Amino acid racemization dating of marine shells: a mound of possibilities

Shell middens are one of the most important and widespread indicators for human exploitation of marine resources and occupation of coastal environments. Establishing an accurate and reliable chronology for these deposits has fundamental implications for understanding the patterns of human evolution and dispersal. This paper explores the potential application of a new methodology of amino acid racemization(AAR) dating of shell middens and describes a simple protocol to test the suitability of different molluscanspecies. This protocol provides a preliminary test for the presence of an intracrystalline fraction of proteins(by bleaching experiments and subsequent heating at high temperature), checking the closed system behaviour of this fraction during diagenesis. Only species which pass both tests can be considered suitable for further studies to obtain reliable age information. This amino acid geochronological technique is also applied to midden deposits at two latitudinal extremes: Northern Scotland and the Southern Red Sea.Results obtained in this study indicate that the application of this new method of AAR dating of shells has the potential to aid the geochronological investigation of shell mounds in different areas of the world

Amino acid racemization dating of marine shells: a mound of possibilities

Shell middens are one of the most important and widespread indicators for human exploitation of marine resources and occupation of coastal environments. Establishing an accurate and reliable chronology for these deposits has fundamental implications for understanding the patterns of human evolution and dispersal. This paper explores the potential application of a new methodology of amino acid racemization(AAR) dating of shell middens and describes a simple protocol to test the suitability of different molluscanspecies. This protocol provides a preliminary test for the presence of an intracrystalline fraction of proteins(by bleaching experiments and subsequent heating at high temperature), checking the closed system behaviour of this fraction during diagenesis. Only species which pass both tests can be considered suitable for further studies to obtain reliable age information. This amino acid geochronological technique is also applied to midden deposits at two latitudinal extremes: Northern Scotland and the Southern Red Sea.Results obtained in this study indicate that the application of this new method of AAR dating of shells has the potential to aid the geochronological investigation of shell mounds in different areas of the world

Wireless Power Transfer Closed-Loop Control for Low-Power Active Implantable Medical Devices

Near-field resonant inductive coupling is the most mature wireless power transfer (WPT) method for implantable medical devices. Common commercial WPT components are not optimized neither to deliver small amounts of power nor to work with other than small air gaps. In this paper, a closed-loop control is integrated with commercial off-the-shelf WPT components to efficiently recharge and power an implantable device for controlled active drug delivery. The system keeps the transmitted power stable and reliable, achieving a 26 % transfer efficiency with delivered power of tens of milliwatts, guaranteeing an autonomy of 5 days with a 4-hour recharge. Overheating is kept around the 2 °C safety limit

Electrostatically gated nanofluidic membrane for ultra-low power controlled drug delivery

Patient-centered therapeutic management for chronic medical conditions is a desired but unmet need, largely attributable to the lack of adequate technologies for tailored drug administration. While triggered devices that control the delivery of therapeutics exist, they often rely on impractical continuous external activation. As such, next-generation continuously tunable drug delivery systems independent of sustained external activation remain an elusive goal. Here we present the development and demonstration of a silicon carbide (SiC)-coated nanofluidic membrane that chieves reproducible and tunable control of drug release via electrostatic gating. By applying a low-intensity voltage to a buried electrode, we showed repeatable and reproducible in vitro release modulation of three model analytes. A small fluorophore (Alexa Fluor 647), a large polymer polyIJsodium 4-styrenesulfonate) and a medically relevant agent (DNA), were selected as representatives of small molecule therapeutics, polymeric drug carriers, and biological therapeutics, respectively. Unlike other drug delivery systems, our technology performed consistently over numerous cycles of voltage modulation, for over 11 days. Importantly, low power consumption and minimal leakage currents were achieved during the study. Further, the SiC coating maintained integrity and chemical inertness, shielding the membrane from degradation under simulated physiological and accelerated conditions for over 4 months. Through leveraging the flexibility offered by electrostatic gating control, our technology provides a valuable strategy for tunable delivery, setting the foundation for the next generation of drug delivery systems

Silicon Carbide-Gated Nanofluidic Membrane for Active Control of Electrokinetic Ionic Transport

Manipulation of ions and molecules by external control at the nanoscale is highly relevant to biomedical applications. We report a biocompatible electrode-embedded nanofluidic channel membrane designed for electrofluidic applications such as ionic field-effect transistors for implantable drug-delivery systems. Our nanofluidic membrane includes a polysilicon electrode electrically isolated by amorphous silicon carbide (a-SiC). The nanochannel gating performance was experimentally investigated based on the current-voltage (I-V) characteristics, leakage current, and power consumption in potassium chloride (KCl) electrolyte. We observed significant modulation of ionic diffusive transport of both positively and negatively charged ions under physical confinement of nanochannels, with low power consumption. To study the physical mechanism associated with the gating performance, we performed electrochemical impedance spectroscopy. The results showed that the flat band voltage and density of states were significantly low. In light of its remarkable performance in terms of ionic modulation and low power consumption, this new biocompatible nanofluidic membrane could lead to a new class of silicon implantable nanofluidic systems for tunable drug delivery and personalized medicine

Intratumoral Gold Nanoparticle-Enhanced CT Imaging: An in Vivo Investigation of Biodistribution and Retention

