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High sensitivity saliva-based biosensor in detection of breast cancer biomarkers: HER2 and CA15-3. 基于唾液的高灵敏度生物传感器用于检测乳腺癌生物标记物:HER2 和 CA15-3。
IF 1.5 4区 工程技术 Q3 ENGINEERING, ELECTRICAL & ELECTRONIC Pub Date : 2024-03-01 Epub Date: 2024-02-13 DOI: 10.1116/6.0003370
Hsiao-Hsuan Wan, Haochen Zhu, Chao-Ching Chiang, Jian-Sian Li, Fan Ren, Cheng-Tse Tsai, Yu-Te Liao, Dan Neal, Josephine F Esquivel-Upshaw, Stephen J Pearton

The prevalence of breast cancer in women underscores the urgent need for innovative and efficient detection methods. This study addresses this imperative by harnessing salivary biomarkers, offering a noninvasive and accessible means of identifying breast cancer. In this study, commercially available disposable based strips similar to the commonly used glucose detection strips were utilized and functionalized to detect breast cancer with biomarkers of HER2 and CA15-3. The results demonstrated limits of detection for these two biomarkers reached as low as 1 fg/ml much lower than those of conventional enzyme-linked immunosorbent assay in the range of 1∼4 ng/ml. By employing a synchronized double-pulse method to apply 10 of 1.2 ms voltage pulses to the electrode of sensing strip and drain electrode of the transistor for amplifying the detected signal, and the detected signal was the average of 10 digital output readings corresponding to those 10 voltage pulses. The sensor sensitivities were achieved approximately 70/dec and 30/dec for HER2 and CA15-3, respectively. Moreover, the efficiency of this novel technique is underscored by its swift testing time of less than 15 ms and its minimal sample requirement of only 3 μl of saliva. The simplicity of operation and the potential for widespread public use in the future position this approach as a transformative tool in the early detection of breast cancer. This research not only provides a crucial advancement in diagnostic methodologies but also holds the promise of revolutionizing public health practices.

女性乳腺癌的发病率突显了对创新、高效检测方法的迫切需求。本研究通过利用唾液生物标记物来解决这一迫切问题,提供了一种无创、便捷的乳腺癌识别方法。在这项研究中,我们利用市售的一次性检测条(类似于常用的葡萄糖检测条),并对其进行功能化处理,以检测带有 HER2 和 CA15-3 生物标志物的乳腺癌。结果表明,这两种生物标记物的检测限低至 1 fg/ml,远低于传统酶联免疫吸附测定法的 1∼4 ng/ml。通过采用同步双脉冲方法,在传感条的电极和晶体管的漏极上施加 10 个 1.2 毫秒的电压脉冲来放大检测信号,检测信号是这 10 个电压脉冲对应的 10 个数字输出读数的平均值。传感器对 HER2 和 CA15-3 的灵敏度分别达到约 70 分贝和 30 分贝。此外,这项新技术的高效性还体现在它的快速测试时间小于 15 毫秒,且只需 3 μl 唾液样本。这种方法操作简单,将来有可能广泛应用于公众,是乳腺癌早期检测领域的一种变革性工具。这项研究不仅在诊断方法上取得了重要进展,而且有望彻底改变公共卫生实践。
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引用次数: 0
Developing Single Layer MOS Quantum Dots for Diagnostic Qubits. 用于诊断量子比特的单层MOS量子点的开发。
IF 1.5 4区 工程技术 Q3 ENGINEERING, ELECTRICAL & ELECTRONIC Pub Date : 2021-01-01 DOI: 10.1116/6.0000549
Yanxue Hong, A N Ramanayaka, Ryan Stein, M D Stewart, J M Pomeroy

The design, fabrication and characterization of single metal gate layer, metal-oxide-semiconductor (MOS) quantum dot devices robust against dielectric breakdown are presented as prototypes for future diagnostic qubits. These devices were developed as a preliminary solution to a longer term goal of a qubit platform for intercomparison between materials or for in-line diagnostics, and to provide a testbed for establishing classical measurements predictive of coherence performance. For this stage, we seek a robust MOS design that is compatible with wafer and chip architectures, that has a reduced process overhead and is sufficiently capable of challenging and advancing our measurement capabilities. In this report, we present our initial batch of silicon MOS devices using a single gate layer, which have not exhibited any failures with gate voltage excursions > 10 V, but do exhibit the reduced electrostatic control expected of a single gate layer design. We observe quantum dot formation, capacitive charge sensing between channels, and reasonable effective electron temperatures that enable spin qubit studies. The costs and benefits of the trade-off between device performance and fabrication efficiency will be discussed, as well as opportunities for future improvements.

