A Collaborative Approach to Bioengineering Education

Various philosophical approaches to bioengineering education result in the development of different pathways and programs. The basic underlying assumptions of the University of Washington program are presented along with a discussion of the operation of a nondepartmental approach. Undergraduate and graduate education are discussed in the context of preparing the engineer for participation in collaborative teams. A key element in the success of such teams is the introduction of the physician or life scientist to the principles of engineering. A program to provide such training is described along with a discussion about its impact on biomedical research particularly at this University.     

The Neurochip BCI: towards a neural prosthesis for upper limb function.

The Neurochip BCI is an autonomously operating interface between an implanted computer chip and recording and stimulating electrodes in the nervous system. By converting neural activity recorded in one brain area into electrical stimuli delivered to another site, the Neurochip BCI could form the basis for a simple, direct neural prosthetic. In tests with normal, unrestrained monkeys, the Neurochip continuously recorded activity of single neurons in primary motor cortex for several weeks at a time. Cortical activity was correlated with simultaneously-recorded electromyogram (EMG) activity from arm muscles during free behavior. In separate experiments with anesthetized monkeys, we found that microstimulation of the cervical spinal cord evoked movements of the arm and hand, often involving multiple muscles synergies. These observations suggest that spinal microstimulation controlled by cortical neurons could help compensate for damaged corticospinal projections.     

Hydrocarbon and Fluorocarbon Monitoring by MIS Sensors Using an Ni Catalytic Thermodestructor

An increase in the number of gases detectable by sensors based on Pd-SiO₂-Si (MIS) and Pt-LaF₃-Si₃N₄ -SiO₂-Si (MEIS) structures was achieved by the application of an external catalyst element (CE). It was shown that as a result of the decomposition of hydrocarbon and fluorocarbon molecules on a Ni coil (CE), the products detectable by metal-insulator-semiconductor (MIS) and metal-electrolyte-insulator-semiconductor (MEIS) sensors are formed. The simultaneous catalytic oxidation of hydrocarbons and their thermal decomposition result in an optimum CE temperature of about 1050 K for propane. The kinetics of the thermal decomposition of gases on Ni were investigated. The activation energy of the reaction for C₃ H₈ and the enthalpy in the case of CF₃-CCl were estimated     

Pathophysiological In Vitro Profile of Neuronal Differentiated Cells Derived from Niemann-Pick Disease Type C2 Patient-Specific iPSCs Carrying the NPC2 Mutations c.58G>T/c.140G>T

Niemann-Pick type C2 (NP-C2) disease is a rare hereditary disease caused by mutations in the NPC2 gene. NPC2 is a small, soluble protein consisting of 151 amino acids, primarily expressed in late endosomes and lysosomes (LE/LY). Together with NPC1, a transmembrane protein found in these organelles, NPC2 accomplishes the exclusion of cholesterol; thus, both proteins are essential to maintain cellular cholesterol homeostasis. Consequently, mutations in the NPC2 or NPC1 gene result in pathophysiological accumulation of cholesterol and sphingolipids in LE/LY. The vast majority of Niemann-Pick type C disease patients, 95%, suffer from a mutation of NPC1, and only 5% display a mutation of NPC2. The biochemical phenotype of NP-C1 and NP-C2 appears to be indistinguishable, and both diseases share several commonalities in the clinical manifestation. Studies of the pathological mechanisms underlying NP-C2 are mostly based on NP-C2 animal models and NP-C2 patient-derived fibroblasts. Recently, we established induced pluripotent stem cells (iPSCs), derived from a donor carrying the NPC2 mutations c.58G>T/c.140G>T. Here, we present a profile of pathophysiological in vitro features, shared by NP-C1 and NP-C2, of neural differentiated cells obtained from the patient specific iPSCs. Profiling comprised a determination of the NPC2 protein level, detection of cholesterol accumulation by filipin staining, analysis of oxidative stress, and determination of autophagy. As expected, the NPC2-deficient cells displayed a significantly reduced amount of NPC2 protein, and, accordingly, we observed a significantly increased amount of cholesterol. Most notably, NPC2-deficient cells displayed only a slight increase of reactive oxygen species (ROS), suggesting that they do not suffer from oxidative stress and express catalase at a high level. As a site note, comparable NPC1-deficient cells suffer from a lack of catalase and display an increased level of ROS. In summary, this cell line provides a valuable tool to gain deeper understanding, not only of the pathogenic mechanism of NP-C2, but also of NP-C1.     

