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Nanoscopic Biosensors in Microfluidics 微流体中的纳米生物传感器
L. Baraban
Synergy between, physics, material sciences and biotechnology during last decade has led to a tremendous scientific progress in the fields of biodetection and nanomedicine. This tight interaction led to the emergence of a new class of bioinspired systems that enables to bring the area of biosensorics e.g. for cell or molecular diagnostics and analytics to the new level. The advances are expected in terms of (i) possibility of early diagnostics of diseases due to the increased sensitivity of the detectors, (ii) real time and high throughput analysis offered by combination of integrated electronics and microfluidic approach, and (iii) establishing the new functional formats for the bioassays. One of the most promising candidates for the future diagnostics are the electronic nanobiosensors that have attracted great attention in the last decades since they provide rich quantitative information for medical and biotechnological assays without pre-treatment and specific optical labelling of the detected species. At the same time, to bring state‐of‐the‐art biomedical diagnostic devices to the hands of the people, it is important to reduce the price of the devices and allow for their high‐volume delivery in a cost‐efficient manner, e.g., container transportation. For the latter, a crucial aspect is to reduce the weight of the device. This can be achieved by replacing the conventional rigid substrates, like Si or glass by light weight and large area polymeric foils. Here I will focus on two flexible diagnostic platforms for the analysis at the micro- and nanoscale, represented by (a) silicon nanowires based field effect transistors and (b) 2D materials based on molybdenum disulfide. [1] Karnaushenko, et al., Adv. Healthc. Mater. 4(10), 1517 (2015). [2] Zhang, et al., Small 15 (23), 1901265 (2019). [3] Baraban, et al. Advanced Science 6 (15), 1900522 (2019).
近十年来,物理学、材料科学和生物技术之间的协同作用导致了生物检测和纳米医学领域的巨大科学进步。这种紧密的相互作用导致了一类新的生物启发系统的出现,使生物传感器领域能够达到新的水平,例如细胞或分子诊断和分析。预计在以下方面将取得进展:(i)由于检测器灵敏度的提高,早期诊断疾病的可能性,(ii)集成电子学和微流体方法相结合提供的实时和高通量分析,以及(iii)为生物测定建立新的功能格式。电子纳米生物传感器是未来诊断最有希望的候选者之一,在过去的几十年里,由于它们为医学和生物技术分析提供了丰富的定量信息,而无需预处理和对被检测物种进行特定的光学标记,因此引起了极大的关注。同时,为了将最先进的生物医学诊断设备带到人们的手中,重要的是降低设备的价格,并允许以具有成本效益的方式(例如集装箱运输)大批量交付。对于后者,一个关键的方面是减轻设备的重量。这可以通过用重量轻、面积大的聚合物箔代替传统的刚性基板,如硅或玻璃来实现。在这里,我将重点介绍两种用于微纳米级分析的灵活诊断平台,分别是(a)基于硅纳米线的场效应晶体管和(b)基于二硫化钼的2D材料。[1]陈晓明,陈晓明。材料4(10),1517(2015)。[2]张志强,等,小型15(23),1901265(2019)。[3]张晓明,张晓明。先进科学6(15),1900522(2019)。
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引用次数: 0
Rapid lipid content screening in Neochloris Oleoabundans by carbon-based dielectrophoresis 碳基介质电泳快速筛选油绿藻脂质含量
R. Parra-Saldívar, V. H. Perez‐Gonzalez, C. M. Galicia‐Medina, Matías Vázquez-Piñón, S. Camacho-Léon, G. S. Alemán-Nava, R. C. Gallo-Villanueva, S. Martínez-Chapa, M. Madou, J. Garcia-Perez, D. Esquivel-Hernández
: The use of microalgae as a biomass source for biofuel production has drawn the attention of many scientists due to several associated environmental advantages over conventional terrestrial crops, including microalgae growing using wastewaters and a higher CO 2 fixation rate, contributing to the reduction of atmospheric concentration. Consequently, a reliable cytoplasmic lipid screening process in microalgae is a valuable asset for harvesting optimization in mass production processes. In this study, the heterogeneous cytoplasmic lipid content of Neochloris oleoabundans was dielec-trophoretically assorted in a microfluidic device using castellated carbon microelectrodes. The ex-periments carried out over a wide frequency window (100 kHz to 30 MHz) at a fixed amplitude of 7 VPP showed a significant contrast between the dielectrophoretic behavior of high lipid content and low lipid content cells at the low frequency range (100–800 kHz). A weak response for the mid and high frequency ranges (1–30 MHz) was also identified for high and low lipid content samples, allowing one to establish an electrokinetic footprint of the studied strain. These results suggest that the development of a reliable screening process for harvesting optimization is possible through a fast and straightforward mechanism, such as dielectrophoresis, which is a low-cost and easy-to-machine material that employs glassy carbon. The experimental setup in this study involved in vitro culturing of nitrogen-replete (N+) and nitrogen-deplete (N-) cell suspensions to promote low and high lipid production in cells, respectively. Cell populations were monitored using spectrophotom-etry, and the resulting lipid development among cells was quantified by Nile red fluorescence.
