Vibrant reflective sensors with percolation film Fabry-Pérot nanocavities.

Dynamically reconfigurable structural colors are promising materials for new smart optical systems. However, improved reflected color quality (e.g., saturation, optical contrast, angular invariance) and larger tuning range/sensitivity are needed. Here, we demonstrate a vibrant, actively tunable system which meets these needs via coupling broadband plasmonic resonators to a responsive polymer film. Our structure consists of near-percolation gold nanoislands deposited on a poly[methyl methacrylate] (PMMA) spacer above a gold mirror, forming a Fabry-Pérot nanocavity. Broadband absorption in this system creates vivid reflected colors, while the polymer spacer enables continuous tuning over a wide color space. By exploiting swelling effects in PMMA, we show fast, reversible color switching in response to organic vapors. Our sensitive optical structure amplifies small vapor-induced changes in the spacer thickness, enabling naked-eye detection of changes as small as 10 nm. Additionally, optical absorption >99% yields modulation contrasts up to 80:1, opening the door to ultra-sensitive on-chip signal measurements, complementing the visual colorimetric readout. This structure has immediate implications for colorimetric bio/chemical sensing and may also find application to reflective displays and flexible/adaptive optical coatings.

ERP evidence for asymmetric orthographic transfer between traditional and simplified Chinese.

Transferring orthographic processing skills from one language to new languages is important for language learning. However, the specific orthography hypothesis and condition-based transfer hypothesis have debated orthographic transfer. No study has ever examined these debates in a logographic language, and the neural correlates of orthographic transfer in a logographic language remain unknown. Therefore, the present study uses event-related potentials to examine orthographic transfer with Hong Kong (Experiment 1) and mainland China (Experiment 2) participants who only use traditional or simplified Chinese, respectively. The participants sequentially read two of the same (repetition) or different (nonrepetition) traditional or simplified Chinese characters and judged whether they were identical. The results showed that the orthography-related N200 component was smaller in the repetition condition than in the nonrepetition condition. Importantly, for traditional Chinses users, this effect was more salient in traditional Chinese than in simplified Chinese, suggesting limited transfer from traditional to simplified Chinese. For simplified Chinese users, this effect was comparable in traditional and simplified Chinese, suggesting a smooth transfer from simplified to traditional Chinese. The results supported the condition-based transfer hypothesis, and showed asymmetric transfer between simple orthographic rules and complex ones. That is, simple orthographic rules can be transferred to complex ones smoothly, but not vice versa.

Fabrication of monodisperse magnetic nanorods for improving hyperthermia efficacy.

BACKGROUND: Hyperthermia is one of the promising cancer treatment strategies enabled by local heating with the use of tumor-targeting magnetic nanoparticles (MNP) under a non-invasive magnetic field. However, one of the remaining challenges is how to achieve therapeutic levels of heat (without causing damages to regular tissues) in tumors that cannot be effectively treated with anti-tumor drug delivery. RESULTS: In this work, we report a facile method to fabricate magnetic nanorods for hyperthermia by one-step wet chemistry synthesis using 3-Aminopropyltrimethoxysilane (APTMS) as the shape-controlling agent and ferric and ferrous ions as precursors. By adjusting the concentration of APTMS, hydrothermal reaction time, ratios of ferric to ferrous ions, magnetic nanorods with aspect ratios ranging from 4.4 to 7.6 have been produced. At the clinically recommended field strength of 300 Oe (or less) and the frequency of 184 kHz, the specific absorption rate (SAR) of these nanorods is approximately 50 % higher than that of commercial Bionized NanoFerrite particles. CONCLUSIONS: This increase in SAR, especially at low field strengths, is crucial for treating deep tumors, such as pancreatic and rectal cancers, by avoiding the generation of harmful eddy current heating in normal tissues.

Flexible Electrostatic Transducer Array with Displacement Control for Haptic Sensing and Actuation.

