proteins by ELISAs and LC-MS/MS and lower detectability of DNA by real-time PCR. Our results suggest reduced allergenicity of roasted lupin seeds used for the production of "lupin coffee"; however, this has to be confirmed in in vivo studies.

An Atomistic View on the Mechanism of Diatom Peptide-Guided Biomimetic Silica Formation.

Deciphering nature's remarkable way of encoding functions in its biominerals holds the potential to enable the rational development of nature-inspired materials with tailored properties. However, the complex processes that convert solution-state precursors into solid biomaterials remain largely unknown. In this study, an unconventional approach is presented to characterize these precursors for the diatom-derived peptides R5 and synthetic Silaffin-1A1 (synSil-1A1). These molecules can form defined supramolecular assemblies in solution, which act as templates for solid silica structures. Using a tailored structural biology toolbox, the structure-function relationships of these self-assemblies are unveiled. NMR-derived constraints are employed to enable a recently developed fractal-cluster formalism and then reveal the architecture of the peptide assemblies in atomistic detail. Finally, by monitoring the self-assembly activities during silica formation at simultaneous high temporal and residue resolution using real-time spectroscopy, the mechanism is elucidated underlying template-driven silica formation. Thus, it is demonstrated how to exercise morphology control over bioinorganic solids by manipulating the template architectures. It is found that the morphology of the templates is translated into the shape of bioinorganic particles via a mechanism that includes silica nucleation on the solution-state complexes' surfaces followed by complete surface coating and particle precipitation.