Lab on a Chip最新文献

{"title":"An electrochemical sensor integrated lab-on-a-CD system for phenylketonuria diagnostics.","authors":"Ipek Akyilmaz, Dilan Celebi-Birand, Naim Yagiz Demir, Deniz Bas, Caglar Elbuken, Memed Duman","doi":"10.1039/d4lc00912f","DOIUrl":"https://doi.org/10.1039/d4lc00912f","url":null,"abstract":"<p><p>Phenylketonuria (PKU) is characterized by an autosomal recessive mutation in the phenylalanine hydroxylase (PAH) gene. Impaired PAH enzyme activity leads to the accumulation of phenylalanine (Phe) and its metabolites in the bloodstream, which disrupts the central nervous system and causes psychomotor retardation. Early diagnosis of PKU is essential for timely intervention. Moreover, continuous monitoring of blood Phe levels is indispensable for prognosis, requiring a robust and reliable monitoring system. This study presents an automated lab-on-a-CD-based system for early diagnosis and monitoring of PKU treatment. This miniaturised system contains CD-shaped disposable cartridges, a mini centrifuge, and an electrochemical sensing unit. Modified screen-printed gold electrodes were used for the electrochemical measurements in cartridges. Electrode modification was conducted by electrochemical graphene oxide reduction and deposition on the electrode surface, which increased the sensitivity of the measurement 1.5 fold. The system used amperometric detection to measure Phe in the blood through oxidation of NAD⁺ to NADH by the enzyme phenylalanine dehydrogenase. The limit of detection (LOD), limit of quantification (LOQ), and sensitivity of the system were 0.0524, 0.1587 mg dL^-1 and 0.3338 μA mg^-1 dL, respectively, within the 0-20 mg dL^-1 measurement range (<i>R</i>² = 0.9955). The performance of the lab-on-a-CD system was compared to the gold standard HPLC method. The accuracy was 83.1% for HPLC and 84.1% for the lab-on-a-CD system. In conclusion, this study successfully developed a portable diagnostic device for rapid (under 20 min), accurate and highly sensitive detection of Phe in whole blood.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A 3D millifluidic model of a dermal perivascular microenvironment on a chip†","authors":"Chiara Martinelli, Alberto Bocconi, Sofia Milone, Teresa Baldissera, Leonardo Cherubin, Giovanni Buccioli, Simone Perottoni, Claudio Conci, Giulio Cerullo, Roberto Osellame, Giuseppe Chirico, Emanuela Jacchetti and Manuela Teresa Raimondi","doi":"10.1039/D4LC00898G","DOIUrl":"10.1039/D4LC00898G","url":null,"abstract":"<p >The process of angiogenesis plays a pivotal role in skin regeneration, ensuring the provision of nutrients and oxygen to the nascent tissue, thanks to the formation of novel microvascular networks supporting functional tissue regeneration. Unfortunately, most of the current therapeutic approaches for skin regeneration lack vascularization, required to promote effective angiogenesis. Thus, <em>in vitro</em> tridimensional models, complemented with specific biochemical signals, can be a valuable tool to unravel the neovascularization mechanisms and develop novel clinical strategies. In this work, we designed and validated a tridimensional microstructured dynamic model of the dermal perivascular microenvironment on a chip. We carried out the fabrication of an array of microstructures by two-photon laser polymerization, then used as a 3D substrate for co-culture of human dermal fibroblasts and endothelial cells. We included the substrate in a miniaturized optically accessible bioreactor (MOAB) which provides the physiological interstitial flow, upon perfusion in the presence or absence of the pro-angiogenic stimuli VEGF and TGF-β1. We determined the parameters to be applied under dynamic conditions by an <em>in silico</em> model simulating individual 3D microenvironments within the bioreactor's chambers. We computed the fluid velocity and wall shear stress acting on endothelial cells along with the oxygen concentration profile, and we chose the most suitable flow rate for maintaining dermal physiological conditions. Experimental results showed the effectiveness of the developed platform as a 3D dynamic model of angiogenesis. This is the first combined experimental and computational study involving chemically stimulated 3D co-cultures for successfully simulating the physiological dermal perivascular microenvironment.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 3","pages":" 423-439"},"PeriodicalIF":6.