A Dynamic Ultrasound Phantom with Tissue-Mimicking Mechanical and Acoustic Properties.

Tissue-mimicking phantoms are valuable tools that aid in improving the equipment and training available to medical professionals. However, current phantoms possess limited utility due to their inability to precisely simulate multiple physical properties simultaneously, which is crucial for achieving a system understanding of dynamic human tissues. In this work, novel materials design and fabrication processes to produce various tissue-mimicking materials (TMMs) for skin, adipose, muscle, and soft tissue at a human scale are developed. Target properties (Young's modulus, density, speed of sound, and acoustic attenuation) are first defined for each TMM based on literature. Each TMM recipe is developed, associated mechanical and acoustic properties are characterized, and the TMMs are confirmed to have comparable mechanical and acoustic properties with the corresponding human tissues. Furthermore, a novel sacrificial core to fabricate a hollow, ellipsoid-shaped bladder phantom complete with inlet and outlet tubes, which allow liquids to flow through and expand this phantom, is adopted. This dynamic bladder phantom with realistic mechanical and acoustic properties to human tissues in combination with the developed skin, soft tissue, and subcutaneous adipose tissue TMMs, culminates in a human scale torso tank and electro-mechanical system that can be systematically utilized for characterizing various medical imaging devices.

An Emerging Era: Conformable Ultrasound Electronics.

Conformable electronics are regarded as the next generation of personal healthcare monitoring and remote diagnosis devices. In recent years, piezoelectric-based conformable ultrasound electronics (cUSE) have been intensively studied due to their unique capabilities, including nonradiative monitoring, soft tissue imaging, deep signal decoding, wireless power transfer, portability, and compatibility. This review provides a comprehensive understanding of cUSE for use in biomedical and healthcare monitoring systems and a summary of their recent advancements. Following an introduction to the fundamentals of piezoelectrics and ultrasound transducers, the critical parameters for transducer design are discussed. Next, five types of cUSE with their advantages and limitations are highlighted, and the fabrication of cUSE using advanced technologies is discussed. In addition, the working function, acoustic performance, and accomplishments in various applications are thoroughly summarized. It is noted that application considerations must be given to the tradeoffs between material selection, manufacturing processes, acoustic performance, mechanical integrity, and the entire integrated system. Finally, current challenges and directions for the development of cUSE are highlighted, and research flow is provided as the roadmap for future research. In conclusion, these advances in the fields of piezoelectric materials, ultrasound transducers, and conformable electronics spark an emerging era of biomedicine and personal healthcare.

Interfacial Delamination at Multilayer Thin Films in Semiconductor Devices.

With the evolution of semiconducting industries, thermomechanical failure induced in a multilayered structure with a high aspect ratio during manufacturing and operation has become one of the critical reliability issues. In this work, the effect of thermomechanical stress on the failure of multilayered thin films on Si substrates was studied using analytical calculations and various thermomechanical tests. The residual stress induced during material processing was calculated based on plate bending theory. The calculations enabled the prediction of the weakest region of failure in the thin films. To verify our prediction, additional thermomechanical stress was applied to induce cracking and interfacial delamination by various tests. We assumed that, when accumulated thermomechanical-residual and externally applied mechanical stress becomes larger than a critical value the thin-film cracking or interfacial delamination will occur. The test results agreed well with the prediction based on the analytical calculation in that the film with maximum tensile residual stress is the most vulnerable to failure. These results will provide useful analytical and experimental prediction tools for the failure of multilayered thin films in the device design stage.

Intrinsically stretchable organic light-emitting diodes.

Soft and conformable optoelectronic devices for wearable and implantable electronics require mechanical stretchability. However, very few researches have been done for intrinsically stretchable light-emitting diodes. Here, we present an intrinsically stretchable organic light-emitting diode, whose constituent materials are all highly stretchable. The resulting intrinsically stretchable organic light-emitting diode can emit light when exposed to strains as large as 80%. The turn-on voltage is as low as 8 V, and the maximum luminance, which is a summation of the luminance values from both the anode and cathode sides, is 4400 cd m-2 It can also survive repeated stretching cycles up to 200 times, and small stretching to 50% is shown to substantially enhance its light-emitting efficiency.

