Peptide-Functionalized Carbon Nanotube Chemiresistors: The Effect of Nanotube Density on Gas Sensing.

Biorecognition element (BRE)-based carbon nanotube (CNT) chemiresistors have tremendous potential to serve as highly sensitive, selective, and power-efficient volatile organic compound (VOC) sensors. While many research groups have studied BRE-functionalized CNTs in material science and device development, little attention has been paid to optimizing CNT density to improve chemiresistor performance. To probe the effect of CNT density on VOC detection, we present the chemiresistor-based sensing results from two peptide-based CNT devices counting more than 60 different individual measurements. We find that a lower CNT density shows a significantly higher noise level and device-to-device variation while exhibiting mildly better sensitivity. Further investigation with SEM images suggests that moderately high CNT density with a stable connection of the nanotube network is desirable to achieve the best signal-to-noise ratio. Our results show an essential design guideline for tuning the nanotube density to provide sensitive and stable chemiresistors.

Fabrication and characterisation of novel algin incorporated bioactive-glass 58S calcium-silicate-based root canal sealer.

Background/purpose: The usage of bioceramic-based root canal sealers has escalated over the years due to their excellent properties. The present study aimed to fabricate a novel algin incorporated bioactive glass 58S calcium-silicate (Bio-G) sealer and characterise its surface microstructure and chemical compositions in comparison to commercially available bioceramic sealers (BioRoot RCS and iRoot SP). Materials and methods: The powder form of experimental Bio-G sealer consisted of synthesised BG 58S particle, calcium silicate, zirconia dioxide, calcium carbonate and alginic acid powder as binder. The liquid composed of 5% calcium chloride solution. Five standardised disc specimens were prepared for each sealer group according to the manufacturer's instructions. Subsequently, sealer disc-specimens were placed in an incubator at 37 °C, 95% relative humidity for 72 h to allow setting prior to testing under scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), Fourier transformed infrared spectroscopy (FTIR) and X-ray diffraction (XRD). Results: Experimental Bio-G sealer revealed irregular micro-sized particles ranging from 0.5 µm to 105 µm aggregated in clusters comparable to those of BioRoot RCS and iRoot SP. EDS microanalysis showed that Bio-G had high content of oxygen, silicon, and calcium, with the presence of aluminium and chloride similar to BioRoot RCS. Meanwhile, the FTIR and XRD findings suggested that all sealers predominantly contained calcium silicate hydrate, calcium carbonate, and zirconium dioxide, while calcium aluminium silicate oxide was detected in Bio-G. Conclusion: The present novel Bio-G sealer demonstrated desirable particle size distribution and acceptable degree of purity. Future studies are warranted to explore its properties and clinical application.

Additive Manufacturing of Polyhydroxyalkanoate-Based Blends Using Fused Deposition Modelling for the Development of Biomedical Devices.

In the last few decades Additive Manufacturing has advanced and is becoming important for biomedical applications. In this study we look at a variety of biomedical devices including, bone implants, tooth implants, osteochondral tissue repair patches, general tissue repair patches, nerve guidance conduits (NGCs) and coronary artery stents to which fused deposition modelling (FDM) can be applied. We have proposed CAD designs for these devices and employed a cost-effective 3D printer to fabricate proof-of-concept prototypes. We highlight issues with current CAD design and slicing and suggest optimisations of more complex designs targeted towards biomedical applications. We demonstrate the ability to print patient specific implants from real CT scans and reconstruct missing structures by means of mirroring and mesh mixing. A blend of Polyhydroxyalkanoates (PHAs), a family of biocompatible and bioresorbable natural polymers and Poly(L-lactic acid) (PLLA), a known bioresorbable medical polymer is used. Our characterisation of the PLA/PHA filament suggest that its tensile properties might be useful to applications such as stents, NGCs, and bone scaffolds. In addition to this, the proof-of-concept work for other applications shows that FDM is very useful for a large variety of other soft tissue applications, however other more elastomeric MCL-PHAs need to be used.

Detection of Asthma Inhaler Use via Terahertz Spectroscopy.