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11701800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A fully integrated microfluidic cartridge for rapid and ultrasensitive nucleic acid detection from oropharyngeal swabs†","authors":"Bao Li, Baobao Lin, Wu Zeng, Yin Gu, Yulan Zhao and Peng Liu","doi":"10.1039/D4LC00770K","DOIUrl":"10.1039/D4LC00770K","url":null,"abstract":"<p >Rapid and accurate molecular diagnostics are crucial for preventing the global spread of emerging infectious diseases. However, the current gold standard for nucleic acid detection, reverse transcription polymerase chain reaction (RT-PCR), relies heavily on traditional magnetic beads or silica membranes for nucleic acid extraction, resulting in several limitations, including time-consuming processes, the need for trained personnel, and complex equipment. Therefore, there is an urgent need for fully integrated nucleic acid detection technologies that are simple to operate, rapid, and highly sensitive to meet unmet clinical needs. In this study, we developed a novel, integrated microfluidic cartridge featuring a unique needle-plug/piston microvalve, which enables stable long-term reagent storage and flexible liquid handling for on-site nucleic acid analysis. Coupled with <em>in situ</em> tetra-primer recombinase polymerase amplification (tp-RPA), we achieved highly sensitive nucleic acid detection with a remarkable limit of detection of 20 copies per mL (0.02 copies per μL) and a short turnaround time of less than 30 minutes. To validate this assay, we tested 48 oropharyngeal swab samples. The positive detection rate reached 64.58% (31/48), significantly exceeding the approximately 50% positive detection rate of the traditional RT-PCR method. Furthermore, our assay demonstrated a 100% concordance rate with RT-PCR in detecting positive samples. Thus, we believe our microfluidic nucleic acid analysis system represents a promising approach for enabling rapid and ultrasensitive nucleic acid detection of pathogenic microorganisms in resource-limited settings and low-income areas.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 3","pages":" 454-464"},"PeriodicalIF":6.1,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142918667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-throughput, combinatorial droplet generation by sequential spraying.","authors":"Rena Fukuda, Nate J Cira","doi":"10.1039/d4lc00656a","DOIUrl":"https://doi.org/10.1039/d4lc00656a","url":null,"abstract":"<p><p>Advancements in bulk and microfluidic emulsion methodologies have enabled highly efficient, high-throughput implementations of biochemical assays. Spray-based techniques offer rapid generation, droplet immobilization, and accessibility, but remain relatively underutilized, likely because they result in random and polydisperse droplets. However, the polydisperse characteristic can be leveraged; at sufficiently high droplet numbers, sequential sprays will generate mixed droplets which effectively populate a combinatorial space. In this paper, we present a method involving the sequential spraying and mixing of solutions encoded with fluorophores. This generates combinatorial droplets with quantifiable concentrations that can be imaged over time. To demonstrate the method's performance and utility, we use it to investigate synergistic and antagonistic pairwise antibiotic interactions.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stretchable impedance electrode array with high durability for monitoring of cells under mechanical and chemical stimulations†","authors":"A Ri Kim, Seok Ju Hong, Han-Byeol Lee and Nae-Eung Lee","doi":"10.1039/D4LC00680A","DOIUrl":"10.1039/D4LC00680A","url":null,"abstract":"<p >Electrochemical impedance spectroscopy (EIS) serves as a non-invasive technique for assessing cell status, while mechanical stretching plays a pivotal role in stimulating cells to emulate their natural environment. Integrating these two domains enables the concurrent application of mechanical stimulation and EIS in a stretchable cell culture system. However, challenges arise from the difficulty in creating a durable and stable stretchable impedance electrode array. To overcome this limitation, we have developed a cell culture system integrated with a stretchable impedance electrode array (SIEA). This design enabled impedance monitoring during cell proliferation under mechanical stimulation over a long period of time due to the high mechanical durability and electrochemical stability of the SIEA. Our evaluation also involved testing the cytotoxicity of doxorubicin on H9C2 cells directly on the SIEA. The results underscore the significant potential of our SIEA device as an effective tool for monitoring cells subjected to mechanical stimulation and as a platform for drug toxicity testing.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 3","pages":" 403-412"},"PeriodicalIF":6.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142918670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D-printed acoustic metasurface with encapsulated micro-air-bubbles for frequency-selective manipulation†","authors":"Miaomiao Ji, Yukai Liu, Zheng Zhang, Rui Xu, Fanyun Pan, Ya Zhang, Rouyu Su, Minghui Lu, Xiujuan Zhang and Guanghui Wang","doi":"10.1039/D4LC00890A","DOIUrl":"10.1039/D4LC00890A","url":null,"abstract":"<p >Acoustic waves provide an effective method for object manipulation in microfluidics, often requiring high-frequency ultrasound in the megahertz range when directly handling microsized objects, which can be costly. Micro-air-bubbles in water offer a solution toward low-cost technologies using low-frequency acoustic waves. Owing to their