A Needle-Free Transdermal Patch for Sampling Interstitial Fluid.

OBJECTIVE: Modern diagnostics is pivoting towards less invasive health monitoring in dermal interstitial fluid, rather than blood or urine. However, the skin's outermost layer, the stratum corneum, makes accessing the fluid more difficult without invasive, needle-based technology. Simple, minimally invasive means for surpassing this hurdle are needed. METHODS: To address this problem, a flexible, Band-Aid-like patch for sampling interstitial fluid was developed and tested. This patch uses simple resistive heating elements to thermally porate the stratum corneum, allowing the fluid to exude from the deeper skin tissue without applying external pressure. Fluid is then transported to an on-patch reservoir through self-driving hydrophilic microfluidic channels. RESULTS: Testing with living, ex-vivo human skin models demonstrated the device's ability to rapidly collect sufficient interstitial fluid for biomarker quantification. Further, finite-element modeling showed that the patch can porate the stratum corneum without raising the skin's temperature to pain-inducing levels in the nerve-laden dermis. CONCLUSION: Relying only on simple, commercially scalable fabrication methods, this patch outperforms the collection rate of various microneedle-based patches, painlessly sampling a human bodily fluid without entering the body. SIGNIFICANCE: The technology holds potential as a clinical device for an array of biomedical applications, especially with the integration of on-patch testing.

Real-Time Detection and Capture of Invasive Cell Subpopulations from Co-Cultures.

Invasion and metastatic spread of cancer cells are the major cause of death from cancer. Assays developed early on to measure the invasive potential of cancer cell populations typically generate a single endpoint measurement that does not distinguish between cancer cell subpopulations with different invasive potential. Also, the tumor microenvironment consists of different resident stromal and immune cells that alter and participate in the invasive behavior of cancer cells. Invasion into tissues also plays a role in immune cell subpopulations fending off microorganisms or eliminating diseased cells from the parenchyma and endothelial cells during tissue remodeling and angiogenesis. Real-Time Cellular Analysis (RTCA) that utilizes impedance biosensors to monitor cell invasion was a major step forward beyond endpoint measurement of invasion: this provides continuous measurements over time and thus can reveal differences in invasion rates that are lost in the endpoint assay. Using current RTCA technology, we expanded dual-chamber arrays by adding a further chamber that can contain stromal and/or immune cells and allows measuring the rate of invasion under the influence of secreted factors from co-cultured stromal or immune cells over time. Beyond this, the unique design allows for detaching chambers at any time and isolating of the most invasive cancer cell, or other cell subpopulations that are present in heterogeneous mixes of tumor isolates tested. These most invasive cancer cells and other cell subpopulations drive malignant progression to metastatic disease, and their molecular characteristics are important for in-depth mechanistic studies, the development of diagnostic probes for their detection, and the assessment of vulnerabilities. Thus, the inclusion of small- or large-molecule drugs can be used to test the potential of therapies that target cancer and/or stromal cell subpopulations with the goal of inhibiting (e.g., cancer cells) or enhancing (e.g., immune cells) invasive behavior.

Modeling Dynamic Surface Tension on Surfactant-Enhanced Polydimethylsiloxane.

Surfactants are often added to aqueous solutions to induce spreading on otherwise unwettable hydrophobic surfaces. Alternatively, they can be introduced directly into solid hydrophobic materials─such as the soft elastomer, polydimethylsiloxane─to induce autonomous wetting without requiring additional surface or liquid modifications. Given the similarity between mechanisms of these two approaches, models that describe wetting by aqueous surfactant solutions should also characterize wetting on surfactant-solid systems. To investigate this theory, multiple surfactants of varying size and chemical composition were added to prepolymerized PDMS samples. After cross-linking, water droplets were placed on the surfaces at set time points, and their contact angles were recorded to track the temporal evolution of the interfacial tension. Multiple nonlinear models were fitted to this data, their parameters were analyzed, and each goodness of fit was compared. An empirical model of dynamic surface tension was found to describe the wetting process better than the single established model found in the literature. The proposed model adapted better to the longer time scales induced by slow molecular diffusivity in PDMS. Siloxane ethoxylate surfactants induced faster and more complete wetting of PDMS by water than oxyoctylphenol ethoxylates did. The generalizability of this model for characterizing nonionic surfactants of a wide range of physiochemical properties was demonstrated.

