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Progress and challenges in biomarker enrichment for cancer early detection 生物标志物富集用于癌症早期检测的进展和挑战
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2021-01-01 DOI: 10.1088/2516-1091/ac1ea3
P. D. Sinawang, Fernando Soto, M. Ozen, D. Akin, U. Demirci
Cancer cells generate and secrete diverse molecules into circulation that could be used as signatures for health and disease. A significant obstacle in detecting such molecules derives from their low signal-to-noise ratio in subsequent downstream analyses. Developing reliable tools and methods for cancer early detection is crucial for advancing global strategies to decrease mortality, monitor disease progression and therapy, and improve the quality of life of patients. This perspective critically addresses recent developments in cancer early detection, highlighting current trends in the enrichment of cancer-related biomarkers, dividing them into biochemical and biophysical methods. Finally, we provide insights into the challenges and opportunities in biomarker isolation and enrichment protocols. Integrating these methods into clinical decision-making pipelines could lead to a better understanding of cancer progression, treatment efficacy, and hence improving the medical outcomes for cancer patients.
癌细胞产生并分泌不同的分子进入循环,这些分子可以作为健康和疾病的标志。在随后的下游分析中,检测此类分子的一个重要障碍是它们的低信噪比。开发可靠的癌症早期检测工具和方法对于推进降低死亡率、监测疾病进展和治疗以及改善患者生活质量的全球战略至关重要。这一观点批判性地阐述了癌症早期检测的最新进展,强调了癌症相关生物标志物富集的当前趋势,并将其分为生化和生物物理方法。最后,我们提供了对生物标志物分离和富集方案的挑战和机遇的见解。将这些方法整合到临床决策流程中,可以更好地了解癌症的进展和治疗效果,从而改善癌症患者的医疗结果。
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引用次数: 4
X-ray to MR: the progress of flexible instruments for endovascular navigation x线到磁共振:血管内导航柔性器械的进展
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2021-01-01 DOI: 10.1088/2516-1091/ac12d6
Mohamed E. M. K. Abdelaziz, Libaihe Tian, M. Hamady, Guang-Zhong Yang, B. Temelkuran
Interventional radiology and cardiology are rapidly growing areas of minimally invasive surgery, covering multiple diagnostic and interventional procedures. Treatment via endovascular techniques has become the go-to approach, thanks to its minimally invasive nature and its effectiveness in reducing hospitalisation and total time to recovery when compared to open surgery. Although x-ray fluoroscopy is currently the gold standard imaging technique for endovascular interventions, it presents occupational safety hazards to medical personnel and potential risks to patients, especially paediatric patients, because of its inherent ionising radiation. Magnetic resonance imaging (MRI), with its unique ability to provide radiation-free imaging, and acquiring morphologic and functional information, holds great promise in the advancement of image-guided navigation through the vasculature. Moreover, MRI has the potential to combine diagnosis, therapy and early evaluation of therapy in the same intervention. However, MR-guided interventions face a major challenge due to the presence of a large magnetic field (1.5/3 Tesla), which limits the set of materials suitable for the construction of key instrumentation (sheaths, catheters and guidewires). Despite these challenges, in recent years, significant progress has been made in the development of interventional devices, which comprise biocompatible, MR safe and MR visible materials. In an attempt to encourage and accelerate the development of MR-guided endovascular instrumentation, we present a systematic and illustrated overview of the plethora of work targeting to overcome the aforementioned limitations which are underpinned by the interdependent advancements in science, technology, engineering, mathematics and medicine (STEMM).