:利用微藻作为生物燃料生产的生物质来源已经引起了许多科学家的注意,因为与传统陆地作物相比,微藻具有一些相关的环境优势,包括利用废水生长的微藻和更高的二氧化碳固定率,有助于降低大气浓度。因此,可靠的微藻细胞质脂质筛选过程是大规模生产过程中收获优化的宝贵资产。在本研究中,在微流控装置中,使用微电极对油丰新绿藻的异质性细胞质脂质含量进行了电介质滋养分类。在宽频率窗(100 kHz至30 MHz) 7 VPP的固定振幅下进行的实验显示,高脂含量细胞和低脂含量细胞在低频范围(100 - 800 kHz)的介电泳行为存在显著差异。对于高脂含量和低脂含量的样品,也确定了中高频率范围(1-30 MHz)的弱响应,从而可以建立所研究菌株的电动足迹。这些结果表明,通过一种快速而直接的机制,例如采用玻璃碳的低成本且易于加工的介质电泳,开发一种可靠的筛选过程来优化收获是可能的。本研究的实验设置包括体外培养富氮(N+)和贫氮(N-)细胞悬浮液,分别促进细胞中低脂和高脂的产生。用分光光度法监测细胞群,用尼罗红荧光定量细胞间脂质发育。
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引用次数: 0
Magneto-Catalytic Janus Micromotors for Selective Inactivation of Bacteria Biofilms 用于细菌生物膜选择性失活的磁催化Janus微电机
B. Jurado‐Sánchez, A. Escarpa, Kaisong Yuan
Janus micromotors are a unique class of materials whose surfaces have two or more distinct physical properties, allowing thus for two types of chemistry to occur simultaneously. Judicious design of the micromotor structure allows to incorporate different functionalities in a single unit to adapt the propulsion behaviour along with the incorporation of specific receptors for a myriad of applications. Herein we report the preparation of graphene oxide (GO)/PtNPs/Fe2O3 Janus micromotors for highly selective capture/inactivation of gram-positive bacteria units and biofilms. The strategy is based on the combination of a lanbiotic (Nisin) with Janus micromotors. Lanbiotics are peptides composed of methyllanthionine residues with a highly selective antimicrobial activity towards multidrug resistant bacteria. Nisin is a natural compound normally used for food preservation, which display specific antimicrobial activity towards gram-positive bacteria. Such peptide can bind to lipid II unit of the bacteria membranes, damaging its morphology and releasing its contents. The coating of micromotors with GO impart them with a Janus structure for the subsequent asymmetric assembly of catalytic (PtNPs) and magnetic (Fe2O3) engines and results in an active rough layer for a higher loading of Nisin via covalent interactions. The micromotors possess adaptative propulsion mechanisms, including catalytic mode (PtNPs) in peroxide solutions or magnetic actuation (fuel free) by the action of an external magnetic field. The enhanced movement and localized delivery of the micromotors (both in catalytic and magnetic actuated mode) results in a 2-fold increase of the capture/killing ability towards Staphylococcus Aureus bacteria in raw media (juice, serum and tap water samples), as compared with free Nisin and static counterparts. The micromotor strategy display also high selectivity towards such bacteria, as illustrated by the dramatically lower capture/killing ability towards gram-negative Escherichia Coli. Unlike previous micromotors based strategies, this approach displays higher selectivity towards a type of bacteria along with enhanced stability, prolonged use and adaptative propulsion modes, holding considerable promise to treat methicillin resistant antibiotic infections, for environmental remediation or food safety, among others applications.
