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The future of microbiome analysis: Biosensor methods for big data collection and clinical diagnostics 微生物组分析的未来:用于大数据收集和临床诊断的生物传感器方法
Pub Date : 2020-04-07 DOI: 10.1002/mds3.10085
Katelyn Sosnowski, Patarajarin Akarapipad, Jeong-Yeol Yoon

The invisible realm of the human microbiota contains patterns that, when properly detected and interpreted, could indicate much about the health or disease of its host, the human body. Biosensing techniques for the detection of the human microbiota have the potential to transform clinical diagnostics, yet point-of-care (POC) biosensors for direct detection of disturbances in microbial communities are not presently available in clinical settings. The objective of this review paper is to explore the potential for biosensors to usher the study of the microbiome into the spaces of clinical diagnostics and big data collection. To achieve this goal, we first outline the types of biosensor methods that have been used to detect multiple targets from clinical and field samples, discuss the challenges inherent in multiplex detection from complex samples and examine the potential for biosensors to integrate microbiome analysis with the diagnostic process. We then consider the potential pitfalls of biosensor-based microbiome analysis and highlight the anticipation for machine-learning techniques to address the unique challenges associated with the large variability in microbiota composition between individuals. We finally conclude that biosensor technologies with integrated machine learning algorithms will shape the future of microbiome analysis by allowing for acquisition of vast amounts of microbiome data that can eventually be harnessed in clinical settings for more rapid and accurate diagnoses.

人类微生物群这一看不见的领域所包含的模式,如果得到适当的检测和解释,可以在很大程度上表明其宿主——人体的健康或疾病。用于检测人类微生物群的生物传感技术具有改变临床诊断的潜力,但用于直接检测微生物群落紊乱的护理点(POC)生物传感器目前还无法在临床环境中使用。这篇综述的目的是探讨生物传感器将微生物组研究引入临床诊断和大数据收集领域的潜力。为了实现这一目标,我们首先概述了用于从临床和现场样品中检测多个目标的生物传感器方法的类型,讨论了从复杂样品中进行多重检测所固有的挑战,并研究了生物传感器将微生物组分析与诊断过程相结合的潜力。然后,我们考虑了基于生物传感器的微生物组分析的潜在缺陷,并强调了对机器学习技术的期望,以解决与个体之间微生物群组成的巨大差异相关的独特挑战。我们最终得出结论,集成机器学习算法的生物传感器技术将通过允许获取大量微生物组数据来塑造微生物组分析的未来,这些数据最终可以在临床环境中用于更快速和准确的诊断。
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引用次数: 6
Non-hermetic packaging of biomedical microsystems from a materials perspective: A review 材料视角下生物医学微系统非密封包装研究进展
Pub Date : 2020-04-04 DOI: 10.1002/mds3.10082
Hao Chong, Steve J.A. Majerus, Kath M. Bogie, Christian A. Zorman

The advancement of reliable encapsulation techniques for long-term implantable biomedical microdevices is of vital importance for the safe and steady operation of implants for chronic applications. Conventional techniques based on titanium or ceramic enclosures, however, cannot meet the packaging requirements of emerging innovations in medical implants due to issues related to scalability, incompatibility with microfabrication processes and challenges with miniaturization. A variety of polymeric materials have been identified for encapsulation of implantable systems, including polyimide, parylene, liquid crystal polymer (LCP), and polydimethylsiloxane (PDMS). These materials are not as hermetic as conventional metal or ceramic packages nor as widely adopted in regulative licensed devices for long-term implantation. However, studies have shown promising results regarding their potential for long-term encapsulation, in particular for devices fabricated on polymeric substrates. This review offers a summary of the encapsulation performance of these emerging polymeric materials with a specific focus on their long-term performance and quantification of their expected lifetime.

