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We propose and demonstrate a converged optical fronthaul network for RF and data services with scalable silicon photonic switching. A 1.5dB power penalty at a 10-9 BER and over 40dB RF dynamic range are demonstrated.

Abstract One-dimensional substrates such as textile fibers and threads offer an excellent opportunity to realize sensors, actuators, energy harvesters/storage, microfluidics, and advanced therapies. A new generation of wearable devices made from smart threads offer ultimate flexibility and seamless integration with the human body and the garments that adorn them. This article reviews the state of the art in thread-based wearable devices for monitoring human activity and performance, diagnoses and manages medical conditions, and provides new and improved human–machine interfaces. In the area of new and improved human–machine interfaces, it discusses novel computing platforms enabled using thread-based electronics and batteries/capacitors. For physical activity monitoring, a review of wearable devices using strain sensing threads is provided. Thread-based devices that can monitor health from biological fluids such as total analysis systems, wearable sweat sensing patches, and smart sutures/smart bandages are also included. The article concludes with an outlook on how fibers and threads are expected to impact and revolutionize the next generation of wearable devices. Knowledge gaps and emerging opportunities are presented. Graphic Abstract

Recent research suggests the widespread existence of the signal-to-noise paradox in seasonal-to-decadal climate predictions. The essence of the paradox is that the signal-to-noise ratio in models can be unrealistically small and models may make better predictions of the observations than they predict themselves. The paradox highlights a potentially serious issue with model predictions as previous studies may underestimate the limit of predictability. The focus of this paper is two-fold: the first objective is to re-examine decadal predictability from the lens of the signal-to-noise paradox in the context of CMIP5 models. We demonstrate that decadal predictability is generally underestimated in CMIP5 models possibly due to the existence of the signal-to-noise paradox. Models underestimate decadal predictability in regions where it is likely for the paradox to exist, especially over the Tropical Atlantic Ocean and Tropical Indian Ocean and eddy-rich regions, including the Gulf Stream, Kuroshio Current, and Southern Ocean. The second objective follows from the results of the first, attempting to determine if this underestimate of decadal predictability is, at least partially, due to missing ocean mesoscale processes and features in CMIP5 models. A suite of coupled model experiments is performed with eddying and eddy-parameterized ocean component. Compared with eddy-parameterized models, the paradox is less likely to exist in eddying models, particularly over eddy-rich regions. These also happen to be regions where increased decadal predictability is identified. We hypothesize that this enhanced predictability is due to the enhanced vertical connectivity in the ocean. The presence of mesoscale ocean features and associated vertical connectivity significantly influence decadal variability, predictability, and the signal-to-noise paradox.

Oxygen plays a key role in human physiology and is abnormally modulated in various disease pathologies making its in situ monitoring quite important. Most oxygen sensors are not able to measure oxygen levels deep inside the tissue or have mismatched electrode-tissue interfaces. In this study we developed a flexible thread-based oxygen sensor that combines the unique advantages of minimal invasiveness and superior flexibility offering the possibility for tissue integration. The sensor is featured by a simple and low-cost fabrication approach which allows for measuring the overall oxygen concentration either over a large surface area or locally at any spot in any three-dimensional environment with high spatial accuracy and high sensitivity. The sensor can sensitively detect dissolved oxygen levels within the physiological range of tissue oxygenation. The sensor's performance is insensitive to pH variation from 5.8 to 8.0. The sensor shows good repeatability and stability over a period of one week in phosphate buffered saline. In addition, the signal variation is less than 10% after hundreds of cycles of physical bending. Using a hydrogel-based tissue model the sensor has been shown to probe dissolved oxygen levels at different spatial locations inside a tissue-like environment.

Fabrication of ultrathin metal nanostructures usually requires some combination of high-vacuum deposition and postgrowth processing, which precludes access to nanostructures of ultrasmall cross sec...

