Cellular Array Research Articles

A symmetric lattice‐based wideband wide phase range digital phase shifter topology

SummaryIn this paper, a novel digital phase shifter topology that achieves wideband and wide phase range is proposed. Wide frequency band operation is accomplished employing symmetrical all‐pass lattice structures. Compact phase shifter size is obtained utilizing the miniaturized microwave monolithic integrated circuit (MMIC) design implementation technology. Therefore, resulting phase shifter units are suitable for various communication systems such as radar and cellular communication smart antenna arrays. This paper provides complete design equations together with design algorithm for the selected phase shift and the center frequency. Design algorithm is developed on MatLab environment. The proposed phase shifting circuit is implemented employing the commercially available 0.18‐μm silicon CMOS technology. The new phase shifter topology provides 00 to 3600 phase shift range over X‐band, even beyond.

(Invited) Bio-Lasers: An Emerging Field Bridging Laser Photonics and Biomedicine

Bio-lasers are emerging technology for next generation biochemical detection and biophotonic applications. Recently, laser-based detection has been exploited as a novel tool in biosensing due to their capability to amplify subtle changes in the gain media caused by underlying biological processes. Laser emission has unique merits over fluorescence, including threshold-gated emission, narrow linewidth, and strong intensity, leading to ultrasensitive detection of intracellular dynamics, and superior contrast for higher spectral/spatial resolution imaging. In this talk, I will introduce the recent advances of biolasers in cells, tissues, and neuronal networks, by using several types of micro-laser cavities, such as optofluidic ring resonators and high-Q Fabry-Pérot mirrors. Next, we demonstrate the possible implementation of biolasers into an automated lasing system for systematic and statistical analysis, including an integrated cellular laser array device and laser-emission microscopy for cancer screening and immuno-diagnosis. Furthermore, optical recording of calcium transients during spontaneous neuronal activities was first demonstrated via neuron lasers with a significantly improved sensitivity, not only for monitoring neuronal network dynamics but an ultra-sensitive detection method for brain-on-chip applications and neuro-analysis. Finally, discussion and outlook is made on the strategies through biolasers and to pioneer novel on-chip devices for future clinical diagnosis, prognosis, and fundamental research in biomedicine.

Ultrasound-assisted biofabrication and bioprinting of preferentially aligned three-dimensional cellular constructs

A critical consideration in tissue engineering is to recapitulate the microstructural organization of native tissues that is essential to their function. Scaffold-based techniques have focused on achieving this via the contact guidance principle wherein topographical cues offered by scaffold fibers direct migration and orientation of cells to govern subsequent cell-secreted extracellular matrix organization. Alternatively, approaches based on acoustophoretic, electrophoretic, photophoretic, magnetophoretic, and chemotactic principles are being investigated in the biofabrication domain to direct patterning of cells within bioink constructs. This work describes a new acoustophoretic three-dimensional (3D) biofabrication approach that utilizes radiation forces generated by superimposing ultrasonic bulk acoustic waves (BAW) to preferentially organize cellular arrays within single and multi-layered hydrogel constructs. Using multiphysics modeling and experimental design, we have characterized the effects of process parameters including ultrasound frequency (0.71, 1, 1.5, 2 MHz), signal voltage amplitude (100, 200 mVpp), bioink viscosity (5, 70 cP), and actuation duration (10, 20 min) on the alignment characteristics, viability and metabolic activity of human adipose-derived stem cells (hASC) suspended in alginate. Results show that the spacing between adjacent cellular arrays decreased with increasing frequency (p < 0.001), while the width of the arrays decreased with increasing frequency and amplitude (p < 0.05), and upon lowering the bioink viscosity (p < 0.01) or increasing actuation duration (p < 0.01). Corresponding to the computational results wherein estimated acoustic radiation forces demonstrated a linear relationship with amplitude and a nonlinear relationship with frequency, the interaction of moderate frequencies at high amplitudes resulted in viscous perturbations, ultimately affecting the hASC viability (p < 0.01). For each combination of frequency and amplitude at the extremities of the tested range, the hASC metabolic activity did not change over 4 d, but the activity of the low frequency-high amplitude treatment was lower than that of the high frequency-low amplitude treatment at day 4 (p < 0.01). In addition to this process-structure characterization, we have also demonstrated the 3D bioprinting of a multi-layered medial knee meniscus construct featuring physiologically-relevant circumferential organization of viable hASC. This work contributes to the advancement of scalable biomimetic tissue manufacturing science and technology.