Janus微电机是一类独特的材料,其表面具有两种或两种以上不同的物理特性,从而允许两种化学反应同时发生。微电机结构的明智设计允许在单个单元中合并不同的功能,以适应推进行为以及针对无数应用的特定受体的合并。在这里,我们报道了氧化石墨烯(GO)/PtNPs/Fe2O3 Janus微电机的制备,用于高选择性捕获/灭活革兰氏阳性细菌单位和生物膜。该策略是基于lanbitics (Nisin)和Janus微型马达的结合。Lanbiotics是由甲基硫氨酸残基组成的多肽,对多重耐药细菌具有高度选择性的抗菌活性。Nisin是一种天然化合物,通常用于食品保存,对革兰氏阳性细菌具有特定的抗菌活性。这种肽可以与细菌膜的脂质II单元结合,破坏其形态并释放其内容物。在微马达表面涂上氧化石墨烯,使其具有双面神结构,用于随后的催化(PtNPs)和磁性(Fe2O3)发动机的不对称组装,并形成一个活性粗糙层,通过共价相互作用使Nisin负载更高。微电机具有自适应推进机制,包括过氧化氢溶液中的催化模式(PtNPs)或由外部磁场作用的磁致动(无燃料)。与游离Nisin和静态同类产品相比,微电机的增强运动和局部递送(在催化和磁驱动模式下)导致对原始培养基(果汁,血清和自来水样品)中金黄色葡萄球菌的捕获/杀死能力提高了2倍。微运动策略对这种细菌也显示出很高的选择性,如对革兰氏阴性大肠杆菌的捕获/杀死能力显着降低所示。与以前基于微电机的策略不同,该方法对一种细菌具有更高的选择性,同时具有增强的稳定性,长时间使用和自适应推进模式,在治疗耐甲氧西林抗生素感染,环境修复或食品安全等应用中具有相当大的前景。
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引用次数: 0
Electro-optical full color display based on nano-particle dispersions 基于纳米粒子分散体的光电全彩显示
Mohammad Ahmadi, Wei Liu, A. Henzen, H. Wyss
Electrokinetic displays are among the most important display technologies because of their low power consumption, wide viewing angle, and outdoor readability. As a result, they are regarded as excellent candidates for electronic paper. These types of displays are based on the controlled movement of charged pigment particles in a non-polar liquid under the influence of an electric field. Free charges practically do not exist in nonpolar colloids due to their low dielectric constant. However, the addition of a surfactant to non-polar colloids often leads to considerable charge-induced effects, such as increased electrical conductivity and particle stabilization. In this project, we aim to develop a novel electrokinetically driven display. An unprecedented display device is proposed, based on the concerted action of electro-osmosis and electrophoresis in a non-polar fluid. This method could reduce the switching time required to display information, and extend the applications of electrokinetic displays, enabling increased video speed and full color in the future.