Water Passivation of Perovskite Nanocrystals Enables Air-Stable Intrinsically Stretchable Color-Conversion Layers for Stretchable Displays.

Conventional organic light-emitting devices without an encapsulation layer are susceptible to degradation when exposed to air, so realization of air-stable intrinsically-stretchable display is a great challenge because the protection of the devices against penetration of moisture and oxygen is even more difficult under stretching. An air-stable intrinsically-stretchable display that is composed of an intrinsically-stretchable electroluminescent device (SELD) integrated with a stretchable color-conversion layer (SCCL) that contains perovskite nanocrystals (PeNCs) is proposed. PeNCs normally decay when exposed to air, but they become resistant to this decay when dispersed in a stretchable elastomer matrix; this change is a result of a compatibility between capping ligands and the elastomer matrix. Counterintuitively, the moisture can efficiently passivate surface defects of PeNCs, to yield significant increases in both photoluminescence intensity and lifetime. A display that can be stretched up to 180% is demonstrated; it is composed of an air-stable SCCL that down-converts the SELD's blue emission and reemits it as green. The work elucidates the basis of moisture-assisted surface passivation of PeNCs and provides a promising strategy to improve the quantum efficiency of PeNCs with the aid of moisture, which allows PeNCs to be applied for air-stable stretchable displays.

Wearable, Luminescent Oxygen Sensor for Transcutaneous Oxygen Monitoring.

We present a new concept for a wearable oxygen (O2) sensor for transcutaneous O2 pressure (tcpO2) monitoring by combining the technologies of luminescent gas sensing and wearable devices. O2 monitoring has been exhaustively studied given its central role in diagnosing various diseases. The ability to quantify the physiological distribution and real-time dynamics of O2 from the subcellular to the macroscopic level is required to fully understand mechanisms associated with both normal physiological and pathological conditions. Despite its profound biological and clinical importance, few effective methods exist for noninvasively quantifying O2 in a physiological setting. The wearable sensor developed here consists of three components: a luminescent sensing film attached onto skin by a carbon tape, an organic light-emitting diode (OLED) as a light source, and an organic photodiode (OPD) as a light detector. All the components are solution-processable and integrated on a plane in a bandage-like configuration. To verify the performance, tcpO2 variations by pressure-induced occlusion were measured in the lower arm and a thumb by the wearable sensor, and the results were comparable to those measured by a commercial instrument. In addition to its flexibility, other features of this sensor render it a potential low-cost solution for the simultaneous monitoring of tcpO2 in any part of a body.

Highly Conformable, Transparent Electrodes for Epidermal Electronics.

We present a highly conformable, stretchable, and transparent electrode for application in epidermal electronics based on polydimethylsiloxane (PDMS) and Ag nanowire (AgNW) networks. With the addition of a small amount of a commercially available nonionic surfactant, Triton X, PDMS became highly adhesive and mechanically compliant, key factors for the development of conformable and stretchable substrates. The polar functional groups present in Triton X interacted with the Pt catalyst present in the PDMS curing agent, thereby hindering the cross-linking reaction of PDMS and modulating the mechanical properties of the polymer. Due to the strong interactions that occur between the polar functional groups of Triton X and AgNWs, AgNWs were effectively embedded in the adhesive PDMS (a-PDMS) matrix, and the highly enhanced conformability, mechanical stretchability, and transparency of the a-PDMS matrix were maintained in the resulting AgNW-embedded a-PDMS matrix. Finally, wearable strain and electrocardiogram (ECG) sensors were fabricated from the AgNW-embedded a-PDMS. The a-PDMS-based strain and ECG sensors exhibited significantly improved sensing performances compared with those of the bare PDMS-based sensors because of the better stretchability and conformability to the skin of the former sensors.

Novel Patterning Method for Nanomaterials and Its Application to Flexible Organic Light-Emitting Diodes.

