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Volume 1 • Issue 3 • September 2015 • Pages 277 -398
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Research
    • Medical Instrumentation
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Big Data for Precision Medicine
Daniel Richard Leff, Guang-Zhong Yang
Engineering . 2015, 1 (3): 277 -279 .   DOI: 10.15302/J-ENG-2015075
Abstract   HTML   PDF (162KB)

This article focuses on the potential impact of big data analysis to improve health, prevent and detect disease at an earlier stage, and personalize interventions. The role that big data analytics may have in interrogating the patient electronic health record toward improved clinical decision support is discussed. We examine developments in pharmacogenetics that have increased our appreciation of the reasons why patients respond differently to chemotherapy. We also assess the expansion of online health communications and the way in which this data may be capitalized on in order to detect public health threats and control or contain epidemics. Finally, we describe how a new generation of wearable and implantable body sensors may improve wellbeing, streamline management of chronic diseases, and improve the quality of surgical implants.

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Precision Burn Trauma Medicine: Application for Molecular Engineering Science
Kristen Jakubowski, Michael Poellmann, Raphael C. Lee
Engineering . 2015, 1 (3): 280 -281 .   DOI: 10.15302/J-ENG-2015073
Abstract   HTML   PDF (254KB)
 
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Engineering for Human Security and Well-Being
Hideaki Koizumi
Engineering . 2015, 1 (3): 282 -287 .   DOI: 10.15302/J-ENG-2015066
Abstract   HTML   PDF (1242KB)
 
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Research
Visual Prostheses: Technological and Socioeconomic Challenges
John B. Troy
Engineering . 2015, 1 (3): 288 -291 .   DOI: 10.15302/J-ENG-2015080
Abstract   HTML   PDF (176KB)

Visual prostheses are now entering the clinical marketplace. Such prostheses were originally targeted for patients suffering from blindness through retinitis pigmentosa (RP). However, in late July of this year, for the first time a patient was given a retinal implant in order to treat dry age-related macular degeneration. Retinal implants are suitable solutions for diseases that attack photoreceptors but spare most of the remaining retinal neurons. For eye diseases that result in loss of retinal output, implants that interface with more central structures in the visual system are needed. The standard site for central visual prostheses under development is the visual cortex. This perspective discusses the technical and socioeconomic challenges faced by visual prostheses.

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Systems Neuroengineering: Understanding and Interacting with the Brain
Bradley J. Edelman, Nessa Johnson, Abbas Sohrabpour, Shanbao Tong, Nitish Thakor, Bin He
Engineering . 2015, 1 (3): 292 -308 .   DOI: 10.15302/J-ENG-2015078
Abstract   HTML   PDF (9823KB)

In this paper, we review the current state-of-the-art techniques used for understanding the inner workings of the brain at a systems level. The neural activity that governs our everyday lives involves an intricate coordination of many processes that can be attributed to a variety of brain regions. On the surface, many of these functions can appear to be controlled by specific anatomical structures; however, in reality, numerous dynamic networks within the brain contribute to its function through an interconnected web of neuronal and synaptic pathways. The brain, in its healthy or pathological state, can therefore be best understood by taking a systems-level approach. While numerous neuroengineering technologies exist, we focus here on three major thrusts in the field of systems neuroengineering: neuroimaging, neural interfacing, and neuromodulation. Neuroimaging enables us to delineate the structural and functional organization of the brain, which is key in understanding how the neural system functions in both normal and disease states. Based on such knowledge, devices can be used either to communicate with the neural system, as in neural interface systems, or to modulate brain activity, as in neuromodulation systems. The consideration of these three fields is key to the development and application of neuro-devices. Feedback-based neuro-devices require the ability to sense neural activity (via a neuroimaging modality) through a neural interface (invasive or noninvasive) and ultimately to select a set of stimulation parameters in order to alter neural function via a neuromodulation modality. Systems neuroengineering refers to the use of engineering tools and technologies to image, decode, and modulate the brain in order to comprehend its functions and to repair its dysfunction. Interactions between these fields will help to shape the future of systems neuroengineering—to develop neurotechniques for enhancing the understanding of whole-brain function and dysfunction, and the management of neurological and mental disorders.