电动显示器是最重要的显示技术之一,因为它们具有低功耗、宽视角和户外可读性。因此,他们被认为是电子论文的优秀候选人。这些类型的显示器是基于带电颜料粒子在电场影响下在非极性液体中的受控运动。由于介电常数低,在非极性胶体中自由电荷几乎不存在。然而,在非极性胶体中加入表面活性剂通常会导致相当大的电荷诱导效应,例如提高导电性和颗粒稳定性。在这个项目中,我们的目标是开发一种新型的电动驱动显示器。基于电渗透和电泳在非极性流体中的协同作用,提出了一种前所未有的显示装置。这种方法可以减少显示信息所需的切换时间,并扩展电动显示器的应用,使未来的视频速度和全彩成为可能。
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引用次数: 0
Manipulation of Microrobots using Chladni Plates and Multimode Membrane Resonators 利用Chladni板和多模膜谐振器操纵微型机器人
Lillian N. Usadi, S. Firebaugh, H. Elbidweihy, S. Yee
The advent of micro/nanorobotics promises to transform the physical, chemical, and biological domains by harnessing opportunities otherwise limited by size. Most notable is the biomedical field in which the ability to manipulate micro/nanoparticles has numerous applications in biophysics, drug delivery, tissue engineering, and microsurgery. Acoustics, the physics of vibrational waves through matter, offers a precise, accurate, and minimally invasive technique to manipulate microrobots or microparticles (stand-ins for microrobots). One example is through the use of flexural vibrations induced in resonant structures such as Chladni plates. In this research, we developed a platform for precise two-dimensional microparticle manipulation via acoustic forces arising from Chladni figures and resonating microscale membranes. The project included two distinct phases: (1) macroscale manipulation with a Chladni plate in air and (2) microscale manipulation using microscale membranes in liquid. In the first phase (macroscale in air), we reproduced previous studies in order to gain a better understanding of the underlying physics and to develop control algorithms based on statistical modeling techniques. In the second phase (microscale in liquid), we developed and tested a new setup using custom microfabricated structures. The macroscale statistical modeling techniques were integrated with microscale autonomous control systems. It is shown that control methods developed on the macroscale can be implemented and used on the microscale with good precision and accuracy.
微/纳米机器人的出现有望通过利用其他受尺寸限制的机会来改变物理,化学和生物领域。最值得注意的是生物医学领域,操纵微/纳米颗粒的能力在生物物理学、药物输送、组织工程和显微外科等领域有许多应用。声学,即振动波穿过物质的物理学,提供了一种精确、准确、微创的技术来操纵微型机器人或微粒(微型机器人的替代品)。一个例子是通过在诸如克拉尼板之类的共振结构中使用引起的弯曲振动。在这项研究中,我们开发了一个平台,通过由克拉德尼图和共振微尺度膜产生的声力来精确地操纵二维微粒。该项目包括两个不同的阶段:(1)在空气中使用克拉尼板进行宏观操作;(2)在液体中使用微尺度膜进行微观操作。在第一阶段(空气中的宏观尺度),我们复制了以前的研究,以便更好地理解潜在的物理现象,并开发基于统计建模技术的控制算法。在第二阶段(液体微尺度),我们开发并测试了一种使用定制微加工结构的新装置。将宏观统计建模技术与微观自主控制系统相结合。结果表明,在宏观尺度上开发的控制方法可以在微观尺度上实现和使用,并且具有良好的精度和准确度。
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引用次数: 3
Lipid-based nanoparticle production in Micromixers 微混合器中脂基纳米颗粒的生产
V. Nerguizian, R. Salazar
Lipid-based nanoparticles have demonstrated to be a versatile vehicle for drugs, genetic material, and labels. These particles are often made of biocompatible and biodegradable materials, enabling a safe interaction with biological systems. The importance of this type of delivery vehicle has been shown recently, as the two leading vaccines are based on lipid-nanoparticles encapsulating mRNA. Passive micromixers produce lipid nanoparticles in a reproducible and controllable way. However, micromixers suffered at the beginning of low production rate, and complicated designs which were difficult to produce and prone to clogging. In recent years, the exploration of different mixing strategies based on the use of curvilinear paths to induce centripetal forces and vortex formation at high speeds as well as the increase of the microchannel cross-sectional area while keeping laminar flow regimes has led to designs capable of producing lipid-based nanoparticles on an industrial-scale. However, there are still challenges in the field which include the removal or substitution of the organic solvents that still need to be addressed. In this presentation, we introduce a general overview of lipid nanoparticle or liposome production in micromixers, the principles of mixing using curvilinear paths, the key variables controlling lipid-based nanoparticle physicochemical characteristics and approaches that help to substitute toxic solvent residues.