Improved performance and maintenance in gas chromatography/isotope ratio mass spectrometry by precolumn solvent removal

The crucial step in current concepts to interface isotope ratio mass spectrometry (IRMS) to gas chromatography (GC) is efficient solvent removal. This is due to the essential postcolumn conversion of the analytes into simple gases, which is performed by either combustion or pyrolysis. The capacity of this step merely suffices to convert the analytes. Already small amounts of solvent present in the respective furnace can cause severe damage. In conventional GC/IRMS interfaces, the solvent is removed after passage of the GC column. Either back-flushing or flow diversion is employed for this purpose. Both techniques necessitate the use of numerous components such as unions, tee pieces, valves, and capillary connections. Often this results in significant deterioration of the chromatographic resolution. In contrast, accurate GC/IRMS measurements require baseline separation of adjacent peaks. Moreover, maintenance of conventional interfaces may be tedious and time consuming, mostly because the numerous connections are prone to leakage. In order to avoid these drawbacks, we propose a concept to efficiently remove the solvent before passage of the GC column. It is based on the use of a cooled injection system operated in solvent vent mode, where the solvent elimination is supported by an auxiliary pump. Most unions and tee pieces thus can be removed. The chromatographic resolution is considerably enhanced. In particular, analysis of high-boiling and polar compounds can be improved. At the same time, the maintenance of the system is significantly facilitated. Under the chosen conditions, partial losses of low-boiling analytes during solvent elimination were not associated with significant isotope fractionation.     

Deciphering the sulfate attack of cementitious materials by high-resolution micro-X-ray diffraction

The durability of cementitious materials depends, among others, on their resistance against chemical attack during the service life of a building. Here, we present an approach to analyze changes in the phase composition due to chemical attack in the form of sulfate ingress within the microstructure. Micro-X-ray (μX-ray) diffraction using synchrotron radiation in Debye-Scherrer (transmission) geometry allowed a spatial resolution of 10 μm. Phase transformations in the wake of damaging processes were observed in a detailed high-resolution imaging study. In comparison, samples containing supplementary cementitious materials were investigated and used to reconstruct the influence of different degeneration processes in detail. Additionally, reaction fronts within the bulk were localized by micro-X-ray fluorescence analysis. The experimental setup provided the possibility for analyzing the phase assemblage of a given sample without destroying the microstructure. The specimens for phase analysis are thick sections of the primary material and can be used for further microscopic analysis of the microstructure and microchemistry, e.g., scanning electron microscopy-energy-dispersive X-ray spectroscopy (SEM-EDX) or Raman spectroscopy.     

Near-field dynamics of optical Yagi-Uda nanoantennas

We present near-field measurements of optical Yagi-Uda nanoantennas that are used in receiving mode. The eigenmode imaging of amplitude and phase by apertureless scanning near-field optical microscopy allows us to investigate the dynamics of the local out-of-plane electric field components and to visualize the temporal evolution of this time-harmonic reception process. The antenna directionality manifests itself by the dependence of the local field enhancement at the feed element on the illumination direction. Simulations taking into account the substrate confirm our observation of the directionality. Our work demonstrates the possibility to characterize multielement nanoantennas by electromagnetic antenna near-field scanners.     

Dicyanovinyl–Substituted Oligothiophenes: Structure‐Property Relationships and Application in Vacuum‐Processed Small Molecule Organic Solar Cells

Efficient synthesis of a series of terminally dicyanovinyl (DCV)‐substituted oligothiophenes, DCVnT 1–6, without solubilizing side chains synthesized via a novel convergent approach and their application as electron donors in vacuum‐processed m‐i‐p‐type planar and p‐i‐n‐type bulk heterojunction organic solar cells is described. Purification of the products via gradient sublimation yields thermally highly stable organic semiconducting materials in single crystalline quality which allows for X‐ray structure analysis. Important insights into the packing features and intermolecular interactions of these promising solar cell materials are provided. Optical absorption spectra and electrochemical properties of the oligomers are investigated and valuable structure–property relationships deduced. Photovoltaic devices incorporating DCVnTs 4–6 showed power conversion efficiencies up to 2.8% for planar and 5.2% for bulk heterojunction organic solar cells under full sun illumination (mismatch corrected simulated AM 1.5G sunlight). The 5.2% efficiency shown here represents one of the highest values ever reported for organic vacuum‐deposited single heterojunction solar cells.     

Enzymatic (2R,4R)-Pentanediol Synthesis – “Putting a Bottle on the Table”

(2R,4R)-Pentanediol is an interesting precursor for the synthesis of chiral ligands. A ketoreductase (KRED) was employed for the asymmetric reduction of acetylacetone to this diol. Biocatalysis often suffers from low concentrations of hydrophobic substrates and low stability of the enzyme in unconventional media. Here, we present an engineered KRED variant applicable in a neat substrate system, including upscaling to the multi-liter scale and downstream processing (DSP). Our engineered KRED applied in a neat substrate system is a powerful technique for the synthesis of chiral diols yielding product concentrations of 208 g L⁻¹.