We developed flexible electrostatic transducers with both a single element and a 2×2 array format to actuate at a precise displacement across a range of loads with a control circuitry and algorithm. The transducer, composed of a moving buckled film with an integrated electrode and a rigid electrode, can be used to simultaneously generate and sense displacements. A circuit and computer program were designed to demonstrate displacement control and quantify the sensing precision of the transducer. Specifically, we applied a range of voltage and load conditions to the transducer and array and measured the displacement while under loading through capacitive sensing. The change in capacitance was linear with respect to the area of the electrode in contact and matched theoretical predictions when described as a function of the displacement. The transducer was loaded with weights in the range of 5-27 mN and capacitance-driving voltage graphs were obtained. An 8Hz driving frequency was used to move the transducer, while a 10.8kHz signal was used to sense the capacitance. These were used to build a predictive model to correct for sensed load to maintain a average displacement. It was found that a transducer of dimensions 10mm × 40mm was able to maintain displacement under loads of 5-27mN, while a matrix composed of 10mm × 20mm transducers was able to maintain displacement under loads of 2.5-11mN. In general, the detection thresholds of human skin can range between 5-20mN of force and 2-20um of displacement for frequencies between 1Hz and 250Hz, so these values are in line with what is needed to build a functional haptic wearable device. The present work provides a method to quantitatively measure and control a new type of flexible transducer for a variety of haptic applications.

Method for Inkjet-printing PEDOT:PSS polymer electrode arrays on piezoelectric PVDF-TrFE fibers.

We present a method for printing conductive polymers onto P(VDF-TrFE) nanofibers to create all-polymer piezoelectric devices. Inkjet printing is an attractive fabrication approach for rapid prototyping of flexible electronics, but until now with limited applications in developing P(VDF-TrFE) nanofiber-based devices. We have demonstrated an approach to infill the void space within a piezoelectric nanofibrous matrix to allow for the inkjet printing of aqueous inks while avoiding leakage that typically leads to electrical shorting and without significant loss of voltage output. This was done using a diluted PDMS solution and a commercially available conductive ink. The 1 cm2 devices showed a 254 mV/N sensitivity to impact as well as a sensitivity to bending. The device was shown to be able to detect breathing and pulse rate when placed superficially to the carotid and radial arteries. Using these techniques, flexible piezoelectric sensing can be done in an array format, shown with applications in foot movement sensing.

Characteristics of Patients with Acute Flaccid Myelitis, United States, 2015-2018.

Observed peaks of acute flaccid myelitis (AFM) cases have occurred biennially since 2014 in the United States. We aimed to determine if AFM etiology differed between peak and nonpeak years, considering that clinical features of AFM differ by virus etiology. We compared clinical and laboratory characteristics of AFM cases that occurred during peak (2016 and 2018, n = 366) and nonpeak (2015 and 2017, n = 50) years. AFM patients in peak years were younger (5.2 years) than those in nonpeak years (8.3 years). A higher percentage of patients in peak years than nonpeak years had pleocytosis (86% vs. 60%), upper extremity involvement (33% vs. 16%), and an illness preceding limb weakness (90% vs. 62%) and were positive for enterovirus or rhinovirus RNA (38% vs. 16%). Enterovirus D68 infection was associated with AFM only in peak years. Our findings suggest AFM etiology differs between peak and nonpeak years.

Evidence runs contrary to digestive stability predicting protein allergenicity.

A dogma has persisted for over two decades that food allergens are more stable to digestion compared with non-allergenic proteins. This belief has become enshrined in regulations designed to assess the allergenic risk of novel food proteins. While the empirical evidence accumulated over the last 20+ years has largely failed to confirm a correlation between digestive stability and the allergenic status of proteins, even those who accept this finding often assert that this shortfall is the result of faulty assay design rather than lack of causality. Here, we outline why digestive stability may not in fact correlate with allergenic potential.

Flexible Piezoelectric Nanogenerators Using Metal-doped ZnO-PVDF Films.