以脂质为基础的纳米颗粒已被证明是药物、遗传物质和标签的多功能载体。这些颗粒通常由生物相容性和可生物降解材料制成,能够与生物系统安全相互作用。这种递送载体的重要性最近得到了证实,因为两种主要的疫苗都是基于脂质纳米颗粒封装mRNA。被动微混合器以可重复和可控的方式生产脂质纳米颗粒。然而,微型混合器在初期存在着生产率低、设计复杂、生产困难、易堵塞等问题。近年来,基于使用曲线路径来诱导高速向心力和涡流形成的不同混合策略的探索,以及在保持层流状态的同时增加微通道横截面积,导致了能够在工业规模上生产基于脂质纳米颗粒的设计。然而,该领域仍然存在挑战,包括有机溶剂的去除或替代仍然需要解决。在本次演讲中,我们介绍了微混合器中脂质纳米颗粒或脂质体生产的总体概述,使用曲线路径混合的原理,控制脂质纳米颗粒物理化学特性的关键变量以及有助于替代有毒溶剂残留物的方法。
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引用次数: 0
Separation microfluidic device fabricated by micromilling techniques 微铣削技术制备的分离微流控装置
I. Gonçalves, R. Lima, Miguel Madureira, Inês Miranda, H. Schütte, A. Moita, G. Minas, S. Gassmann
: The diagnosis of several diseases can be performed by analyzing the blood plasma of a patient. Despite extensive research work, there is still a need to improve current low-cost fabrication techniques and devices for the separation of plasma from blood cells. Microfluidic biomedical devices have great potential for that process. Hence, a microfluidic device made by micromilling and sealed with an oxygen plasma technique was tested by means of two different blood analogue fluids. The device has four microchannels with similar geometries but different channel depths. A high-speed video microscopy system was used for the visualization and acquisition of the flow of the analogue fluids throughout the microchannels of the device. Then, the separation of particles and plasma was evaluated with the ImageJ software by measuring and comparing the grey values at the entrance and the exit of the channel. The device showed a significant reduction of the amount of cells between the entrance and the exit of the microchannels. The depth of the channels and the size of the particles were not found to exert any major influence on the separation process. However, it was found that the flow rate affected the separation results, as the best results were obtained for a flow rate of 100 μ L/min. Though these results are promising, further analyses and optimizations of microfluidic devices, as well as comparisons between devices sealed using different methods such as the solvent bonding technique, will be conducted in future works.