介绍了抗介电击穿的单金属栅层、金属氧化物半导体(MOS)量子点器件的设计、制造和表征,作为未来诊断量子比特的原型。这些设备的开发是为了实现量子比特平台的长期目标的初步解决方案,用于材料之间的相互比较或在线诊断,并为建立预测相干性能的经典测量提供测试平台。在这个阶段,我们寻求一种强大的MOS设计,它与晶圆和芯片架构兼容,降低了工艺开销,并有足够的能力挑战和提高我们的测量能力。在本报告中,我们展示了使用单栅极层的第一批硅MOS器件,该器件在栅极电压漂移bbb10 V时没有表现出任何故障,但确实表现出单栅极层设计所期望的静电控制降低。我们观察到量子点的形成,通道之间的电容电荷传感,以及能够进行自旋量子比特研究的合理有效电子温度。将讨论器件性能和制造效率之间权衡的成本和收益,以及未来改进的机会。
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引用次数: 0
Detecting nanoscale contamination in semiconductor fabrication using through-focus scanning optical microscopy. 利用透焦扫描光学显微镜检测半导体制造中的纳米级污染。
IF 1.5 4区 工程技术 Q3 ENGINEERING, ELECTRICAL & ELECTRONIC Pub Date : 2020-01-01 DOI: 10.1116/6.0000352
Min-Ho Rim, Emil Agocs, Ronald Dixson, Prem Kavuri, András E Vladár, Ravi Kiran Attota

This paper reports high-throughput, light-based, through-focus scanning optical microscopy (TSOM) for detecting industrially relevant sub-50 nm tall nanoscale contaminants. Measurement parameter optimization to maximize the TSOM signal using optical simulations made it possible to detect the nanoscale contaminants. Atomic force and scanning electron microscopies were used as reference methods for comparison.

本文报道了用于检测工业相关的50 nm以下高纳米级污染物的高通量,光基,透焦扫描光学显微镜(TSOM)。利用光学模拟优化测量参数以最大化TSOM信号,使检测纳米级污染物成为可能。原子力和扫描电镜作为对照方法。
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引用次数: 0
Time multiplexed deep reactive ion etching of germanium and silicon-A comparison of mechanisms and application to x-ray optics. 锗和硅的时间复用深度反应离子刻蚀——机理比较及其在x射线光学中的应用。
4区 工程技术 Q3 ENGINEERING, ELECTRICAL & ELECTRONIC Pub Date : 2018-01-01 Epub Date: 2018-01-04 DOI: 10.1116/1.4991875
Vincent J Genova, David N Agyeman-Budu, Arthur R Woll

Although the mechanisms of deep reactive ion etching (DRIE) of silicon have been reported extensively, very little by comparison has been discussed concerning DRIE of germanium. By directly comparing silicon and germanium etching in a time multiplexed DRIE process, the authors extract significant differences in etch mechanisms from a design of experiment and discuss how these differences are relevant to the design and fabrication of silicon and germanium collimating channel array x-ray optics. The differences are illuminated by characteristics such as reactive ion etching (RIE)-lag, aspect ratio dependent etching, and sidewall passivation. Specifically, the authors demonstrate the more severe nature of RIE-lag in germanium, especially at aspect ratios exceeding 13:1. In addition, the differences in the profile evolution between silicon and germanium are shown to be a result of differences in sidewall passivation. There is also a correlation between the different sidewall passivation and the inherent lack of scalloping in the case of germanium DRIE.

虽然硅的深度反应离子刻蚀(DRIE)机理已被广泛报道,但对锗的深度反应离子刻蚀(DRIE)机理的讨论却很少。通过直接比较时间复用DRIE工艺中硅和锗的蚀刻,作者从实验设计中提取了蚀刻机制的显著差异,并讨论了这些差异如何与硅和锗准直通道阵列x射线光学系统的设计和制造相关。反应性离子蚀刻(RIE)滞后、依赖宽高比的蚀刻和侧壁钝化等特性阐明了两者的差异。具体来说,作者证明了锗中更严重的rie滞后性质,特别是在纵横比超过13:1时。此外,硅和锗在剖面演化上的差异是由于侧壁钝化的差异造成的。在锗DRIE的情况下,不同的侧壁钝化与固有的扇贝缺失之间也存在相关性。
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引用次数: 2
Minimizing open-loop piezoactuator nonlinearity artifacts in atomic force microscope measurements. 在原子力显微镜测量中最小化开环压电致动器非线性伪影。
4区 工程技术 Q3 ENGINEERING, ELECTRICAL & ELECTRONIC Pub Date : 2017-09-01 Epub Date: 2017-09-08 DOI: 10.1116/1.4994315
Chi-Fu Yen, Sanjeevi Sivasankar