长期植入式生物医学微装置的可靠封装技术的发展对于长期应用的植入物的安全稳定运行至关重要。然而,基于钛或陶瓷外壳的传统技术无法满足医疗植入物新兴创新的封装要求,原因是与可扩展性、与微加工工艺的不兼容性以及小型化方面的挑战相关的问题。多种聚合物材料已被确定用于可植入系统的封装,包括聚酰亚胺、聚对二甲苯、液晶聚合物(LCP)和聚二甲基硅氧烷(PDMS)。这些材料不像传统的金属或陶瓷包装那样密封,也不像在长期植入的监管许可设备中广泛采用。然而,研究已经显示了它们长期封装的潜力,特别是在聚合物衬底上制造的设备。本文综述了这些新兴聚合物材料的封装性能,重点介绍了它们的长期性能和预期寿命的量化。
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引用次数: 10
A fibrinogen biosensing platform based on plasmonic Ga nanoparticles and aminosilane–titanate antibody trapping 基于等离子体纳米粒子和氨基硅烷-钛酸酯抗体捕获的纤维蛋白原生物传感平台
Pub Date : 2020-04-04 DOI: 10.1002/mds3.10083
Alvaro J. Magdaleno, Nuria Gordillo, Jose Luis Pau, Miguel Manso Silván

The era of personalized medicine calls for rapid detection of key biomolecules, such as serum proteins, as general indicators of a healthy/sickness state. The fabrication, biofunctionalization and calibration of a fibrinogen biosensing platform based on plasmonic gallium nanoparticles are detailed in the present work. The first step consisted in the deposition of Ga nanoparticles on Si substrates by means of Joule-effect thermal evaporation technique. A distribution of nanodroplets could be evidenced by scanning electron microscopy. The biofunctionalization of the samples was carried out using aminosilane–titanate thin hybrid layers prepared by a sol–gel route. The integration of functional amino groups could be confirmed by spectroscopic methods. Then, in order to sensitize the platform surface to fibrinogen, specific immunoglobulins have been immobilized. We monitored the plasmon wavelength changes along the fabrication cascade and during detection assays with calibrated fibrinogen solutions in phosphate-buffered saline. From the ellipsometric analysis, three operational ranges as a function of fibrinogen concentration can be identified, with an out-of-range response for low concentration, a linear response behaviour in the 1–10 µM healthy range and a tendency to saturation at high concentration.

个性化医疗的时代要求快速检测关键生物分子,如血清蛋白,作为健康/疾病状态的一般指标。本文详细介绍了基于等离子体纳米镓的纤维蛋白原生物传感平台的制备、生物功能化和标定。第一步是利用焦耳效应热蒸发技术在Si衬底上沉积Ga纳米颗粒。扫描电镜可以证明纳米液滴的分布。采用溶胶-凝胶法制备的氨基硅烷-钛酸盐薄杂化层对样品进行了生物功能化处理。功能氨基的整合可以用光谱方法证实。然后,为了使平台表面对纤维蛋白原敏感,特异性免疫球蛋白被固定化。我们用校准过的纤维蛋白原溶液在磷酸盐缓冲盐水中监测等离子体波长沿制造级联和检测分析期间的变化。从椭偏分析中,可以确定纤维蛋白原浓度的三个工作范围,低浓度时的超范围响应,1-10µM健康范围内的线性响应行为,高浓度时趋于饱和。
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引用次数: 3
Investigation of 3D-printed PLA–stainless-steel polymeric composite through fused deposition modelling-based additive manufacturing process for biomedical applications 基于熔融沉积建模的3d打印pla -不锈钢聚合物复合材料生物医学应用研究
Pub Date : 2020-03-14 DOI: 10.1002/mds3.10080
Navin Sakthivel, Jon Bramsch, Phi Voung, Isaac Swink, Saadyah Averick, Hitesh D. Vora

Among the several 3D printing technologies, fused deposition modelling (FDM) is gaining popularity because it can fabricate geometrically complex shapes of polymeric bio-implants at reasonable quality and cost mainly due to lower cost of FDM-based 3D printers as well as the filament form of feedstock material. Particularly, to cater the need of cost-effective biomedical applications, both poly(lactic) acid (PLA) and stainless-steel materials individually displayed the biocompatibility for various biomedical applications. The pure polymeric components are generally lower in mechanical strength, but these limitations can be resolved by developing a polymer–metallic composite; therefore, the recently developed PLA–stainless-steel composite was selected for the present work. This is new material and the current literature lacks in providing the necessary FDM processing parameters to obtain desired functional properties of PLA–stainless-steel components with unaltered biocompatibility. Therefore, the objective here is to obtain the optimized processing parameters through the design of experiments that shows the desired functional properties of PLA–stainless-steel specimens manufactured by FDM and later validate the structural strength through the tensile and impact tests. It was observed that the PLA–stainless-steel composite has a toughness of 18 kJ/m2 and has an ultimate tensile strength of ~69 MPa at 45° and ~23 MPa at 90° raster orientation of the print. Biocompatibility of the PLA–stainless-steel polymeric composite was assessed using pre-osteoblast cells, and materials were found to have biocompatibility unchanged from pure PLA. Overall, it was proved from this work that the low-cost desktop FDM printer can be numerically optimized using statistical analyses to fabricate the next-generation biomaterials for biomedical implants with tailored dimensions and surface finish with required mechanical strength and biocompatibility.

