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Liquid biopsy technologies: innovations and future directions in breast cancer biomarker detection.
IF 3 4区 医学 Q3 ENGINEERING, BIOMEDICAL Pub Date : 2025-01-24 DOI: 10.1007/s10544-025-00734-5
Linhong Cao, Qingli Duan, Zixin Zhu, Xuejing Xu, Jinbo Liu, Baolin Li

Globally, breast cancer is the most frequent type of cancer, and its early diagnosis and screening can significantly improve the probability of survival and quality of life of those affected. Liquid biopsy-based targets such as circulating tumor cells, circulating tumor DNA, and exosomes have been instrumental in the early discovery of cancer, and have been found to be effective in stage therapy, recurrence monitoring, and drug selection. Biosensors based on these target related biomarkers convert the tested substances into quantifiable signals such as electrical and optical signals through signal transduction, which has the advantages of high sensitivity, simple operation, and low invasiveness. This review provides an overview of the latest progress of liquid biopsy biomarkers in the diagnosis, prognosis and treatment of breast cancer, compares the application and advantages of different biosensors based on these biomarkers in the diagnosis of breast cancer, and analyzes the limitations and solutions of biosensor based methods.

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引用次数: 0
Quantitative investigation of a 3D bubble trapper in a high shear stress microfluidic chip using computational fluid dynamics and L*A*B* color space 基于计算流体动力学和L* a *B*色彩空间的高剪切应力微流控芯片三维气泡捕集器定量研究
IF 3 4区 医学 Q3 ENGINEERING, BIOMEDICAL Pub Date : 2025-01-13 DOI: 10.1007/s10544-024-00727-w
Warisara Boonsiri, Hein Htet Aung, Jirasin Aswakool, Siraphob Santironnarong, Phattarin Pothipan, Rungrueang Phatthanakun, Wares Chancharoen, Aekkacha Moonwiriyakit

Microfluidic chips often face challenges related to the formation and accumulation of air bubbles, which can hinder their performance. This study investigated a bubble trapping mechanism integrated into microfluidic chip to address this issue. Microfluidic chip design includes a high shear stress section of fluid flow that can generate up to 2.7 Pa and two strategically placed bubble traps. Commercially available magnets are used for fabrication, effectively reducing production costs. The trapping efficiency is assessed through video recordings with a phone camera and analysis of captured air volumes by injecting dye at flow rates of 50, 100, and 150 µL/min. This assessment uses L*A*B* color space with analysis of the perceptual color difference ∆E and computational fluid dynamics (CFD) simulations. The results demonstrate successful application of the bubble trap mechanism for lab-on-chip bubble detection, effectively preventing bubbles from entering microchannels and mitigating potential damage. Furthermore, the correlation between the L*A*B* color space and volume fraction from CFD simulations allows accurate assessment of trap performance. Therefore, this observation leads to the hypothesis that ∆E could be used to estimate the air volume inside the bubble trap. Future research will validate the bubble trap performance in cell cultures and develop efficient methods for long-term air bubble removal.

Graphical abstract

微流控芯片经常面临与气泡的形成和积累有关的挑战,这可能会阻碍其性能。为了解决这一问题,本研究将气泡捕获机制集成到微流控芯片中。微流控芯片设计包括流体流动的高剪切应力部分,可产生高达2.7 Pa和两个战略性放置的气泡陷阱。商用磁铁用于制造,有效地降低了生产成本。通过手机摄像头的视频记录和以50、100和150µL/min的流速注入染料对捕获空气量的分析来评估捕获效率。该评估使用L*A*B*色彩空间,并分析感知色差∆E和计算流体动力学(CFD)模拟。结果表明,气泡陷阱机制成功地应用于芯片上的实验室气泡检测,有效地防止气泡进入微通道并减轻潜在的损害。此外,通过CFD模拟,L*A*B*颜色空间与体积分数之间的相关性可以准确评估陷阱性能。因此,这一观察结果导致了一个假设,即∆E可以用来估计气泡捕集器内的空气体积。未来的研究将验证气泡阱在细胞培养中的性能,并开发长期去除气泡的有效方法。图形抽象
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引用次数: 0
Wireless power-up and readout from a label-free biosensor 无线供电和读数从一个无标签的生物传感器
IF 3 4区 医学 Q3 ENGINEERING, BIOMEDICAL Pub Date : 2025-01-10 DOI: 10.1007/s10544-024-00728-9
Hassan Raji, Pengfei Xie, Muhammad Tayyab, Zhuolun Meng, Seyed Reza Mahmoodi, Mehdi Javanmard