Photodynamic therapy (PDT) is a promising strategy in cancer treatment that utilizes photosensitizers (PSs) to produce reactive oxygen species (ROS) and eliminate cancer cells under specific wavelength light irradiation. However, special tumor environments, such as those with overexpression of glutathione (GSH), which will consume PDT-mediated ROS, as well as hypoxia in the tumor microenvironment (TME) could lead to ineffective treatment. Moreover, PDT is highly light-dependent and therefore can be hindered in deep tumor cells where light cannot easily penetrate. To solve these problems, we designed oxygen-dual-generating nanosystems MnO2@Chitosan-CyI (MCC) for enhanced phototherapy. Methods: The TME-sensitive nanosystems MCC were easily prepared through the self-assembly of iodinated indocyanine green (ICG) derivative CyI and chitosan, after which the MnO2 nanoparticles were formed as a shell by electrostatic interaction and Mn-N coordinate bonding. Results: When subjected to NIR irradiation, MCC offered enhanced ROS production and heat generation. Furthermore, once endocytosed, MnO2 could not only decrease the level of GSH but also serve as a highly efficient in situ oxygen generator. Meanwhile, heat generation-induced temperature increase accelerated in vivo blood flow, which effectively relieved the environmental tumor hypoxia. Furthermore, enhanced PDT triggered an acute immune response, leading to NIR-guided, synergistic PDT/photothermal/immunotherapy capable of eliminating tumors and reducing tumor metastasis. Conclusion: The proposed novel nanosystems represent an important advance in altering TME for improved clinical PDT efficacy, as well as their potential as effective theranostic agents in cancer treatment.

This paper for the first time reports an O-band micro-ring resonator-based switch-and-select silicon photonic switch fabric with bent couplers. An average crosstalk ratio of below -40dB is achieved with a 3dB passband of 43.6GHz.

It is an important part of an intelligent pipeline nondestructive testing robot to detect the welded circular seams from a frame image which is captured by the robot’s camera. By use of prior knowledge of the contour shape of a welded circular seam, a circular convolution along a circular ring is deigned and an auto-encoding deep learning network is proposed based the circular convolutional neural network this paper. In the stage of training the auto-encoding network, a training frame image is automatically partitioned into concentricity rings. Each ring is visually and easily notated as a welded seam ring or a background ring and then used as a sample to train the network. In the stage of testing, the testing frame is automatically partitioned into concentricity rings according to the sample frame and then the each ring is auto-encoded and recognized if it is welded seam ring. The welded seam is thus coarsely segmented by the circular convolution based auto-encoding deep network. Then OTSU is used to segment out the welded seam from the welded seam ring finely and effectively. The experimental results show that the proposed circular convolution based auto-encoding deep network and segmentation algorithm are effective and efficient.

Cortisol levels in saliva is an important biomarker of stress and its rapid detection is a significant need for overall management of health and wellness. Herein, we demonstrate two novel SERS-based approaches for the detection of cortisol directly in saliva using regular and novel hexagonal gold nanoparticles (AuNPs) on a paper substrate. Using the direct SERS method, we first show the detection of cortisol by mixing the cortisol solution with highly concentrated AuNPs on a Parchment paper surface as an active SERS substrate. We also propose an alternate lateral flow SERS (LFS) approach, which employs paper as a chromatographic channel to reduce interference from background saliva matrix for the detection using SERS. A rapid detection of spiked cortisol in saliva down to 100 µg/ml concentration by employing the ‘lateral flow SERS’ (LFS) platform is shown. Results indicate a promising route for point-of-care detection of stress biomarkers.

The ability to monitor the release of neurotransmitters during synaptic transmission would significantly impact the diagnosis and treatment of neurological diseases. Here, we present a DNA-based enzymatic nanosensor for quantitative detection of acetylcholine (ACh) in the peripheral nervous system of living mice. ACh nanosensors consist of DNA as a scaffold, acetylcholinesterase as a recognition component, pH-sensitive fluorophores as signal generators, and α-bungarotoxin as a targeting moiety. We demonstrate the utility of the nanosensors in the submandibular ganglia of living mice to sensitively detect ACh ranging from 0.228 to 358 μM. In addition, the sensor response upon electrical stimulation of the efferent nerve is dose dependent, reversible, and we observe a reduction of ∼76% in sensor signal upon pharmacological inhibition of ACh release. Equipped with an advanced imaging processing tool, we further spatially resolve ACh signal propagation on the tissue level. Our platform enables sensitive measurement and mapping of ACh transmission in the peripheral nervous system.

We for the first time propose a silicon photonic switching architecture for digital radio-over-fibre fronthaul links. An RF input power dynamic range of 55dB is demonstrated for 8% EVM with system receiver sensitivity of -23.9dBm.