high compressibility and low elastic modulus, these bubbles can exhibit significant expansion and contraction in response to even kilohertz acoustic waves, leading to resonances with frequencies determined and tuned by air-bubble size. The resonances amplify vibrational amplitude and generate localized turbulence, enabling selective, non-invasive, and high-precision manipulation of microsized objects. However, conventional bubble formation relies on the shear force of the liquid flow and bubble surface tension, facing challenges of instability and random vibration that can impair manipulation precision and performance. To address these issues, we propose a coupled vibration structure with 3D-printed circular microsized air holes encapsulated by a PDMS film. These airholes act as artificial micro-air-bubbles, with their expansion and contraction stabilized by acoustic hard boundaries. The PDMS film further regulates vibration modes through the interaction between air movement and the film's vibration, eliminating randomness. Compared to conventional air-bubbles held by surface tension, these artificial air-bubbles are mechanically stable, allowing for enhanced gas volume changes and stronger forces for object manipulation. We experimentally confirm the stable vibration modes and their frequency-dependent behavior using laser Doppler vibrometry. Precise aggregation, rotation, and separation of micro-objects are demonstrated by adjusting the film's vibration mode. Furthermore, we propose a metasurface design featuring a multi-size microbubble array for frequency-selective manipulation, enabling flexible control of sample trajectory by changing the exciting frequency of an embedded piezoelectric transducer. Our low-frequency acoustic metasurface device offers a versatile, cost-effective solution for drug screening and automated sample handling.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 2","pages":" 263-274"},"PeriodicalIF":6.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering the acoustic field with a Mie scatterer for microparticle patterning†","authors":"Xingyu Jiang, Yunpeng Zhao, Minjie Shen, Xiao Zhou, Bin Chen, Bruce W. Drinkwater and Liangfei Tian","doi":"10.1039/D4LC00577E","DOIUrl":"10.1039/D4LC00577E","url":null,"abstract":"<p >The utilization of acoustic fields offers a contactless approach for microparticle manipulation in a miniaturized system, and plays a significant role in medicine, biology, chemistry, and engineering. Due to the acoustic radiation force arising from the scattering of the acoustic waves, small particles in the Rayleigh scattering range can be trapped, whilst their impact on the acoustic field is negligible. Manipulating larger particles in the Mie scattering regime is challenging due to the diverse scattering modes, which impacts the local acoustic field. The rapid movement of free-moving Mie scatterers in an acoustic standing wave field makes it difficult to study the interaction between a sound field and a Mie scatterer in an engineering context. Here, a combined approach that integrates theoretical analysis and experimental investigation was developed to explore the influence of a Mie scatterer on the acoustic field by fabricating an acoustic trapping device featuring a fixed Mie scatterer at its center. We demonstrate that an insonified Mie scatterer can operate as an acoustic emitter in water, enabling dynamic and versatile modulation of the total acoustic field. Such a scatterer can interact with one or multiple incident propagating acoustic waves, leading to the generation of a localized standing wave field in the vicinity of the scatterer. This local field can be controlled by the relative location of the scatterer with respect to the incident field leading to control over the transformation from an incident 1D acoustic field into a 2D acoustic field. This control paves the way for localized and multi-scale micro-object manipulation.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 3","pages":" 413-422"},"PeriodicalIF":6.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A FET-based flexible biosensor system for dynamic behavior observation of lipid membrane with nanoparticles in vitro†","authors":"Keyi Zhu, Hanjing Lu, Qiannan Xue, Feng Zhou, Wenlan Guo, Chen Sun and Xuexin Duan","doi":"10.1039/D4LC00801D","DOIUrl":"10.1039/D4LC00801D","url":null,"abstract":"<p >Nanoparticles have become widely used materials in various fields, yet their mechanism of action at the cellular level after entering the human body remains unclear. Accurately observing the effect of nanosize dimensions on particle internalization and toxicity in cells is crucial, particularly under the conditions of biological activity. With the aim of helping to study the interactions between nanoparticles of varying sizes and active cell membranes, we propose a flexible biosensor system based on a field effect transistor (FET). We constructed lipid bilayers on the device <em>in vitro</em> to simulate the interaction between nanoparticles and lipid membranes under