Inhaled medications are commonplace for administering bronchodilators, anticholinergics, and corticosteroids. While they have a defined legitimate use, they are also used in sporting events as performance-enhancing drugs. These performance enhancers can be acquired via both legal (i.e., at a pharmacy through over-the-counter medications or through a prescription) and illicit (i.e., black market and foreign pharmacies) means, thus making monitoring procurement impossible. While urine tests can detect these pharmacological agents hours after they have been inhaled, there is a significant lag time before they are observed in urine. Direct detection of these inhaled agents is complicated and requires a multiplexed approach due to the sheer number of inhaled pharmacological agents. Therefore, detection of propellants, which carry the drug into the lungs, provides a simpler path forward toward detection of broad pharmacological agents. In this paper, we demonstrate the first use of terahertz spectroscopy (THz) to detect inhaled medications in human subjects. Notably, we were able to detect and quantitate the propellant, HFA-134a, in breath up to 30 min after using an asthma inhaler, enabling the use of a point-of-care device to monitor exhaled breath for the presence of propellants. We also demonstrate via simulations that the same approach can be leveraged to detect and identify next-generation propellants, specifically HFA-152a. As a result, we provide evidence that a single point-of-care THz sensor can detect when individuals have used pressure-mediated dose inhalers (pMDIs) without further modification of the hardware.

Microfluidic Thermal Flowmeters for Drug Injection Monitoring.

This paper presents a microfluidic thermal flowmeter for monitoring injection pumps, which is essential to ensure proper patient treatment and reduce medication errors that can lead to severe injury or death. The standard gravimetric method for flow-rate monitoring requires a great deal of preparation and laboratory equipment and is impractical in clinics. Therefore, an alternative to the standard method suitable for remote, small-scale, and frequent infusion-pump monitoring is in great demand. Here, we propose a miniaturized thermal flowmeter consisting of a silicon substrate, a platinum heater layer on a silicon dioxide thin-membrane, and a polymer microchannel to provide accurate flow-rate measurement. The present thermal flowmeter is fabricated by the micromachining and micromolding process and exhibits sensitivity, linearity, and uncertainty of 0.722 mW/(g/h), 98.7%, and (2.36 ± 0.80)%, respectively, in the flow-rate range of 0.5-2.5 g/h when the flowmeter is operated in the constant temperature mode with the channel width of 0.5 mm. The measurement range of flow rate can be easily adjusted by changing the cross-sectional microchannel dimension. The present miniaturized thermal flowmeter shows a high potential for infusion-pump calibration in clinical settings.

Biomarkers and Detection Platforms for Human Health and Performance Monitoring: A Review.

Human health and performance monitoring (HHPM) is imperative to provide information necessary for protecting, sustaining, evaluating, and improving personnel in various occupational sectors, such as industry, academy, sports, recreation, and military. While various commercially wearable sensors are on the market with their capability of "quantitative assessments" on human health, physical, and psychological states, their sensing is mostly based on physical traits, and thus lacks precision in HHPM. Minimally or noninvasive biomarkers detectable from the human body, such as body fluid (e.g., sweat, tear, urine, and interstitial fluid), exhaled breath, and skin surface, can provide abundant additional information to the HHPM. Detecting these biomarkers with novel or existing sensor technologies is emerging as critical human monitoring research. This review provides a broad perspective on the state of the art biosensor technologies for HHPM, including the list of biomarkers and their physiochemical/physical characteristics, fundamental sensing principles, and high-performance sensing transducers. Further, this paper expands to the additional scope on the key technical challenges in applying the current HHPM system to the real field.

Portable Skin Analyzers with Simultaneous Measurements of Transepidermal Water Loss, Skin Conductance and Skin Hardness.