介入放射学和心脏病学是微创外科快速发展的领域,涵盖多种诊断和介入程序。与开放手术相比,血管内技术的微创性和减少住院时间和总恢复时间的有效性使其成为首选治疗方法。虽然x线透视目前是血管内介入的金标准成像技术,但由于其固有的电离辐射,它给医务人员带来了职业安全危害,给患者,特别是儿科患者带来了潜在风险。磁共振成像(MRI)以其独特的能力提供无辐射成像,并获得形态和功能信息,在通过血管系统的图像引导导航的进步中具有很大的希望。此外,MRI具有在同一干预中结合诊断、治疗和早期治疗评估的潜力。然而,由于存在大磁场(1.5/3特斯拉),核磁共振引导干预面临重大挑战,这限制了适用于构建关键仪器(护套、导管和导丝)的材料集。尽管存在这些挑战,但近年来,介入装置的发展取得了重大进展,这些装置包括生物相容性、核磁共振安全性和核磁共振可见材料。为了鼓励和加速核磁共振引导的血管内仪器的发展,我们提出了一个系统的和说明的概述,以克服上述局限性为目标的大量工作,这些局限性是由科学、技术、工程、数学和医学(STEMM)的相互依存的进步所支撑的。
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引用次数: 15
Ingestible devices for long-term gastrointestinal residency: a review 长期胃肠道住院治疗的可消化装置:综述
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2021-01-01 DOI: 10.1088/2516-1091/ac1731
M. M. Mau, Sunandita Sarker, B. Terry
Ingestible devices have been gaining attention from the medical community due to their noninvasive use in diagnostics and treatment of the gastrointestinal (GI) tract. However, their passive locomotion limits their GI residency period. Ingestible sensors residing in the GI tract are capable of providing continuous data, while long-acting ingestible drug delivery systems can reduce medication nonadherence. This paper presents a comprehensive overview of the state-of-the-art, long-term ingestible devices (LTIDs). Additionally, this review summarizes the current status of ingestible devices that persist in the GI tract for a prolonged period, as well as their inhabitance mechanisms and applications. Also included are relevant information about the GI structure and design considerations for understanding the significance and challenges associated with LTIDs. Finally, we discuss several potential applications of the LTIDs for therapeutic intervention in the GI tract and monitoring the physiology and pathophysiology of the GI tract for an extended period.
可消化装置因其在胃肠道诊断和治疗中的无创使用而受到医学界的关注。然而,它们的被动运动限制了它们在GI的居住时间。驻留在胃肠道的可摄取传感器能够提供连续的数据,而长效可摄取药物输送系统可以减少药物依从性。本文提出了一个全面的概述,最先进的,长期可摄取装置(ltid)。此外,本文还综述了长期存在于胃肠道中的可消化装置的现状,以及它们的存在机制和应用。还包括有关GI结构和设计注意事项的相关信息,以便了解与ltid相关的重要性和挑战。最后,我们讨论了LTIDs在胃肠道治疗干预和长时间监测胃肠道生理和病理生理方面的几种潜在应用。
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引用次数: 12
Is in vivo sensing in a total hip replacement a possibility? A review on past systems and future challenges 全髋关节置换术中的体内传感是可能的吗?回顾过去的制度和未来的挑战
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2021-01-01 DOI: 10.1088/2516-1091/ac1b7f
O. Vickers, P. Culmer, G. Isaac, R. Kay, M. P. Shuttleworth, T. Board, S. Williams
Surgery to implant a total hip replacement (THR) is very successful in reducing pain and restoring function. This procedure has become more prevalent, and projections estimate further increases in demand. However, complications can arise, and current diagnostic techniques often fail to expose underlying issues before they result in a catastrophic failure that requires revision surgery. An instrumented implant, with embedded sensors capable of real time condition monitoring, would be an attractive proposition to incorporate within a THR. Continued advances in the performance and miniaturisation of electronic components, embedded systems, sensing and wireless communications have given the tools and resources medical device manufacturers need to innovate in the field of implantable medical devices. Smart implants are already being widely used in healthcare including pacemakers, cochlear implants, glucose monitors and insulin pumps however, a widely used smart THR has not yet been realised. Since the implantation of the first instrumented hip implant in the 1960s there have been several in vitro studies monitoring levels of implant loosening. Additionally, significant research has been conducted using instrumented THRs to perform in vivo measurement of biomechanical metrics, including force and moments. To date less than 100 patients have successfully received an instrumented implant. The results of these studies have aided researchers, designers and surgeons in wider research projects, however, the motivation behind the work was to provide discrete biomechanical data sets and not provide real-time condition monitoring of an implants performance or highlight early indications for revision surgery. If in vivo sensing within a THR is to be achieved and adopted in regular clinical practice then the following challenges need to be addressed: choice of the sensing method, biocompatibility and integration within the implant, power supply, communication, and regulatory considerations.
