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This article presents a novel plasmonic sensing platform designed for the detection of low molecular weight molecules, offering significant advancements in diagnostic applications. The platform features a periodic array of gold nanodisks on a 20 nm thin silica layer, supported by a 100 nm thick gold substrate. By leveraging the coupling between localized and propagating surface plasmon resonances, this design significantly enhances the sensitivity and specificity of molecular detection. Finite element method simulations are conducted to characterize the optical properties and reflectance response of the nanodisks array in the visible to near‐infrared range. Ellipsometric analysis is performed to measure the reflectance of the sample at various angles. Additionally, scanning near‐field optical microscopy in reflectance mode validates the design by revealing well‐defined plasmonic hot spots and interference patterns consistent with the simulated results. The findings demonstrate the platform's effectiveness in amplifying optical signals, achieving a limit of detection of 50 μM for molecules with a molecular weight of less than 1 KDa. This high sensitivity and specificity highlight the potential of the proposed plasmonic platform to advance the development of highly sensitive sensors for low molecular weight molecules, making it a valuable tool for diagnostics and precise molecular detection. [ABSTRACT FROM AUTHOR]

Dielectrophoresis (DEP) cell separation technology is an effective means of separating target cells which are only marginally present in a wide variety of cells. To develop highly efficient cell separation devices, detailed analysis of the nonuniform electric field's intensity distribution within the device is needed, as it affects separation performance. Here we analytically expressed the distributions of the electric field and DEP force in a parallel-plate cell separation DEP device by employing electrostatic analysis through the Fourier series method. The solution was approximated by extrapolating a novel approximate equation as a boundary condition for the potential between adjacent fingers of interdigitated electrodes and changing the underlying differential equation into a solvable form. The distributions of the potential and electric fields obtained by the analytical solution were compared with those from numerical simulations using finite element method software to verify their accuracy. As a result, it was found that the two agreed well, and the analytical solution was obtained with good accuracy. Three-dimensional fluorescence imaging analysis was performed using live non-tumorigenic human mammary (MCF10A) cells. The distribution of cell clusters adsorbed on the interdigitated electrodes was compared with the analytically obtained distribution of the DEP force, and the mechanism underlying cell adsorption on the electrode surface was discussed. Furthermore, parametric analysis using the width and spacing of these electrodes as variables revealed that spacing is crucial for determining DEP force. The results suggested that for cell separation devices using interdigitated electrodes, optimization by adjusting electrode spacing could significantly enhance device performance. [ABSTRACT FROM AUTHOR]

Chronic lymphocytic leukemia (CLL), the most common type of leukemia, remains incurable with conventional therapy. Despite advances in therapies targeting Bruton's tyrosine kinase and anti-apoptotic protein BCL-2, little is known about their effect on red blood cell (RBC) aggregation in blood flow. In this study, we applied a microfluidic device and a newly developed Software Image Flow Analysis to assess the extent of RBC aggregation in CLL patients and to elucidate the hemorheological effects of the commonly applied therapeutics Obinutuzumab/Venetoclax and Ibrutinib. The results revealed that, in RBC samples from untreated CLL patients, complex 3D clusters of large RBC aggregates are formed, and their number is significantly increased compared to healthy control samples. The application of the Obinutuzumab/Venetoclax combination did not affect this aspect of RBCs' rheological behavior. In contrast, targeted therapy with Ibrutinib preserves the aggregation state of CLL RBCs to levels seen in healthy controls, demonstrating that Ibrutinib mitigates the alterations in the rheological properties of RBCs associated with CLL. Our findings highlight the alterations in RBC aggregation in CLL and the impact of different targeted therapies on RBCs' rheological properties, which is critical for predicting the potential complications and side effects of CLL treatments, particularly concerning blood flow dynamics. [ABSTRACT FROM AUTHOR]