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Optical Molecular Imaging Frontiers in Oncology: The Pursuit of Accuracy and Sensitivity
Kun Wang,Chongwei Chi,Zhenhua Hu,Muhan Liu,Hui Hui,Wenting Shang,Dong Peng,Shuang Zhang,Jinzuo Ye,Haixiao Liu,Jie Tian
Engineering . 2015, 1 (3): 309 -323 .   DOI: 10.15302/J-ENG-2015082
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Cutting-edge technologies in optical molecular imaging have ushered in new frontiers in cancer research, clinical translation, and medical practice, as evidenced by recent advances in optical multimodality imaging, Cerenkov luminescence imaging (CLI), and optical image-guided surgeries. New abilities allow in vivo cancer imaging with sensitivity and accuracy that are unprecedented in conventional imaging approaches. The visualization of cellular and molecular behaviors and events within tumors in living subjects is improving our deeper understanding of tumors at a systems level. These advances are being rapidly used to acquire tumor-to-tumor molecular heterogeneity, both dynamically and quantitatively, as well as to achieve more effective therapeutic interventions with the assistance of real-time imaging. In the era of molecular imaging, optical technologies hold great promise to facilitate the development of highly sensitive cancer diagnoses as well as personalized patient treatment—one of the ultimate goals of precision medicine.

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Smartphone-Imaged HIV-1 Reverse-Transcription Loop-Mediated Isothermal Amplification (RT-LAMP) on a Chip from Whole Blood
Gregory L. Damhorst, Carlos Duarte-Guevara, Weili Chen, Tanmay Ghonge, Brian T. Cunningham, Rashid Bashir
Engineering . 2015, 1 (3): 324 -335 .   DOI: 10.15302/J-ENG-2015072
Abstract   HTML   PDF (12306KB)

Viral load measurements are an essential tool for the long-term clinical care of human immunodeficiency virus (HIV)-positive individuals. The gold standards in viral load instrumentation, however, are still too limited by their size, cost, and sophisticated operation for these measurements to be ubiquitous in remote settings with poor healthcare infrastructure, including parts of the world that are disproportionately affected by HIV infection. The challenge of developing a point-of-care platform capable of making viral load more accessible has been frequently approached but no solution has yet emerged that meets the practical requirements of low cost, portability, and ease-of-use. In this paper, we perform reverse-transcription loop-mediated isothermal amplification (RT-LAMP) on minimally processed HIV-spiked whole blood samples with a microfluidic and silicon microchip platform, and perform fluorescence measurements with a consumer smartphone. Our integrated assay shows amplification from as few as three viruses in a ~ 60 nL RT-LAMP droplet, corresponding to a whole blood concentration of 670 viruses per μL of whole blood. The technology contains greater power in a digital RT-LAMP approach that could be scaled up for the determination of viral load from a finger prick of blood in the clinical care of HIV-positive individuals. We demonstrate that all aspects of this viral load approach, from a drop of blood to imaging the RT-LAMP reaction, are compatible with lab-on-a-chip components and mobile instrumentation.

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An Ultrasonic Backscatter Instrument for Cancellous Bone Evaluation in Neonates
Chengcheng Liu, Rong Zhang, Ying Li, Feng Xu, Dean Ta, Weiqi Wang
Engineering . 2015, 1 (3): 336 -343 .   DOI: 10.15302/J-ENG-2015079
Abstract   HTML   PDF (5181KB)

Ultrasonic backscatter technique has shown promise as a noninvasive cancellous bone assessment tool. A novel ultrasonic backscatter bone diagnostic (UBBD) instrument and an in vivo application for neonatal bone evaluation are introduced in this study. The UBBD provides several advantages, including noninvasiveness, non-ionizing radiation, portability, and simplicity. In this study, the backscatter signal could be measured within 5 s using the UBBD. Ultrasonic backscatter measurements were performed on 467 neonates (268 males and 199 females) at the left calcaneus. The backscatter signal was measured at a central frequency of 3.5 MHz. The delay (T1) and duration (T2) of the backscatter signal of interest (SOI) were varied, and the apparent integrated backscatter (AIB), frequency slope of apparent backscatter (FSAB), zero frequency intercept of apparent backscatter (FIAB), and spectral centroid shift (SCS) were calculated. The results showed that the SOI selection had a direct influence on cancellous bone evaluation. The AIB and FIAB were positively correlated with the gestational age (|R| up to 0.45, P<0.001) when T1 was short (<8 µs), while negative correlations (|R| up to 0.56, P<0.001) were commonly observed for T1>10 µs. Moderate positive correlations (|R| up to 0.45, P<0.001) were observed for FSAB and SCS with gestational age when T1 was long (>10 µs). The T2 mainly introduced fluctuations in the observed correlation coefficients. The moderate correlations observed with UBBD demonstrate the feasibility of using the backscatter signal to evaluate neonatal bone status. This study also proposes an explicit standard for in vivo SOI selection and neonatal cancellous bone assessment.