Fabrication of ultrathin metal nanostructures usually requires some combination of high-vacuum deposition and postgrowth processing, which precludes access to nanostructures of ultrasmall cross sections for most materials. DNA nanowires (NWs) are versatile insulating templates with intrinsic sub-10 nm line width. Here, we demonstrate a method of DNA template fabrication with precise control over the location and orientation of the DNA NWs. We further demonstrate that this template can be used to support formation of ultrathin metal NWs for derivative nanodevices: a metal is incrementally deposited, and electrical transport measurement is performed

This protocol provides a detailed decription of the experimental procedure, including nanosensor farbication and characterization, in vivo microinjection, and in vivo imaging of acetylcholine release in the submandibular ganglion of mice.

The ability to monitor the release of neurotransmitters during synaptic transmission would significantly impact the diagnosis and treatment of neurological disease. Here, we present a DNA-based enzymatic nanosensor for quantitative detection of acetylcholine (ACh) in the peripheral nervous system of living mice. ACh nanosensors consist of DNA as a scaffold, acetylcholinesterase as a recognition component, pH-sensitive fluorophores as signal generators, and α-bungarotoxin as a targeting moiety. We demonstrate the utility of the nanosensors in the submandibular ganglia of living mice to sensitively detect ACh ranging from 0.228 μM to 358 μM. In addition, the sensor response upon electrical stimulation of the efferent nerve is dose-dependent, reversible, and we observe a reduction of ~76% in sensor signal upon pharmacological inhibition of ACh release. Equipped with an advanced imaging processing tool, we further spatially resolve ACh signal propagation on the tissue level. Our platform enables sensitive measurement and mapping of ACh transmission in the peripheral nervous system.

Cell-mediated drug delivery systems utilize living cells as vehicles to achieve controlled delivery of drugs. One of the systems features integrating cells with disk-shaped microparticles termed microdevices into cell-microdevice complexes that possess some unique advantages over their counterparts. Human mesenchymal stem cells (hMSCs) have been extensively studied as therapeutic cells and used as carrier cells for drug-loaded nanoparticles or other functional nanoparticles. This article presents the development of a microdevice-based hMSC-mediated drug delivery system for the first time. This study revealed that the microdevices could be attached to the hMSCs in a controlled and versatile manner; the produced hMSC-microdevice complexes were stable over cultivation and trypsinization, and the microdevice attachment did not affect the viability and proliferation of the hMSCs. Moreover, cultured microdevice-bound hMSCs retained their abilities to migrate on a flat surface, form a spheroid, and actively dissociate from the spheroid. These results indicate that this microdevice-based hMSC-mediated system promises to be further developed into a clinically viable drug delivery system.

Stem cell-derived cardiomyocytes and vascular cells can be used for a variety of applications such as studying human heart development and modelling human disease in culture. In particular, protocols based on modulation of Wnt signaling were able to produce high quality of cardiomyocytes or vascular cells from human pluripotent stem cells (hPSCs). However, the mechanism behind the development of 3D cardiovascular spheroids into either vascular or cardiac cells has not been well explored. Hippo/Yes-associated protein (YAP) signaling plays important roles in the regulation of organogenesis, but its impact on cardiovascular differentiation has been less evaluated. In this study, the effects of seeding density and a change in YAP signaling on 3D cardiovascular spheroids patterning from hPSCs were evaluated. Compared to 2D culture, 3D cardiovascular spheroids exhibited higher levels of sarcomeric striations and higher length-to-width ratios of α-actinin+ cells. The spheroids with high seeding density exhibited more α-actinin+ cells and less nuclear YAP expression. The 3D cardiovascular spheroids were also treated with different small molecules, including Rho kinase inhibitor (Y27632), Cytochalasin D, Dasatinib, and Lysophosphatidic acid to modulate YAP localization. Nuclear YAP inhibition resulted in lower expression of active β-catenin, vascular marker, and MRTF, the transcription factor mediated by RhoGTPases. Y27632 also promoted the gene expression of MMP-2/-3 (matrix remodeling) and Notch-1 (Notch signaling). These results should help our understanding of the underlying effects for the efficient patterning of cardiovascular spheroids after mesoderm formation from hPSCs.