Atomic force microscopes (AFMs) are widely used to study molecular interactions with piconewton force sensitivity. In an AFM, interaction forces are measured by reflecting a laser beam off a cantilever onto a position sensitive detector and monitoring cantilever deflection. Precise measurements of interaction forces rely on accurately determining the optical lever sensitivity, i.e., the relationship between cantilever deflection and changes in detector voltage. The optical lever sensitivity is measured by pressing the cantilever against a hard substrate using a piezoactuator and recording the resulting change in detector voltage. However, nonlinearities in the motion of commonly used open-loop piezo actuators introduce significant errors in measured optical lever sensitivities. Here, the authors systematically characterize the effect of piezo actuator hysteresis and creep on errors in optical lever sensitivity and identify measurement conditions that minimize these errors.

原子力显微镜(AFMs)被广泛用于研究具有皮牛顿力灵敏度的分子相互作用。在AFM中,通过将激光束从悬臂梁反射到位置敏感探测器并监测悬臂梁挠度来测量相互作用力。相互作用力的精确测量依赖于精确地确定光学杠杆的灵敏度,即悬臂梁挠度与探测器电压变化之间的关系。光学杠杆的灵敏度是通过使用压电致动器将悬臂压在坚硬的衬底上并记录探测器电压的变化来测量的。然而,在常用的开环压电致动器的运动非线性引入显著误差测量光学杠杆的灵敏度。在这里,作者系统地描述了压电致动器的滞后和蠕变对光学杠杆灵敏度误差的影响,并确定了最小化这些误差的测量条件。
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引用次数: 1
Interfacial reactions at Fe/topological insulator spin contacts. Fe/拓扑绝缘体自旋接触的界面反应。
4区 工程技术 Q3 ENGINEERING, ELECTRICAL & ELECTRONIC Pub Date : 2017-07-01 Epub Date: 2017-07-06 DOI: 10.1116/1.4991331
Sarmita Majumder, Karalee Jarvis, Sanjay K Banerjee, Karen L Kavanagh

The authors study the composition and abruptness of the interfacial layers that form during deposition and patterning of a ferromagnet, Fe on a topological insulator (TI), Bi2Se3, Bi2Te3, and SiOx/Bi2Te3. Such structures are potentially useful for spintronics. Cross-sectional transmission electron microscopy, including interfacial elemental mapping, confirms that Fe reacts with Bi2Se3 near room temperature, forming an abrupt 5 nm thick FeSe0.92 single crystalline binary phase, predominantly (001) oriented, with lattice fringe spacing of 0.55 nm. In contrast, Fe/Bi2Te3 forms a polycrystalline Fe/TI interfacial alloy that can be prevented by the addition of an evaporated SiOx separating Fe from the TI.

作者研究了铁磁体Fe在拓扑绝缘体(TI)、Bi2Se3、Bi2Te3和SiOx/Bi2Te3上沉积和图像化过程中形成的界面层的组成和突发性。这种结构对自旋电子学有潜在的用处。包括界面元素映射在内的截面透射电子显微镜证实,Fe与Bi2Se3在室温附近发生反应,形成5 nm厚的FeSe0.92单晶二元相,主要取向为(001),晶格条纹间距为0.55 nm。相反,Fe/Bi2Te3形成多晶Fe/TI界面合金,可以通过添加蒸发的SiOx将Fe与TI分离来阻止。
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引用次数: 5
Review Article: Progress in fabrication of transition metal dichalcogenides heterostructure systems. 综述:过渡金属二硫族化合物异质结构体系的制备进展。
4区 工程技术 Q3 ENGINEERING, ELECTRICAL & ELECTRONIC Pub Date : 2017-05-01 DOI: 10.1116/1.4982736
Rui Dong, Irma Kuljanishvili