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Characterizing Thermal Augmentation of Convection-Enhanced Drug Delivery with the Fiberoptic Microneedle Device
R. Lyle Hood, Rudy T. Andriani, Tobias E. Ecker, John L. Robertson, Christopher G. Rylander
Engineering . 2015, 1 (3): 344 -350 .   DOI: 10.15302/J-ENG-2015077
Abstract   HTML   PDF (9041KB)

Convection-enhanced delivery (CED) is a promising technique leveraging pressure-driven flow to increase penetration of infused drugs into interstitial spaces. We have developed a fiberoptic microneedle device for inducing local sub-lethal hyperthermia to further improve CED drug distribution volumes, and this study seeks to quantitatively characterize this approach in agarose tissue phantoms. Infusions of dye were conducted in 0.6% (w/w) agarose tissue phantoms with isothermal conditions at 15 °C, 20 °C, 25 °C, and 30 °C. Infusion metrics were quantified using a custom shadowgraphy setup and image-processing algorithm. These data were used to build an empirical predictive temporal model of distribution volume as a function of phantom temperature. A second set of proof-of-concept experiments was conducted to evaluate a novel fiberoptic device capable of generating local photothermal heating during fluid infusion. The isothermal infusions showed a positive correlation between temperature and distribution volume, with the volume at 30 °C showing a 7-fold increase at 100 min over the 15 °C isothermal case. Infusions during photothermal heating (1064 nm at 500 mW) showed a similar effect with a 3.5-fold increase at 4 h over the control (0 mW). These results and analyses serve to provide insight into and characterization of heat-mediated enhancement of volumetric dispersal.

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A Confocal Endoscope for Cellular Imaging
Jiafu Wang, Min Yang, Li Yang, Yun Zhang, Jing Yuan, Qian Liu, Xiaohua Hou, Ling Fu
Engineering . 2015, 1 (3): 351 -360 .   DOI: 10.15302/J-ENG-2015081
Abstract   HTML   PDF (9477KB)

Since its inception, endoscopy has aimed to establish an immediate diagnosis that is virtually consistent with a histologic diagnosis. In the past decade, confocal laser scanning microscopy has been brought into endoscopy, thus enabling in vivo microscopic tissue visualization with a magnification and resolution comparable to that obtained with the ex vivo microscopy of histological specimens. The major challenge in the development of instrumentation lies in the miniaturization of a fiber-optic probe for microscopic imaging with micron-scale resolution. Here, we present the design and construction of a confocal endoscope based on a fiber bundle with 1.4-μm lateral resolution and 8-frames per second (fps) imaging speed. The fiber-optic probe has a diameter of 2.6 mm that is compatible with the biopsy channel of a conventional endoscope. The prototype of a confocal endoscope has been used to observe epithelial cells of the gastrointestinal tracts of mice and will be further demonstrated in clinical trials. In addition, the confocal endoscope can be used for translational studies of epithelial function in order to monitor how molecules work and how cells interact in their natural environment.

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Development of 8-inch Key Processes for Insulated-Gate Bipolar Transistor
Guoyou Liu, Rongjun Ding, Haihui Luo
Engineering . 2015, 1 (3): 361 -366 .   DOI: 10.15302/J-ENG-2015043
Abstract   HTML   PDF (3079KB)

Based on the construction of the 8-inch fabrication line, advanced process technology of 8-inch wafer, as well as the fourth-generation high-voltage double-diffused metal-oxide semiconductor (DMOS+) insulated-gate bipolar transistor (IGBT) technology and the fifth-generation trench gate IGBT technology, have been developed, realizing a great-leap forward technological development for the manufacturing of high-voltage IGBT from 6-inch to 8-inch. The 1600 A/1.7 kV and 1500 A/3.3 kV IGBT modules have been successfully fabricated, qualified, and applied in rail transportation traction system.

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High-Throughput Multi-Plume Pulsed-Laser Deposition for Materials Exploration and Optimization
Samuel S. Mao, Xiaojun Zhang
Engineering . 2015, 1 (3): 367 -371 .   DOI: 10.15302/J-ENG-2015065
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A high-throughput multi-plume pulsed-laser deposition (MPPLD) system has been demonstrated and compared to previous techniques. Whereas most combinatorial pulsed-laser deposition (PLD) systems have focused on achieving thickness uniformity using sequential multilayer deposition and masking followed by post-deposition annealing, MPPLD directly deposits a compositionally varied library of compounds using the directionality of PLD plumes and the resulting spatial variations of deposition rate. This system is more suitable for high-throughput compound thin-film fabrication.