Oil spills can result in changes in chemical concentrations along coastlines. In prior work, these concentration changes were used to evaluate the date sediment was impacted by oil (i.e., oil exposure date). The objective of the current study was to build upon prior work by using the oil exposure date to compute oil spill chemical (OSC) concentrations in shoreline sediments before and after exposure. The new method was applied to OSC concentration measures collected during the Deepwater Horizon oil spill with an emphasis on evaluating before and after concentrations in muddy versus sandy regions. The procedure defined a grid that overlaid coastal areas with chemical concentration measurement locations. These grids were then aggregated into clusters to allow the assignment of chemical concentration measurements to a uniform coastal type. Performance of the method was illustrated for ten chemicals individually by cluster, and collectively for all chemicals and all clusters. Results show statistically significant differences between chemical concentrations before and after the calculated oil exposure dates (p

Locating the welded seam on the inner surface of a pipeline from the frame image captured by the monocular optical camera is a key and challenging problem in intelligentizing the defect inspection robot. Due to the lack of feature points and feature straight lines on the image of the welded seam, the existing visual odometry method cannot be used to locate the welded seam relative to the inspector robot. In this paper, an innovative method is proposed for locating the welded circular seam on the inner surface cylinder pipeline to inspector robot. In this method, the whole shape of the welded seam is retrieved from the frame captured by the monocular camera of the robot and is used as the feature for the location. Through combining the retried shape features and the moving velocity of the robot, the distance from the robot to the welded seam can be calculated quickly based on the optical imaging principle. Experiments show that our method can effectively locate the welded seam. Our method can used in intelligent pipeline inspector robot to locate the welded seam to defect test.

Oil spills can result in changes in chemical contaminant concentrations along coastlines. When concentrations are measured along the Gulf of Mexico over time, this information can be used to evaluate oil spill shoreline exposure dates. The objective of this research was to identify more accurate oil exposure dates based on oil spill chemical concentrations changes (CCC) within sediments in coastal zones after oil spills. The results could be used to help improve oil transport models and to improve estimates of oil landings within the nearshore. The CCC method was based on separating the target coastal zone into segments and then documenting the timing of large increases in concentration for specific oil spill chemicals (OSCs) within each segment. The dataset from the Deepwater Horizon (DWH) oil spill was used to illustrate the application of the method. Some differences in exposure dates were observed between the CCC method and between oil spill trajectories. Differences may have been caused by mixing at the freshwater and sea water interface, nearshore circulation features, and the possible influence of submerged oil that is unaccounted for by oil spill trajectories. Overall, this research highlights the benefit of using an integrated approach to confirm the timing of shoreline exposure.

Functional theranostic systems for drug delivery capable of concurrent near-infrared (NIR) fluorescence imaging, active tumor targeting and anticancer therapies are desired for concise cancer diagnosis and treatment. Dendrimers with controllable size and surface functionalities are good candidates for such platforms. However, integration of active targeting ligands and imaging agents separately on the surface or encapsulation of the imaging agents in the inner core of the dendrimers will result in a more complex composition or reduced drug loading efficiency. Herein, we reported a PAMAM-based theranostic system, with a simple integrin-specific imaging ligand prepared from two motifs. One motif is a NIR carbocyanine fluorescent dye (Cyp) for precise in vivo monitoring of the system and identification of tumor or cancer cells, and the other is a novel tumor-penetrating cyclic peptide (CRGDKGPDC, abbreviated iRGD). BSA was non-covalently bonded with Cyp to reduce NIR agent fluorescence-quenching aggregates and enhance imaging signals. The chemotherapy effect of these dendritic systems was achieved by encapsulating paclitaxel into the hydrophobic interior of the dendrimers. In vitro and in vivo targeting and penetrating studies revealed that a significantly high amount of the dendritic systems was endocytosed by HepG2 cells and enhanced accumulation and penetration at tumor sites. Our safety evaluation showed that masking of cationic-end groups of PAMAM to neutral or anionic groups has resulted in decreased or even zero-toxicity. The preliminary antitumor efficacy of the dendritic system was evaluated. In vitro and in vivo studies confirmed that paclitaxel-encapsulated functionalized PAMAM can efficiently kill HepG2 cancer cells. In conclusion, our functionalized theranostic dendritic system could be a promising nanocarrier to effectively deliver drugs to deep tumor regions for anticancer therapy.