通过分析病人的血浆可以诊断多种疾病。尽管进行了大量的研究工作,但仍需要改进目前用于分离血浆和血细胞的低成本制造技术和设备。微流体生物医学设备在这一过程中具有很大的潜力。因此,用两种不同的血液模拟流体对一种由微铣削和氧等离子体密封技术制成的微流体装置进行了测试。该设备有四个微通道,几何形状相似,但通道深度不同。高速视频显微系统用于模拟流体在整个装置微通道中的流动的可视化和采集。然后,利用ImageJ软件通过测量和比较通道入口和出口的灰度值来评价粒子和等离子体的分离效果。该装置显示微通道入口和出口之间的细胞数量显著减少。通道的深度和颗粒的大小对分离过程没有任何重大影响。流速对分离效果有较大影响,当流速为100 μ L/min时,分离效果最好。虽然这些结果是有希望的,但在未来的工作中,将进一步分析和优化微流控器件,以及使用不同方法(如溶剂键合技术)密封的器件之间的比较。
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引用次数: 1
Lab-on-chip platform for on-field analysis of Grapevine leafroll-associated virus 3 用于葡萄叶相关病毒3现场分析的芯片实验室平台
Ilaria Buja, Erika Sabella, A. Monteduro, M. Chiriacò, S. Rizzato, L. Bellis, A. Luvisi, G. Maruccio
Phytopathological adversities are often attributable to human activities (as a consequence of the globalization of trade or tourism mass, changes in common agricultural practices and climate change), adding food losses due to pathogens such as fungi, bacteria, viruses etc. For this, we are developing a lab-on-chip as a diagnostic approach to phytopathological problems caused by infectious agents capable of spreading in agro-ecosystems, such as the Xylella fastidiosa epidemic in Puglia (Chiriaco et al., 2018) or other bacteriosis and virosis such as Grapevine leafroll-associated virus 3 (GLRaV-3). In particular, grapevine leafroll disease (GLD) is one of the most important grapevine viral diseases, affecting grapevines worldwide. Several viruses from the family Closteroviridae are associated with it and Grapevine leafroll-associated virus 3(GLRaV-3) is considered as the most important causative agent. Symptoms of GLD can vary greatly with the season, grape cultivar, and climatic conditions and some varieties can be completely symptomless. (Maree et al., 2013). There is no cure for the virus but only preventive actions. In fact, fighting strategy is based exclusively on the use of plant material free from virus, such as the use of certified material. These pathogens can have serious economic and environmental repercussions on two of the major cultivated woody plant of Mediterranean basin, due to the absence of therapeutic techniques and the need of rapid, in-field and low-cost detection methods. Here we present a lab-on-chip platform coupled with microfluidic module, based on an electrochemical transduction method, able to recognize serial dilutions of Grapevine leafroll-associated virus 3. LOC represents smart and versatile devices due to their miniaturization. They require small sample volumes, allowing a rapid detection of the targets, offering also the opportunity to study biomechanical properties of plants (Nezhad et al., 2013) and other plant cells studies (Nezhad et al., 2014; Julich et al., 2011). In particular, thanks the aid of a microfluidic component, such as polydimethylsiloxane (PDMS), is possible to realize biochemistry conventional laboratories functions such as sample preparation, reaction, separation and detection (McDonald et al, 2000). This device can show competitive performances with conventional diagnostic methods in terms of reliability, with further advantages of portability, low costs and ease of use, making the difference in real time detection of the pathogens.