在几种3D打印技术中,熔融沉积建模(FDM)越来越受欢迎,因为它可以以合理的质量和成本制造几何形状复杂的聚合物生物植入物,这主要是由于基于FDM的3D打印机成本较低以及原料的长丝形式。特别是,为了满足成本效益高的生物医学应用的需要,聚乳酸(PLA)和不锈钢材料分别显示了各种生物医学应用的生物相容性。纯聚合物组分的机械强度通常较低,但这些限制可以通过开发聚合物金属复合材料来解决;因此,本文选择了新开发的pla -不锈钢复合材料。这是一种新材料,目前的文献缺乏提供必要的FDM加工参数,以获得具有不变生物相容性的pla -不锈钢部件所需的功能特性。因此,本文的目标是通过实验设计获得优化的工艺参数,以显示FDM制造的pla -不锈钢试样所需的功能性能,然后通过拉伸和冲击试验验证结构强度。结果表明,pla -不锈钢复合材料的韧性为18 kJ/m2,在45°和90°光栅方向的拉伸强度分别为~69 MPa和~23 MPa。使用成骨前细胞评估PLA -不锈钢聚合物复合材料的生物相容性,发现材料具有与纯PLA相同的生物相容性。总的来说,这项工作证明了低成本桌面FDM打印机可以通过统计分析进行数值优化,以制造具有定制尺寸和表面光洁度的下一代生物医学植入物生物材料,并具有所需的机械强度和生物相容性。
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引用次数: 7
Do chick and rodent neuron biosensors function similarly? 小鸡和啮齿动物神经元生物传感器的功能相似吗?
Pub Date : 2020-03-13 DOI: 10.1002/mds3.10078
Serena Y. Kuang, Xiaoqi Yang, Lina Wei, Ting Huang, Zhonghai Wang, Tingfei Xi, Bruce Z. Gao

A growing number of research papers report similarities in cell types, neuronal connections and information-processing principles between chick and rodent cortical tissues, which have very different architectures. This paper extends these comparisons beyond the cortical tissues. Using microelectrode array technology, we report three remarkable functional similarities between our original chick data and rodent data from the literature: (a) the pattern of spontaneous spiking activity from chick spinal cord neuron biosensors is very similar to that of rodent spinal cord neuron biosensors (i.e. rodent counterparts). (b) The spontaneous spiking activity pattern of the chick forebrain neuron biosensors is very similar to that of the rodent cortical neuron biosensors, but chick forebrain neuron biosensors contain not only cortical neurons, but also diencephalic neurons. In other words, chick forebrain neuron biosensors cannot be considered the counterparts of rodent cortical neuron biosensors. (c) Chick forebrain neuron biosensors respond to several classical neuroactive agents in a way similar to rodent cortical neuron biosensors as reflected in their agent-specific concentration–response curves and their values of EC50 (the effective concentration that causes 50% of the maximal effect of an agent). These preliminary findings provide both direct and indirect support for a positive answer to the big research question in the title: ‘Do chick and rodent neuron biosensors function similarly’ if the sources of the neurons are homologous between chick and rodent? Our findings are of particular value to comparative biology/physiology, pharmacology, neurotoxicology and bioengineering and to research on the more cost-effective extended application of chick neuron biosensors.

