Valeria Garzarelli, Alessia Foscarini, Vanessa Indirli, Ilaria Menon, Diego Mangiullo, Tiziano Verri, Elisabetta Primiceri, Annamaria Nigro, Angelo Quattrini, Alessandro Romano, Maria Serena Chiriacò, Giuseppe Gigli, Francesco Ferrara
{"title":"Lab on chips for liquid biopsy: a flexible and customized approach through microfabrication.","authors":"Valeria Garzarelli, Alessia Foscarini, Vanessa Indirli, Ilaria Menon, Diego Mangiullo, Tiziano Verri, Elisabetta Primiceri, Annamaria Nigro, Angelo Quattrini, Alessandro Romano, Maria Serena Chiriacò, Giuseppe Gigli, Francesco Ferrara","doi":"10.1007/s10544-025-00757-y","DOIUrl":"10.1007/s10544-025-00757-y","url":null,"abstract":"<p><p>Cancer early detection is one of the most challenging purposes of preventive medicine. Liquid biopsy represents a revolutionary approach, fostering access to early screening and increasing patients' compliance, two crucial issues in reaching the largest possible audience in prevention campaigns. To facilitate this approach, the deployment of innovative methods for easy manipulation of biological fluids and the availability of devices for the rapid and low-cost detection of biomarkers is essential. The aim of this study was the optimization of multifunctional Lab-On-Chips with the final aim of realizing a platform for oral carcinoma cells trapping from a complex biological fluid as saliva and for specific subcellular components like extracellular vesicles (EVs) from the neuroblastoma cell model. A set of different microfluidic building blocks was realized through poly-methyl methacrylate (PMMA) micromilling, microfabricated and functionalized to optimize surface chemistry for capturing tumor cells or EVs in multiple channels, assess working concentration for biological fluids and combine sample preparation with detection modules all in the same chip. After optimization, a proof-of-concept device was realized mimicking liquid biopsy analysis from saliva, a biological fluid readily available and with a high compliance from patients, useful for the early diagnosis of cancer.</p>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"27 2","pages":"26"},"PeriodicalIF":3.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144245596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jooin Bang, Jiyoung Yeo, Su Ji Lee, Hansol Lee, Jinyoung Kim, Sohyeon Jeong, Eeseul Kang, Hoon Suk Rho, YongTae Kim, Jun-Ook Park
{"title":"A 3D vascularized tumor spheroid microfluidic platform for head and neck cancer research: new insights.","authors":"Jooin Bang, Jiyoung Yeo, Su Ji Lee, Hansol Lee, Jinyoung Kim, Sohyeon Jeong, Eeseul Kang, Hoon Suk Rho, YongTae Kim, Jun-Ook Park","doi":"10.1007/s10544-025-00748-z","DOIUrl":"10.1007/s10544-025-00748-z","url":null,"abstract":"<p><p>Conventional in vitro cancer models often fail to replicate the complexity of the tumor microenvironment. We have developed a 3D micro-engineered vascularized organoid chip (VOC) platform to enhance the physiological relevance of in vivo tumor models. This platform incorporates patient-derived tumor spheroids from head and neck cancer patients, providing a more accurate simulation of the native tumor microenvironment. We evaluated the efficacy of 5-fluorouracil (5-FU) and sunitinib on angiogenic sprouting and cell viability of red fluorescent protein-expressing human umbilical vein endothelial cells (RFP-HUVECs) and head and neck cancer patient-derived tumor spheroids cultured in the VOC platform. A 3D micro-engineered VOC platform was developed to provide a physiologically relevant environment for RFP-HUVECs and head and neck cancer patient-derived tumor spheroids. Cellular responses to 5-FU and sunitinib were examined over 14 days, focusing on interactions and behavior in the VOC setup. 5-FU and sunitinib significantly inhibited angiogenic sprouting and reduced cell viability. Notably, these drugs induced changes in cellular network formation and disrupted the structural integrity of patient-derived spheroids, emphasizing the effectiveness of these drugs in a model that closely simulates the tumor microenvironment of head and neck cancer. Our study demonstrates the potential of the 3D vascularized tumor spheroid microfluidic chip as a valuable tool for personalized treatment and investigation of head and neck squamous cell carcinoma. This platform simulates the tumor microenvironment and offers exceptional precision in evaluating drug efficacy.</p>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"27 2","pages":"25"},"PeriodicalIF":3.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mafalda Abrantes, Tiago Pereira, Patrícia Silva, Margarida Falcão, Jérôme Borme, Pedro Alpuim, Luis Jacinto