Transition metal dichalcogenide (TMDC) semiconductors have attracted significant attention because of their rich electronic/photonic properties and importance for fundamental research and novel device applications. These materials provide a unique opportunity to build up high quality and atomically sharp heterostructures because of the nature of weak van der Waals interlayer interactions. The variable electronic properties of TMDCs (e.g., band gap and their alignment) provide a platform for the design of novel electronic and optoelectronic devices. The integration of TMDC heterostructures into the semiconductor industry is presently hindered by limited options in reliable production methods. Many exciting properties and device architectures which have been studied to date are, in large, based on the exfoliation methods of bulk TMDC crystals. These methods are generally more difficult to consider for large scale integration processes, and hence, continued developments of different fabrication strategies are essential for further advancements in this area. In this review, the authors highlight the recent progress in the fabrication of TMDC heterostructures. The authors will review several methods most commonly used to date for controllable heterostructure formation. One of the focuses will be on TMDC heterostructures fabricated by thermal chemical vapor deposition methods which allow for the control over the resulting materials, individual layers and heterostructures. Another focus would be on the techniques for selective growth of TMDCs. The authors will discuss conventional and unconventional fabrication methods and their advantages and drawbacks and will provide some guidance for future improvements. Mask-assisted and mask-free methods will be presented, which include traditional lithographic techniques (photo- or e-beam lithography) and some unconventional methods such as the focus ion beam and the recently developed direct-write patterning approach, which are shown to be promising for the fabrication of quality TMDC heterostructures.

过渡金属二硫族化合物(TMDC)半导体由于其丰富的电子/光子特性以及在基础研究和新型器件应用中的重要性而引起了人们的广泛关注。由于弱范德华层间相互作用的性质,这些材料为建立高质量和原子尖锐的异质结构提供了独特的机会。TMDCs的可变电子特性(例如,带隙及其对准)为设计新型电子和光电子器件提供了平台。TMDC异质结构集成到半导体工业目前阻碍了有限的选择可靠的生产方法。迄今为止研究的许多令人兴奋的特性和器件结构在很大程度上是基于块体TMDC晶体的剥离方法。这些方法通常很难考虑大规模集成过程,因此,不同制造策略的持续发展对于该领域的进一步发展至关重要。本文综述了近年来在TMDC异质结构制备方面的研究进展。作者将回顾几种迄今为止最常用的可控异质结构形成方法。其中一个重点将是通过热化学气相沉积方法制造的TMDC异质结构,该方法允许控制所得到的材料,单个层和异质结构。另一个重点将是TMDCs的选择性生长技术。作者将讨论传统和非常规的制造方法及其优缺点,并对未来的改进提供一些指导。将介绍掩模辅助和无掩模方法,包括传统的光刻技术(光刻或电子束光刻)和一些非常规的方法,如聚焦离子束和最近开发的直接写入图像化方法,这些方法被证明有希望制造高质量的TMDC异质结构。
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引用次数: 107
Clinical probe utilizing surface enhanced Raman scattering. 利用表面增强拉曼散射的临床探针。
4区 工程技术 Q3 ENGINEERING, ELECTRICAL & ELECTRONIC Pub Date : 2014-11-01 Epub Date: 2014-09-26 DOI: 10.1116/1.4896479
Jeonghwan Kim, Dooyoung Hah, Theda Daniels-Race, Martin Feldman

Conventional Raman scattering is a well-known technique for detecting and identifying complex molecular samples. In surface enhanced Raman scattering, a nanorough metallic surface close to the sample enormously enhances the Raman signal. In previous work, the metallic surface was a thin layer of gold deposited on a rough transparent epoxy substrate. The advantage of the clear substrate was that the Raman signal could be obtained by passing light through the substrate, on to opaque samples simply placed against its surface. In this work, a commercially available Raman spectrometer was coupled to a distant probe. Raman signals were obtained from the surface, and from the interior, of a solid specimen located more than 1 m away from the spectrometer. The practical advantage of this arrangement is that it opens up surface enhanced Raman spectrometry to a clinical environment, with a patient simply sitting or lying near the spectrometer.