WIND EFFECT ANALYSIS ON AIR TRAFFIC CONGESTION IN TERMINAL AREA VIA CELLULAR AUTOMATA

The behavior of any traffic flow is sensitive to the speed pattern of the vehicles involved. The heavier the traffic, the more sensitive the behavior is to speed changes. Focusing on air traffic flow, weather condition has a major role in the deviations of aircraft operational speed from the desired speed and causes surplus delays. In this paper, the effects of wind on delays in a terminal area are analyzed using a Cellular Automaton (CA) model. Cellular automata are discrete models that are widely used for simulating complex emerging properties of dynamic systems. A one-dimensional cellular array is used to model the flow of the terminal traffic into a wind field. The proposed model, due to the quickness and acceptable level of accuracy, can be utilized online in the tactical phase of air traffic control processes and system-level decision-makings, where quick response and system behavior are needed. The modeled route is an RNAV STAR route to Atlanta International Airport. The model is verified by real traffic data in a non-delayed scenario. Based on simulation results, the proposed model exhibits an acceptable level of accuracy (3–15% accuracy drop), with worthy time and computational efficiency (about 2.9 seconds run time for a 2-hour operation).

The human oncogene SCL/TAL1 interrupting locus (STIL) promotes tumor growth through MAPK/ERK, PI3K/Akt and AMPK pathways in prostate cancer

The morbidity and mortality of prostate cancer (PCa) in China have increased obviously, which became the second leading cause of death in men with cancer. Hedgehog (Hh) signaling pathway is a key signaling pathway involved in the prostate cancer progression. The human oncogene SCL/TAL1 interrupting locus (STIL) can modulate the Hh signaling pathway, but its function in PCa has not been reported. Here, we showed that STIL was increased in high grade prostate cancer tissue. Knockdown of STIL in prostate cancer cells PC-3 and DU 145 significantly decreased the proliferation of cells and induced cellular apoptosis through casepase3/7 mediated pathway. Moreover, the colony formation ability was also inhibited when knockdown of STIL by lentivirus-mediated shRNA. Furthermore, the cellular signaling antibody array analysis revealed which signaling pathway was affected when silencing STIL. Altogether, we found that STIL could affect MAPK/ERK, PI3K/Akt and AMPK signaling pathways, thus promoting cellular proliferation, colony formation and suppressing cellular apoptosis in prostate cancer.

Epidermis-Inspired Ultrathin 3D Cellular Sensor Array for Self-Powered Biomedical Monitoring

Sensing devices with wearability would open the door to many advanced applications including soft robotics, artificial intelligence, and healthcare monitoring. Here, inspired by the configuration of the human epidermis, we present a flexible three-dimensional (3D) cellular sensor array (CSA) via a one-step thermally induced phase separation method. The CSA was framed by the 3D cellular electret with caged piezoelectric nanoparticles, which was ultrathin (80 μm), lightweight, and highlyrobust. For biomedical sensing, the 3D-CSA holds a decent pressure sensitivity up to 0.19 V kPa-1 with a response time of less than 16 ms. Owing to its rigid structural symmetry, the 3D-CSA could be identically operated from itsboth sides.It was demonstrated to successfully measure the human heartbeat, detect the eyeball motion for sleeping monitoring, and tactile imaging. Mimicking the functionalities of the human skin with a self-powered operation feature, the 3D-CSA was expected to represent a substantial advancement in wearable electronics for healthcare.

Synergy of Paracrine Signaling During Early-Stage Mouse Ovarian Follicle Development In Vitro.

