{"title":"Acoustic manipulations of droplets with high-speed automatic route planning and navigation","authors":"Shuchang Liu, Luyao Li, Shuying Wang, Bohan Liang, Hao Zhang, Weiwei Cui","doi":"10.1007/s10404-025-02830-7","DOIUrl":"10.1007/s10404-025-02830-7","url":null,"abstract":"<div><p>The development of digital microfluidics has inspired significant advancements in diverse applications such as virus detection, molecular hybridization, and chemical reactions. The capabilities of digital microfluidics, taking Electrowetting-on-Dielectric (EWOD) for example, are precise handling and detecting targets based on the fundamental manipulations such as transportation, merging, mixing, and splitting of droplets. However, digital microfluidic systems suffer from complex electrode layouts, poor dynamic performance, and low-efficiency droplet manipulation. To address these limitations, we present a digital microfluidic system with enhanced dynamic properties using unidirectional emission surface acoustic waves. Surface acoustic wave device with resonance frequency of 300 MHz has been carefully designed with an acoustic reflector next to one end driving path from the other end, which is demonstrated as long as 600 times the wavelength for droplet transportation. By arranging the SAW array, the system enables precise and high-speed droplet transportation within a large programmed area. A smart platform is developed to automatically program and control droplets with preplanned routes. The SAW droplet manipulation system has shown excellent performance in high speed, ultra-long pathways, and automatic navigation, greatly promoting the acoustic manipulation advancements for biomedical research and chemical engineering.</p></div>","PeriodicalId":706,"journal":{"name":"Microfluidics and Nanofluidics","volume":"29 8","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145164539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Using dimensionless numbers to understand interfacial mass transfer for parallel flow in a microchannel","authors":"Anand Sudha, Martin Rohde","doi":"10.1007/s10404-025-02828-1","DOIUrl":"10.1007/s10404-025-02828-1","url":null,"abstract":"<div><p>Liquid-liquid Extraction has emerged as a major technique for radioisotope extraction in recent years. This technique is particularly advantageous in the microscale as the surface-volume ratio is much larger. Since some of these radioisotopes have short half-lives, parallel flow in the microscale is used to extract them as it eliminates the need for separating the two fluids. Though such a configuration has been experimentally studied, dimensionless numbers have not been employed to understand the mass transfer mechanisms. This study uses three dimensionless numbers—the Biot, Peclet and Damkohler numbers—to delve deeper into mass transfer with a chemical reaction at the interface. Mass transfer simulations are performed using a Finite Difference model to solve the 2D Convection-Diffusion Equation with a first-order reaction at the interface, and these numbers are varied. The Damkohler number was observed to have the maximal impact on the extraction efficiency, and this was confirmed to be the case when the extraction efficiency didn’t change much as long as the Damkohler number was kept constant. In general, a higher Damkohler number results in a higher extraction efficiency and a correlation was proposed to quantify this influence.</p></div>","PeriodicalId":706,"journal":{"name":"Microfluidics and Nanofluidics","volume":"29 8","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12241239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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":"Optimization techniques in digital microfluidic biochips: a survey of sample preparation algorithmic solutions and challenges","authors":"Nirmala Natarajan, Gracia Nirmala Rani Duraisamy","doi":"10.1007/s10404-025-02829-0","DOIUrl":"10.1007/s10404-025-02829-0","url":null,"abstract":"<div><p>Digital Micro Fluidic Biochips (DMFBs) are a revolutionary way to automate biochemical processes which are accurate, handy, and multifunctional. However, limitations in droplet manipulation, resource allocation, and assay execution continue to serve as considerable obstacles to effective sample preparation. Using electrical actuation techniques, these biochips accurately automate fluid sample analysis, simplifying essential laboratory tasks including cleaning, mixing, separating, and merging. Solutions with a predetermined target volume can be generated due to this technique. This process consists of combining various solutions of chemicals in a specified volume ratio by carrying out a different procedure. By using these methods, DMFBs can perform tests with little use of sample or reagent, opening up possibilities for use in drug research, gene