Wearable and implantable biosensors have rapidly entered the fields of health and biomedicine to diagnose diseases and physiological monitoring. The use of wired medical devices causes surgical complications, which can occur when wires break, become infected, generate electrical noise, and are incompatible with implantable applications. In contrast, wireless power transfer is ideal for biosensing applications since it does not necessitate direct connections between measurement tools and sensing systems, enabling remote use of the biosensors. In addition, wireless sensors eliminate the need for a battery or energy harvester, reducing the size of the sensor. As far as we are aware, this is the first report ever describing a new method for wireless readout of a label-free electronic biosensor for detecting protein biomarkers. Our results reveal that we are able to successfully detect target protein and corresponding antibodies within this wireless setup. We are able to distinguish target protein in purified samples from a blank PBS sample as a negative control by tracking gradual changes in impedance at the input of the transmitter (P-value = 0.00788). We also demonstrate real-time wireless quantification of cytokines within rheumatoid arthritis patient serum samples (P-value = 0.00891). A Fine Gaussian Support Vector Machine is also used to differentiate protein from negative controls with the highest accuracy from a dataset of 54 experiments.

可穿戴和植入式生物传感器已迅速进入健康和生物医学领域,用于疾病诊断和生理监测。使用有线医疗设备会导致手术并发症,当电线断裂、感染、产生电噪声以及与植入式应用不兼容时,就会发生手术并发症。相比之下,无线电力传输是生物传感应用的理想选择,因为它不需要在测量工具和传感系统之间直接连接,从而可以远程使用生物传感器。此外,无线传感器消除了对电池或能量收集器的需求,减小了传感器的尺寸。据我们所知,这是第一份描述无线读取无标签电子生物传感器用于检测蛋白质生物标志物的新方法的报告。我们的研究结果表明,我们能够成功地检测目标蛋白和相应的抗体在这种无线设置。通过跟踪发射器输入处阻抗的逐渐变化(p值= 0.00788),我们能够将纯化样品中的目标蛋白与空白PBS样品作为阴性对照区分开来。我们还演示了类风湿性关节炎患者血清样本中细胞因子的实时无线量化(p值= 0.00891)。精细高斯支持向量机还用于从54个实验的数据集中以最高的精度区分蛋白质和阴性对照。
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引用次数: 0
Retraction Note: Label-free microfluidic chip for segregation and recovery of circulating leukemia cells: clinical applications in acute myeloid leukemia 无标记微流控芯片分离和回收循环白血病细胞:急性髓性白血病的临床应用
IF 3 4区 医学 Q3 ENGINEERING, BIOMEDICAL Pub Date : 2024-12-18 DOI: 10.1007/s10544-024-00731-0
Dongfang Ouyang, Ningxin Ye, Yue Jiang, Yiyang Wang, Lina Hu, Shuen Chao, Martin Yarmush, Memet Tuner, Yonghua Li, Bin Tang
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引用次数: 0
Non-contact sensor module for rapid detection of extravasation during intravenous drug administration 非接触式传感器模块,用于快速检测静脉给药过程中的外渗
IF 3 4区 医学 Q3 ENGINEERING, BIOMEDICAL Pub Date : 2024-12-13 DOI: 10.1007/s10544-024-00730-1
Muhammad Salman Al Farisi, June Okazaki, Yoshihiro Hasegawa, Miyoko Matsushima, Tsutomu Kawabe, Mitsuhiro Shikida

Intravenous drug administration delivers medication directly into the bloodstream, providing rapid and controlled effects, making it highly beneficial for emergencies or when immediate drug action is required. However, several risks are associated with intravenous drug administration, including infiltration and extravasation, which can lead to serious complications due to the rapid absorption of medication to the surrounding tissues. To prevent complications, here we proposed a non-contact sensor module to rapidly detect such events. The system does not interfere with the human skin, nor contaminating the flowing medication since only biocompatible materials are exposed to the liquid. The proposed sensor module was assembled as a flow channel with flow rate and pressure sensing functions. The flow rate sensing was realized using a micromachined thermal flow sensor fabricated on a thin polyimide film, while the pressure sensing was realized using a diaphragm structure and a MEMS pressure sensor. Basic characteristics of each function was evaluated and a proof of concept experiment demonstrated a rapid detection of infiltration/extravasation within a few s. Measurement of leaked fluid volume during the event was also demonstrated.