{"title":"Small form factor implantable neural probe with efficient flip chip µLED for in vivo optogenetics.","authors":"Mafalda Abrantes, Tiago Pereira, Patrícia Silva, Margarida Falcão, Jérôme Borme, Pedro Alpuim, Luis Jacinto","doi":"10.1007/s10544-025-00754-1","DOIUrl":"10.1007/s10544-025-00754-1","url":null,"abstract":"","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"27 2","pages":"24"},"PeriodicalIF":3.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peng Zheng, Yongtao Wei, Keren Cao, Chen Xu, Shanshan Yu, Yang Liu, Min Li, Chunyan Zhang, Tao Wang
{"title":"Sustained - release microspheric gel of meloxicam: Preparation, evaluation in vitro and in vivo.","authors":"Peng Zheng, Yongtao Wei, Keren Cao, Chen Xu, Shanshan Yu, Yang Liu, Min Li, Chunyan Zhang, Tao Wang","doi":"10.1007/s10544-025-00753-2","DOIUrl":"10.1007/s10544-025-00753-2","url":null,"abstract":"","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"27 2","pages":"23"},"PeriodicalIF":3.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nayeem Imtiaz, William A Stoddard, Abdelrahman Ghazy, Steven W Day
{"title":"Oxygen transport in nanoporous SiN membrane compared to PDMS and polypropylene for microfluidic ECMO.","authors":"Nayeem Imtiaz, William A Stoddard, Abdelrahman Ghazy, Steven W Day","doi":"10.1007/s10544-025-00750-5","DOIUrl":"10.1007/s10544-025-00750-5","url":null,"abstract":"<p><p>Extracorporeal Membrane Oxygenation (ECMO) serves as a crucial intervention for patients with severe pulmonary dysfunction by facilitating oxygenation and carbon dioxide removal. While traditional ECMO systems are effective, their large priming volumes and significant blood-contacting surface areas can lead to complications, particularly in neonates and pediatric patients. Microfluidic ECMO systems offer a promising alternative by miniaturizing the ECMO technology, reducing blood volume requirements, and minimizing device surface area to improve safety and efficiency. This study investigates the oxygen transport performance of three membrane types- polydimethylsiloxane (PDMS), polypropylene, and a novel nanoporous silicon nitride (NPSiN) membrane-in a microfluidic ECMO platform. While nanoporous membranes rely on pore-mediated diffusion and PDMS on polymer lattice diffusion, results show no significant differences in device oxygenation efficiency (p > 0.05). Blood-side factors, including the diffusion rate of oxygen through the red blood cell (RBC) membrane, RBC residence time, and hemoglobin binding kinetics, were identified as primary bottlenecks. Even computational models of a hypothetical infinitely permeable membrane corroborate the limited impact of membrane material. These findings suggest a shift in ECMO design priorities from membrane material to blood-side enhancements. This research provides a foundation for optimizing ECMO systems.</p>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"27 2","pages":"22"},"PeriodicalIF":3.0,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12119709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Flexible porous microneedle array for bioelectric skin patch","authors":"Soichiro Tottori, Mirai Matsuura, Sae Ichinose, Haechang Cho, Tarryn Galloway, Natsuho Moriyama, Matsuhiko Nishizawa","doi":"10.1007/s10544-025-00749-y","DOIUrl":"10.1007/s10544-025-00749-y","url":null,"abstract":"<div><p>Microneedles with porous internal structures can provide pathways for transdermal ionic current and drug delivery by penetrating the stratum corneum of the skin. However, conventional porous microneedle arrays are typically monolithic and rigid, limiting their flexibility and adaptability to curved skin surfaces. To address the issue, a method to directly integrate an array of porous microneedles to a flexible substrate is proposed, preserving their skin penetration capability while enhancing flexibility. The resulting array conforms to curved skin surfaces while effectively reducing transdermal ionic resistance. Numerical and analytical modeling demonstrates that the limited number of needles on a flexible array is sufficient to reduce transdermal resistance. Further, an enzymatic battery is combined to create a fully organic, porous microneedle-based bioelectric skin patch that can generate stable transdermal current suitable for stimulation and drug delivery applications.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"27 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10544-025-00749-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mousam Bhowmik, Rajamma A. J., Sateesha S. B., Chandan R. S., Girija E. K., Punith M, Ebna Azizal Omar, Rajesh R