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Materials Design on the Origin of Gap States in a High-κ/GaAs Interface
Weichao Wang, Cheng Gong, Ka Xiong, Santosh K.C., Robert M. Wallace, Kyeongjae Cho
Engineering . 2015, 1 (3): 372 -377 .   DOI: 10.15302/J-ENG-2015052
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Given the demand for constantly scaling microelectronic devices to ever smaller dimensions, a SiO2 gate dielectric was substituted with a higher dielectric-constant material, Hf(Zr)O2, in order to minimize current leakage through dielectric thin film. However, upon interfacing with high dielectric constant (high-κ) dielectrics, the electron mobility in the conventional Si channel degrades due to Coulomb scattering, surface-roughness scattering, remote-phonon scattering, and dielectric-charge trapping. III-V and Ge are two promising candidates with superior mobility over Si. Nevertheless, Hf(Zr)O2/III-V(Ge) has much more complicated interface bonding than Si-based interfaces. Successful fabrication of a high-quality device critically depends on understanding and engineering the bonding configurations at Hf(Zr)O2/III-V(Ge) interfaces for the optimal design of device interfaces. Thus, an accurate atomic insight into the interface bonding and mechanism of interface gap states formation becomes essential. Here, we utilize first-principle calculations to investigate the interface between HfO2 and GaAs. Our study shows that As−As dimer bonding, Ga partial oxidation (between 3+ and 1+) and Ga− dangling bonds constitute the major contributions to gap states. These findings provide insightful guidance for optimum interface passivation.

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Single-Seed Casting Large-Size Monocrystalline Silicon for High-Efficiency and Low-Cost Solar Cells
Bing Gao, Satoshi Nakano, Hirofumi Harada, Yoshiji Miyamura, Takashi Sekiguchi, Koichi Kakimoto
Engineering . 2015, 1 (3): 378 -383 .   DOI: 10.15302/J-ENG-2015032
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To grow high-quality and large-size monocrystal-line silicon at low cost, we proposed a single-seed casting technique. To realize this technique, two challenges—polycrystalline nucleation on the crucible wall and dislocation multiplication inside the crystal—needed to be addressed. Numerical analysis was used to develop solutions for these challenges. Based on an optimized furnace structure and operating conditions from numerical analysis, experiments were performed to grow monocrystalline silicon using the single-seed casting technique. The results revealed that this technique is highly superior to the popular high-performance multicrystalline and multiseed casting mono-like techniques.

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Effects of Vapor Pressure and Super-Hydrophobic Nanocomposite Coating on Microelectronics Reliability
Xuejun Fan, Liangbiao Chen, C. P. Wong, Hsing-Wei Chu, G. Q. Zhang
Engineering . 2015, 1 (3): 384 -390 .   DOI: 10.15302/J-ENG-2015034
Abstract   HTML   PDF (1651KB)

Modeling vapor pressure is crucial for studying the moisture reliability of microelectronics, as high vapor pressure can cause device failures in environments with high temperature and humidity. To minimize the impact of vapor pressure, a super-hydrophobic (SH) coating can be applied on the exterior surface of devices in order to prevent moisture penetration. The underlying mechanism of SH coating for enhancing device reliability, however, is still not fully understood. In this paper, we present several existing theories for predicting vapor pressure within microelectronic materials. In addition, we discuss the mechanism and effectiveness of SH coating in preventing water vapor from entering a device, based on experimental results. Two theoretical models, a micro-mechanics-based whole-field vapor pressure model and a convection-diffusion model, are described for predicting vapor pressure. Both methods have been successfully used to explain experimental results on uncoated samples. However, when a device was coated with an SH nanocomposite, weight gain was still observed, likely due to vapor penetration through the SH surface. This phenomenon may cast doubt on the effectiveness of SH coatings in microelectronic devices. Based on current theories and the available experimental results, we conclude that it is necessary to develop a new theory to understand how water vapor penetrates through SH coatings and impacts the materials underneath. Such a theory could greatly improve microelectronics reliability.

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A Precision-Positioning Method for a High-Acceleration Low-Load Mechanism Based on Optimal Spatial and Temporal Distribution of Inertial Energy
Xin Chen, Youdun Bai, Zhijun Yang, Jian Gao, Gongfa Chen
Engineering . 2015, 1 (3): 391 -398 .   DOI: 10.15302/J-ENG-2015063
Abstract   HTML   PDF (2784KB)

High-speed and precision positioning are fundamental requirements for high-acceleration low-load mechanisms in integrated circuit (IC) packaging equipment. In this paper, we derive the transient nonlinear dynamicresponse equations of high-acceleration mechanisms, which reveal that stiffness, frequency, damping, and driving frequency are the primary factors. Therefore, we propose a new structural optimization and velocity-planning method for the precision positioning of a high-acceleration mechanism based on optimal spatial and temporal distribution of inertial energy. For structural optimization, we first reviewed the commonly flexible multibody dynamic optimization using equivalent static loads method (ESLM), and then we selected the modified ESLM for optimal spatial distribution of inertial energy; hence, not only the stiffness but also the inertia and frequency of the real modal shapes are considered. For velocity planning, we developed a new velocity-planning method based on nonlinear dynamic-response optimization with varying motion conditions. Our method was verified on a high-acceleration die bonder. The amplitude of residual vibration could be decreased by more than 20% via structural optimization and the positioning time could be reduced by more than 40% via asymmetric variable velocity planning. This method provides an effective theoretical support for the precision positioning of high-acceleration low-load mechanisms.

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