Abstract Organoids are stem cell-derived three-dimensional tissue cultures composed of multiple cell types that recapitulate the morphology and functions of their in vivo counterparts. Organ-on-a-chip devices are tiny chips with interconnected wells and channels designed using a perfusion system and microfluidics to precisely mimic the in vivo physiology and mechanical forces experienced by cells in the body. These techniques have recently been used to reproduce the structure and function of organs in vitro and are expected to be promising alternatives for animal experiments in the future. In the present study, we designed and fabricated an organ-on-a-chip system for mounting organoids from mammary tumor-affected cats (FMT organoids) and normal intestinal organoids from mice (MI organoids) and perfused them with anti-cancer drugs. The effects of drug perfusion on FMT and MI organoids were examined by measuring cell viability and performing genetic analysis. After 48 h of perfusion with toceranib (10 µM) or doxorubicin (1 µM), cell viability of FMT organoids was decreased compared to the non-perfusion condition. The expression of apoptosis-related genes, such as p53 and Caspase-9 was significantly upregulated in FMT organoids with drug perfusion. The rate of cell death drastically differed before and after branching in the device, owing to differences in flow velocity and drug infiltration. Perfusion of MI organoids with toceranib also reduced viability, as observed in FMT organoids; however, this was due to the induction of necrosis rather than apoptosis. In conclusion, our established multi-organoid-on-chip system could be used to evaluate anti-cancer drug sensitivity and side effects in vitro, which might contribute to developing personalized medicine for cancer patients.

Tissue on a chip or organ-on-chip (OOC) is a technology that's dignified to form a transformation in drug discovery through the use of advanced platforms. These are 3D in-vitro cell culture models that mimic micro-environment of human organs or tissues on artificial microstructures built on a portable microfluidic chip without involving sacrificial humans or animals.This review article aims to offer readers a thorough and insightful understanding of technology. It begins with an in-depth understanding of chip design and instrumentation, underlining its pivotal role and the imperative need for its development in the modern scientific landscape. The review article explores into the myriad applications of OOC technology, showcasing its transformative impact on fields such as radiobiology, drug discovery and screening, and its pioneering use in space research. In addition to highlighting these diverse applications, the article provides a critical analysis of the current challenges that OOC technology faces. It examines both the biological and technical limitations that hinder its progress and efficacy and discusses the potential advancements and innovations that could drive the OOC technology forward. Through this comprehensive review, readers will gain a deep appreciation of the significance, capabilities, and evolving landscape of OOC technology.

The presented study demonstrates the capability of the template-based electrokinetic assembly (TEA) and guidance to manipulate and capture individual biological cells within a microfluidic platform. Specifically, dielectrophoretic (DEP) focusing of K-562 cells towards lithographically-defined wells on the microelectrodes and positioning singles cells withing these wells was demonstrated. K-562 lymphoblast cells, are widely used in immunology research. The DEP guidance, particularly involving positive DEP (pDEP), enables the controlled guidance and positioning of conductive and dielectric particles, including biological cells, opening new directions for the accurate and efficient microassembly of biological entities, which is crucial for single cell analysis and other applications in biotechnology. The investigation explores the use of glassy carbon and gold as electrode materials. It was established previously that undiluted physiological buffer is unsuitable for inducing positive DEP (pDEP); therefore, the change of media into a lower ionic concentration is necessary. After pDEP was observed, the cells are resubmerged in the Iscoves modified Dulbeccos medium (IMEM), a cell culturing media, and incubated. A dead/alive staining assay was performed on the cells to determine their survival in the diluted buffer for the period required to capture them. The staining assay confirmed the cells survival after being immersed in the diluted biological buffer necessary for electrokinetic handling. The results indicate the promise of the proposed electrokinetic bio-sorting technology for applications in tissue engineering, lab-on-a-chip devices, and organ-on-a-chip models, as well as contributing to the advancement of single cell analysis.

Abstract Inflammatory microenvironments often become acidic (pH

Background: Sperm DNA fragmentation is an important factor that affects male fertility. This study intends to evaluatethe impact of sperm DNA damage [single-strand breaks (SSB) and double-strand breaks (DSB)] on fertilisationand embryonic euploidy after intracytoplasmic sperm injection (ICSI). Of the different sperm selection techniques,the novel microfluidic sperm sorting (MSS) ZyMōt™ ICSI device reduces both SSB and DSB in semen samples. Thesecond objective is to study the impact of this MSS device on fertilisation and embryonic euploidy.Materials and Methods: This retrospective study included data from 167 ICSI treatments. The alkaline and neutralComet assays were used to analyse SSB and DSB, respectively. Analysis of fertilisation and embryo euploidy rateswas performed in four groups of patients with normal/altered SSB or DSB values. Density gradient centrifugation(DGC) and the ZyMōt™ ICSI MSS device were used for semen preparation.Results: Fertilisation rates in 167 ICSI cycles were higher when using sperm from patients with normal SSB values(70.84%) and patients with abnormal SSB whose samples were processed using the MSS device (69.71%) comparedto patients with abnormal SSB values using DGC (58.49%). Preimplantation genetic testing for aneuploidies (PGTA)revealed a higher embryo euploidy rate in patients with normal DSB values (60.00%) and patients with abnormalDSB whose samples were processed using the MSS device (44.59%) compared to patients with abnormal DSB valuesusing DGC (36.84%). When female age was considered, there were fewer euploid embryos in women ≥35 years ofage compared to younger women, independently of SSB and DSB. The number of euploid embryos increased whenthe MSS device was used.Conclusion: High SSB and DSB values in semen samples decreased fertilisation rates and embryonic euploidy, respectively.The ZyMōt™ ICSI device for semen preparation increased both rates, especially in couples that includedwomen