Paracrine signals, such as soluble cytokines and extracellular matrix cues, are essential for the survival and development of multicellular ovarian follicles. While it is well established that hydrogel-based culture systems successfully support the growth of late-stage follicles for fertility preservation, growing small, early-stage ovarian follicles still proves to be challenging. We hypothesized that paracrine factors secreted from neighboring follicles may be crucial for improving the survival of early-stage follicles in vitro. To test our hypothesis, we investigated the bi-directional crosstalk of the paracrine signals, such as cell-secreted cytokines, sex hormones and transcription factors (TFs), in follicles encapsulated and cultured for 12days in alginate in groups of five (5×) and ten (10×). The differential profiles of TF activity and secretome during folliculogenesis were analyzed using TRanscriptional Activity CEllular aRray (TRACER) and data-driven multivariate modeling approach. The mechano- and oxygen-responsive TFs, NF-κB and HIF1, exhibited a unique upregulation signature in 10× follicles. Consistently, levels of proangiogenic factors, such as VEGF-A and angiopoietin-2, were significantly higher in 10× follicles than those in 5× follicles, reaching 269.77 and 242.82pg/mL on the last day of culture. The analysis of TRACER and secreted cytokines also revealed critical early interactions between cytokines and TFs, correlating with the observed phenotypical and functional differences between conditions. We identified unique signatures of synergism during successful early-stage ovarian follicle development. These findings bring us closer to understanding of mechanisms underlying the downstream effects of interactions between the extracellular microenvironment and early-stage folliculogenesis in vitro.

Biomimetic soft fibrous hydrogels for contractile and pharmacologically responsive smooth muscle

The ability to assess changes in smooth muscle contractility and pharmacological responsiveness in normal or pathological-relevant vascular tissue environments is critical to enable vascular drug discovery. However, major challenges remain in both capturing the complexity of in vivo vascular remodeling and evaluating cell contractility in complex, tissue-like environments. Herein, we developed a biomimetic fibrous hydrogel with tunable structure, stiffness, and composition to resemble the native vascular tissue environment. This hydrogel platform was further combined with the combinatory protein array technology as well as advanced approaches to measure cell mechanics and contractility, thus permitting evaluation of smooth muscle functions in a variety of tissue-like microenvironments. Our results demonstrated that biomimetic fibrous structure played a dominant role in smooth muscle function, while the presentation of adhesion proteins co-regulated it to various degrees. Specifically, fibre networks enabled cell infiltration and upregulated expression of actomyosin proteins in contrast to flat hydrogels. Remarkably, fibrous structure and physiologically relevant stiffness of hydrogels cooperatively enhanced smooth muscle contractility and pharmacological responses to vasoactive drugs at both the single cell and intact tissue levels. Together, this study is the first to demonstrate alterations of human vascular smooth muscle contractility and pharmacological responsiveness in biomimetic soft, fibrous environments with a cellular array platform. The integrated platform produced here could enable investigations for pathobiology and pharmacological interventions by developing a broad range of patho-physiologically relevant in vitro tissue models. Statement of SignificanceEngineering functional smooth muscle in vitro holds the great potential for diseased tissue replacement and drug testing. A central challenge is recapitulating the smooth muscle contractility and pharmacological responses given its significant phenotypic plasticity in response to changes in environment. We present a biomimetic fibrous hydrogel with tunable structure, stiffness, and composition that enables the creation of functional smooth muscle tissues in the native-like vascular tissue microenvironment. Such fibrous hydrogel is further combined with the combinatory protein array technology to construct a cellular array for evaluation of smooth muscle phenotype, contraction, and cell mechanics. The integrated platform produced here could be promising for developing a broad range of normal or diseased in vitro tissue models.

Multi-parametric cell profiling with a CMOS quad-modality cellular interfacing array for label-free fully automated drug screening.

Cells are complex systems with concurrent multi-physical responses, and cell physiological signals are often encoded with spatiotemporal dynamics and further coupled with multiple cellular activities. However, most existing electronic sensors are only single-modality and cannot capture multi-parametric cellular responses. In this paper, a 1024-pixel CMOS quad-modality cellular interfacing array that enables multi-parametric cell profiling for drug development is presented. The quad-modality CMOS array features cellular impedance characterization, optical detection, extracellular potential recording, and biphasic current stimulation. The fibroblast transparency and surface adhesion are jointly monitored by cellular impedance and optical sensing modalities for comprehensive cell growth evaluation. Simultaneous current stimulation and opto-mechanical monitoring based on cardiomyocytes are demonstrated without any stimulation/sensing dead-zone. Furthermore, drug dose-dependent multi-parametric feature extractions in cardiomyocytes from their extracellular potentials and opto-mechanical signals are presented. The CMOS array demonstrates great potential for fully automated drug screening and drug safety assessments, which may substantially reduce the drug screening time and cost in future new drug development.