Micro/nanoparticles have great potentials in biomedical applications, especially for drug delivery. Existing studies identified that major micro/nanoparticle features including size, shape, surface property and component materials play vital roles in their in vitro and in vivo applications. However, a demanding challenge is that most conventional particle synthesis techniques such as emulsion can only generate micro/nanoparticles with a very limited number of shapes (i.e., spherical or rod shapes) and have very loose control in terms of particle sizes. We reviewed the advanced manufacturing techniques for producing micro/nanoparticles with precisely defined characteristics, emphasizing the use of these well-controlled micro/nanoparticles for drug delivery applications. Additionally, to illustrate the vital roles of particle features in therapeutic delivery, we also discussed how the above-mentioned micro/nanoparticle features impact in vitro and in vivo applications. Through this review, we highlighted the unique opportunities in generating controllable particles via advanced manufacturing techniques and the great potential of using these micro/nanoparticles for therapeutic delivery.

An unmet need in nanomedicine is to prepare biocompatible and renal clearable nanoparticles by controlling the diameter, composition and surface properties of the nanoparticles. This paper reports cellulose nanofiber templated synthesis of ultra-small bismuth nanoparticles, and their uses in enhanced X-ray radiation therapy. The interstitial spaces between adjacent fibers are the adsorption sites of bismuth ions and also stabilize nanoparticles generated by chemical reduction. The sizes of nanoparticles are tailored in the 2-10 nm range using cellulose nanofibers with various amounts of carboxyl groups. In vitro cytotoxicity, reactive oxygen species (ROS) and in vivo animal tests with tumor-bearing mice are studied in order to enhance X-ray radiation therapy using cellulose nanofiber-templated bismuth nanoparticles. Bismuth nanoparticles show strong X-ray attenuation ability, concentration-dependent cytotoxicity and high level production of ROS upon X-ray exposure, which is consistent with enhanced cellular damage and retarded growth of tumors in animals.

Use of live cells as carriers for drug-laden particulate structures possesses unique advantages for drug delivery. In this work, we report on the development of a novel type of particulate structures called microdevices for cell-borne drug delivery. The microdevices were fabricated by soft lithography with a disklike shape. Each microdevice was composed of a layer of biodegradable thermoplastic such as poly(lactic-co-glycolic acid). One face of the thermoplastic layer was covalently grafted with a cell-adhesive polyelectrolyte such as poly-l-lysine. This asymmetric structure allowed the microdevices to bind to live cells through bulk mixing without causing cell aggregation. Moreover, the cell-microdevice complexes were largely stable, and the viability and proliferation ability of the cells were not affected by the microdevices over a week. In addition, sustained release of a mock drug from the microdevices was demonstrated. This type of microdevice promises to be clinically useful for sustained intravascular drug delivery.

Controlled alignment of long DNA nanofibers is challenging. This communication reports a method to align human genomic DNA with nearly unlimited length using lithographically produced micro-patterns of self-assembled monolayers (SAMs) with positively charged terminal groups. The micro-patterns act as local DNA reservoirs to supply DNAs for nanofiber formation, and can also stretch and align DNA nanofibers to form an ordered array by controlling the dewetting profile. By reducing the size and inter-patch distance of a micro-patch, a nearly uniform array of long DNA nanofibers can be patterned over a large area. A controlled motion of a DNA containing droplet allows for free patterning of DNA nanofibers and production of complex structures without a transfer process. Bending of DNA nanofibers due to local distortion of the contact line bridges more adjacent micro-patches and increases the chance of producing continuous nanofibers. The interplay between surface tension and electrostatic attraction of positively charged micro-patterns allows the production of long DNA nanofibers in a simple yet powerful way.

Cell population based toxicity assays cannot distinguish responses of single cells and sub-cellular organelles; while single cell assays are limited by low statistical power due to small number of cells examined. This article reports a new single cell array based toxicity assay, in which cell responses at population level, single cell level and sub-cellular level can be obtained simultaneously at high throughput. The single cell array was produced by microcontact printing and selected area cell attachment, and exposed to damaging X-ray radiation, which was followed by fluorescence imaging after staining. Two image processing softwares written in Python and MATLAB were used to determine the expressions of proteins associated with cell migration and invasion, and production of reactive oxygen species (ROS), respectively. The results showed significant differences in responses at single cell level and distinctive molecular heterogeneity at sub-cellular level in a large population of cells upon exposure to radiation.