This study aims to evaluate the in vivo distribution of Gold Nanoparticles (GNPs) at different time points after intratumoral (IT) injection, exploiting their properties as contrast agents for Computed Tomography (CT). GNPs approximately 40 nm in diameter were synthesized with a surface plasmon peak at ~530 nm, capped with Bovine Serum Albumin (BSA) to improve colloidal stability, and characterized with standard methods. CT phantom imaging was performed to quantify X-ray attenuation as a function of GNP concentration and surface functionalization and to determine the appropriate particle dose for in vivo studies. Concentrated GNPs were intratumorally (IT) injected into Lewis Lung Carcinoma (LLC) solid tumors grown on the right flank of 6-week old female C57BL/6 mice. Ten days post-injection, follow up CT imaging was performed to assess the distribution and retention of the particles in the tumor. Using the CT attenuation quantification, images for each timepoint were segmented, and 3D volumes rendered, to conduct biodistribution analyses. The successful retention and permanence of the GNPs into the solid tumor after ten days suggests the significance of GNPs as a potential theranostic agent

A Periodic Transmission Line Model for Body Channel Communication

Body channel communication (BCC) is a technique for data transmission exploiting the human body as communication channel. Even though it was pioneered about 25 years ago, the identification of a good electrical model behind its functioning is still an open research question. The proposed distributed model can then serve as a supporting tool for the design, allowing to enhance the performances of any BCC system. A novel finite periodic transmission line model was developed to describe the human body as transmission medium. According to this model, for the first time, the parasitic capacitance between the transmitter and the receiver is assumed to depend on their distance. The parameters related to the body and electrodes are acquired experimentally by fitting the bio-impedentiometric measurements, in the range of frequencies from 1 kHz to 1 MHz, obtaining a mean absolute error lower than 4° and 30Ω for the phase angle and impedance modulus, respectively. The proposed mathematical framework has been successfully validated by describing a ground-referred and low-complexity system called Live Wire, suitable as supporting tool for visually impaired people, and finding good agreement between the measured and the calculated data, marking a ±3% error for communication distances ranging from 20 to 150 cm. In this work we introduced a new circuital approach, for capacitive-coupling systems, based on finite periodic transmission line, capable to describe and model BCC systems allowing to optimize the performances of similar systems

Unexpected behaviors in molecular transport through size-controlled nanochannels down to the ultra-nanoscale

Ionic transport through nanofluidic systems is a problem of fundamental interest in transport physics and has broad relevance in desalination, fuel cells, batteries, filtration, and drug delivery. When the dimension of the fluidic system approaches the size of molecules in solution, fluid properties are not homogeneous and a departure in behavior is observed with respect to continuum-based theories. Here we present a systematic study of the transport of charged and neutral small molecules in an ideal nanofluidic platform with precise channels from the sub-microscale to the ultra-nanoscale (<5 nm). Surprisingly, we find that diffusive transport of nano-confined neutral molecules matches that of charged molecules, as though the former carry an effective charge. Further, approaching the ultra-nanoscale molecular diffusivities suddenly drop by up to an order of magnitude for all molecules, irrespective of their electric charge. New theoretical investigations will be required to shed light onto these intriguing results

Silicon Nanofluidic Membrane for Electrostatic Control of Drugs and Analytes Elution

Individualized long-term management of chronic pathologies remains an elusive goal despite recent progress in drug formulation and implantable devices. The lack of advanced systems for therapeutic administration that can be controlled and tailored based on patient needs precludes optimal management of pathologies, such as diabetes, hypertension, rheumatoid arthritis. Several triggered systems for drug delivery have been demonstrated. However, they mostly rely on continuous external stimuli, which hinder their application for long-term treatments. In this work, we investigated a silicon nanofluidic technology that incorporates a gate electrode and examined its ability to achieve reproducible control of drug release. Silicon carbide (SiC) was used to coat the membrane surface, including nanochannels, ensuring biocompatibility and chemical inertness for long-term stability for in vivo deployment. With the application of a small voltage (&le; 3 V DC) to the buried polysilicon electrode, we showed in vitro repeatable modulation of membrane permeability of two model analytes&mdash;methotrexate and quantum dots. Methotrexate is a first-line therapeutic approach for rheumatoid arthritis; quantum dots represent multi-functional nanoparticles with broad applicability from bio-labeling to targeted drug delivery. Importantly, SiC coating demonstrated optimal properties as a gate dielectric, which rendered our membrane relevant for multiple applications beyond drug delivery, such as lab on a chip and micro total analysis systems (&micro;TAS)

Design of a Closed-Loop Wireless Power Transfer System for an Implantable Drug Delivery Device

Active Implantable Medical Devices (AIMDs) have seen a significant increase in popularity in recent years due to their ability to provide continuous therapy unobtrusively. One of the key challenges in developing next generation AIMDs is the design of a safe and reliable Wireless Power Transfer (WPT) system. Standard commercial WPT components are not optimized to deliver small amounts of power or to work with other than small air gaps. We developed a near-field resonant inductive coupling WPT system with closed-loop real-time control, based on the commercial off-the-shelf components and leveraging the already integrated wireless communication system. The system was used to recharge a secondary battery and power supply the Nanochannel Delivery System (nDS). We tested the system’s robustness by varying the coil spacing to a maximum of 20mm, and by misaligning the coils laterally and angularly up to 8mm and 12°, respectively. We performed these tests by simulating battery charging from 2.8 V to 4.1 V and we tested four coils, from 6mm to 19mm in diameter, to evaluate the best trade-off between effectiveness and miniaturization. Finally, we recharged the selected battery for two distances, 2.5mm and 6.5mm. The results show that the 17mm and 19mm coils have the highest peak efficiencies of 31.3% and 32.3% (26% and 26.3% on average), respectively, and provide a complete and reliable battery recharge in less than 5 hours while keeping the receiver coil temperature within 2 °C