Simultaneous measurement of skin physiological and physical properties are important for the diagnosis of skin diseases and monitoring of human performance, since it provides more comprehensive understanding on the skin conditions. Current skin analysis devices, however, require each of probes and unique protocols for the measurement of individual skin properties, resulting in inconvenience and increase of measurement uncertainty. This paper presents a pen-type skin analyzing device capable tomeasure three key skin properties at the same time: transepidermal water loss (TEWL), skin conductance, and skin hardness. It uses a single truncated hollow cone (THC) probe integrated with a humidity sensor, paired electrodes, and a load cell for the multimodal assessment of the skin properties. The present device measured TEWL with a sensitivity of 0.0068 (%/s)/(g/m2/h) and a linearity of 99.63%, conductance with a sensitivity of 1.02 µS/µS and a linearity of 99.36%, and hardness with a sensitivity of 0.98 Shore 00/Shore 00 and a linearity of 99.85%, within the appropriate ranges for the human skin. The present pen-type device has a high potential for the skin health diagnosis as well as the human performance monitoring applications.

Structural analyses of human thymidylate synthase reveal a site that may control conformational switching between active and inactive states.

Thymidylate synthase (TS) is the sole enzyme responsible for de novo biosynthesis of thymidylate (TMP) and is essential for cell proliferation and survival. Inhibition of human TS (hTS) has been extensively investigated for cancer chemotherapy, but several aspects of its activity and regulation are still uncertain. In this study, we performed comprehensive structural and biophysical studies of hTS using crystallography and thermal shift assay and provided the first detailed structural information on the conformational changes induced by ligand binding to the hTS active site. We found that upon binding of the antifolate agents raltitrexed and nolatrexed, the two insert regions in hTS, the functions of which are unclear, undergo positional shifts toward the catalytic center. We investigated the inactive conformation of hTS and found that the two insert regions are also involved in the conformational transition between the active and inactive state of hTS. Moreover, we identified a ligand-binding site in the dimer interface, suggesting that the cavity in the dimer interface could serve as an allosteric site of hTS to regulate the conformational switching between the active and inactive states. On the basis of these findings, we propose a regulatory mechanism of hTS activity that involves allosteric regulation of interactions of hTS with its own mRNA depending on cellular demands for TMP.

Structure of the Open Reading Frame 49 Protein Encoded by Kaposi's Sarcoma-Associated Herpesvirus.

Herpesviruses alternate between the latent and the lytic life cycle. Switching into the lytic life cycle is important for herpesviral replication and disease pathogenesis. Activation of a transcription factor replication and transcription activator (RTA) has been demonstrated to govern this switch in Kaposi's sarcoma-associated herpesvirus (KSHV). The protein encoded by open reading frame 49 from KSHV (ORF49KSHV) has been shown to upregulate lytic replication in KSHV by enhancing the activities of the RTA. We have solved the crystal structure of the ORF49KSHV protein to a resolution of 2.4 Å. The ORF49KSHV protein has a novel fold consisting of 12 alpha-helices bundled into two pseudodomains. Most notably are distinct charged patches on the protein surface, which are possible protein-protein interaction sites. Homologs of the ORF49KSHV protein in the gammaherpesvirus subfamily have low sequence similarities. Conserved residues are mainly located in the hydrophobic regions, suggesting that they are more likely to play important structural roles than functional ones. Based on the identification and position of three sulfates binding to the positive areas, we performed some initial protein-DNA binding studies by analyzing the thermal stabilization of the protein in the presence of DNA. The ORF49KSHV protein is stabilized in a dose-responsive manner by double-stranded oligonucleotides, suggesting actual DNA interaction and binding. Biolayer interferometry studies also demonstrated that the ORF49KSHV protein binds these oligonucleotides. IMPORTANCE: Kaposi's sarcoma-associated herpesvirus (KSHV) is a tumorigenic gammaherpesvirus that causes multiple cancers and lymphoproliferative diseases. The virus exists mainly in the quiescent latent life cycle, but when it is reactivated into the lytic life cycle, new viruses are produced and disease symptoms usually manifest. Several KSHV proteins play important roles in this reactivation, but their exact roles are still largely unknown. In this study, we report the crystal structure of the open reading frame 49 protein encoded by KSHV (ORF49KSHV). Possible regions for protein interaction that could harbor functional importance were found on the surface of the ORF49KSHV protein. This led to the discovery of novel DNA binding properties of the ORF49KSHV protein. Evolutionary conserved structural elements with the functional homologs of ORF49KSHV were also established with the structure.