Microcontact printing (μCP) of polyelectrolytes is a facile and powerful method for surface micro/nanopatterning and functionalization. Poly(4-aminostyrene) (PAS) is a polyelectrolyte that can be converted to aryldiazonium salt and exhibits pH-dependent hydrophobicity. Here we demonstrate μCP of PAS and the expansion of this technique in various directions. First, the microcontact-printed PAS can be diazotized to micropattern biomolecules including DNA and protein and nanomaterials including single-walled carbon nanotubes and gold nanoparticles. Second, the diazotized PAS enables μCP of a metallic structure on a carbon surface. Third, the hydrophobic nature of PAS at the neutral pH allows the microcontact-printed PAS-based polyelectrolyte multilayer to be used as masks for wet etching. Lastly, this technique allows facile fabrication of highly engineered microparticles with a unique structure. Overall, this work has established a novel μCP platform with various potential applications.

Adsorption of the 40-residue Alzheimer’s β-amyloid peptide (Aβ40) on a hydrophobic surface leads to formation of potentially disease-relevant aggregates. Existing techniques are limited in characterizing the adsorbed Aβ40 and producing potentially useful Aβ40 microstructures such as microarrays and microparticles. In this paper, a novel approach based on microcontact printing (μCP) to studying and utilizing adsorption of Aβ40 monomers and fibril fragments on hydrophobic surface of polydimethylsiloxane (PDMS) stamps has been developed. By transferring the adsorbed layer from the stamp to a glass substrate, this approach allows easy measurement of thickness of the adsorbed layer. It also enables characterization of the face of the adsorbed layer in contact with the stamp surface. This face exhibits significant higher thioflavin T fluorescence than the face exposed to water, suggesting β-sheet formation induced by the PDMS surface. The intrinsic stability of the adsorbed layer is evaluated by printing the layer on a water-soluble substrate and exposing it to water vapor or water. Stable particulate microstructures in water are obtained by chemically crosslinking the adsorbed peptides. Moreover, co-micropatterning of the different states of Aβ40 (monomers and fibril fragments) is demonstrated. This μCP-based approach is simple, versatile, and holds potential for various applications.

Enzymes have been used to treat various human diseases and traumas. However, the therapeutic utility of free enzymes is impeded by their short circulation time, lack of targeting ability, immunogenicity, and inability to cross biological barriers. Cell-mediated drug delivery approach offers the unique capability to overcome these limitations, but the traditional cell-mediated enzyme delivery techniques suffer from drawbacks such as risk of intracellular degradation of and low loading capacity for the payload enzyme. This article presents the development of a novel cell-mediated enzyme delivery technique featuring the use of micrometer-sized disk-shaped particles termed microdevices. The microdevices are fabricated by layer-by-layer assembly and soft lithography with catalase being used as a model therapeutic enzyme. The amount of catalase in the microdevices can be controlled with the number of catalase layers. Catalase in the microdevices is catalytically active, and active catalase is slowly released from the microdevices. Moreover, cell-microdevice complexes are produced by attaching the catalase-laden microdevices to the external surface of both K562 cells and mouse embryonic stem cells. This technique is potentially applicable to other enzymes and cells and promises to be clinically useful.