sequencing, DNA analysis, medical diagnostics, and other fields. An extensive overview of optimization methods used for sample preparation in DMFBs is given in this paper, with an emphasis on algorithmic solutions that improve scheduling, dilution, and mixing. We categorize and evaluate current methods according to their computational methodologies and trade-offs between performance and adaptation to various biochip layouts. We also look at important issues, including real-time reconfiguration and waste droplet management. Lastly, we explore future research prospects in developing digital microfluidic biochip technologies and emphasize the suggested sample preparation scheduling method. The purpose of this survey is to assist researchers in creating DMFB sample preparation techniques that are more dependable and effective.</p></div>","PeriodicalId":706,"journal":{"name":"Microfluidics and Nanofluidics","volume":"29 8","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145163474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fiona Sze Nee Lye, Yan Shan Loo, Intan Diana Mat Azmi, Choy Sin Lee, N. Idayu Zahid, Thiagarajan Madheswaran
{"title":"Microfluidic-enabled nanomedicine: a comprehensive review of recent advances and translational potential","authors":"Fiona Sze Nee Lye, Yan Shan Loo, Intan Diana Mat Azmi, Choy Sin Lee, N. Idayu Zahid, Thiagarajan Madheswaran","doi":"10.1007/s10404-025-02826-3","DOIUrl":"10.1007/s10404-025-02826-3","url":null,"abstract":"<div><p>Microfluidic technology is designed for the liquid handling and manipulation of fluids and materials at a small scale. This technology offers distinct advantages that address the limitations of conventional methods such as precision control, reproducibility, efficiency, and rapid processing. These advantages signify a paradigm shift in the field of biomedical and pharmaceutical research, particularly in the preparation of nanomedicines. This review briefly introduces microfluidics along with its principles and fundamentals, including the key components, different types of microfluidic mixing mechanisms, and materials used in microfluidic devices. It also comprises a detailed discussion of the benefits and challenges of using microfluidics in preparing nanoformulations (such as lipid-based, polymer-based, inorganic-based, and hybrid-based) and biomedical applications. This review also discusses the advancement of microfluidic and nanomedicine preparation, such as modular microfluidics, digital microfluidics, three-dimensional (3D) printed chips, automated microfluidics, artificial intelligence (AI), and healthcare wearable devices (HWDs). The review concludes by encouraging cooperation between multiple parties for the success of nanomedicine and offering better patient care to the public.</p></div>","PeriodicalId":706,"journal":{"name":"Microfluidics and Nanofluidics","volume":"29 8","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145161425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abraham Ochoa-Guerrero, Luis F. Olguín, Eugenia Corvera-Poiré
{"title":"Evaluation of dynamical-billiard-shaped chambers as divergent elements of passive micromixers","authors":"Abraham Ochoa-Guerrero, Luis F. Olguín, Eugenia Corvera-Poiré","doi":"10.1007/s10404-025-02817-4","DOIUrl":"10.1007/s10404-025-02817-4","url":null,"abstract":"<div><p>Efficient mixing of fluid streams in microfluidic devices remains a critical challenge due to the dominance of laminar flow, where mixing relies solely on diffusion. To overcome this limitation, various microfluidic mixers have been developed to transition from laminar to non-laminar regimes, enabling faster mixing rates. Passive micromixers utilize geometric channel designs instead of external energy sources, making them advantageous due to their simplicity. Among these, convergent-divergent micromixers employ alternating narrow and wide channels to stretch and fold fluid streams, enhancing the mixing process. This study explores a novel series of microfluidic mixers based on dynamical-billiard-shaped chambers. Each microfluidic mixer comprises twenty consecutive nanoliter billiard-shaped chambers connected by relatively narrow channels of equal or variable lengths. Six chamber designs were analyzed: three chaotic billiard shapes (Bunimovich-stadium, diamond-shape, and Sinai-billiard) and their respective non-chaotic counterparts (ellipse, triangle, and ring). Two spatial arrangements—<i>out-of-axis</i> and <i>on-axis</i> chambers—were tested to evaluate their impact on mixing efficiency. Key findings reveal that an <i>out-of-axis</i> chamber configuration significantly enhances mixing, as does connectors with varying lengths. Orientation of the initial chamber at a 36° angle further improves performance. However, chaotic chambers did not consistently outperform non-chaotic ones, likely due to limitations in flow rates. Comparisons with a previously reported baffled structure, considered an excellent micromixer, showed improved mixing efficiency using both chaotic and non-chaotic chambers. These results provide valuable insights into passive mixing mechanisms, contributing to the design of more efficient microfluidic mixers adaptable to specific experimental conditions.