Hybrid organic-inorganic nano-composites for solid-state battery electrolytes

Desired properties of solid electrolytes are high ionic conductivity and transference number, high shear modulus to prevent dendrite growth, chemical compatibility with electrodes, and ease of fabrication into thin films. Especially, elastic stiffness and ionic mobility are opposing attributes in a homogenous material, and a composite approach towards designing novel electrolytes is therefore advisable. We use a two-step sol-gel method to synthesize silica-based hybrid organic-inorganic materials for this application. First, a continuous porous silica structure is created that provides electrochemical stability and mechanical rigidity. This network also contains unreacted epoxy groups. In step 2, single-sided amine-functionalized polyethene glycol (PEG-NH2) infiltrates the pores via fluid exchange. As PEG-NH2 fills the pores, the amine groups react with the epoxy groups and anchor the polymer to the silica network, which provides highly conductive pathways. IR spectroscopy, Raman and Brillouin light scattering, impedance spectroscopy, small angel x-ray scattering (SAXS), charge-discharge cell testing is performed to identify the structural and chemical origins that underlie the performance of these hybrid electrolytes. A room temperature ionic conductivity in excess of 10-5 S/cm is reached (Fig. 1). Please click Additional Files below to see the full abstract

Generation of an in vitro 3D PDAC stroma rich spheroid model

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a prominent desmoplastic/stromal reaction, which contributes to the poor clinical outcome of this disease. Therefore, greater understanding of the stroma development and tumor-stroma interactions is highly required. Pancreatic stellate cells (PSC) are myofibroblast-like cells that located in exocrine areas of the pancreas, which as a result of inflammation produced by PDAC migrate and accumulate in the tumor mass, secreting extracellular matrix components and producing the dense PDAC stroma. Currently, only a few orthotopic or ectopic animal tumor models, where PDAC cells are injected into the pancreas or subcutaneous tissue layer, or genetically engineered animals offer tumors that encompass some stromal component. Herein, we report generation of a simple 3D PDAC in vitro micro-tumor model without an addition of external extracellular matrix, which encompasses a rich, dense and active stromal compartment. We have achieved this in vitro model by incorporating PSCs into 3D PDAC cell culture using a modified hanging drop method. It is now known that PSCs are the principal source of fibrosis in the stroma and interact closely with cancer cells to create a tumor facilitatory environment that stimulates local and distant tumor growth. The 3D micro-stroma models are highly reproducible with excellent uniformity, which can be used for PDAC-stroma interaction analysis and high throughput automated drug-screening assays. Additionally, the increased expression of collagenous regions means that molecular based perfusion and cytostaticity of gemcitabine is decreased in our Pancreatic adenocarcinoma stroma spheroids (PDAC-SS) model when compared to spheroids grown without PSCs. We believe this model will allow an improved knowledge of PDAC biology and has the potential to provide an insight into pathways that may be therapeutically targeted to inhibit PSC activation, thereby inhibiting the development of fibrosis in PDAC and interrupting PSC-PDAC cell interactions so as to inhibit cancer progression

Development of Hybrid Electrolytes for Solid-State Batteries

Lithium-ion batteries that use solid-state electrolytes are crucial energy storage devices with widespread applications in small and large electronics, electric vehicles, electric aircrafts and grid-level energy storage. Conventional lithium-ion batteries based on liquid electrolytes lack chemical stability, have inherent safety issues, and incur a high production cost. Solid state electrolytes (SSEs) not only have the potential to correct these drawbacks but exhibit improved mechanical properties, which allows one to reduce the battery size, suppress dendrite growth, opening the possibility for metal anodes, and thus increase its energy density. However, power density requires good charge carrier mobility, which varies conversely with the factors that control mechanical properties. Thus, to simultaneously achieve high ionic conductivity and elastic moduli, we pursue a hybrid organic-inorganic composite materials design approach for creating the required SSEs. Our hybrid electrolytes consist of a nano-porous silica backbone obtained through sol-gel synthesis that provides a three-dimensional percolating mechanically rigid scaffold. Polymer is subsequently deposited in the pores of this network via solution exchange, where it establishes the conducting phase. This unique approach allows us to decouple mechanical from cation transport properties of the material and achieve both high elastic stiffness and ionic conductivity. To increase the cation transference number, and thereby the Coulomb efficiency of the devices, we tether the cation donor to the silica scaffold. Initially, we aimed to do this with polymer chains as the intermediary. While this approach did not yield the desired outcome, we discovered that the properties of the gel-cast material are strongly influenced by unexpected structural evolution during drying, to the effect that ionic conductivities can vary by up to three orders of magnitude in these hybrids, without modifying their chemical makeup. Depending on the sample shape and aspect ratio, the drying process occurs inhomogeneously, imparting various degrees of anisotropy and spatial gradients that can be affect the development of the network topology. Cylindrical disk-shaped samples dry and rigidify first on their periphery, causing tensile stresses to build towards the center as the drying front progresses inward. This causes reconditioning of the network structure at the core of the disk, resulting in a markedly higher conductivity with minimal reduction of mechanical stiffness. We successfully developed an alternative approach for immobilizing cation donors and increasing the transference number of Li+ to greater than 0.9. To this end we modified sulfonyl (trifluoromethylsulfonyl) imide (STFSI) chemistry by functionalizing the side chain of tetraethyl orthosilicate to incorporate the STFSI cation donor directly into the silica backbone. This approach significantly enhances the ionic mobility without negatively impacting the chemical or physical stability of the material. Moreover, we show that of anchoring oligo-PEO to the silica backbone, entangles with additional non-bonded short-chain PEO further enhances ionic conductivity in the solid electrolyte. To boost the ionic conductivity even more, a mixture of propylene carbonate (PC) and ethylene carbonate (EC) with various weight fractions was introduced in the silica backbone. This configuration yields the highest conductivity for the composite system, while the nano-confinement enhances the physical stability of EC and PC.PHDMaterials Science and EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/174532/1/kvazrik_1.pd