静脉给药将药物直接输送到血液中,提供快速和可控的效果,使其在紧急情况或需要立即药物作用时非常有益。然而,静脉给药存在一些风险,包括浸润和外渗,由于药物被周围组织迅速吸收,可能导致严重的并发症。为了防止并发症,我们提出了一种非接触式传感器模块来快速检测此类事件。该系统不会干扰人体皮肤,也不会污染流动的药物,因为只有生物相容性材料暴露在液体中。所提出的传感器模块被组装成一个具有流量和压力传感功能的通道。流量传感采用聚酰亚胺薄膜微机械热流量传感器,压力传感采用膜片结构和MEMS压力传感器。评估了每个功能的基本特征,概念验证实验证明了在几秒内快速检测渗透/外渗。还演示了事件期间泄漏流体体积的测量。
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引用次数: 0
Smartphone-driven centrifugal microfluidics for diagnostics in resource limited settings 智能手机驱动的离心微流体技术用于资源有限环境下的诊断。
IF 3 4区 医学 Q3 ENGINEERING, BIOMEDICAL Pub Date : 2024-10-26 DOI: 10.1007/s10544-024-00726-x
Noa Lapins, Ahmad S. Akhtar, Indradumna Banerjee, Amin Kazemzadeh, Inês F. Pinto, Aman Russom

The broad availability of smartphones has provided new opportunities to develop less expensive, portable, and integrated point-of-care (POC) platforms. Here, a platform that consists of three main components is introduced: a portable housing, a centrifugal microfluidic disc, and a mobile phone. The mobile phone supplies the electrical power and serves as an analysing system. The low-cost housing made from cardboard serves as a platform to conduct tests. The electrical energy stored in mobile phones was demonstrated to be adequate for spinning a centrifugal disc up to 3000 revolutions per minute (RPM), a rotation speed suitable for majority of centrifugal microfluidics-based assays. For controlling the rotational speed, a combination of magnetic and acoustic tachometry using embedded sensors of the mobile phone was used. Experimentally, the smartphone-based tachometry was proven to be comparable with a standard laser-based tachometer. As a proof of concept, two applications were demonstrated using the portable platform: a colorimetric sandwich immunoassay to detect interleukin-2 (IL-2) having a limit of detection (LOD) of 65.17 ng/mL and a fully automated measurement of hematocrit level integrating blood-plasma separation, imaging, and image analysis that takes less than 5 mins to complete. The low-cost platform weighing less than 150 g and operated by a mobile phone has the potential to meet the REASSURED criteria for advanced diagnostics in resource limited settings.

智能手机的广泛普及为开发成本较低、便携式集成护理点(POC)平台提供了新的机遇。这里介绍的平台由三个主要部分组成:便携式外壳、离心微流体盘和手机。移动电话提供电力并充当分析系统。用硬纸板制成的低成本外壳是进行测试的平台。实验证明,手机中储存的电能足以让离心盘旋转到每分钟 3000 转(RPM),这一转速适合大多数离心微流体检测。为了控制转速,使用了手机嵌入式传感器的磁性和声学转速测量组合。实验证明,基于智能手机的转速计可与基于激光的标准转速计相媲美。作为概念验证,使用便携式平台演示了两个应用:检测白细胞介素-2(IL-2)的比色夹心免疫测定,其检测限(LOD)为 65.17 纳克/毫升;以及全自动测量血细胞比容水平,该测量集血浆分离、成像和图像分析于一体,只需不到 5 分钟即可完成。该平台成本低廉,重量不到 150 克,可通过手机操作,有望在资源有限的环境中满足先进诊断的 REASSURED 标准。
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引用次数: 0
Enhancing biomedical imaging: the role of nanoparticle-based contrast agents 增强生物医学成像:基于纳米粒子的造影剂的作用。
IF 3 4区 医学 Q3 ENGINEERING, BIOMEDICAL Pub Date : 2024-10-23 DOI: 10.1007/s10544-024-00725-y
Mohammad Habeeb, Hariharan Thirumalai Vengateswaran, Arpan Kumar Tripathi, Smita Tukaram Kumbhar, Huay Woon You,  Hariyadi

Biomedical imaging plays a critical role in early detection, precise diagnosis, treatment planning, and monitoring responses, but traditional methods encounter challenges such as limited sensitivity, specificity, and inability to monitor therapeutic responses due to factors like short circulation half-life and potential toxicity. Nanoparticles are revolutionizing biomedical imaging as contrast agents across modalities like computed tomography (CT), optical, magnetic resonance imaging (MRI), and ultrasound, exploiting unique attributes such as those of metal-based, polymeric, and lipid nanoparticles. They shield imaging agents from immune clearance, extending circulation time, and enhancing bioavailability at tumor sites. This results in improved imaging sensitivity. The study highlights advancements in multifunctional nanoparticles for targeted imaging, tackling concerns regarding toxicity and biocompatibility. Critically evaluating conventional contrast agents, emphasizes the shortcomings that nanoparticles aim to overcome. This review provides insight into the current status of nanoparticle-based contrast agents, illuminating their potential to reshape therapeutic monitoring and precision diagnostics.