Design of Generalized Pipeline Cellular Array in Quantum-Dot Cellular Automata

Cellular arrays have been the topic of interest in computer arithmetic and architecture for the last four decades. In this letter, an overall quantum-dot cellular automata (QCA) design for a generalized pipeline cellular array is presented. QCA is one of the promising emerging nanotechnologies that are being considered as possible alternatives to complementary metal-oxide semiconductor technology due to the physical limitations of CMOS. The QCA designs for arithmetic cell and control cell used in the pipeline array are discussed in detail. The equivalent majority logic networks to these cells are generated using the best existing majority logic synthesis method in order to obtain the optimal majority networks which require fewer QCA cells and clock zones compared to other synthesis methods. The proposed array can perform all the basic arithmetic operations such as squaring, square rooting, multiplication, division, etc., which could be quite valuable in considering future large-scale QCA designs.

Cell-Based Microarrays Using Superhydrophobic Platforms Patterned with Wettable Regions.

The use of patterned platforms to print cellular arrays enables the high-throughput study of cell behavior under a multitude of different conditions. This rapid, cost-saving and systematic way of acquiring biologically relevant information has found application in diverse scientific and industrial fields. In an initial stage of development, platforms targeting high-throughput cellular studies were restricted to standard two-dimensional (2D) setups. The design of novel platforms compatible with three-dimensional (3D) cell culture arose after the elucidation of the extreme importance of culturing cells in matrices resembling the native extracellular matrix-cells and cell-cell interactions. This need for biomimetic environments has been established in fields like drug discovery and testing, disease model development, and regenerative medicine. Here, we provide a description of the processing of flat platforms based on wettability contrast, compatible with the high-throughput generation and study of cell response in 3D biomaterials, including cell-laden hydrogels and porous 3D scaffolds. The application of the aforementioned platforms to produce 3D microtissues, which may find application as tissue models for drug screening or as biomimetic building blocks for tissue engineering, is also addressed. In this chapter, a description of the steps for (1) high-throughput platform processing, (2) deposition of cell and biomaterial arrays, and (3) image-based results screening is provided.

Artificial niche microarrays for identifying extrinsic cell-fate determinants.

The complex cellular microenvironment plays an important role in determining cell fate. For example, stem cells located in a microenvironment termed niche integrate a wide variety of extrinsic cues to take distinct fate choices. Capturing this multiple-input/multiple-output system in vitro has proven to be very challenging. In order to address this issue, we developed and validated a microfabricated cellular array platform, termed artificial niche microarrays, which is capable of performing high-throughput single-cell assays under physiologically relevant conditions. The platform allows exposing cultured cells to differential signaling cues displayed on soft hydrogel substrates having variable stiffness. The behavior of the seeded cells can be readily quantified across over 2000 multivariate microenvironments. Here we describe a pipeline for performing multifactorial, image-based assays with these artificial niche microarrays. The procedure details the steps from microarray production, cell culture, cell phenotyping, data extraction to statistical analysis.

Liver Lesions Detection and Classification in Ultrasound Images Using Gabor Characterization, Edge Detection and Artificial Neural Networks