越来越多的研究论文报道了小鸡和啮齿动物皮层组织在细胞类型、神经元连接和信息处理原理上的相似性,它们的结构非常不同。本文将这些比较扩展到皮层组织之外。利用微电极阵列技术,我们报告了原始小鸡数据和文献中啮齿动物数据之间三个显著的功能相似性:(a)小鸡脊髓神经元生物传感器的自发尖峰活动模式与啮齿动物脊髓神经元生物传感器非常相似(即啮齿动物)。(b)鸡前脑神经元生物传感器的自发尖峰活动模式与啮齿动物皮质神经元生物传感器非常相似,但鸡前脑神经元生物传感器不仅包含皮质神经元,还包含间脑神经元。换句话说,鸡前脑神经元生物传感器不能被认为是啮齿类动物皮层神经元生物传感器的对应物。(c)小鸡前脑神经元生物传感器对几种经典神经活性药物的反应方式与啮齿动物皮质神经元生物传感器类似,这反映在它们的药物特异性浓度-反应曲线和它们的EC50值(引起药物最大作用的50%的有效浓度)上。如果小鸡和啮齿动物之间的神经元来源是同源的,那么这些初步发现为标题中的重大研究问题“小鸡和啮齿动物的神经元生物传感器功能相似吗”提供了直接和间接的支持。我们的发现对比较生物学/生理学、药理学、神经毒理学和生物工程以及研究鸡神经元生物传感器的更经济有效的扩展应用具有特别的价值。
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引用次数: 3
Electrophoretic deposition of spherical carbon nanoobjects—A comparison of different biocompatible surfaces 球形碳纳米物体的电泳沉积——不同生物相容性表面的比较
Pub Date : 2020-03-13 DOI: 10.1002/mds3.10075
Monika Zięba, Emil Korczeniewski, Wojciech Zięba, Paulina Bolibok, Joanna Czarnecka, Marta E. Płońska-Brzezińska, Artur P. Terzyk

Spherical carbon nanomaterial coatings on the purified carbon fibres were obtained and characterized. The use of exactly the same conditions of electrophoretic deposition process made it possible to compare the impact of the initial carbon nanomaterial properties on the behaviour of various prepared surfaces. Obtained samples were characterized by scanning electron microscopy, atomic force microscopy, flat surface ζ-potential and water contact angle measurements. Additionally, cytotoxic tests were carried out to compare biocompatibility of coated carbon fibres. Presented results show the impact of the initial materials properties on the characteristics of the deposited coatings.

在纯化碳纤维表面制备了球形碳纳米材料涂层,并对其进行了表征。使用完全相同的电泳沉积工艺条件,可以比较初始碳纳米材料性能对各种制备表面行为的影响。通过扫描电子显微镜、原子力显微镜、平面ζ电位和水接触角测量对所得样品进行了表征。此外,还进行了细胞毒性测试,以比较涂层碳纤维的生物相容性。结果表明,初始材料性能对镀层性能的影响。
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引用次数: 2
Development of durable microelectrodes for the detection of hydrogen peroxide and pH 用于过氧化氢和pH检测的耐用微电极的研制
Pub Date : 2020-03-13 DOI: 10.1002/mds3.10074
Caelen M. Clark, Brandon M. Ruszala, Mark T. Ehrensberger

Cathodic electrical stimulation has been investigated as a way to treat implant-associated infection of orthopaedic devices. One of the proposed mechanisms of these effects is the changes in chemical gradients adjacent to the implant generated by the cathodic reaction products. Of these reaction products, both alkaline pH and hydrogen peroxide have been implicated as antimicrobial agents. However, direct measurement of these chemical effects has yet to be fully characterized for orthopaedic biomaterials. Microelectrodes are powerful tools that can be used to measure localized chemical conditions. Most commercially available sensors are fabricated from pulled glass pipettes, which make them quite fragile. In order to more easily make measurements of the effects of electrical stimulation, more durable sensors are desired. Solid-state electrodes were fabricated from platinum and iridium micro-wires to make H2O2 and pH-sensitive electrodes, respectively. Additionally, a similar method was used to fabricate electrodes that were housed within a stainless steel needle, which could be used to penetrate and measure in solid samples without damaging the sensor. The H2O2 microelectrode was found to have a sensitivity of 34.1 pA/µM and a R2 value of .996. The pH microelectrode was found to have a linear calibration from 2 to 12 with a sensitivity of 76.7 mV/pH and a R2 of .996. The needle-based electrodes were found to be able to detect changes in both H2O2 and pH when tested in an agar gel model.