Graphical Abstract

生物医学成像在早期检测、精确诊断、治疗规划和监测反应方面发挥着至关重要的作用,但传统方法面临着灵敏度和特异性有限以及因循环半衰期短和潜在毒性等因素而无法监测治疗反应等挑战。纳米粒子作为造影剂,正在计算机断层扫描(CT)、光学、磁共振成像(MRI)和超声波等各种模式中彻底改变生物医学成像,利用了金属基、聚合物和脂质纳米粒子的独特属性。它们能使成像剂免受免疫清除,延长循环时间,提高在肿瘤部位的生物利用度。这就提高了成像灵敏度。该研究强调了用于靶向成像的多功能纳米粒子的进步,解决了有关毒性和生物相容性的问题。通过对传统造影剂的严格评估,强调了纳米粒子旨在克服的缺点。这篇综述深入分析了基于纳米粒子的造影剂的现状,揭示了它们重塑治疗监测和精确诊断的潜力。
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引用次数: 0
Panoramic review on polymeric microneedle arrays for clinical applications 聚合物微针阵列临床应用全景综述。
IF 3 4区 医学 Q3 ENGINEERING, BIOMEDICAL Pub Date : 2024-09-23 DOI: 10.1007/s10544-024-00724-z
Tien Dat Nguyen, Thi-Hiep Nguyen, Van Toi Vo, Thanh-Qua Nguyen

Transdermal drug delivery (TDD) has significantly advanced medical practice in recent years due to its ability to prevent the degradation of substances in the gastrointestinal tract and avoid hepatic metabolism. Among different available approaches, microneedle arrays (MNAs) technology represents a fascinating delivery tool for enhancing TDD by penetrating the stratum corneum painless and minimally invasive for delivering antibacterial, antifungal, and antiviral medications. Polymeric MNAs are extensively utilized among many available materials due to their biodegradability, biocompatibility, and low toxicity. Therefore, this review provides a comprehensive discussion of polymeric MNAs, starting with understanding stratum corneum and developing MNA technology. Furthermore, the engineering concepts, fundamental considerations, challenges, and future perspectives of polymeric MNAs in clinical applications are properly outlined, offering a comprehensive and unique overview of polymeric MNAs and their potential for a broad spectrum of clinical applications.

Graphical Abstract

透皮给药(TDD)能够防止药物在胃肠道降解并避免肝脏代谢,因此近年来大大推动了医疗实践的发展。在现有的各种方法中,微针阵列(MNAs)技术是一种令人着迷的给药工具,它能无痛、微创地穿透角质层,给药抗菌、抗真菌和抗病毒药物,从而提高了透皮给药的效果。聚合物 MNA 具有生物降解性、生物相容性和低毒性,在众多可用材料中得到广泛应用。因此,本综述从了解角质层和开发 MNA 技术入手,对聚合物 MNA 进行了全面讨论。此外,还适当概述了聚合 MNA 在临床应用中的工程概念、基本考虑因素、挑战和未来前景,为聚合 MNA 及其在广泛临床应用中的潜力提供了全面而独特的概述。
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引用次数: 0
Construction of a pumpless gravity-driven vascularized Skin-on-a-Chip for the study of hepatocytotoxicity in percutaneous exposure to exogenous chemicals 构建无泵重力驱动血管化皮肤芯片,用于研究经皮暴露于外源化学品时的肝细胞毒性。
IF 3 4区 医学 Q3 ENGINEERING, BIOMEDICAL Pub Date : 2024-09-20 DOI: 10.1007/s10544-024-00723-0
Su Zhou, Rui Li, Jie Sun, Minyang Gu, Dan Gao, Liming Tang, Jiangbo Zhu