{"title":"Cyanocobalamin-loaded dissolving microneedles for enhanced transdermal delivery: development, characterization, and pharmacokinetic evaluation","authors":"Mousam Bhowmik, Rajamma A. J., Sateesha S. B., Chandan R. S., Girija E. K., Punith M, Ebna Azizal Omar, Rajesh R","doi":"10.1007/s10544-025-00747-0","DOIUrl":"10.1007/s10544-025-00747-0","url":null,"abstract":"<div><p>This study demonstrates cyanocobalamin-loaded dissolving microneedles (CNBL-MNs) as a minimally invasive transdermal solution for managing cyanocobalamin (CNBL) deficiency, offering an alternative to intramuscular injections and oral supplements. The CNBL-MNs were developed using biodegradable, water-soluble polymers such as polyvinylpyrrolidone K25, Dextran K40, and chitosan to ensure controlled and gradual release of the CNBL. The formulation’s stability and integrity were assessed through FTIR and XRD analyses. SEM imaging revealed well-formed microneedles with a height of 800 μm, a 200 μm base diameter, and a 500 μm pitch. EDS confirmed the successful incorporation of CNBL in the microneedle array. The Parafilm<sup>®</sup> membrane insertion test revealed that the microneedles had strong mechanical properties and achieved 100% penetration efficiency. The microneedle array also demonstrated excellent (<i>P</i> > 0.05) flexibility and structural stability. Ex-vivo release studies showed that 88.51% of the CNBL was released over 48 h, following a first-order kinetic model. The <i>n</i> value of 0.51 for Korsmeyer-Peppas model indicate an anomalous transport mechanism, suggesting a combination of diffusion and erosion. The in-vivo pharmacokinetic evaluation in Wistar rats demonstrates that CNBL-MNs-2 exhibited a larger area under the curve (AUC₀–t) (61.57 ± 4.23 ng·h/mL) than the IP injection (37.04 ± 5.83 ng·h/mL), indicating significant (<i>p</i> > 0.05) increase in systemic availability and sustained release. The Cmax of CNBL-MNs-2 (6.10 ± 0.533 ng/mL) was comparable to that of the IP injection (6.20 ± 1.5 ng/mL), confirming efficient systemic absorption <i>via</i> the microneedle system. Additionally, Tmax was significantly (<i>p</i> > 0.05) prolonged with CNBL-MNs-2 (8 h) compared to the IP injection (2 h), suggesting a slower, more controlled CNBL release.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"27 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143892593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ali Fardoost, Koosha Karimi, Jaydeep Singh, Heneil Patel, Mehdi Javanmard
{"title":"Enhancing glaucoma care with smart contact lenses: An overview of recent developments","authors":"Ali Fardoost, Koosha Karimi, Jaydeep Singh, Heneil Patel, Mehdi Javanmard","doi":"10.1007/s10544-025-00740-7","DOIUrl":"10.1007/s10544-025-00740-7","url":null,"abstract":"<div><p>Glaucoma is a leading cause of irreversible blindness worldwide, affecting millions of individuals due to its progressive damage to the optic nerve, often caused by elevated intraocular pressure (IOP). Conventional methods of IOP monitoring, such as tonometry, provide sporadic and often inaccurate readings due to fluctuations throughout the day, leaving significant gaps in diagnosis and treatment. This review explores the transformative potential of smart contact lenses equipped with continuous IOP monitoring and therapeutic capabilities. These lenses integrate advanced materials such as graphene, nanogels, and magnetic oxide nanosheets alongside sophisticated biosensing and wireless communication systems. By offering continuous, real-time data, these lenses can detect subtle IOP fluctuations and provide immediate feedback to patients and clinicians. Moreover, drug-eluting capabilities embedded in these lenses present a groundbreaking approach to glaucoma therapy by improving medication adherence and providing controlled drug release directly to the eye. Beyond IOP management, these innovations also pave the way for monitoring biochemical markers and other ocular diseases. Challenges such as biocompatibility, long-term wearability, and affordability remain, but the integration of cutting-edge technologies in smart contact lenses signifies a paradigm shift in glaucoma care. These developments hold immense promise for advancing personalized medicine, improving patient outcomes, and mitigating the global burden of blindness.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"27 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10544-025-00740-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143852507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reddy Govindappagari Hemalatha, Manoharan Arun Kumar, Girish Shankar Mishra, MohanKumar N, Kamal Batcha Mohamed Ismail, Shanmugam Mahalingam, Junghwan Kim