Introduction: In the last decade one of the main reasons for people mortality and disability is liver diseases. Early detection of these diseases can help adopt appropriate treatment methods. Ultrasound imaging is a non-invasive method for visualizing tissue specification and liver lesions detection which its resolution is lower than CT and MRI images. Precise determination of liver tissue lesions and progression degree of disease is possible with advanced computer techniques such as artificial neural networks (ANN) from medical images. In this paper, a classification-based method is presented to identify and diagnose liver lesions using the Gabor wavelet features and edge detection. In this method, the vector of features from healthy and damaged tissues is trained to the network based on Gabor filters. Then the suspected cases of tissue lesions in various liver diseases are identified by features extraction of entry images. After that, the edge detection technique is implemented and the internal points of the edge are tested as an inputs of a neural network which determine the healthy and unhealthy liver tissues.&#x0D; Methods: Image features are extracted and processed by Gabor wavelet. Also the ANN is used to liver disease classification based on the images features. The forward multilayer perceptron neural network is organized with three layers of input, hidden and output. The training of this network is done with back propagation method and all of the data include "healthy tissues" and "damaged tissues" of the liver are collected in a large cellular array. Furthermore, an edge detection technique is used to indicate the points where the intensity of the light changes sharply. The sharp changes in image characteristics are usually representative of important events and changes in environments characteristics.&#x0D; Results: The results of the implementation indicate a significant reduction in processing time of liver ultrasound images and also increase the precision and accuracy of liver lesions detection (approximately 5%) among different classified groups of hepatic patients compared with the similar image processing methods. In the proposed method, the total time of operations include feature extraction, image processing, lesions detection and diagnosis of the disease has been decreased by reduction of the number of examined points. In addition, an edge detection technique had been used to diagnose the size of damaged tissues in various liver diseases, which helps improve the early detection of tissue lesions because of reduction of the checking domain of points.&#x0D; Conclusion: In this paper, a new method was presented to identify liver tissue lesions. Gabor wavelet method is employed to extract the features of the liver ultrasound images. These wavelets provide the context to understand the images frequency and their analysis in the area of the space, and given their great advantage, which is slow changes in the frequency domain, it is an appropriate filter to extract the image features. Then, the extracted features of the ultrasound images of various liver patients are stored to train a neural network, and finally the image processing method is performed to identify the healthy and damaged tissues and also to diagnose the type of disease. The search scope of problem is minimized as the input of the neural network to find the liver damaged tissue by the edge detection technique which is lead to errors reduction in identifying the tissue damages, increasing the detection speed of these lesions, and diagnosing the disease as well as determining the damage degree of liver.&#x0D;

Directionally solidified dilute Zn-Mg alloys: Correlation between microstructure and corrosion properties

Zinc–Magnesium (Zn–Mg) alloys have been addressed as potential biodegradable biomaterials. These alloys enable to overcome the main drawbacks of Mg, its high corrosion rate and hydrogen evolution. Moreover, homogeneous corrosion degradation is also an interesting issue to ensure the success of load-bearing biodegradable implants. In this work, two directionally solidified dilute alloys, Zn-0.3wt-%Mg and Zn-0.5wt-%Mg were studied. Both alloys having different microstructural morphologies (cellular and dendritic arrays) depending of the distance to the cooling bottom were evaluated to correlate their microstructural features with corrosion properties. Kinetics and corrosion mechanism have been evaluated by means of DC and AC electrochemical techniques in low chloride containing solution, 0.06 M NaCl. Coarser microstructures are shown to promote higher corrosion rate. Like Zn the corrosion mechanism occurs throughout a multistep dissolution process involving the formation of intermediate monovalent ZnI, and soluble zinc hydroxychloride compounds resulting of the reaction of zincate ions with chloride ions.

Convection Effects During Bulk Transparent Alloy Solidification in DECLIC-DSI and Phase-Field Simulations in Diffusive Conditions

To study the dynamical formation and evolution of cellular and dendritic arrays under diffusive growth conditions, three-dimensional (3D) directional solidification experiments were conducted in microgravity on a model transparent alloy onboard the International Space Station using the Directional Solidification Insert in the DEvice for the study of Critical LIquids and Crystallization. Selected experiments were repeated on Earth under gravity-driven fluid flow to evidence convection effects. Both radial and axial macrosegregation resulting from convection are observed in ground experiments, and primary spacings measured on Earth and microgravity experiments are noticeably different. The microgravity experiments provide unique benchmark data for numerical simulations of spatially extended pattern formation under diffusive growth conditions. The results of 3D phase-field simulations highlight the importance of accurately modeling thermal conditions that strongly influence the front recoil of the interface and the selection of the primary spacing. The modeling predictions are in good quantitative agreements with the microgravity experiments.