We present a simple, low-cost, and scalable method to form various patterns of nanomaterials with different dimensions and shapes using capillary and centrifugal forces. The desired patterns were formed on the surfaces of poly(dimethylsiloxane) (PDMS) stamps, and the PDMS stamps were conformally contacted with the surfaces of flexible polymer substrates. Solutions of nanomaterials, such as metal nanowires and nanoparticles, were then drop-casted at one open end of the microchannels formed at the interface of the polymer substrate and PDMS stamp. The nanomaterial solutions penetrated the microchannels due to capillary force interactions between the surfaces and the fluid. The solvents of the nanomaterial solutions exfiltrated from the entrance of microchannels because of the coffee ring effect. Then, the solvent remaining in the microchannels was discharged by applying a centrifugal force by spinning the polymer substrate/PDMS stamp system. Because of the synergistic effect of the capillary force, coffee ring effect, and centrifugal force, uniform patterns of the nanomaterials with clearly defined edges were formed for a variety of pattern shapes and substrates. Furthermore, the direct patterning approach resulted in a significant reduction in the amount of wasted materials. Finally, flexible organic light-emitting diodes were successfully fabricated on the finely patterned nanowire electrodes.

Wearable and Transparent Capacitive Strain Sensor with High Sensitivity Based on Patterned Ag Nanowire Networks.

In this study, a transparent and stretchable thin-film capacitive strain sensor based on patterned Ag nanowire networks (AgNWs) was successfully fabricated. The AgNWs were patterned using a capillary force lithography (CFL) method and were embedded onto the surface of the polydimethylsiloxane substrate. The strain (ε) sensitivity of the capacitive strain sensor was controlled and enhanced by patterning the AgNWs into electrodes with an interdigitated shape. The interdigitated capacitive strain sensor (ICSS) is expected to have -1.57 gauge factor (GF) at 30% ε by calculation, which is much higher than the sensitivity of typical parallel-plate-type capacitive strain sensors. Because of the interdigitated pattern of the electrodes, the GF of the ICSS was increased up to -2.0. The ICSS had no hysteresis behavior up to ε values of 15% and showed stable ε sensing performance during the repeated stretching test at ε values of 10% for 1000 cycles. Furthermore, there was no cross talk between ε and pressure sensing in the AgNW-based ICSS, which was found to be insensitive to externally applied pressure. The ICSS was then used to detect the finger and wrist muscle motions of the human body to simulate its application to large and small ε sensing.

Silica nanoparticle-based dual imaging colloidal hybrids: cancer cell imaging and biodistribution.

In this study, fluorescent dye-conjugated magnetic resonance (MR) imaging agents were investigated in T mode. Gadolinium-conjugated silica nanoparticles were successfully synthesized for both MR imaging and fluorescence diagnostics. Polyamine and polycarboxyl functional groups were modified chemically on the surface of the silica nanoparticles for efficient conjugation of gadolinium ions. The derived gadolinium-conjugated silica nanoparticles were investigated by zeta potential analysis, transmission electron microscopy, inductively coupled plasma mass spectrometry, and energy dispersive x-ray spectroscopy. MR equipment was used to investigate their use as contrast-enhancing agents in T1 mode under a 9.4 T magnetic field. In addition, we tracked the distribution of the gadolinium-conjugated nanoparticles in both lung cancer cells and organs in mice.

Foldable Transparent Substrates with Embedded Electrodes for Flexible Electronics.

We present highly flexible transparent electrodes composed of silver nanowire (AgNW) networks and silica aerogels embedded into UV-curable adhesive photopolymers (APPs). Because the aerogels have an extremely high surface-to-volume ratio, the enhanced van der Waals forces of the aerogel surfaces result in more AgNWs being uniformly coated onto a release substrate and embedded into the APP when mixed with an AgNW solution at a fixed concentration. The uniform distribution of the embedded composite electrodes of AgNWs and aerogels was verified by the Joule heating test. The APP with the composite electrodes has a lower sheet resistance (Rs) and a better mechanical stability compared with APP without aerogels. The APP with the embedded electrodes is a freestanding flexible substrate and can be used as an electrode coating on a polymer substrate, such as polydimethylsiloxane and polyethylene terephthalate. On the basis of the bending test results, the APPs with composite electrodes were sufficiently flexible to withstand a 1 mm bending radius (rb) and could be foldable with a slight change in Rs. Organic light emitting diodes were successfully fabricated on the APP with the composite electrodes, indicating the strong potential of the proposed flexible TEs for application as highly flexible transparent conductive substrates.

A trachea-inspired bifurcated microfilter capturing viable circulating tumor cells via altered biophysical properties as measured by atomic force microscopy.