手术植入全髋关节置换术(THR)在减轻疼痛和恢复功能方面非常成功。这一程序已变得更加普遍,预计需求将进一步增加。然而,并发症可能会出现,目前的诊断技术往往不能在导致需要翻修手术的灾难性失败之前暴露潜在的问题。一种带有嵌入式传感器的仪器植入物,能够实时监测状态,将是一个有吸引力的提议,纳入THR。电子元件、嵌入式系统、传感和无线通信的性能和小型化的持续进步,为医疗设备制造商提供了在植入式医疗设备领域进行创新所需的工具和资源。智能植入物已经广泛应用于医疗保健领域,包括起搏器、耳蜗植入物、血糖监测仪和胰岛素泵,然而,广泛使用的智能THR尚未实现。自20世纪60年代首次植入人工髋关节以来,已经进行了几项体外研究,监测人工髋关节松动的水平。此外,已经进行了大量研究,使用仪器化的THRs进行生物力学指标的体内测量,包括力和力矩。迄今为止,只有不到100名患者成功接受了器械植入。这些研究的结果在更广泛的研究项目中为研究人员、设计师和外科医生提供了帮助,然而,这项工作背后的动机是提供离散的生物力学数据集,而不是提供植入物性能的实时状态监测或突出修复手术的早期适应症。如果要在THR内实现体内传感并在常规临床实践中采用,则需要解决以下挑战:传感方法的选择、植入物内的生物相容性和整合、电源、通信和监管考虑。
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引用次数: 2
Deep learning in medical image registration 医学图像配准中的深度学习
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2020-12-14 DOI: 10.1088/2516-1091/abd37c
Xiang Chen, A. Diaz-Pinto, N. Ravikumar, Alejandro F Frangi
Image registration is a fundamental task in multiple medical image analysis applications. With the advent of deep learning, there have been significant advances in algorithmic performance for various computer vision tasks in recent years, including medical image registration. The last couple of years have seen a dramatic increase in the development of deep learning-based medical image registration algorithms. Consequently, a comprehensive review of the current state-of-the-art algorithms in the field is timely, and necessary. This review is aimed at understanding the clinical applications and challenges that drove this innovation, analysing the functionality and limitations of existing approaches, and at providing insights to open challenges and as yet unmet clinical needs that could shape future research directions. To this end, the main contributions of this paper are: (a) discussion of all deep learning-based medical image registration papers published since 2013 with significant methodological and/or functional contributions to the field; (b) analysis of the development and evolution of deep learning-based image registration methods, summarising the current trends and challenges in the domain; and (c) overview of unmet clinical needs and potential directions for future research in deep learning-based medical image registration.
图像配准是多种医学图像分析应用中的一项基本任务。随着深度学习的出现,近年来各种计算机视觉任务的算法性能取得了重大进展,包括医学图像配准。在过去的几年里,基于深度学习的医学图像配准算法的发展有了显著的增长。因此,对该领域当前最先进的算法进行全面审查是及时的,也是必要的。本综述旨在了解推动这一创新的临床应用和挑战,分析现有方法的功能和局限性,并为开放的挑战和尚未满足的临床需求提供见解,这些挑战和需求可能会影响未来的研究方向。为此,本文的主要贡献是:(a)讨论了自2013年以来发表的所有基于深度学习的医学图像配准论文,这些论文在方法和/或功能上对该领域有重大贡献;(b)分析了基于深度学习的图像配准方法的发展和演变,总结了该领域当前的趋势和挑战;(c)基于深度学习的医学图像配准未满足的临床需求和未来研究的潜在方向。
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引用次数: 57
Hydrogel biomaterials to support and guide vascularization 水凝胶生物材料支持和引导血管形成
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2020-11-10 DOI: 10.1088/2516-1091/abc947
R. Chapla, J. West
Biomaterials can be intentionally designed to support and even guide vascularization for applications ranging from engineered organs to treatment of ischemic diseases like myocardial infarction and stroke. In order to appropriately design bioactive biomaterials for vascularization, it is important to understand the cellular and molecular events involved in angiogenesis and vasculogenesis. Cell-matrix and signaling biomolecule interactions that initiate and promote formation of vasculature in vivo can often be mimicked in biomaterial platforms. Hydrogels are frequently used in these applications because they are soft and hydrated with mechanical properties similar to soft tissues and because many synthetic hydrogels are essentially bioinert, allowing one to engineer in specific cell-material interactions. A variety of both naturally-derived and synthetic hydrogel bases are used for supporting vascularization, and these gels are tailored to possess mechanical properties, biodegradation, cell adhesive interactions, biochemical signaling, and/or architectural properties that can promote assembly and tubulogenesis by vascular cells. This article serves to review current hydrogel materials and the innovative design modifications implemented to guide and support the vascularization process.
