We have designed and implemented a practical nanoelectronic interface to G-protein coupled receptors (GPCRs), a large family of membrane proteins whose roles in the detection of molecules outside eukaryotic cells make them important pharmaceutical targets. Specifically, we have coupled olfactory receptor proteins (ORs) with carbon nanotube transistors. The resulting devices transduce signals associated with odorant binding to ORs in the gas phase under ambient conditions and show responses that are in excellent agreement with results from established assays for OR–ligand binding. The work represents significant progress on a path toward a bioelectronic nose that can be directly compared to biological olfactory systems as well as a general method for the study of GPCR function in multiple domains using electronic readout.
A nanoenabled gravimetric chemical sensor prototype based on the large scale integration of single-stranded DNA (ss-DNA) decorated single-walled carbon nanotubes (SWNTs) as nanofunctionalization layer for aluminum nitride contour-mode resonant microelectromechanical (MEM) gravimetric sensors has been demonstrated. The capability of two distinct single strands of DNA bound to SWNTs to enhance differently the adsorption of volatile organic compounds such as dinitroluene (simulant for explosive vapor) and dymethyl-methylphosphonate (simulant for nerve agent sarin) has been verified experimentally. Different levels of sensitivity (17.3 and 28 KHz μm2/fg) due to separate frequencies of operation (287 and 450 MHz) on the same die have also been shown to prove the large dynamic range of sensitivity attainable with the sensor. The adsorption process in the ss-DNA decorated SWNTs does not occur in the bulk of the material, but solely involves the surface, which permits to achieve 50% recovery in less than 29 s.
Background: There are many clinical practice guidelines (CPGs) for the prevention, diagnosis, and treatment of knee osteoarthritis (OA). They differ by region, considering local health care systems, along with cultural and economic factors. Currently, there are conflicting CPG recommendations across the various publications, which makes it difficult for clinicians to fully understand the optimal treatment decisions for knee OA management. Purpose: To summarize the current published CPG recommendations for the role of injections in the nonoperative management of knee OA, specifically with the use of intra-articular hyaluronic acid (IA-HA), intra-articular corticosteroids (IA-CS), and platelet-rich plasma (PRP). Study Design: Systematic review. Methods: A comprehensive search identified all nonoperative knee OA CPGs within the ECRI (formerly Emergency Care Research Institute) Guidelines Trust database, the Guidelines International Network database, Google Scholar, and the Trip (formerly Turning Research Into Practice) database. Guideline recommendations were categorized into strong, conditional, or uncertain recommendations for or against the use of IA-HA, IA-CS, or PRP. Guideline recommendations were summarized and depicted graphically to identify trends in recommendations over time. Results: The search strategy identified 27 CPGs that provided recommendations. There were 20 recommendations in favor of IA-HA use, 21 recommendations in favor of IA-CS use, and 9 recommendations that were uncertain or unable to make a formal recommendation for or against PRP use based on current evidence. Most recommendations considered IA-HA and IA-CS use for symptom relief when other nonoperative options are ineffective. IA-CS were noted to provide fast and short-acting symptom relief for acute episodes of disease exacerbation, while IA-HA may demonstrate a relatively delayed but prolonged effect in comparison. The CPGs concluded that PRP recommendations currently lack evidence to definitively recommend for or against use. Conclusion: Available CPGs provide recommendations on injectables for knee OA treatment. General guidance from a global perspective concluded that IA-CS and IA-HA are favored for different needed responses and can be utilized within the knee OA treatment paradigm, while PRP currently has insufficient evidence to make a conclusive recommendation for or against its use.
Instrumentation for clinical breath analysis is being developed using a variety of sensor technologies and information processing strategies. One type of instrumentation for clinical breath analysis uses an array of sensors for detection of volatile analytes in breath and pattern recognition and categorization algorithms able to learn and store information about the constant and variable components of human breath samples. This later approach is known as electronic olfaction. We present a new sensor technology for electronic olfaction that offers the potential to develop miniature sensor chips deploying hundreds of diverse and sensitive sensors based on DNA-decorated semiconducting single-walled carbon nanotubes. We have made sensor devices sensitive to some components of human breath (organic acids, trimethylamine). Screening of further DNA oligomers for their ability to render DNA-coated nanotubes sensitive to additional volatile components of human breath is needed to fully exploit this new sensor technology for clinical breath analysis.
Neurological drugs delivered to the olfactory region can enter the brain via olfactory pathways and bypass the blood-brain barrier. However, clinical applications of the direct nose-to-brain delivery are rare because of the extremely low olfactory doses using conventional nasal devices. This poor bioavailability is mainly caused by two factors: the complex nasal structure that traps particles in the anterior nose and the complete lack of control over particle motions after their release at the nostrils. In this study, the feasibility of electric-guided delivery to the olfactory region was tested in an anatomically accurate nasal airway model both experimentally and numerically. The nose replicas were prepared using 3-D printing and could be dissembled to reveal the local deposition patterns within the nasal cavity. A test platform was developed that included a dry powder charging system and a particle point-release nozzle. Numerical modeling was conducted using COMSOL and compared to corresponding experiments. Compared to conventional nasal devices, electric-guidance of charged particles noticeably reduced particle losses in the anterior nose and increased depositions in the olfactory region. The thickness and relative permittivity of the wall were observed to affect the electric field strength and olfactory dosages. Consistent deposition patterns were obtained between experiments and numerical simulations in both 2-D and 3-D nose models. Two conceptual designs were proposed to generate, charge, and control aerosols. Results of this study indicate that it is feasible to use an electric field to control charged particles in the human nose. Both electric-guidance and point-release of particles are essential to achieve targeted olfactory delivery. Future studies to refine the aerosol charging and release systems are needed for further enhancement of olfactory dosages.
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