The utilization of existing Skin-on-a-Chip (SoC) is constrained by the complex structures, the multiplicity of auxiliary devices, and the inability to evaluate exogenous chemicals that are hepatotoxic after percutaneous metabolism. In this study, a gravity-driven SoC without any auxiliary devices was constructed for the hepatocytotoxicity study of exogenous chemicals. The SoC possesses 3 layers of culture chambers, from top to bottom, for human skin equivalent (HSE), Human Umbilical Vein Endothelial Cells (HUVEC) and hepatocytes (HepG2), and the maintenance and expression capacity of the corresponding cells on the SoC were verified by specificity parameters. The reactivity of the SoC to exogenous chemicals was verified by 2-aminofluorene (2-AF). The SoC can realistically simulate the in vivo exposure process of exogenous chemicals that are percutaneously exposed and metabolized into the bloodstream and then to the liver to produce toxicity, and it can achieve the same effects on transcriptome as those of animal tests at lower exposure levels while examining multiple toxicological targets of the skin, vascular endothelial cells, and hepatocytes. Both in terms of species similarity, the principles of reduction, replacement and refinement (3R), or the level of exposure suggest that the present SoC has a degree of replacement for animal models in assessing exogenous chemicals, especially those that are hepatotoxic after percutaneous metabolism.

现有的片上皮肤(SoC)结构复杂,辅助装置繁多,而且无法评估经皮代谢后具有肝毒性的外源性化学物质,这些都限制了片上皮肤(SoC)的使用。本研究构建了一个无任何辅助装置的重力驱动 SoC,用于外源化学物质的肝细胞毒性研究。SoC 从上到下有三层培养室,分别用于培养人皮肤等效物(HSE)、人脐静脉内皮细胞(HUVEC)和肝细胞(HepG2),并通过特异性参数验证了相应细胞在 SoC 上的维持和表达能力。2-aminofluorene (2-AF) 验证了 SoC 对外源化学物质的反应性。SoC能真实模拟外源化学物质经皮暴露并代谢到血液再到肝脏产生毒性的体内暴露过程,在检测皮肤、血管内皮细胞和肝细胞等多个毒理学靶点的同时,还能在较低暴露水平下实现与动物试验相同的转录组效应。无论是从物种相似性、减少、替代和改进(3R)原则,还是从暴露水平来看,目前的 SoC 在一定程度上可以替代动物模型来评估外源化学品,尤其是经皮代谢后具有肝毒性的化学品。
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引用次数: 0
Functionalization of microbubbles in a microfluidic chip for biosensing application 微流控芯片中微气泡的功能化,用于生物传感应用
IF 3 4区 医学 Q3 ENGINEERING, BIOMEDICAL Pub Date : 2024-09-17 DOI: 10.1007/s10544-024-00721-2
Marc Prudhomme, Chaimaa Lakhdar, Jacques Fattaccioli, Mahmoud Addouche, Franck Chollet

Microbubbles are widely used for biomedical applications, ranging from imagery to therapy. In these applications, microbubbles can be functionalized to allow targeted drug delivery or imaging of the human body. However, functionalization of the microbubbles is quite difficult, due to the unstable nature of the gas/liquid interface. In this paper, we describe a simple protocol for rapid functionalization of microbubbles and show how to use them inside a microfluidic chip to develop a novel type of biosensor. The microbubbles are functionalized with biochemical ligand directly at their generation inside the microfluidic chip using a DSPE-PEG-Biotin phospholipid. The microbubbles are then organized inside a chamber before injecting the fluid with the bioanalyte of interest through the static bubbles network. In this proof-of-concept demonstration, we use streptavidin as the bioanalyte of interest. Both functionalization and capture are assessed using fluorescent microscopy thanks to fluorescent labeled chemicals. The main advantages of the proposed technique compared to classical ligand based biosensor using solid surface is its ability to rapidly regenerate the functionalized surface, with the complete functionalization/capture/measurement cycle taking less than 10 min.

微气泡被广泛应用于从成像到治疗等各种生物医学领域。在这些应用中,可对微气泡进行功能化处理,以实现有针对性的药物输送或人体成像。然而,由于气/液界面的不稳定性,微气泡的功能化相当困难。在本文中,我们介绍了一种快速功能化微气泡的简单方案,并展示了如何在微流控芯片中使用微气泡开发新型生物传感器。微气泡在微流体芯片内生成时,直接使用 DSPE-PEG-Biotin 磷脂对其进行生化配体功能化。然后,在通过静态气泡网络注入含有相关生物分析物的液体之前,将微气泡组织在一个腔体内。在这次概念验证演示中,我们使用链霉亲和素作为相关生物分析物。通过荧光标记的化学物质,利用荧光显微镜对功能化和捕获进行评估。与使用固体表面的基于配体的传统生物传感器相比,该技术的主要优点是能够快速再生功能化表面,整个功能化/捕获/测量周期不超过 10 分钟。
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引用次数: 0
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Biomedical Microdevices
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