生物材料可以有意设计用于支持甚至指导血管形成,应用范围从工程器官到心肌梗死和中风等缺血性疾病的治疗。为了适当地设计用于血管生成的生物活性生物材料,了解血管生成和血管生成中涉及的细胞和分子事件是重要的。启动和促进体内血管系统形成的细胞-基质和信号传导生物分子相互作用通常可以在生物材料平台中模拟。水凝胶经常用于这些应用,因为它们柔软且水合,具有类似于软组织的机械性能,并且因为许多合成水凝胶基本上是生物惰性的,允许人们在特定的细胞-材料相互作用中进行工程。各种天然和合成的水凝胶基质都用于支持血管形成,这些凝胶经过定制,具有机械性能、生物降解、细胞粘附相互作用、生物化学信号和/或结构特性,可以促进血管细胞的组装和管生成。本文综述了目前的水凝胶材料以及为指导和支持血管形成过程而进行的创新设计修改。
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引用次数: 7
Modeling metastasis: engineering approaches to study the metastatic cascade 转移模型:转移级联研究的工程方法
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2020-10-21 DOI: 10.1088/2516-1091/abc34f
Hawley C. Pruitt, S. Gerecht
Tumor progression and metastasis requires a complex interplay between tumor cells and their surrounding environment. Conventional 2D and 3D tissue culture models lack the precision and spatiotemporal control required to accurately model the complexity of the tumor microenvironment and metastatic cascade. Advances in biomedical engineering have allowed us to generate precise and versatile model systems to elucidate mechanisms vital to tumor progression and metastasis. The incorporation of novel biomaterials creates a specific mechanical environment that has facilitated controlled studies of cancer cell mechano-transduction. In addition, microfluidic devices have not only allowed for the incorporation of flow and shear forces into vascularized tumor models, but also elucidated vital mechanisms of cancer cell migration that have shifted paradigms about the mode in which cancer cells initiate metastasis. Here, we review the latest developments in biomedical engineering approaches to model the tumor microenvironment and metastatic cascade. We discuss how these approaches have advanced the field of cancer biology and enhanced our understanding of the mechanisms driving metastasis. We initially focus on physical and mechanical aspects of the primary microenvironment that impact tumor cell invasion. We then transition to tumor cell migration using models of tumor extracellular matrix including confined migration. Finally, we review models of intravasation/extravasation and colonization of secondary sites.
肿瘤的进展和转移需要肿瘤细胞和周围环境之间复杂的相互作用。传统的2D和3D组织培养模型缺乏精确模拟肿瘤微环境和转移级联的复杂性所需的精度和时空控制。生物医学工程的进步使我们能够产生精确和通用的模型系统来阐明肿瘤进展和转移的重要机制。新型生物材料的结合创造了一个特定的机械环境,促进了癌细胞机械转导的受控研究。此外,微流体装置不仅允许将流动和剪切力纳入血管化肿瘤模型,而且还阐明了癌细胞迁移的重要机制,改变了关于癌细胞启动转移模式的范式。在这里,我们回顾了生物医学工程方法模拟肿瘤微环境和转移级联的最新进展。我们讨论了这些方法如何推动了癌症生物学领域的发展,并增强了我们对肿瘤转移机制的理解。我们首先关注影响肿瘤细胞侵袭的初级微环境的物理和机械方面。然后我们使用肿瘤细胞外基质模型过渡到肿瘤细胞迁移,包括有限迁移。最后,我们回顾了内渗/外渗和继发部位定植的模型。
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引用次数: 0
Critical review on where CRISPR meets molecular diagnostics 评述CRISPR与分子诊断的交集
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2020-10-08 DOI: 10.1088/2516-1091/abbf5e
A. Lau, C. Ren, Luke P Lee
Simple yet powerful clustered regularly-interspaced short palindromic repeats (CRISPR) technology has led to the advent of numerous developments in life sciences, biotechnology, therapeutics, and molecular diagnostics, enabled by gene editing capability. By exploiting the CRISPR-Cas system’s nucleic acid sequence detection abilities, CRISPR-based molecular diagnostics have been developed. Here, we review the development of rapid, sensitive, and inexpensive CRISPR-based molecular diagnostics. We introduce the transition of CRISPR technology to precision molecular diagnostic devices from tube to device. Next, we discuss the various nucleic acid (NA) detection methods by CRISPR. We address the importance of significant sample preparation steps for a future sample-to-answer solution, which is lacking in current CRISPR-based molecular diagnostic technology. Lastly, we discuss the extension of CRISPR-based molecular diagnostics to various critical applications. We envision CRISPR technology holds great promise for widespread use in precision NA detection applications after particular technical challenges are overcome.