Circulating tumor cells (CTCs), though exceedingly rare in the blood, are nonetheless becoming increasingly important in cancer diagnostics. Despite this keen interest and the growing number of potential clinical applications, there has been limited success in developing a CTC isolation platform that simultaneously optimizes recovery rates, purity, and cell compatibility. Herein, a novel tracheal carina-inspired bifurcated (TRAB) microfilter system is reported, which uses an optimal filter gap size satisfying both 100% theoretical recovery rate and purity, as determined by biomechanical analysis and fluid-structure interaction (FSI) simulations. Biomechanical properties are also used to clearly discriminate between cancer cells and leukocytes, whereby cancer cells are selectively bound to melamine microbeads, which increase the size and stiffness of these cells. Nanoindentation experiments are conducted to measure the stiffness of leukocytes as compared to the microbead-conjugated cancer cells, with these parameters then being used in FSI analyses to optimize the filter gap size. The simulation results show that given a flow rate of 100 µL min(-1), an 8 µm filter gap optimizes the recovery rate and purity. MCF-7 breast cancer cells with solid microbeads are spiked into 3 mL of whole blood and, by using this flow rate along with the optimized microfilter dimensions, the cell mixture passes through the TRAB filter, which achieves a recovery rate of 93% and purity of 59%. Regarding cell compatibility, it is verified that the isolation procedure does not adversely affect cell viability, thus also confirming that the re-collected cancer cells can be cultured for up to 8 days. This work demonstrates a CTC isolation technology platform that optimizes high recovery rates and cell purity while also providing a framework for functional cell studies, potentially enabling even more sensitive and specific cancer diagnostics.

Assessing the activity and diversity of fumarate-fed denitrifying bacteria by performing field single-well push-pull tests.

In situ biological denitrification has been proposed as an important metabolic activity in the remediation of nitrate-contaminated groundwater. In this study, the effects of fumarate, an electron donor for biological denitrification, on the in situ denitrifying activity were determined by using three types of single-well push-pull tests; transport, biostimulation and activity tests. During the tests, changes in microbial community composition were also investigated using denaturing gradient gel electrophoresis (DGGE) of 16S rRNA genes. Transport test demonstrated that non-reactive tracer and biologically reactive solutes behaved similarly. A biostimulation test was conducted to stimulate the denitrifying activities of native microorganisms, which were monitored by detecting the simultaneous production of CO(2) and drastic degradations of both nitrate and fumarate after the injection of fumarate as an electron donor and/or carbon source, with nitrate as an electron acceptor. A phylogenetic analysis suggested that the taxonomic affiliation of the dominant species before biostimulation was γ-Proteobacteria, including Acinetobacter species and Pseudomonas fluorescens, while the dominant species after biostimulation were affiliated with ß-Proteobacteria, cytophaga-Flavobacterium-Bacteroides and high G+C gram-positive bacteria. These results suggest that the analyses of groundwater samples using a combination of single well push pull tests with DGGE can be applied to investigate the activity, diversity and composition shift of denitrifying bacteria in a nitrate-contaminated aquifer.

Efficient intracellular siRNA delivery strategy through rapid and simple two steps mixing involving noncovalent post-PEGylation.

Two different and well-defined methacrylate-based (co)polymers were employed as a polymeric siRNA delivery system. siRNA, poly(2-(dimethylamino) ethyl methacrylate) homopolymers (PDMAEMA) and poly(2-(dimethylamino) ethyl methacrylate)-b-poly (ethyleneglycol) alpha-methoxy, omega-methacrylate (PDMAEMA-b-PMAPEG) palm-tree-like copolymer ternary complexes were prepared using a rapid and simple two-step mixing protocol involving noncovalent post-PEGylation, and physicochemical properties including hydrodynamic diameter, zeta-potential and siRNA condensation efficiency were characterized. Transfection efficiency, intracellular uptake, and cytotoxicity of ternary complexes were also evaluated. Ternary complexes provide efficient condensation and compaction of siRNA within the cationic core of complexes. Noncovalent post-PEGylation provides the ternary complexes with enzymatic and serum stability without harming complex formation and condensation of siRNA. Thereby, under an optimal N/P ratio, ternary complexes exhibited brilliant gene silencing efficiency with low cytotoxicity in media containing 10% serum. Confocal microscopy clearly showed efficient and even intracellular uptake of complexes by cells via endocytosis. This study highlights the excellent properties of noncovalent post-PEGylated ternary complexes produced by rapid and simple mixing. Accordingly, these findings suggest that the formation of ternary complexes could be utilized as a safe and effective polymeric siRNA delivery strategy.