Abstract Engineered biological neural networks are indispensable models for investigation of neural function and dysfunction from the subcellular to the network level. Notably, advanced neuroengineering approaches are of significant interest for their potential to replicate the topological and functional organization of brain networks. In this study, we reverse engineered feedforward neural networks of primary cortical and hippocampal neurons, using a custom-designed multinodal microfluidic device with Tesla valve inspired microtunnels. By interfacing this device with nanoporous microelectrodes, we show that the reverse engineered multinodal neural networks exhibit capacity for both segregated and integrated functional activity, mimicking brain network dynamics. To advocate the broader applicability of our model system, we induced localized perturbations with amyloid beta to study the impact of pathology on network functionality. Additionally, we demonstrate long-term culturing of subregion- and layer specific neurons extracted from the entorhinal cortex and hippocampus of adult Alzheimer’s-model mice and rats. Our results thus highlight the potential of our approach for reverse engineering of anatomically relevant multinodal neural networks to study dynamic structure-function relationships in both healthy and pathological conditions.

Hydrogel‐based microchannels with biologically similar morphologies and properties can provide excellent platforms for advanced tissue/organ formation in vitro. However, there are still many restrictions on channel morphology, material selection, tubing connections, etc. Here, a novel and versatile method is proposed that couples cononsolvency photopolymerization, which enables the incorporation of porous structures into hydrogels, with on‐chip microchannels formed by buckling of a thin film. This method provides a hydrogel‐based microchannel with improved permeability while maintaining its mechanical properties by incorporating a continuous porous structure into a synthetic polymer network with excellent mechanical properties. Furthermore, by culturing vascular endothelial cells into the microchannel, it is demonstrated that the microchannel works as a vessel‐on‐a‐chip platform that can be used for the evaluation of barrier function, fabrication of various channel shapes, and development of co‐culture systems. This method, which can be adapted to various swellable hydrogels, can provide platforms with properties and functions tailored to the tissue/organ and, thus, it will contribute to the creation of physiologically relevant biological models. [ABSTRACT FROM AUTHOR]

The incidence of stroke is on the rise globally. This affects one in every four individuals each year, underscoring the urgent need for early warning and prevention systems. The existing research highlights the significance of monitoring blood viscosity in stroke risk evaluations. However, the current methods lack the precision to measure viscosity under low shear rate conditions (<100 s⁻¹), which are observed during pulsatility flow. This study addresses this gap by introducing a novel microfluidic platform designed to measure blood viscosity with high precision under pulsatility flow conditions. The systolic blood viscosity (SBV) and diastolic blood viscosity (DBV) can be differentiated and evaluated by using this system. The non-Newtonian behavior of blood is captured across specific shear rate conditions. The platform employs a meticulously designed microarray to simulate the variations in blood viscosity during pulsation within blood vessels.The results demonstrate an impressive accuracy of 95% and excellent reproducibility when compared to traditional viscometers and rheometers and are within the human blood viscosity range of 1–10 cP. This monitoring system holds promise as a valuable addition to stroke risk evaluation methods, with the potential to enhance prediction accuracy. [ABSTRACT FROM AUTHOR]

A microfluidic chip is introduced for generating double emulsion droplets, consisting of a coaxial focusing center structure combined with a flow-focusing structure. The volume of fluid method (VOF) was adopted to numerically simulate and validate the formation of double emulsion droplets in the device. The impact of microfluidics on the dimensions and molding position of double emulsion droplets was examined under varying flow parameters and physical properties. Results demonstrate that the impact of the alteration in the flow rate of the middle phase is pivotal in the droplet generation process in comparison to the outer phase. An increase in the flow rate of the middle phase results in a notable enlargement of the double emulsion droplets. An increase in viscosity affects the forming regime, causing a transition in the droplet regime. Furthermore, interfacial tension exerts a notable impact on the positioning of droplet formation. The microfluidic device outlined in this paper effectively generates double emulsion droplets characterized by high monodispersity and excellent stability, which serves as a new reference for the practical generation of double emulsion droplets. [ABSTRACT FROM AUTHOR]