Piezoelectric nanomaterial-polymer composites represent a unique paradigm for making flexible energy harvesting and sensing devices with enhanced devices' performance. In this work, we studied various metal doped ZnO nanostructures, fabricated and characterized ZnO nanoparticle-PVDF composite thin film, and demonstrated both enhanced energy generation and motion sensing capabilities. Specifically, a series of flexible piezoelectric nanogenerators (PENGs) were designed based on these piezoelectric composite thin films. The voltage output from cobalt (Co), sodium (Na), silver (Ag), and lithium (Li) doped ZnO-PVDF composite as well as pure ZnO-PVDF samples were individually studied and compared. Under the same experimental conditions, the Li-ZnO based device produces the largest peak-to-peak voltage (3.43 Vpp) which is about 9 times of that of the pure ZnO based device, where Co-ZnO, Na-ZnO and Ag-ZnO are 1.2, 4.9 and 5.4 times, respectively. In addition, the effect of doping ratio of Li-ZnO is studied, and we found that 5% is the best doping ratio in terms of output voltage. Finally, we demonstrated that the energy harvested by the device from finger tapping at ~2 Hz can charge a capacitor with a large output power density of 0.45 W/cm3 and light up an ultraviolet (UV) light-emitting diode (LED). We also showed the device as a flexible wearable motion sensor, where different hand gestures were detected by the device with distinctive output voltage amplitudes and patterns.

Metallic photonic crystal-based sensor for cryogenic environments.

We investigate the design, characterization, and application of metallic photonic crystal (MPC) structures, consisting of plasmonic gold nanogratings on top of a photonic waveguide, as transducers for lab-on-chip biosensing in cryogenic environments. The compact design offers a promising approach to sensitive, in situ biosensing platforms for astrobiology applications (e.g., on the "icy moons" of the outer solar system). We fabricated and experimentally characterized three MPC sensor geometries, with variable nanograting width, at temperatures ranging from 300 K to 180 K. Sensors with wider nanogratings were more sensitive to changes in the local dielectric environment. Temperature-dependent experiments revealed an increase in plasmonic resonance intensity of around 13% at 180 K (compared with 300 K), while the coupled plasmonic-photonic resonance was less sensitive to temperature, varying by less than 5%. Simulation results confirm the relative temperature stability of the plasmonic-photonic mode and, combined with its high sensitivity, suggest a novel application of this mode as the sensing transduction mechanism over wide temperature ranges. To our knowledge, this is among the first reports of the design and characterization of a nanoplasmonic sensor specifically for low-temperature sensing operation.

Microfluidic continuous flow synthesis of functional hollow spherical silica with hierarchical sponge-like large porous shell.

Microfluidics brings unique opportunities for engineering micro-/nanomaterials with well-controlled physicochemical properties. Herein, using a miniaturized multi-run spiral-shaped microreactor, we develop a flow synthesis strategy to continuously produce hollow spherical silica (HSS) with hierarchical sponge-like pore sizes ranging from several nanometers to over one hundred nanometers. The formation of HSS is realized by mixing two reactant flows, one containing cetyltrimethylammonium bromide (CTAB) and diluted ammonia and the other 1,3,5-trimethylbenzene (TMB) and diluted tetraethyl orthosilicate (TEOS), at a flow rate as high as 5 mL/min. The effect of the reactant concentration and the flow rate on the structural change of the resultant materials is examined. Functional small-sized nanoparticles (magnetic nanoparticle, quantum dot, and silver nanoparticle) can be separately assembled into HSS and high molecular weight protein (bovine serum albumin) can be successfully loaded into HSS and delivered into cancer cells afterward, making them promising in the fields of separation and purification, bioimaging, catalysis, and theranostics.

Microfluidics-enabled rational design of ZnO micro-/nanoparticles with enhanced photocatalysis, cytotoxicity, and piezoelectric properties.