Tuning the Polarity of MoTe2 FETs by Varying the Channel Thickness for Gas-Sensing Applications.

In this study, electrical characteristics of MoTe2 field-effect transistors (FETs) are investigated as a function of channel thickness. The conductivity type in FETs, fabricated from exfoliated MoTe2 crystals, switched from p-type to ambipolar to n-type conduction with increasing MoTe2 channel thickness from 10.6 nm to 56.7 nm. This change in flake-thickness-dependent conducting behavior of MoTe2 FETs can be attributed to modulation of the Schottky barrier height and related bandgap alignment. Change in polarity as a function of channel thickness variation is also used for ammonia (NH3) sensing, which confirms the p- and n-type behavior of MoTe2 devices.

Highly aligned and geometrically structured poly(glycerol sebacate)-polyethylene oxide composite fiber matrices towards bioscaffolding applications.

The biocompatible and biodegradable polymer poly(glycerol sebacate), or PGS, is a rubber-like material that finds use in several biomedical applications. PGS is often cast into a mold to form desired structures; alternatively, blending PGS with other reinforcing polymers produces viscous solutions that can be spun into non-woven fibrous scaffolds. For tissue scaffolding applications, ordered fibrous matrices are advantageous and have been shown to promote cell orientation and proliferation by contact guidance, providing topographical cues for the seeded cells. The development of techniques for easily producing aligned fibrous matrices is therefore a priority. PGS nanofibers have been fabricated successfully using electrospinning techniques. For producing PGS microfibers, we introduce the electro-less STRAND (Substrate Translation and Rotation for Aligned Nanofiber Deposition) process as an alternative to electrospinning. STRAND provides superior control of fiber properties including diameter, alignment, spacing, and therefore deposition density by mechanically drawing polymer fibers from solution. The goal in using this method is the simple production of aligned PGS fiber matrices for retinal tissue scaffolding.

Automated Mechanical Exfoliation of MoS2 and MoTe2 Layers for 2D Materials Applications.

An automated technique is presented for mechanically exfoliating single-layer and few-layer transition metal dichalcogenides using controlled shear and normal forces imposed by a parallel plate rheometer. A thin sample that is removed from bulk MoS2 or MoTe2 is initially attached to the movable upper fixture of the rheometer using blue dicing tape while the lower base plate also has the same tape to capture and exfoliate samples when the two plates are brought into contact then separated. A step-and-repeat exfoliation process is initiated using a preprogrammed contact force and liftoff speed. It was determined that atomically thin films of these materials could be obtained reproducibly using this technique, achieving single-layer and few-layer thicknesses for engineering novel 2D transistor devices for future electronic technologies. We show that varying the parameters of the rheometer program can improve the mechanical exfoliation process.

Control of polarity in multilayer MoTe2 field-effect transistors by channel thickness.

In this study, electronic properties of field-effect transistors (FETs) fabricated from exfoliated MoTe2 single crystals are investigated as a function of channel thickness. The conductivity type in FETs gradually changes from n-type for thick MoTe2 layers (above ≈ 65 nm) to ambipolar behavior for intermediate MoTe2 thickness (between ≈ 60 and 15 nm) to p- type for thin layers (below ≈ 10 nm). The n-type behavior in quasi-bulk MoTe2 is attributed to doping with chlorine atoms from the TeCl4 transport agent used for the chemical vapor transport (CVT) growth of MoTe2. The change in polarity sign with decreasing channel thickness may be associated with increasing role of surface states in ultra-thin layers, which in turn influence carrier concentration and dynamics in the channel due to modulation of Schottky barrier height and band-bending at the metal/semiconductor interface.

Hysteresis modeling in ballistic carbon nanotube field-effect transistors.