Conventional testing of novel contrast agents for magnetic resonance imaging (MRI) involves cell and animal studies. However, 2D cultures lack dynamic flow and in vivo MRI is limited by regulatory approval of long‐term anesthesia use. Microfluidic tumor models (MTMs) offer a cost‐effective, reproducible, and high throughput platform for bridging cell and animal models. Yet, MRI of microfluidic devices is challenging, due to small fluid volumes generating low sensitivity. For the first time, an MRI of MTMs was performed at low field strength (1 T) using conventional imaging equipment without microcoils. To enable longitudinal MRI, we developed (1) CHAMP‐3 (controlled heating apparatus for microfluidics and portability) which heats MTMs during MRI scans and (2) an MRI‐compatible temperature monitoring system. CHAMP‐3 maintained chip surface temperature at ~37°C and the media inside at ~35.5°C. Enhanced T1‐weighted MRI contrast was achieved in 3D MTMs with free manganese (Mn2+) solutions and Mn2+ labeled tumor cells. [ABSTRACT FROM AUTHOR]

Safe and healthy food is the fundamental right of every citizen. Problems caused by foodborne pathogens have always raised a threat to food safety and human health. Centers for Disease Control and Prevention (CDC) estimates that around 48 million people are affected by food intoxication, and 3000 people succumb to death. Hence, it is inevitable that an approach that is efficient, reliable, sensitive, and rapid approach that can replace the conventional analytical methods such as microbiological and biochemical methods, high throughput next-generation sequence (NGS), polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay (ELISA), etc. Even though the accuracy of conventional methods is high, it is tedious; increased consumption of reagents/samples, false positives, and complex operations are the drawbacks of these methods. Microfluidic devices have shown remarkable advances in all branches of science. They serve as an alternative to conventional ways to overcome the abovementioned drawbacks. Furthermore, coupling microfluidics can improve the efficiency and accuracy of conventional methods such as surface plasma resonance, loop-mediated isothermal amplification, ELISA, and PCR. This article reviewed the progress of microfluidic devices in the last ten years in detecting foodborne pathogens. Microfluidic technology has opened the research gateway for developing low-cost, on-site, portable, and rapid assay devices. The article includes the application of microfluidic-based devices to identify critical food pathogens and briefly discusses the necessary research in this area. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is one of the deadliest malignant tumors. Despite significant advances in RCC treatment over the past decade, complete remission is rarely achieved. Consequently, there is an urgent need to explore and develop new therapies to improve the survival rates and quality of life for patients. In recent years, the development of tumor organoid technology has attracted widespread attention as it can more accurately simulate the spatial structure and physiological characteristics of tumors within the human body. In this review, we summarize the main methods currently used to construct kidney cancer organoids, as well as their various biological and clinical applications. Furthermore, combining organoids with other technologies, such as co-culture techniques and microfluidic technologies, can further develop organoids and address their limitations, creating more practical models. This approach summarizes the interactions between different tissues or organs during tumor progression. Finally, we also provide an outlook on the construction and application of kidney cancer organoids. These rapidly evolving kidney cancer organoids may soon become a focal point in the development of in vitro clinical models and therapeutic research for kidney cancer. [ABSTRACT FROM AUTHOR]

Inflammatory microenvironments often become acidic (pH < 7.4) due to tissue oxygen deprivation and lactate release in glycolysis by activated immune cells. Although neutrophils are known to accumulate in such microenvironments, the effects of pH on their migration are not fully understood. Here, we first investigated the pH control around cultured cells with a microfluidic device, which was equipped with two gas channels above three parallel media channels. By supplying gas mixtures with predefined carbon dioxide (CO2) concentrations to the gas channels, the gas exchange adjusted the dissolved CO2 and affected the chemical equilibrium of sodium hydrogen carbonate in the cell culture medium. A pH gradient from 8.3 to 6.8 was generated along the media channels when gas mixtures containing 1% and 50% CO2 were supplied to the left and right gas channels, respectively. Neutrophil-like differentiated human promyelocytic leukemia cells (HL-60) were then seeded to the fibronectin-coated media channels and their migratory behaviors were quantified while varying the pH. The cell migration became more active and faster under high pH than under low pH conditions. However, no directional migration along the pH gradient was detected during the three-hour observation. Thus, the microfluidic device is useful to elucidate pH-dependent cellular dynamics. [ABSTRACT FROM AUTHOR]