Introduction Appropriate neural patterning of human induced pluripotent stem cells (hiPSCs) is critical to generate specific neural cells/tissues and even mini-brains that are physiologically relevant to model neurological diseases. However, the capacity of signaling factors that regulate 3-D neural tissue patterning in vitro and differential responses of the resulting neural populations to various biomolecules have not yet been fully understood. Methods By tuning neural patterning of hiPSCs with small molecules targeting sonic hedgehog (SHH) signaling, this study generated different 3-D neuronal cultures that were mainly comprised of either cortical glutamatergic neurons or motor neurons. Results Abundant glutamatergic neurons were observed following the treatment with an antagonist of SHH signaling, cyclopamine, while Islet-1 and HB9-expressing motor neurons were enriched by an SHH agonist, purmorphamine. In neurons derived with different neural patterning factors, whole-cell patch clamp recordings showed similar voltage-gated Na + /K + currents, depolarization-evoked action potentials and spontaneous excitatory post-synaptic currents. Moreover, these different neuronal populations exhibited differential responses to three classes of biomolecules, including (1) matrix metalloproteinase inhibitors that affect extracellular matrix remodeling; (2) N-methyl- d -aspartate that induces general neurotoxicity; and (3) amyloid β (1–42) oligomers that cause neuronal subtype-specific neurotoxicity. Conclusions This study should advance our understanding of hiPSC self-organization and neural tissue development and provide a transformative approach to establish 3-D models for neurological disease modeling and drug discovery. Statement of Significance Appropriate neural patterning of human induced pluripotent stem cells (hiPSCs) is critical to generate specific neural cells, tissues and even mini-brains that are physiologically relevant to model neurological diseases. However, the capability of sonic hedgehog-related small molecules to tune different neuronal subtypes in 3-D differentiation from hiPSCs and the differential cellular responses of region-specific neuronal subtypes to various biomolecules have not been fully investigated. By tuning neural patterning of hiPSCs with small molecules targeting sonic hedgehog signaling, this study provides knowledge on the differential susceptibility of region-specific neuronal subtypes derived from hiPSCs to different biomolecules in extracellular matrix remodeling and neurotoxicity. The findings are significant for understanding 3-D neural patterning of hiPSCs for the applications in brain organoid formation, neurological disease modeling, and drug discovery.

The successful transfer of oil-soluble quantum dots (QDs) into water is critical for many of their bioapplications. In this paper, the impacts of four various strategies (i.e., via micelles, nanohydrogels, amphiphilic polymers and water-soluble thiol small molecules) on the phase transfer of oil-soluble oleic acid-capped NIR-emitting PbS QDs into water were evaluated systematically. It was found that the process of water transfer and the optical property of the resulting water-soluble QDs highly hinge on the type of the phase transfer agents used due to their different interactions with QD surface. Among all these phase transfer agents, SOC micelles and glutathione (thiol) molecules are more favorable for retaining the optical property of the initial oil-soluble PbS QDs. As a result, the obtained water-soluble QDs show strong NIR fluorescence (PL QY > 30% in water). However, in the case of nanohydrogel and amphiphilic polymers, the corresponding water-soluble ones display relatively weak fluorescence emission. These results suggest fully that "correct" phase transfer agents should be selected in order to obtain high-quality water-soluble PbS QDs. The possible reasons for this obvious difference were further analyzed and revealed. Besides, the preliminary results obtained also indicate that the NIR-emitting PbS QDs will be a potential probe in the in vivo biomedical imaging of small animals.

Colloidal PbS quantum dots (QDs) with tunable photoemission throughout the near-infrared (NIR) region (ca. 750–1000 nm) were synthesized by a two-phase approach. Here, oil-soluble lead oleate formed by a reaction of lead acetate and oleic acid (OA, the capping agent) in n-decane at 130 °C was used as lead precursor, and water-soluble Na2S, thioacetamide (TAA), and thiourea, each having a different reactivity, were used as sulfur sources. When an n-decane solution of lead precursor and an aqueous solution of sulfur precursor were mixed at the appointed temperature, oil-soluble, near-infrared-emitting PbS QDs were achieved. In this study, we investigated the influence of the reactivity of water-soluble sulfur sources on the synthesis of PbS QDs. The morphology and crystal structure of the as-prepared PbS QDs were characterized by (high-resolution) transmission electron microscopy (TEM), selected area electron diffraction (SAED), and X-ray diffraction (XRD).

A challenge of X-ray radiation therapy is that high dose X-rays at therapeutic conditions damage normal cells. This paper describes the use of gold nanoparticle-loaded multilayer microdisks to enhance X-ray radiation therapy, where each microdisk contains over 10(5) radiosensitizing nanoparticles. The microdisks are attached on cell membranes through electrostatic interaction. Upon X-ray irradiation, more photoelectrons and Auger electrons are generated in the vicinity of the nanoparticles, which cause water ionization and lead to the formation of free radicals that damage the DNA of adjacent cancer cells. By attaching a large amount of gold nanoparticles on cancer cells, the total X-ray dose required for DNA damage and cell killing can be reduced. Due to their controllable structure and composition, multilayer microdisks can be a viable choice for enhanced radiation therapy with nanoparticles.