</p></div>","PeriodicalId":706,"journal":{"name":"Microfluidics and Nanofluidics","volume":"29 8","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10404-025-02817-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145161704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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":"Matrix-free microfluidic 3D biomimetic chip for identifying type I collagen on doxorubicin treated MDA-MB-231 cell","authors":"Qian Wu, Shuxuan Jin, Shiqi Chang, Shuang Xu, Zhiping Xu, Shaojiang Zeng, Xiaohua Huang, Huipeng Ma","doi":"10.1007/s10404-025-02827-2","DOIUrl":"10.1007/s10404-025-02827-2","url":null,"abstract":"<div><p>The development of drug resistance in breast cancer cells posed significant challenges that necessitate overcoming. Traditional two-dimensional cell research models failed to replicate the tumor microenvironment (TME) in vivo, thus necessitating the utilization of three-dimensional cell culture models for anti-cancer drug research. In this study, we utilized a matrix-free microfluidic three-dimensional (3D) biomimetic chip to generate uniformly sized and highly viable tumor cell spheroids, setting it apart from conventional matrix-based spheroid models. Simultaneously, these cell spheroids were accurately retrieved and embedded within type I collagen to establish the TME environment and further investigate the mechanism by which type I collagen influences doxorubicin resistance in breast cancer cells. The research findings demonstrated that type I collagen enhanced the doxorubicin resistance in breast cancer cells by upregulating the expression levels of Bcl-2, Bcl-XL, and MRP1 proteins. Additionally, the up-regulation of MRP1 is mediated through the ERK1/2 signaling pathway. In conclusion, we posited that this microfluidic biomimetic chip offered a novel and sophisticated platform for three-dimensional tumor research. This platform was expected to facilitate a more comprehensive elucidation of the pharmacokinetic properties of tumor cells within the extracellular matrix (ECM) in future studies, thereby enhancing the efficiency and accuracy of in vitro drug screening.</p></div>","PeriodicalId":706,"journal":{"name":"Microfluidics and Nanofluidics","volume":"29 8","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145171328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Investigating the binding strength between subtypes red blood cells and their corresponding antibodies and rapidly differentiating subtypes in a microchannel","authors":"Ding-Ping Chen, Yi-Jin Ho, Hsieh-Fu Tsai, Fan-Chun Cheng, Feng-Yu Jiang, Yen-Heng Lin","doi":"10.1007/s10404-025-02823-6","DOIUrl":"10.1007/s10404-025-02823-6","url":null,"abstract":"<div><p>Identifying blood type is a routine procedure for blood transfusion, typically performed using forward and reverse typing methods. However, distinguishing blood subtypes remains a challenging task in clinical practice. This study proposes a novel approach to rapidly differentiate blood subtypes based on the distinct binding strengths between red blood cells (RBCs) and antibodies immobilized on a micro-channel surface. Different blood subtypes can be distinguished by measuring the ratio of RBCs before and after applying a shear force with a wash buffer. Experimental results demonstrate residual ratios of approximately 99.5%, 31.8–39.8%, 7.4–7.6%, and 10.0–11.1% for B, B<sub>3</sub> (including AB<sub>3</sub>), B<sub>el</sub>, and A<sub>el</sub> types, respectively. Notably, this method makes it possible to differentiate subtypes with minimal surface antigens, such as B<sub>el</sub> and A<sub>el</sub>, within 15 min—significantly faster and less complex than the conventional adsorption–elution method used in clinical settings. This proposed approach offers a promising solution for rapidly differentiating rare blood subtypes.</p></div>","PeriodicalId":706,"journal":{"name":"Microfluidics and Nanofluidics","volume":"29 7","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145168356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Free-standing open space microfluidic devices by dry resist lamination","authors":"Rui Liu, Esteban Pedrueza-Villalmanzo, Farah Fatima, Aldo Jesorka","doi":"10.1007/s10404-025-02818-3","DOIUrl":"10.1007/s10404-025-02818-3","url":null,"abstract":"<div><p>We present a cleanroom-compatible fabrication route to open space microfluidic devices, utilizing a multilayer lamination/photolithography process on the wafer scale. The devices were applied to generate and maintain molecular surfactant films. In a dedicated setup, film stability was investigated in conjunction with 108 kHz ultrasonic sound, and response to acoustic waves in the audible range was determined.</p></div>","PeriodicalId":706,"journal":{"name":"Microfluidics and Nanofluidics","volume":"29 7","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10404-025-02818-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145168355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hongwei Guan, Jian Feng, Qingyi Cai, Yi Yang, Chao Liu, Duo Sun, Jienan Shen, Hongpeng Zhang, Lin Zeng, Hui Yang