Novel Cellular Active Array Antenna System at Base Station for Beyond 4G

Novel Cellular Active Array Antenna System at Base Station for Beyond 4G

Hardware implementation of hexagonal sampling based bio-inspired retinal encoder

This paper addresses hardware implementation of a power efficient retinal encoder system used in visual prosthesis equipment for blind people. The hardware architecture is inspired from the retinal receptive fields in mammalian vision system. The captured image is passed through several filter banks in different filtering stages in primate vision system. As the photoreceptors in the primate vision system are arranged in hexagonal fashion, the hexagonal tessellation scheme was found to be the most suitable sampling scheme for retinal image processing. In this work, the hardware implementation of different retinal filtering stages and final edge detection scheme is performed in Altera Cyclone II FPGA and in Synopsys Design Vision. An area efficient Cellular Logic Array Processing (CLAP) algorithm is used as the final stage edge detector. Both rectangular and hexagonal edge detection schemes were tested and their performance was analysed using Berkeley Segmentation Dataset and ROC performance scheme.

Hardware implementation of hexagonal sampling based bio-inspired retinal encoder

This paper addresses hardware implementation of a power efficient retinal encoder system used in visual prosthesis equipment for blind people. The hardware architecture is inspired from the retinal receptive fields in mammalian vision system. The captured image is passed through several filter banks in different filtering stages in primate vision system. As the photoreceptors in the primate vision system are arranged in hexagonal fashion, the hexagonal tessellation scheme was found to be the most suitable sampling scheme for retinal image processing. In this work, the hardware implementation of different retinal filtering stages and final edge detection scheme is performed in Altera Cyclone II FPGA and in Synopsys Design Vision. An area efficient Cellular Logic Array Processing (CLAP) algorithm is used as the final stage edge detector. Both rectangular and hexagonal edge detection schemes were tested and their performance was analysed using Berkeley Segmentation Dataset and ROC performance scheme.

Detailed Microstructural Characterization and Restoration Mechanisms of Duplex and Superduplex Stainless Steel Friction-Stir-Welded Joints

Duplex stainless steels are successfully used in a wide variety of applications in areas such as the food industry, petrochemical installations, and sea water desalination plants, where high corrosion resistance and high mechanical strength are required. However, during fusion welding operations, there can be changes to the favorable microstructure of these materials that compromise their performance. Friction stir welding with a non-consumable pin enables welded joints to be obtained in the solid state, which avoids typical problems associated with solidification of the molten pool, such as segregation of alloying elements and the formation of solidification and liquefaction cracks. In the case of superduplex stainless steels, use of the technique can avoid unbalanced proportions of ferrite and austenite, formation of deleterious second phases, or growth of ferritic grains in the heat-affected zone. Consolidated joints with full penetration were obtained for 6-mm-thick plates of UNS S32101 and S32205 duplex stainless steels, and S32750 and S32760 superduplex steels. The welding heat cycles employed avoided the conditions required for formation of deleterious phases, except in the case of the welded joint of the S32760 steel, where SEM images indicated the formation of secondary phases, as corroborated by decreased mechanical performance. Analysis using EBSD and transmission electron microscopy revealed continuous dynamic recrystallization by the formation of cellular arrays of dislocations in the ferrite and discontinuous dynamic recrystallization in the austenite. Microtexture evaluation indicated the presence of fibers typical of shear in the thermomechanically affected zone. These fibers were not obviously present in the stir zone, probably due to the intensity of microstructural reformulation to which this region was subjected.

Performance of New Pb-Bi Alloys for Pb-Acid Battery Applications: EIS and Polarization Study

The present investigation is focused on the evaluation of electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization results, associated with resulting microstructural features of two distinct as-cast Pb-Bi alloys (i.e., 1 and 2.5 wt.% Bi). EIS, potentiodynamic polarization curves, and equivalent circuits are used to analyze the corrosion behavior. The electrochemical parameters show that the corrosion resistance increases when the matrix microstructure is characterized by coarser cells when compared with finer ones. However, when a coarse cellular array is associated with increase in Bi content caused by macrosegregation during casting, the corrosion resistance decreases significantly. Bismuth modifies the anode/cathode area ratio increasing drastically the corrosion action.