Capability to detect or track macrophages in vivo is important for developing macrophage-based therapies. Dispersed carbon nanotubes (CNTs) have been used for Raman labeling of cells and a top-down approach has been developed to fabricate disk-shaped microparticles for the same application. This study presents the first fabrication of disk-shaped microparticles termed microdevices containing densely packed CNTs and Raman labeling of macrophages with the microdevices. The fabrication is featured by the use of spray coating of CNTs to produce the microdevices. Raman detection of a single microdevice at a centimeter-scale working distance and the feasibility of using chemically modified CNTs for multiplexed Raman labeling were demonstrated. Macrophages were stably labeled with the microdevices by simply adding the microdevices to cultivated macrophages. The labeling slightly reduced viability of the macrophages and the labeled macrophages retained their ability to capture foreign particles. Moreover, Raman detection of a single macrophage was demonstrated. The microdevices promise to be useful for detection or tracking of macrophages in vivo as well as for other biomedical applications.

Micro/nanoparticles containing densely packed gold nanoparticles (AuNPs) possess unique properties potentially useful for various biomedical applications. The micro/nanoparticles are conventionally produced by the bottom-up methods, which have limited capability for controlling the particle size, shape and structure. This article reports development of a top-down method that integrates layer-by-layer assembly and microcontact printing to fabricate disk-shaped microparticles named microdisks composed of densely packed AuNPs. This method allows precise control of not only the size, shape and structure of the microdisks but also the amount of the AuNPs in the microdisks. The microdisks can be loaded with different Raman reporters to generate characteristic surface-enhanced Raman scattering spectra under the near infrared excitation over a centimetre-scale lens–sample distance. Moreover, the microdisks can be attached to single live cells. This microdisk platform holds potential for multiplex Raman labelling of therapeutic cells for in vivo tracking of the cells.

The functionalization and assembly of live cells with microfabricated polymeric biomaterials have attracted considerable interest in recent years, but the conventional methods suffer from high cost, high complexity, long processing time or inadequate capability. The present study reports on the development of a novel method for functionalizing and assembling live cells by integrating microcontact printing of polymeric biomaterials with a temperature-sensitive sacrificial layer prepared by spin-coating. This method has been used not only to functionalize live cells with microscopic polyelectrolyte and thermoplastic structures of various sizes and shapes, but also to assemble the cells into macroscopic stripes and sheets. The method is applicable to multiple types of cells, including human leukemic cells, mouse embryonic stem cells and human mesenchymal stem cells in the forms of single cells and cell aggregates. In addition, the microcontact-printed structures can be prepared using biodegradable and biocompatible polyelectrolytes and thermoplastic. The unique combination of low cost, ease of use and high versatility renders this method potentially useful for diverse biomedical applications, including drug delivery, cell tracking and tissue engineering.

Paper indicators based on colorimetric assays are widely used for nitrite detection, but their application to liquids with strong colours is restricted. We report a novel paper indicator that allows for sensing nitrite by colorimetric assay, Raman spectroscopy, and electron paramagnetic resonance spectroscopy with non-overlapping signal wavelength ranges through non-contact means. The paper indicator was prepared by impregnating poly(4-aminostyrene), 2-naphthol and single-walled carbon nanotubes in a regular filter paper. All three ingredients were essential to realize the triple-modality sensing. This method is simple and inexpensive, and promises to have wider applicability than the existing paper indicators.

We investigate in this paper the influence of slow light on the balance between the Kerr and two-photon absorption (TPA) processes in silicon slotted hybrid nonlinear waveguides. Three typical silicon photonic waveguide geometries are studied to estimate the influence of the light slow-down factor on the mode field overlap with the silicon region, as well as on the complex effective nonlinear susceptibility. It is found that slotted photonic crystal modes tend to focalize in their hollow core with increasing group index (nG) values. Considering a hybrid integration of nonlinear polymers in such slotted waveguides, a relative decrease of the TPA process by more factor of 2 is predicted from nG=10 to nG=50. As a whole, this work shows that the relative influence of TPA decreases for slotted waveguides operating in the slow light regime, making them a suitable platform for third-order nonlinear optics.