Theoretical models are adapted to describe the hysteresis effects seen in the electrical characteristics of carbon nanotube field-effect transistors. The ballistic transport model describes the contributions of conduction energy sub-bands over carbon nanotube field-effect transistor drain current as a function of drain-source and gate-source voltages as well as other physical parameters of the device. The limiting-loop proximity model, originally developed to understand magnetic hysteresis, is also utilized in this work. The curves obtained from our developed model corroborate well with the experimentally derived hysteretic behavior of the transistors. Modeling the hysteresis behavior will enable designers to reliably use these effects in both analog and memory applications.

Using electrospun poly(ethylene-oxide) nanofibers for improved retention and efficacy of bacteriolytic antibiotics.

The aim of this study was to demonstrate targeted delivery of protein-based bactericidal antibiotics using electrospun polymer nanofibers. Previous studies have utilized electrospinning to create nanofibers for the localized delivery of therapeutic agents, including non-steroidal anti-inflammatory drugs (NSAIDs) and low molecular weight heparin. By employing established electrospinning techniques, nanofibers of varying diameters (100-500 nm) were generated from a 0.05 % solution of poly(ethylene-oxide) (PEO) and the antimicrobial peptide, LL-37 was incorporated into the nanofiber meshwork. Initial experiments determined that the strong electric fields caused by electrospinning do not disrupt the antimicrobial properties of LL-37, thus justifying the application of LL-37 as an electrospun component. Disk diffusion assays and especially bacterial filtration studies with E. coli were conducted to quantify the drug delivery potential of the nanofibers. Disk diffusion revealed a small zone of inhibition of about 1 mm around the LL-37-incorporated nanofiber disk. Filtration tests demonstrated that electrospun PEO fibers were capable of delivering LL-37 consistently while still maintaining their antimicrobial abilities.

Electron-hole transport and photovoltaic effect in gated MoS2 Schottky junctions.

Semiconducting molybdenum disulfphide has emerged as an attractive material for novel nanoscale optoelectronic devices due to its reduced dimensionality and large direct bandgap. Since optoelectronic devices require electron-hole generation/recombination, it is important to be able to fabricate ambipolar transistors to investigate charge transport both in the conduction band and in the valence band. Although n-type transistor operation for single-layer and few-layer MoS2 with gold source and drain contacts was recently demonstrated, transport in the valence band has been elusive for solid-state devices. Here we show that a multi-layer MoS2 channel can be hole-doped by palladium contacts, yielding MoS2 p-type transistors. When two different materials are used for the source and drain contacts, for example hole-doping Pd and electron-doping Au, the Schottky junctions formed at the MoS2 contacts produce a clear photovoltaic effect.

Novel in-situ decoration of single-walled carbon nanotube transistors with metal nanoparticles.

The carbon nanotube-metal nanoparticle complex has attracted a lot of research interest because of their potential applications in catalysis and gas sensing. Here we introduce a novel electrochemical method to realize in-situ decoration of single-walled carbon nanotube field effect transistors (CNT-FET) with metal nanoparticles using a sacrificial electrode. In this process, metal atoms are first ionized into an electrolyte solution by applying a potential difference between the sacrificial electrode and the grounded source/drain electrodes connecting the nanotube of the CNT-FET. The positive metal ions migrate under the influence of the electric field, and deposit on the grounded nanotube as metal nanoparticles. This method provides for better control over the quantity and size of the deposited nanoparticles compared to other decoration methods. We demonstrate successful deposition of Au and Ag nanoparticles on carbon nanotube field effect devices, with the quantity and size of the nanoparticles varying as a function of the applied potential. We show that the metal nanoparticle size can vary from 10 nm to over 300 nm, and the spatial distribution can change from very scarce decoration to a near continuous coating. Such metal nanoparticles have potential applications in chemical sensors, as they interact with gas molecules and generate an electrical signal in the nanotube, which can be detected. They can also be explored as biological anchoring sites for bio-functionalization of the nanotube, which is critical to developing highly sensitive and selective bio-sensors.