Microfluidics-based reactors enables the controllable synthesis of micro-/nanostructures for a broad spectrum of applications from materials science, bioengineering to medicine. In this study, we first develop a facile and straightforward flow synthesis strategy to control zinc oxide (ZnO) of different shapes (sphere, ellipsoid, short rod, long rod, cube, urchin, and platelet) on a few seconds time scale, based on the 1.5-run spiral-shaped microfluidic reactor with a relative short microchannel length of ca. 92 mm. The formation of ZnO is realized simply by mixing reactants through two inlet flows, one containing zinc nitrate and the other sodium hydroxide. The structures of ZnO are tuned by choosing appropriate flow rates and reactant concentrations of two inlet fluids. The formation mechanism behind microfluidics is proposed. The photocatalysis, cytotoxicity, and piezoelectric capabilities of as-synthesized ZnO from microreactors are further examined, and the structure-dependent efficacy is observed, where higher surface area ZnO structures generally behave better performance. These results bring new insights not only in the rational design of functional micro-/nanoparticles from microfluidics, but also for deeper understanding of the structure-efficacy relationship when translating micro-/nanomaterials into practical applications.

Assessing the impact of delayed blastulation using time lapse morphokinetics and preimplantation genetic testing in an IVF patient population.

PURPOSE: There is clinical evidence that early cleavage timing parameters predictive of blastocyst development also correlate with embryo implantation potential. The aim of this study is to determine the developmental competency of embryos with delayed blastulation. METHODS: Retrospective study performed from 2015 to 2016 at the Division of Reproductive Endocrinology and Infertility at Northwestern University. RESULTS: A total of 2,292 embryos from 524 patients were included. Day 6 blastocysts had statistically significant longer times for every time point analyzed than day 5 blastocysts (p < 0.001). We found no statistically significant difference in euploidy rates between day 5 (44%) and day 6 (41%) embryos (p = 0.573). t7 and t8 time points were independent predictors of euploidy after controlling for day of biopsy (p < 0.015 and p < 0.014, respectively). Intrauterine pregnancy (IUP) and live birth (LB) were less likely to occur after transferring day 6 embryos (p = 0.0033 and p = 0.0359) without previous genetic testing. However, in embryos that undergo preimplantation genetic testing for aneuploidy (PGT-A), there were no significant differences in IUP or LB rates. CONCLUSION: Early time-lapse points can be used to predict embryo development. Day of blastulation may be an independent predictor IUP, with day 6 blastocysts having lower pregnancy and live birth rates. Our data suggests that day 5 and day 6 PGT-A tested embryos show similar rates of euploidy, suggesting that differences in PR seen in the non-PGT-A tested group may be caused by factors other than aneuploidy. Genetic testing technologies in combination with time-lapse microscopy may provide further information to improve IVF outcomes.

Advances in liquid biopsy on-chip for cancer management: Technologies, biomarkers, and clinical analysis.

Liquid biopsy, as a minimally invasive method of gleaning insight into the dynamics of diseases through a patient fluid sample, has been growing in popularity for cancer diagnosis, prognosis, and monitoring. While many technologies have been developed and validated in research laboratories, there has also been a push to expand these technologies into other clinical settings and as point of care devices. In this article, we discuss and evaluate microchip-based technologies for circulating tumor cell (CTC), exosome, and circulating tumor nucleic acid (ctNA) capture, detection, and analysis. Such integrated systems streamline otherwise multiple-step, manual operations to get a sample-to-answer quantitation. In addition, analysis of disease biomarkers is suited to point of care settings because of ease of use, low consumption of sample and reagents, and high throughput. We also cover the basics of biomarkers and their detection in biological fluid samples suitable for liquid biopsy on-chip. We focus on emerging technologies that process a small patient sample with high spatial-temporal resolution and derive clinically meaningful results through on-chip biomarker sensing and downstream molecular analysis in a simple workflow. This critical review is meant as a resource for those interested in developing technologies for capture, detection, and analysis platforms for liquid biopsy in a variety of settings.

Combined immunomagnetic capture coupled with ultrasensitive plasmonic detection of circulating tumor cells in blood.