传统的拉曼散射是一种众所周知的检测和鉴定复杂分子样品的技术。在表面增强拉曼散射中,靠近样品的纳米级金属表面极大地增强了拉曼信号。在以前的工作中,金属表面是一层薄薄的金,沉积在粗糙的透明环氧基板上。透明衬底的优点是,拉曼信号可以通过将光穿过衬底,照射到不透明的样品上而获得。在这项工作中,一个商用拉曼光谱仪与一个遥远的探测器耦合在一起。拉曼信号是从距离光谱仪1米以上的固体样品的表面和内部获得的。这种安排的实际优势在于,它将表面增强拉曼光谱法应用于临床环境,患者只需坐在或躺在光谱仪附近。
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引用次数: 8
Nanorough gold for enhanced Raman scattering. 纳米金增强拉曼散射。
4区 工程技术 Q3 ENGINEERING, ELECTRICAL & ELECTRONIC Pub Date : 2013-11-01 Epub Date: 2013-10-29 DOI: 10.1116/1.4826701
Jeonghwan Kim, Kyung-Nam Kang, Anirban Sarkar, Pallavi Malempati, Dooyoung Hah, Theda Daniels-Race, Martin Feldman

Conventional Raman scattering is a workhorse technique for detecting and identifying complex molecular samples. In surface enhanced Raman scattering, a nanorough metallic surface close to the sample enhances the Raman signal enormously. In this work, the surface is on a clear epoxy substrate. The epoxy is cast on a silicon wafer, using 20 nm of gold as a mold release. This single step process already produces useful enhanced Raman signals. However, the Raman signal is further enhanced by (1) depositing additional gold on the epoxy substrate and (2) by using a combination of wet and dry etches to roughen the silicon substrate before casting the epoxy. The advantage of a clear substrate is that the Raman signal may be obtained by passing light through the substrate, with opaque samples simply placed against the surface. Results were obtained with solutions of Rhodamine 6G in deionized water over a range of concentrations from 1 nM to 1 mM. In all cases, the signal to noise ratio was greater than 10:1.

传统的拉曼散射是检测和鉴定复杂分子样品的主要技术。在表面增强拉曼散射中,靠近样品的纳米级金属表面极大地增强了拉曼信号。在这项工作中,表面是在一个透明的环氧基板上。环氧树脂被浇铸在硅片上,使用20纳米的金作为脱模剂。这个单步过程已经产生了有用的增强拉曼信号。然而,拉曼信号通过(1)在环氧基板上沉积额外的金和(2)在铸造环氧基板之前使用干湿蚀刻的组合来粗糙硅基板来进一步增强。透明衬底的优点是,拉曼信号可以通过光通过衬底获得,不透明的样品简单地放置在表面上。结果是在去离子水中的罗丹明6G溶液在1 nM到1 mM的浓度范围内得到的。在所有情况下,信噪比均大于10:1。
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引用次数: 5
Bifunctional nanoarrays for probing the immune response at the single-molecule level. 用于探测单分子水平免疫反应的双功能纳米阵列。
4区 工程技术 Q3 ENGINEERING, ELECTRICAL & ELECTRONIC Pub Date : 2013-11-01 Epub Date: 2013-10-08 DOI: 10.1116/1.4823764
Haogang Cai, David Depoil, Matteo Palma, Michael P Sheetz, Michael L Dustin, Shalom J Wind

Bifunctional nanoarrays were created to simulate the immunological synapse and probe the T-cell immune response at the single-molecule level. Sub-5 nm AuPd nanodot arrays were fabricated using both e-beam and nanoimprint lithography. The nanoarrays were then functionalized by two costimulatory molecules: antibody UCHT1 Fab, which binds to the T-cell receptor (TCR) and activates the immune response, bound to metallic nanodots; and intercellular adhesion molecule-1, which enhances cell adhesion, on the surrounding area. Initial T-cell experiments show successful attachment and activation on the bifunctional nanoarrays. This nanoscale platform for single-molecule control of TCR in living T-cells provides a new approach to explore how its geometric arrangement affects T-cell activation and behavior, with potential applications in immunotherapy. This platform also serves as a general model for single-molecule nanoarrays where more than one molecular species is required.

创建双功能纳米阵列来模拟免疫突触并在单分子水平上探测t细胞免疫反应。采用电子束和纳米压印技术制备了5 nm以下的AuPd纳米点阵列。然后,两种共刺激分子使纳米阵列功能化:抗体UCHT1 Fab,与t细胞受体(TCR)结合并激活免疫反应,与金属纳米点结合;细胞间粘附分子-1,增强细胞在周围区域的粘附。最初的t细胞实验显示双功能纳米阵列成功附着和激活。这种单分子控制活t细胞中TCR的纳米级平台为探索其几何排列如何影响t细胞活化和行为提供了一种新的方法,在免疫治疗中具有潜在的应用前景。该平台也可作为单分子纳米阵列的通用模型,其中需要多个分子物种。
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引用次数: 11
期刊
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