植物病理逆境通常可归因于人类活动(由于贸易或旅游业的全球化、常见农业做法的变化和气候变化),加上真菌、细菌、病毒等病原体造成的粮食损失。为此,我们正在开发一种芯片实验室,作为一种诊断方法,用于诊断由能够在农业生态系统中传播的传染性病原体引起的植物病理学问题,例如Puglia的木杆菌流行(Chiriaco等人,2018)或其他细菌病和病毒病,例如葡萄藤叶卷相关病毒3 (glav -3)。特别是葡萄叶卷病(GLD)是影响世界各地葡萄的最重要的葡萄病毒性病害之一。来自Closteroviridae科的几种病毒与该病有关,其中葡萄叶相关病毒3(glav -3)被认为是最重要的病原体。GLD的症状随季节、葡萄品种和气候条件的不同而有很大差异,有些品种可能完全没有症状。(Maree et al., 2013)。这种病毒无法治愈,只能采取预防措施。事实上,防治战略完全基于使用无病毒的植物材料,例如使用经认证的材料。由于缺乏治疗技术和需要快速、现场和低成本的检测方法,这些病原体可能对地中海盆地的两种主要栽培木本植物产生严重的经济和环境影响。在此,我们提出了一个基于电化学转导方法的芯片实验室平台,结合微流控模块,能够识别一系列稀释度的葡萄叶相关病毒3。由于其小型化,LOC代表了智能和多功能设备。它们需要小样品量,允许快速检测目标,也提供了研究植物生物力学特性的机会(Nezhad等人,2013)和其他植物细胞研究(Nezhad等人,2014;Julich et al., 2011)。特别是,借助微流体组件,如聚二甲基硅氧烷(PDMS),可以实现生物化学常规实验室功能,如样品制备、反应、分离和检测(McDonald et al, 2000)。该设备在可靠性方面可与传统诊断方法相媲美,并具有便携性、低成本和易于使用的优势,在病原体的实时检测方面具有重要意义。
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引用次数: 1
Stable Porous Silicon Membranes for Fast Bacterial Detection 用于细菌快速检测的稳定多孔硅膜
L. Francis, Roselien Vercauteren, A. Leprince, J. Mahillon
: The rapid detection of hazardous bacteria is important for healthcare situations, where such identification can lead to substantial gains for patient treatment and recovery and a reduced usage of broad-spectrum antibiotics. Potential biosensors must be able to provide a fast, sensitive and selective response with as little sample preparation as possible. Indeed, some of these pathogens, such as Staphylococcus aureus, can be yet harmful at very low concentrations in the blood stream, e.g., below 10 colony forming units per mL (CFU/mL). These stringent requirements limit the number of candidates, especially for point-of-care applications. Amongst several biosensing techniques, optical sensing using porous silicon (PSi) substrate has been widely suggested in recent years thanks to unique features such as a large surface area, tunable optical characteristics, and above all relatively easy and affordable fabrication techniques. In most configurations, PSi optical biosensors are close-ended porous layers; this limits their sensitivity and responsiveness due to diffusion-limited infiltration of the analytes in the porous layer. Also, PSi is a reactive material, its oxidation in buffer solutions results in time-varying shifts. Despite its attractive properties, several challenges must still be overcome in order to reach practical applications. Our work addresses three main improvement points. The first one is the stability over time in saline solutions helped by atomic layer deposition of metal oxides inside the pores. Besides a better stability, our solution is helping with an increase of the optical signal to noise ratio, thus reducing the limit of detection. The second one is to perform the lysis of the bacteria prior to its exposure to the sensor, such that the selective detection is based upon the percolation of bacterial residues inside the pores rather than the bacteria themselves. The third one is to remove the bulk silicon below a PSi layer to create a membrane, that allows for flow-through of the analytes, thus enhancing the interactions between the lysate and the sensor’s surface. This approach allows us to avoid the step of surface functionalization used in classical biosensors. We tested thanks to these improvements the selective detection of Bacillus cereus lysate with concentrations between 103 and 105 CFU/mL. Future works are dedicated to further improvements, including optical signal enhancement techniques and dielectrophoretic assisted percolation in the porous silicon membrane.