Enhanced MRI relaxivity of aquated Gd3+ﾠions by carboxyphenylated water-dispersed graphene nanoribbons

The present study demonstrates that highly water-dispersed graphene nanoribbons dispersed by carboxyphenylated substituents and conjugated to aquated Gd3+ﾠions can serve as a high-performance contrast agent (CA) for applications inﾠT1- andﾠT2-weighted magnetic resonance imaging (MRI) with relaxivity (r1,2) values outperforming currently-available clinical CAs by up to 16 times forﾠr1ﾠand 21 times forﾠr2

Optimizing non-invasive radiofrequency hyperthermia treatment for improving drug delivery in 4T1 mouse breast cancer model

Interactions of high-frequency radio waves (RF) with biological tissues are currently being investigated as a therapeutic platform for non-invasive cancer hyperthermia therapy. RF delivers thermal energy into tissues, which increases intra-tumoral drug perfusion and blood-flow. Herein, we describe an optical-based method to optimize the short-term treatment schedules of drug and hyperthermia administration in a 4T1 breast cancer model via RF, with the aim of maximizing drug localization and homogenous distribution within the tumor microenvironment. This method, based on the analysis of fluorescent dyes localized into the tumor, is more time, cost and resource efficient, when compared to current analytical methods for tumor-targeting drug analysis such as HPLC and LC-MS. Alexa-Albumin 647 nm fluorphore was chosen as a surrogate for nab-paclitaxel based on its similar molecular weight and albumin driven pharmacokinetics. We found that RF hyperthermia induced a 30-40% increase in Alexa-Albumin into the tumor micro-environment 24 h after treatment when compared to non-heat treated mice. Additionally, we showed that the RF method of delivering hyperthermia to tumors was more localized and uniform across the tumor mass when compared to other methods of heating. Lastly, we provided insight into some of the factors that influence the delivery of RF hyperthermia to tumors

Surfactant-free Gd3+-ion-containing carbon nanotube MRI contrast agents for stem cell labeling

There is an ever increasing interest in developing new stem cell therapies. However, imaging and tracking stem cells in vivo after transplantation remains a serious challenge. In this work, we report new, functionalized and high-performance Gd3+-ion-containing ultra-short carbon nanotube (US-tube) MRI contrast agent (CA) materials which are highly-water-dispersible (ca. 35 mg ml−1) without the need of a surfactant. The new materials have extremely high T1-weighted relaxivities of 90 (mM s)−1 per Gd3+ ion at 1.5 T at room temperature and have been used to safely label porcine bone-marrow-derived mesenchymal stem cells for MR imaging. The labeled cells display excellent image contrast in phantom imaging experiments, and TEM images of the labeled cells, in general, reveal small clusters of the CA material located within the cytoplasm with 109 Gd3+ ions per cell

Real-time RF-IVM imaging and post capture analysis.

<p>RF exposure shows transport of fluorescently bound albumin across the perfusion barrier into tumor region. Figure (A) and (B) depict the blue image channel (albumin) before and after (4.5 min) RF exposure. This data is shown superimposed with the tumor (red) channel in Figure (C) and (D). Figure (E) Control mouse (no RF) was imaged for 30 minutes on both channels. There is no transport of albumin into the tumor across the perfusion barrier. (F) Time lapsed images of the data shown in Figure (A) and (B). Figure (G) 4T1 tumor slices immunohistologically stained to the antibodies CD31 (green, vasculature endothelial cells), and albumin (red) for both RF (left image) and non-RF (right image) groups. Figure (H) depicts positive area fraction (PAF) of albumin accumulation in tumor slices. Finally, (I) is a quantitative video analysis of relative increase in albumin fluorescence (RAIF) in multiple 4T1 tumor surfaces exposed to RF under IVM (n = 4).</p

Portable RF system retrofitted to the IVM.

<p>(A) The RF system integrated into the intravital microscope (IVM) for real-time imaging under RF exposure. (B) Mouse manipulation for imaging–an incision is made to expose and gently manipulate the 4T1 tumor for IVM imaging. (C) 4T1 tumor under IVM illumination with a x4 objective lens.</p

Modulation of tumor temperature using RF exposure.

<p>(A) Thermal fiber optic probe placement. Probes #1–3 are positioned (i) under the skin but above the tumor; (ii) under the skin in between the tumor and the main body; and (iii) under the skin next to the intraperitoneal cavity. (B) Extracted thermal probe data. The recorded temperature of the probes was modulated by turning on and off the RF system (+RF and–RF). The system was turned off once the tumor temperature (probe #1) reached 45°C, 43°C, and 41°C, respectively, and was turned on when all probes had values in the range ~29–31°C. (C) The IR camera simultaneously measured the surface temperature of the points where the thermal probes were located.</p