阴极电刺激作为一种治疗骨科植入物相关感染的方法已被研究。这些效应的机制之一是由阴极反应产物产生的植入物附近化学梯度的变化。在这些反应产物中,碱性pH和过氧化氢都被认为是抗菌剂。然而,这些化学效应的直接测量尚未完全表征骨科生物材料。微电极是一种强大的工具,可用于测量局部化学条件。大多数商业上可用的传感器都是由拉出的玻璃移液管制成的,这使得它们非常脆弱。为了更容易地测量电刺激的效果,需要更耐用的传感器。采用铂微丝和铱微丝制备固态电极,分别制备H2O2和ph敏感电极。此外,一个类似的方法被用来制造被安置在不锈钢针内的电极,它可以用来穿透和测量固体样品,而不会损坏传感器。H2O2微电极的灵敏度为34.1 pA/µM, R2值为0.996。pH微电极的线性校准范围为2 ~ 12,灵敏度为76.7 mV/pH, R2为0.996。在琼脂凝胶模型中测试时,发现针状电极能够检测H2O2和pH的变化。
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引用次数: 4
Label-free in situ pH monitoring in a single living cell using an optical nanoprobe 使用光学纳米探针在单个活细胞中进行无标记的原位pH监测
Pub Date : 2020-03-12 DOI: 10.1002/mds3.10079
Qingbo Yang, Xiaobei Zhang, Yang Song, Ke Li, Honglan Shi, Hai Xiao, Yinfa Ma

Intracellular pH plays critical roles in cell and tissue functions during processes such as metabolism, proliferation, apoptosis, ion transportation, endocytosis and muscle contraction. It is thus an important biomarker that can readily be used to monitor the physiological status of a cell. Thus, disrupted intracellular pH may serve as an early indicator of cell dysfunction and deterioration. Various methods have been developed to detect cellular pH, such as pH-sensitive labelling reagents with fluorescent or Raman signals. However, excessive cellular uptake of these reagents will not only disrupt cell viability but also compromise effective long-term monitoring. Here, we present a novel fibre-optic fluorescent nanoprobe with a high spatial resolution for label-free, subcellular pH sensing. The probe has a fast response time (~20 s) with minimum invasiveness and excellent pH resolution (0.02 pH units) within a biologically relevant pH environment ranging from 6.17 to 8.11. Its applicability was demonstrated on cultured A549 lung cancer cells, and its efficacy was further testified in two typical cytotoxic cases using carbonylcyanide 3-chlorophenyl hydrazine, titanium dioxide and nanoparticles. The probe can readily detect the pH variations among cells under toxin/nanoparticles administration, enabling direct monitoring of the early onset of physiological or pathological events with high spatiotemporal resolution. This platform has excellent promise as a minimum invasive diagnostic tool for pH-related cellular mechanism studies, such as inflammation, cytotoxicity, drug resistance, carcinogenesis and stem cell differentiation.

细胞内pH值在细胞和组织的代谢、增殖、凋亡、离子运输、内吞和肌肉收缩等过程中起着至关重要的作用。因此,它是一种重要的生物标志物,可以很容易地用于监测细胞的生理状态。因此,细胞内pH值的破坏可以作为细胞功能障碍和恶化的早期指标。已经开发了各种方法来检测细胞pH值,例如具有荧光或拉曼信号的pH敏感标记试剂。然而,过量的细胞摄取这些试剂不仅会破坏细胞活力,还会损害有效的长期监测。在这里,我们提出了一种新型的光纤荧光纳米探针,具有高空间分辨率,用于无标记的亚细胞pH传感。该探针具有快速响应时间(~20 s),最小的侵入性和出色的pH分辨率(0.02 pH单位),在生物学相关的pH环境范围为6.17至8.11。在培养的A549肺癌细胞上验证了其适用性,并利用羰基氰化物3-氯苯肼、二氧化钛和纳米颗粒在2例典型细胞毒性病例中进一步验证了其有效性。该探针可以很容易地检测到毒素/纳米颗粒给药下细胞的pH变化,从而能够以高时空分辨率直接监测生理或病理事件的早期发生。该平台具有良好的前景,可作为ph相关细胞机制研究的微创诊断工具,如炎症、细胞毒性、耐药性、癌变和干细胞分化。
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引用次数: 2
Modification of relevant polymeric materials for medical applications and devices 用于医疗应用和设备的相关聚合物材料的改性
Pub Date : 2020-03-12 DOI: 10.1002/mds3.10073
Marlene A. Velazco-Medel, Luis A. Camacho-Cruz, Emilio Bucio

The present review compiles different biomedical relevant polymers that have been modified to enhance their properties, giving hydrophilicity to their surfaces, antifouling properties to avoid bacterial adhesion, biocompatibility, incorporation of drug delivery systems and the improving of their mechanical properties to use them in the manufacturing of medical devices as prosthesis or implants, or other medical applications as wound dressers or scaffolds to cell culture. Other content of this work is a general description of the different techniques to modify and graft molecules, biomolecules and other polymers onto polymeric matrices in order to obtain high-performance biomaterials and medical devices.