*快速检测有害细菌对保健情况很重要,在这种情况下,这种识别可为患者的治疗和康复带来重大收益,并减少广谱抗生素的使用。潜在的生物传感器必须能够在尽可能少的样品制备的情况下提供快速、敏感和选择性的反应。事实上,其中一些病原体,如金黄色葡萄球菌,在血液中浓度很低时仍可能有害,例如,低于每毫升10个菌落形成单位(CFU/mL)。这些严格的要求限制了候选人的数量,特别是对于护理点应用程序。在几种生物传感技术中,利用多孔硅(PSi)衬底的光学传感技术近年来被广泛提出,这得益于其独特的特性,如大表面积,可调谐的光学特性,以及最重要的是相对容易和负担得起的制造技术。在大多数配置中,PSi光学生物传感器是封闭的多孔层;由于分析物在多孔层中的扩散限制渗透,这限制了它们的灵敏度和响应性。此外,PSi是一种反应性材料,它在缓冲溶液中的氧化会导致时变位移。尽管它具有吸引人的特性,但为了达到实际应用,还必须克服一些挑战。我们的工作涉及三个主要改进点。第一个是在孔隙内金属氧化物的原子层沉积的帮助下,在盐水溶液中随时间的稳定性。除了更好的稳定性外,我们的解决方案还有助于提高光信噪比,从而降低检测极限。第二个是在细菌暴露于传感器之前进行裂解,这样选择性检测是基于细菌残留物在毛孔内的渗透,而不是细菌本身。第三种方法是去除PSi层以下的大块硅,形成一层膜,允许分析物流过,从而增强裂解物与传感器表面之间的相互作用。这种方法使我们能够避免经典生物传感器中使用的表面功能化步骤。由于这些改进,我们测试了蜡样芽孢杆菌裂解液在103 ~ 105 CFU/mL之间的选择性检测。未来的工作将致力于进一步的改进,包括光信号增强技术和多孔硅膜中的介电泳辅助渗透。
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引用次数: 0
Optimization of Manufacturing Parameters of 3D Printed Solid Microneedles for Transdermal Drug Delivery 经皮给药用3D打印固体微针制造参数优化
Kenan Muhamedagic, A. Tucak, M. Sirbubalo, O. Rahić, Lamija Hindija, J. Hadžiabdić, E. Vranić, A. Çekiç
Microneedles (MNs) have been manufactured using a variety of methods from a range of materials, but most of them are expensive and time-consuming for screening new designs and making any modifications. Therefore, stereolithography (SLA) has emerged as a promising approach for MN fabrication due to its numerous advantages, including simplicity, low cost, and the ability to manufacture complex geometrical products at any time, including modifications to the original designs. This work aimed to print MNs using SLA technology and investigate the effects of post-printing curing conditions on the mechanical properties of 3D-printed MNs. Solid MNs were designed using CAD software and printed with grey resin (Formlabs, UK) using Form 3 printer (Formlabs, UK). MNs dimensions were 1.2 × 0.4 × 0.05 mm, arranged in 6 rows and 6 columns on a 10 × 10 mm baseplate. MNs were then immersed in an isopropyl alcohol bath to remove unpolymerized resin residues and cured in a UV-A heated chamber (Formlabs, UK). In total, nine samples were taken for each combination of curing temperature (35°C, 50°C, and 70°C) and curing time (5 min, 20 min, and 60 min). Fracture tests were conducted using a hardness apparatus TB24 (Erweka, Germany). MNs were placed on the moving probe of the machine and compressed until fracture. The optimization of the SLA process parameters for improving the strength of MNs was performed using the Taguchi method. The design of experiments was carried out based on the Taguchi L9 orthogonal array. Experimental results showed that the curing temperature has a significant influence on MN strength improvements. Improvement of the MN strength can be achieved by increasing the curing temperature and curing time.
微针(MNs)的制造方法多种多样,材料也多种多样,但大多数方法在筛选新设计和进行任何修改时都是昂贵且耗时的。因此,立体光刻(SLA)已成为锰制造的一种有前途的方法,因为它具有许多优点,包括简单,低成本,以及随时制造复杂几何产品的能力,包括对原始设计的修改。这项工作旨在使用SLA技术打印纳米颗粒,并研究打印后固化条件对3d打印纳米颗粒机械性能的影响。使用CAD软件设计实体mn,并使用Form 3打印机(Formlabs, UK)使用灰色树脂(Formlabs, UK)进行打印。MNs尺寸为1.2 × 0.4 × 0.05 mm,在10 × 10 mm的底板上按6排6列排列。然后将纳米颗粒浸入异丙醇浴中以去除未聚合的树脂残留物,并在UV-A加热室中固化(Formlabs, UK)。在养护温度(35°C、50°C和70°C)和养护时间(5分钟、20分钟和60分钟)的不同组合下,共采集9个样品。断裂试验采用TB24硬度仪(Erweka, Germany)进行。将MNs放置在机器的移动探针上并压缩直至断裂。采用田口法对SLA工艺参数进行优化,以提高纳米颗粒的强度。实验设计基于田口L9正交阵列。实验结果表明,养护温度对MN强度的提高有显著影响。通过提高固化温度和固化时间可以提高MN的强度。
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Proceedings of Micromachines 2021 — 1st International Conference on Micromachines and Applications (ICMA2021)
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