Microfluid-derived liposomes (M-Lipo) exhibit great potential as drug and functional substance carriers in pharmaceutical and food science. However, the low liposome membrane stability, attributed to the liquid core, limits their application range. Oleosin, a natural surfactant protein, can improve the stability of the lipid nanoparticle membrane against various environmental stresses, such as heat, drying, and pH change; in addition, it can enable sustained drug release. Here, we proposed the fabrication of oleosin-coated M-Lipo (OM-Lipo) through self-assembly on a microfluidic chip and the evaluation of its anticancer drug (carmustine) delivery efficiency. Nanoparticle characterization revealed that the oleosin coating slightly lowered the membrane potential of M-Lipo and greatly improved their dispersibility. Additionally, the in vitro drug release profile showed that the oleosin coating improved the sustained release of the hydrophobic drug from the phospholipid bilayer in body temperature. Our results suggest that OM-Lipo has sufficient potential in various fields, based on its easy production, excellent stability, and biocompatibility. [ABSTRACT FROM AUTHOR]

Human norovirus (HuNoV) is recognized as the leading causative agent of foodborne outbreaks of epidemic gastroenteritis. Consequently, there is a high demand for developing point-of-care testing for HuNoV. We developed an origami microfluidic device that facilitates rapid detection of murine norovirus 1 (MNV-1), a surrogate for HuNoV, encompassing the entire process from sample preparation to result visualization. This process includes RNA absorption via a paper strip, RNA amplification using recombinase polymerase amplification (RPA), and a lateral flow assay for signal readout. The on-chip detection of MNV-1 was completed within 35 min, demonstrating 100% specificity to MNV-1 in our settings. The detection limit of this microfluidic device for MNV-1 was 200 PFU/mL, comparable to the in-tube RPA reaction. It also successfully detected MNV-1 in lettuce and raspberries at concentrations of 170 PFU/g and 230 PFU/g, respectively, without requiring extra concentration steps. This device demonstrates high compatibility with isothermal nucleic acid amplification and holds significant potential for detecting foodborne viruses in agri-food products in remote and resourcelimited settings. IMPORTANCE HuNoV belongs to the family of Caliciviridae and is a leading cause of acute gastroenteritis that can be transmitted through contaminated foods. HuNoV causes around one out of five cases of acute gastroenteritis that lead to diarrhea and vomiting, placing a substantial burden on the healthcare system worldwide. HuNoV outbreaks can occur when food is contaminated at the source (e.g., wild mussels exposed to polluted water), on farms (e.g., during crop cultivation, harvesting, or livestock handling), during packaging, or at catered events. The research outcomes of this study expand the approaches of HuNoV testing, adding value to the framework for routine testing of food products. This microfluidic device can facilitate the monitoring of HuNoV outbreaks, reduce the economic loss of the agri-food industry, and enhance food safety. [ABSTRACT FROM AUTHOR]

Background: In vitro maturation (IVM) is a promising technique in assisted reproductive technologies, offering benefits such as reducing the risk of ovarian hyperstimulation syndrome. Objective: This study aimed to evaluate the effects of timed follicular fluid meiosis-activating sterol (FF-MAS) supplementation on the IVM of germinal vesicle oocytes using a dynamic microfluidic system. Materials and Methods: In this lab trial study, 266 germinal vesicle oocytes were collected from the Infertility Center of Fatemieh hospital, Hamedan, Iran between June 2023 and January 2024. The oocytes were allocated into 3 groups for dynamic microfluidic culture. Each group received culture medium at a flow rate of 0.36 µL/min for 24 hr through inlet A and FF-MAS supplementation through inlet B for 1, 2, and 6 hr. The study evaluated maturation and fertilization rates, embryo development, and mitochondrial status, which was assessed using the JC-1 mitochondrial membrane potential assay. Results: Maturation rates were significantly higher in the medium-term FF-MAS exposure (MTG) and long-term FF-MAS exposure groups compared to the short-term FF-MAS group (STG) (p < 0.05). Fertilization rates were also higher in the MTG and long-term FF-MAS group compared to the STG (p <0.05). Embryo formation rates and the proportion of good-quality embryos were higher in the MTG compared to the STG (100% vs. 75%; p = 0.03) and (83.3% vs. 33.3%; p = 0.01), respectively. Mitochondrial peripheral distribution was significantly higher in the MTG than in the STG (p = 0.04). Conclusion: Optimizing FF-MAS exposure duration enhances IVM efficiency, offering a promising strategy to increase oocyte utilization in in vitro fertilization programs. [ABSTRACT FROM AUTHOR]