{"title":"On-chip inductive sensor for ultra-high-throughput integrated detection of oil contamination and viscosity","authors":"Hongwei Guan, Jian Feng, Qingyi Cai, Yi Yang, Chao Liu, Duo Sun, Jienan Shen, Hongpeng Zhang, Lin Zeng, Hui Yang","doi":"10.1007/s10404-025-02824-5","DOIUrl":"10.1007/s10404-025-02824-5","url":null,"abstract":"<div><p>A novel on-chip inductive detection sensor has been developed, offering a new method for analyzing contaminants and viscosity in hydraulic oil. An ultra-high-throughput microchannel with a rectangular cross-section has been designed, along with a dual-core coil resonant method to generate a large-scale magnetic field with high sensitivity on the chip. The inductive sensing unit consists of two symmetrically arranged rectangular magnetic core coils, creating a detection area with a high magnetic field strength. A rectangular microchannel with a cross-sectional area of up to 6 mm<sup>2</sup> passes between the two magnetic core coils. Compared to traditional micro-inductive sensors, the throughput increased by nearly 2 orders of magnitude, reaching 120 mL/h. Using the microchannel and resonance measurement method, we successfully detected 30 μm iron particles and 80 μm copper particles. Furthermore, we have established a model that correlates oil viscosity with its transit time through the microchannel. Through the inductance signal, we can determine the time it takes for the oil to pass through the coils and subsequently calculate its viscosity using our theoretical model. This method allows for the integration of inductive detection and viscosity measurement without the need for additional sensor. In the experiment, we measured hydraulic oils of different viscosities and compared the results with measurements obtained using a viscometer to verify the accuracy of the viscosity measurements. </p></div>","PeriodicalId":706,"journal":{"name":"Microfluidics and Nanofluidics","volume":"29 7","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145167632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Microstrip line-based microfluidic sensors for glucose monitoring using microwave approach: a review","authors":"Ying Qing Lua, Chia Chao Kang, Wendy Wai Yeng Yeo, Zi-Neng Ng, Jian Ding Tan, Mohammadmahdi Ariannejad","doi":"10.1007/s10404-025-02822-7","DOIUrl":"10.1007/s10404-025-02822-7","url":null,"abstract":"<div><p>Glucose monitoring is critical for diabetes management, yet traditional invasive methods remain fraught with discomfort and logistical challenges. Recent advancements in microwave-based microstrip line sensors offer a transformative alternative, leveraging electromagnetic interactions with biological tissues to detect glucose-induced dielectric changes non-invasively. This review examines the evolution of microstrip line-based sensors, emphasizing their design principles, operational mechanisms, and clinical applicability. Current challenges, such as environmental interference, tissue heterogeneity, and signal stability, hinder widespread adoption. Among the diverse technologies evaluated, resonator-based sensors, particularly split-ring (SRR) and swastika-shaped geometries that demonstrate superior performance due to their multi-parameter sensing capabilities, high sensitivity (e.g., 148.367 Ω/(mg/mL)), and compact design. These sensors integrate reflection coefficient phase, magnitude, and impedance measurements, enhancing robustness against noise and biological variability. While metamaterial and implantable antennas show promise, their limitations in scalability or biocompatibility underscore the practicality of resonator-based systems. Future efforts must prioritize clinical validation and integration with machine learning to address individual variability. In conclusion, resonator-based microstrip sensors represent the most viable path toward reliable, continuous glucose monitoring, combining innovation with practicality to redefine diabetes care.</p></div>","PeriodicalId":706,"journal":{"name":"Microfluidics and Nanofluidics","volume":"29 7","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145166915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}