Antiobesity effects and improvement of insulin sensitivity by 1-deoxynojirimycin in animal models.

The alpha-glucosidase inhibitor 1-deoxynojirimycin (DNJ) is one of the simplest naturally occurring carbohydrate mimics, with promising biological activity in vivo. Although there is considerable interest in the pharmacological effects of DNJ, the antidiabetic effects of DNJ in type 2 diabetes mellitus have received little attention. In this work, DNJ was isolated from the silkworm (Bombyx mori), and its antidiabetic effects were evaluated in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an established animal model of human type 2 diabetes mellitus, and in control Long-Evans Tokushima Otsuka (LETO) rats. DNJ treatment showed significant antidiabetic effects in OLETF rats, with significant improvements in fasting blood glucose levels and glucose tolerance and, especially, increased insulin sensitivity. Furthermore, there was significant loss of body weight in both groups. DNJ also showed significant antihyperglycemic effects in streptozotocin- and high-fat-diet-induced hyperglycemic rats. Its efficacy and dose profiles were better than those of acarbose, a typical alpha-glucosidase inhibitor in clinical use. Furthermore, a substantial fraction of DNJ was absorbed into the bloodstream within a few minutes of oral administration. DNJ was also detected in the urine. These findings suggest that its postprandial hypoglycemic effect in the gastrointestinal tract is a possible but insufficient mechanism of action underlying the antidiabetic effects of DNJ. Its antiobesity effect and improvement of insulin sensitivity are other possible antidiabetic effects of DNJ.

Use of omentum as an in vivo cell culture system in tissue engineering.

Many modifications of in vitro culture techniques have been applied to promote tissue formation, resulting in limitations. Because the omentum is composed of lobes of adipose tissue with abundant blood vessels and has been used for organ reconstruction, we used the omentum as an in vivo culture system to promote cellular proliferation upon the scaffold. Two kinds of autogenous cells, oral epithelial cells and rib chondrocytes, obtained from canine were isolated and then seeded on porous poly-lactic-glycolic acid scaffolds of a pre-determined shape and size. Comparison was performed in two groups. In Group 1, cell-polymer constructs were cultured in vitro for 2 weeks, and in group 2, cell-polymer constructs were cultured in vitro for 1 week following the same protocol as group 1 but were then implanted into the omentum of same canines for the next week. We performed histologic analysis of tissue formation between the two groups. In group 1, seeded cells were presented spatially along the porous polymer surface only. However, in group 2, the cell-polymer constructs maintained their original dimensions and showed formation of a multicell layered structure with abundant blood vessels. We concluded that the use of the omentum as an in vivo culture medium offers possibilities as an efficient and effective method for tissue engineering with greater vascularization and more consistent cell spacing throughout the construct.

Effect of different particles on cell proliferation in polymer scaffolds using a solvent-casting and particulate leaching technique.

Solvent-casting and particulate leaching are widely used in the manufacturing of porous polymer scaffolds. Salt is the most commonly used particulate because it is easily available and very easy to handle. Gelatin particles are another candidate for this method because they are known as a material that enhances cell attachment and proliferation. In this study, we compared the biocompatibility of the two scaffolds made from either salt (salt scaffold) or gelatin particles (gelatin scaffold). Sieved particles of salt and gelatin (particle size ranging 100-180 um) were dispersed in a poly-lactic-co-glycolic acid (PLGA)/chloroform solution and cast in a Teflon container. The solvent was allowed to evaporate and residual amounts were removed by vacuum drying. The particles were allowed to leach out by immersion in warm water (40 degrees C). Cultured chondrocytes (from knee cartilage) and smooth muscle cells (from bladder) were seeded on each scaffolds (5 x 10(6)/cm2) and cultured for 3 weeks, and their proliferation was compared using hematoxylin and eosin staining. These results demonstrated that the gelatin scaffold showed better attachment of cells at the initial stage, and both cell types showed much better proliferation of cells during 3 months. The better performance of a gelatin scaffold also contributed to the better connection of pores at the same porosity.