We demonstrate enhanced on-chip circulating tumor cell (CTC) detection through the incorporation of plasmonic-enhanced near-infrared (NIR) fluorescence screening. Specifically, the performance of plasmonic gold coated chips was evaluated on our previously reported immunomagnetic CTC capture system and compared to the performance of a regular chip. Three main performance metrics were evaluated: capture efficiency, capture reproducibility, and clinical efficacy. Use of the plasmonic chip to capture SK-BR-3 cells in PBS, resulted in a capture efficiency of 82%, compared to 76% with a regular chip. Both chips showed excellent capture reproducibility for all three cells lines evaluated (MCF-7, SK-BR-3, Colo 205) in both PBS and peripheral blood, with R2 values ranging from 0.983 to 0.996. Finally, performance of the plasmonic chip was evaluated on thirteen peripheral blood samples in patients with both breast and prostate cancer. The regular chip detected 2-8 cells per 5 mL of blood, while the plasmonic chip detected 8-85 cells per 5 mL of blood in parallel samples. In summary, we successfully demonstrate improved CTC capture and detection capabilities through use of plasmonic-enhanced near-infrared (NIR) fluorescence screening in both in vitro and ex vivo experiments. This work not only has the potential to improve clinical outcomes though improved CTC analysis, but also demonstrates successful interface design between plasmonic materials and cell capture for bioanalytical applications.

Biomimetic hierarchical walnut kernel-like and erythrocyte-like mesoporous silica nanomaterials: controllable synthesis and versatile applications.

We developed a facile and controllable strategy to fabricate biomimic walnut kernel-like mesoporous silica nanomaterial (WMSN) and erythrocyte-like mesoporous silica nanomaterial (EMSN). The former possesses unique multi-shell hollow structure and surface wrinkles while the latter has special multi-stack structure and bowl-shaped depression. These hierarchical materials with distinct structures can be finely tuned by changing the molar ratios of two surfactants, cetyltrimethylammonium bromide and 11-mercaptoundecanoic acid. The mechanism of structural formation through intermolecular interactions was revealed and validated experimentally. The promising potential applications of WMSN and EMSN in adsorption, cellular imaging, drug delivery, and cancer theranostics were further identified.

Do patients who achieve pregnancy using IVF-PGS do the recommended genetic diagnostic testing in pregnancy?

PURPOSE: Patients undergoing in-vitro fertilization (IVF) with preimplantation genetic screening (PGS) are counseled about the limitations of this technique. As part of the consent process for PGS, physicians recommend diagnostic genetic testing performed in early pregnancy to definitively rule out chromosomal abnormalities. We have noted anecdotally, however, that few patients undergo the recommended diagnostic testing. In this study, we are examining if women who conceived using IVF-PGS did early pregnancy chromosomal testing, and if they did, what type of testing they had. METHODS: This study was performed from 2015 to 2017 in the Division of Reproductive Endocrinology and Infertility at Northwestern University. We included patients who became pregnant after IVF-PGS who were seen by the Division of Reproductive Genetics and non-PGS control group. RESULTS: Sixty-eight patients were included. A total of 50 patients (73.5%) opted for non-invasive prenatal screening; 5 (7.4%) had invasive testing (4 had chorionic villus sampling and 1 had amniocentesis). A total of 13 patients (19%) declined further genetic testing. When comparing demographic data, the mean age was significantly higher in the group of patients who pursued non-invasive testing than in the group who declined further testing (37.15 vs 34.05 years old, p < 0.05). Control group declined invasive diagnostic testing. CONCLUSIONS: Most patients who conceive using IVF-PGS do not pursue diagnostic prenatal chromosomal testing. Future studies focusing on decision making in this patient group are warranted to further elucidate why a small percentage of patients opt for diagnostic testing, even when adequately counseled about the inherent limitations of PGS.

Patterned Plasmonic Surfaces-Theory, Fabrication, and Applications in Biosensing.

Low-profile patterned plasmonic surfaces are synergized with a broad class of silicon microstructures to greatly enhance near-field nanoscale imaging, sensing, and energy harvesting coupled with far-field free-space detection. This concept has a clear impact on several key areas of interest for the MEMS community, including but not limited to ultra-compact microsystems for sensitive detection of small number of target molecules, and "surface" devices for optical data storage, micro-imaging and displaying. In this paper, we review the current state-of-the-art in plasmonic theory as well as derive design guidance for plasmonic integration with microsystems, fabrication techniques, and selected applications in biosensing, including refractive-index based label-free biosensing, plasmonic integrated lab-on-chip systems, plasmonic near-field scanning optical microscopy and plasmonics on-chip systems for cellular imaging. This paradigm enables low-profile conformal surfaces on microdevices, rather than bulk material or coatings, which provide clear advantages for physical, chemical and biological-related sensing, imaging, and light harvesting, in addition to easier realization, enhanced flexibility, and tunability.