active conditions, with the aim of investigating the effect of differently sized nanoparticles on the cell membrane. The experimental results revealed that nanoparticles with a diameter smaller than 50 nm tend to induce mild strain and repairable damage to the membrane, whereas nanoparticles larger than 50 nm may cause more severe damage, and even transmembrane penetration, by creating unrecoverable pores. The stretching of the lipid membrane exacerbated the deformation and destruction caused by nanoparticles, even in the case of smaller particles. These above results are consistent with previous theories on the interactions between cell membranes and nanoparticles. The proposed biosensors provide a valuable tool for investigating how the nanosize dimensions of particles affect their ability to penetrate and cause destruction in dynamic cell membranes, contributing to the improvement of a more comprehensive theoretical system for understanding the interaction process between nanoparticles and cell membranes.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 3","pages":" 393-402"},"PeriodicalIF":6.1,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142918665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-time cell barrier monitoring by spatial transepithelial electrical resistance measurement on a microelectrode array integrated Transwell†","authors":"Yimin Shi, Sheng Sun, Hui Liu, Mingda Zhao, Meiyan Qin, Jinlong Liu, Jingfang Hu, Yang Zhao, Mingxiao Li, Lingqian Zhang and Chengjun Huang","doi":"10.1039/D4LC00817K","DOIUrl":"10.1039/D4LC00817K","url":null,"abstract":"<p >Transepithelial electrical resistance (TEER) measurement is a label free, rapid and real-time technique, which is commonly used to evaluate the integrity of cell barriers. TEER characterization is important for applications, such as tissue (brain, intestines, lungs) barrier modeling, drug screening, and cell growth monitoring. Traditional TEER methods usually only show the average impedance of the whole cell layer, and lack accuracy and the characterization of internal spatial differences within cell layer regions. Here, we introduce a new spatial TEER strategy that utilizes microelectrode arrays (MEA) integrated in a Transwell to dynamically monitor TEER. A new electrical model which could reveal spatial impedance non-uniformity was proposed to extract accurate resistance from the measured data. Based on our method, the TEER signals from 16 different regions were successfully monitored in real time. The mapped impedance hotspots in different regions closely correlate with both fluorescence cell staining signals and calculated cell coverage, indicating the effectiveness of the developed spatial TEER system in monitoring local cell growth <em>in vitro</em>. The real-time spatial TEER responses to ethylene glycol-bis(β-aminoethylether)-<em>N</em>,<em>N</em>,<em>N</em>′,<em>N</em>′-tetraacetic acid (EGTA) and cisplatin were studied, which could either reduce barrier integrity or inhibit cellular growth. The obtained results demonstrated the spatial TEER's applicability for cell barrier function and cell growth monitoring. Our approach provides accurate spatial electrical information of cell barriers and holds potential applications in drug development and screening.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 2","pages":" 253-262"},"PeriodicalIF":6.1,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stepwise isolation of diverse metabolic cell populations using sorting by interfacial tension (SIFT)†","authors":"Matthew Shulman, Thomas Mathew, Aria Trivedi, Azam Gholizadeh, Charlotte Colcord, Ryan Wiley, Kiron S. Allen, Lakshmi Thangam, Kelsey Voss and Paul Abbyad","doi":"10.1039/D4LC00792A","DOIUrl":"10.1039/D4LC00792A","url":null,"abstract":"<p >We present here a passive and label-free droplet microfluidic platform to sort cells stepwise by lactate and proton secretion from glycolysis. A technology developed in our lab, Sorting by Interfacial Tension (SIFT), sorts droplets containing single cells into two populations based on pH by using interfacial tension. Cellular glycolysis lowers the pH of droplets through proton secretion, enabling passive selection based on interfacial tension and hence single-cell glycolysis. The SIFT technique is expanded here by exploiting the dynamic droplet acidification from surfactant adsorption that leads to a concurrent increase in interfacial tension. This allows multiple microfabricated rails at different downstream positions to isolate cells with distinct glycolytic levels. The device is used to correlate sorted cells with three levels of glycolysis with a conventional surface marker for T-cell activation. As glycolysis is associated with both disease and cell state, this technology facilitates the sorting and analysis of crucial cell subpopulations for applications in oncology, immunology and immunotherapy.</p>","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":" 3","pages":" 383-392"},"PeriodicalIF":6.1,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}