简单而强大的规则间隔短回文重复序列(CRISPR)技术在基因编辑能力的推动下,在生命科学、生物技术、治疗学和分子诊断学领域取得了许多发展。通过利用CRISPR-Cas系统的核酸序列检测能力,开发了基于CRISPR的分子诊断。在这里,我们回顾了快速、灵敏和廉价的基于CRISPR的分子诊断的发展。我们介绍了CRISPR技术向精密分子诊断设备的转变,从试管到设备。接下来,我们将讨论CRISPR检测核酸(NA)的各种方法。我们讨论了重要的样本制备步骤对未来样本应答解决方案的重要性,这是当前基于CRISPR的分子诊断技术所缺乏的。最后,我们讨论了基于CRISPR的分子诊断技术在各种关键应用中的扩展。我们设想,在克服特定的技术挑战后,CRISPR技术有望在精确NA检测应用中广泛应用。
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引用次数: 17
Fundamentals of the gut for capsule engineers 太空舱工程师的肠道基础知识
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2020-09-25 DOI: 10.1088/2516-1091/abab4c
L. Barducci, J. Norton, Sunandita Sarker, Sayeed Mohammed, Ryan Jones, P. Valdastri, B. Terry
The gastrointestinal (GI) tract is a complex environment comprised of the mouth, esophagus, stomach, small and large intestines, rectum and anus, which all cooperate to form the complete working GI system. Access to the GI using endoscopy has been augmented over the past several decades by swallowable diagnostic electromechanical devices, such as pill cameras. Research continues today and into the foreseeable future on new and more capable miniature devices for the purposes of systemic drug delivery, therapy, tissue biopsy, microbiome sampling, and a host of other novel ground-breaking applications. The purpose of this review is to provide engineers in this field a comprehensive reference manual of the GI environment and its complex physical, biological, and chemical characteristics so they can more quickly understand the constraints and challenges associated with developing devices for the GI space. To accomplish this, the work reviews and summarizes a broad spectrum of literature covering the main anatomical and physiological properties of the GI tract that are pertinent to successful development and operation of an electromechanical device. Each organ in the GI is discussed in this context, including the main mechanisms of digestion, chemical and mechanical processes that could impact devices, and GI motor behavior and resultant forces that may be experienced by objects as they move through the environment of the gut.
胃肠道是一个复杂的环境,由口腔、食道、胃、小肠和大肠、直肠和肛门组成,它们共同合作形成完整的胃肠道系统。在过去的几十年里,通过可吞咽的机电诊断设备,如药丸相机,增加了使用内窥镜检查胃肠道的机会。在可预见的未来,研究人员将继续研究新的、功能更强的微型设备,用于全身药物输送、治疗、组织活检、微生物组采样和许多其他新颖的突破性应用。本综述的目的是为该领域的工程师提供GI环境及其复杂的物理、生物和化学特性的综合参考手册,以便他们能够更快地了解与开发GI空间设备相关的限制和挑战。为了实现这一目标,本研究回顾和总结了广泛的文献,这些文献涵盖了胃肠道的主要解剖和生理特性,这些特性与机电设备的成功开发和操作有关。在此背景下讨论了胃肠道中的每个器官,包括消化的主要机制,可能影响设备的化学和机械过程,以及胃肠道运动行为和物体在肠道环境中移动时可能经历的合力。
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引用次数: 19
The magic bullet as cancer therapeutic—has nanotechnology failed to find its mark? 癌症治疗药物纳米技术的灵丹妙药没有找到它的标记?
Q1 ENGINEERING, BIOMEDICAL Pub Date : 2020-09-24 DOI: 10.1088/2516-1091/abb008
G. Xiong, K. Venkatraman, S. Venkatraman
Ever since the term ‘Magic Bullet’ was coined by Nobel laureate Paul Ehrlich to denote selective activity of a therapeutic medicine against a particular target tissue or organism, researchers have been attempting to develop the concept, with the major part of the work directed towards cancer targets. In this review, we define four major technologies that embody the Magic Bullet concept, and discuss the status of the therapeutic in each case. The reasons for relative success and failure of the four technologies are assessed based on the clinical outcomes. There have been failures of ancillary concepts (to enable selectivity) such as the enhanced permeation and retention effect, which will be discussed in context. The outlook is hopeful, with the advent of immunotherapies, that the idealized Magic Bullet will see the light of day in the near future.
自从诺贝尔奖获得者保罗·埃利希创造了“灵丹妙药”一词来表示治疗药物对特定靶组织或生物体的选择性活性以来,研究人员一直在尝试发展这一概念,其主要工作是针对癌症靶点。在这篇综述中,我们定义了体现魔术子弹概念的四种主要技术,并讨论了每种情况下的治疗现状。根据临床结果评估这四种技术相对成功和失败的原因。辅助概念(实现选择性)已经失败,例如增强的渗透和保留效应,这将在上下文中讨论。随着免疫疗法的出现,人们对理想化的灵丹妙药将在不久的将来重见天日充满希望。
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引用次数: 5
期刊
Progress in biomedical engineering (Bristol, England)
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