Multifunctional Magnetic Particles for Combined Circulating Tumor Cells Isolation and Cellular Metabolism Detection.

We for the first time demonstrate multi-functional magnetic particles based rare cell isolation combined with the downstream laser desorption/ionization mass spectrometry (LDI-MS) to measure the metabolism of enriched circulating tumor cells (CTCs). The characterization of CTCs metabolism plays a significant role in understanding the tumor microenvironment, through exploring the diverse cellular process. However, characterizing cell metabolism is still challenging due to the low detection sensitivity, high sample complexity, and tedious preparation procedures, particularly for rare cells analysis in clinical study. Here we conjugate ferric oxide magnetic particles with anti-EpCAM on the surface for specific, efficient enrichment of CTCs from PBS and whole blood with cells concentration of 6-100 cells per mL. Moreover, these hydrophilic particles as matrix enable sensitive and selective LDI-MS detection of small metabolites (MW<500 Da) in complex bio-mixtures and can be further coupled with isotopic quantification to monitor selected molecules metabolism of ~50 CTCs. Our unique approach couples the immunomagnetic separation of CTCs and LDI-MS based metabolic analysis, which represents a key step forward for downstream metabolites analysis of rare cells to investigate the biological features of CTCs and their cellular responses in both pathological and physiological phenomena.

Decreased functional connectivity of insula-based network in young adults with internet gaming disorder.

The insula is a region that integrates interoception and drug urges, but little is known about its role in behavioral addiction such as internet addiction. We investigated insula-based functional connectivity in participants with internet gaming disorder (IGD) and healthy controls (HC) using resting-state functional MRI. The right and left insula subregions (posterior, ventroanterior, and dorsoanterior) were used as seed regions in a connectivity analysis. Compared with the HC group, the IGD group showed decreased functional connectivity between left posterior insula and bilateral supplementary motor area and middle cingulated cortex, between right posterior insula and right superior frontal gyrus, and decreased functional integration between insular subregions. The finding of reduced functional connectivity between the interoception and the motor/executive control regions is interpreted to reflect reduced ability to inhibit motor responses to internet gaming or diminished executive control over craving for internet gaming in IGD. The results support the hypothesis that IGD is associated with altered insula-based network, similar to substance addiction such as smoking.

Plasmonic nanograting enhanced quantum dots excitation for cellular imaging on-chip.

We present the design and integration of a two-dimensional (2D) plasmonic nanogratings structure on the electrode of colloidal quantum dot-based light-emitting diodes (QDLEDs) as a compact light source towards arrayed on-chip imaging of tumor cells. Colloidal quantum dots (QDs) were used as the emission layer due to their unique capabilities, including multicolor emission, narrow bandwidth, tunable emission wavelengths, and compatibility with silicon fabrication. The nanograting, based on a metal-dielectric-metal plasmonic waveguide, aims to enhance the light intensity through the resonant reflection of surface plasmon (SP) waves. The key parameters of plasmonic nanogratings, including periodicity, slit width, and thicknesses of the metal and dielectric layers, were designed to tailor the frequency bandgap such that it matches the wavelength of operation. We fabricated QDLEDs with the integrated nanogratings and demonstrated an increase in electroluminescence intensity, measured along the direction perpendicular to the metal electrode. We found an increase of 34.72% in QDLED electroluminescence intensity from the area of the pattern and an increase of 32.63% from the photoluminescence of QDs deposited on a metal surface. We performed ex vivo transmission-mode microscopy to evaluate the nucleus-cytoplasm ratios of MDA-MB 231 cultured breast cancer cells using QDLEDs as the light source. We showed wavelength dependent imaging of different cell components and imaging of cells at higher magnification using enhanced emission from QDLEDs with integrated plasmonic nanogratings.