{"title":"Design and Simulation of advanced boron-doped GaN cap layer on AlGaN/GaN MOSHEMTs for enhanced label-free biosensing applications","authors":"Reddy Govindappagari Hemalatha, Manoharan Arun Kumar, Girish Shankar Mishra, MohanKumar N, Kamal Batcha Mohamed Ismail, Shanmugam Mahalingam, Junghwan Kim","doi":"10.1007/s10544-025-00746-1","DOIUrl":"10.1007/s10544-025-00746-1","url":null,"abstract":"<div><p>This study focuses on the design and simulation of a biosensor based on HEMT technology, with a focus on a GaN/AlGaN MOSHEMT architecture with a cavity and a boron-doped GaN cap layer, for identifying label-free biological molecules. The inclusion of a boron-doped GaN cap layer in the AlGaN/GaN heterostructure facilitates E-mode operation. We examined the influence of neutral or label-free biomolecules on the electron concentration and device sensitivity. The Sentaurus TCAD device simulation tool was used to analyze the MOSHEMT structure. Our findings suggest that low dielectric biomolecules increase the drain current, whereas higher dielectric values decrease the drain current. We also evaluated the device performance across various cavity lengths (100 nm, 200 nm, 300 nm, and 400 nm). The AlGaN/GaN MOSHEMT provides excellent sensitivity and precision in biological detection. The proposed GaN cap layer MOSHEMT biosensor is designed to detect biomolecules such as Keratin, Zein, ChOx, Biotin, Streptavidin, and Urease. The addition of these biomolecules to the nanocavity significantly enhances the drain current, transconductance (g<sub>m</sub>), output conductance (g<sub>d</sub>), and sensitivity. The device demonstrates high sensitivity (~ 73%) under optimized parameters, making it suitable for precise label-free biosensing applications.</p></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"27 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143852506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"On-site analysis of cortisol in saliva based on microchannel lateral flow assay (mLFA) on polymer lab-on-a-chip (LOC)","authors":"V. Thiyagarajan Upaassana, Supreeth Setty, Heeyeong Jang, Sthitodhi Ghosh, Chong Ahn","doi":"10.1007/s10544-025-00733-6","DOIUrl":"10.1007/s10544-025-00733-6","url":null,"abstract":"<div><p>Unbound cortisol in saliva, detectable through non-invasive sampling, is widely recognized as a validated biomarker for the biochemical evaluation of common mental disorders such as chronic stress, depression, anxiety, and post-traumatic stress disorder (PTSD). In this work, we report a novel polymer lab-on-a-chip (LOC) for microfluidic lateral flow assay (mLFA) with on-chip dried reagents for the detection of unbound cortisol in saliva using a competitive immunoassay protocol. The new polymer microchannel lateral flow assay on lab-on-a-chip (mLFA-LOC), replicated using injection molding technology, are composed of sequentially connected microchannels for sample loading, detection antibody immobilization, flow delay, sensing spirals for test and control, and a capillary pump at the end. The competitive immunoassay of cortisol can be autonomously performed through the microchannels after sample loading of the filtered saliva, and the fluorescence signals emitted from the sensing spirals are detected and quantified by a custom-designed, portable fluorescence analyzer developed in this work. For the evaluation of cortisol assay, artificial saliva samples spiked with unbound cortisol were analyzed using mLFA-LOC and the portable analyzer. The performed competitive assay of unbound cortisol showed a limit of detection (LoD) of 1.8 ng/mL and an inter-chip coefficient of variation (CV) of 4.0%, which covers the clinical range for on-site unbound salivary cortisol analysis. The newly developed mLFA-LOC platform certainly works successfully for the rapid on-site sampling and analysis of salivary biomarkers.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":490,"journal":{"name":"Biomedical Microdevices","volume":"27 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10544-025-00733-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143809106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}