本综述汇编了不同的生物医学相关聚合物,这些聚合物已被改性以增强其性能,赋予其表面亲水性,防污性能以避免细菌粘附,生物相容性,药物输送系统的结合以及其机械性能的改善,以用于制造医疗器械,如假体或植入物,或其他医疗应用,如伤口敷料或细胞培养支架。这项工作的其他内容是对不同技术的一般描述,以修饰和接枝分子,生物分子和其他聚合物到聚合物基质上,以获得高性能的生物材料和医疗器械。
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引用次数: 4
Functionalization of silicon dioxide and silicon nitride surfaces with aminosilanes for optical biosensing applications 用氨基硅烷修饰二氧化硅和氮化硅表面的光学生物传感应用
Pub Date : 2020-03-12 DOI: 10.1002/mds3.10072
Maria Antoniou, Dimitra Tsounidi, Panagiota S. Petrou, Konstantinos G. Beltsios, Sotirios E. Kakabakos

The development of optical biosensors based on silicon dioxide or silicon nitride transducers requires the chemical activation of their surface to achieve stable, repeatable and homogeneous binding of biomolecules. In the present study, the chemical activation of silicon dioxide and silicon nitride surfaces with 3-aminopropyl-triethoxysilane (APTES) was optimized so as to enable the immobilization of biomolecules by adsorption or covalent bonding. Chemical activation was performed with either aqueous or organic solution of APTES, and the surfaces were used to immobilize directly protein molecules by physical adsorption or further modified with glutaraldehyde to allow covalent binding of protein molecules. The protein immobilization capacity of the chemically activated silicon dioxide and silicon nitride surfaces was evaluated through incubation with mouse γ-globulins and reaction with a fluorescently labelled goat antimouse IgG antibody. By determining the surface fluorescence signal intensity, it was found that modification with 5% (v/v) APTES solution in ethanol followed by modification with glutaraldehyde provided 30% higher fluorescence signals than all the other protocols tested. In addition, this method provided the lower signal variation between different chips. To test the possible advantages of the chemical activation protocols for optical biosensing applications, they were also applied to a label-free white light interference spectroscopy sensor and evaluated through (a) real-time monitoring of the reaction between immobilized on the sensor surface mouse γ-globulins with an unlabelled goat antimouse IgG antibody and (b) a non-competitive immunoassay for the determination of C-reactive protein. The results showed that in case of antibody, physical absorption provided marginally higher binding capacity to covalent bonding.

基于二氧化硅或氮化硅换能器的光学生物传感器的发展需要对其表面进行化学活化,以实现生物分子的稳定、可重复和均匀结合。本研究优化了3-氨基丙基三乙氧基硅烷(APTES)对二氧化硅和氮化硅表面的化学活化,从而实现生物分子的吸附或共价键固定。用APTES水溶液或有机溶液进行化学活化,并通过物理吸附或进一步用戊二醛修饰使蛋白质分子共价结合,直接固定蛋白质分子。通过小鼠γ-球蛋白孵养和荧光标记山羊抗小鼠IgG抗体反应,评价化学活化二氧化硅和氮化硅表面的蛋白固定化能力。通过对表面荧光信号强度的测定,发现用5% (v/v) APTES溶液在乙醇中修饰,再用戊二醛修饰,其荧光信号比其他所有测试方案高30%。此外,该方法提供了较小的信号在不同芯片之间的变化。为了测试化学激活方案在光学生物传感应用中的可能优势,他们还将其应用于无标记白光干涉光谱传感器,并通过(a)实时监测固定在传感器表面的小鼠γ-球蛋白与未标记的山羊抗小鼠IgG抗体之间的反应,以及(b)用于测定c反应蛋白的非竞争性免疫分析法来评估。结果表明,在抗体的情况下,物理吸收对共价键的结合能力略高。
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引用次数: 14
期刊
Medical devices & sensors
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