Background: Sperm DNA fragmentation is an important factor that affects male fertility. This study intends to evaluate the impact of sperm DNA damage [single-strand breaks (SSB) and double-strand breaks (DSB)] on fertilisation and embryonic euploidy after intracytoplasmic sperm injection (ICSI). Of the different sperm selection techniques, the novel microfluidic sperm sorting (MSS) ZyMōt™ ICSI device reduces both SSB and DSB in semen samples. The second objective is to study the impact of this MSS device on fertilisation and embryonic euploidy. Materials and Methods: This retrospective study included data from 167 ICSI treatments. The alkaline and neutral Comet assays were used to analyse SSB and DSB, respectively. Analysis of fertilisation and embryo euploidy rates was performed in four groups of patients with normal/altered SSB or DSB values. Density gradient centrifugation (DGC) and the ZyMōt™ ICSI MSS device were used for semen preparation. Results: Fertilisation rates in 167 ICSI cycles were higher when using sperm from patients with normal SSB values (70.84%) and patients with abnormal SSB whose samples were processed using the MSS device (69.71%) compared to patients with abnormal SSB values using DGC (58.49%). Preimplantation genetic testing for aneuploidies (PGT-A) revealed a higher embryo euploidy rate in patients with normal DSB values (60.00%) and patients with abnormal DSB whose samples were processed using the MSS device (44.59%) compared to patients with abnormal DSB values using DGC (36.84%). When female age was considered, there were fewer euploid embryos in women ≥35 years of age compared to younger women, independently of SSB and DSB. The number of euploid embryos increased when the MSS device was used. Conclusion: High SSB and DSB values in semen samples decreased fertilisation rates and embryonic euploidy, respectively. The ZyMōt™ ICSI device for semen preparation increased both rates, especially in couples that included women <35 years old. [ABSTRACT FROM AUTHOR]

Microfluidics are crucial for managing small-volume analytical solutions for various applications, such as disease diagnostics, drug efficacy testing, chemical analysis, and water quality monitoring. The precise control of flow control devices can generate diverse flow patterns using pneumatic control with solenoid valves and a microcontroller. This system enables the active modulation of the pneumatic pressure through Arduino programming of the solenoid valves connected to the pressure source. Additionally, the incorporation of solenoid valve sets allows for multichannel control, enabling simultaneous creation and manipulation of various microflows at a low cost. The proposed microfluidic flow controller facilitates accurate flow regulation, especially through periodic flow modulation beneficial for droplet generation and continuous production of microdroplets of different sizes. Overall, we expect the proposed microfluidic flow controller to drive innovative advancements in technology and medicine owing to its engineering precision and versatility. [ABSTRACT FROM AUTHOR]

Abstract Background The prognostic value of circulating tumor cells (CTCs) in metastatic breast cancer (MBC) has been extensively studied and verified by the CellSearch® system. Varieties of microfluidic systems have been developed to improve capture efficiency with the lack of standardization and automation. This study systematically verified the positive threshold for prognosis and its guidance value in anti-HER2 therapy based on a novel automated microfluidic system OmiCell®. Methods CTCs isolation, enumeration and labeling were performed using the OmiCell® system. CTCs identification and reporting were performed using the DeepSight® scanning system. Results The capture efficiency and specificity of OmiCell® system was 91.9% and 90%, respectively. Then, 65 MBC patients with known HER2 status of their metastatic tumors were enrolled. In the cohort, we detected ≥ 1 CTCs in 59 patients (90.8%, range: 1–55 CTCs, median = 6),

Microplastics have emerged as ubiquitous contaminants, attracting increasing global attention. Recent evidence confirms the presence of microplastics in human blood, suggesting their potential to interact with cells and induce adverse physiological reactions in various organs as blood circulates. To quantify the distribution of microplastics and assess their potential effects on human health, the effective separation of microplastics from blood is crucial. However, current methods for separating microplastics from blood are limited in effectiveness and simplicity. This study proposes a microfluidic device that utilizes traveling surface acoustic waves to separate microplastics from blood. While traveling surface acoustic waves have been employed to separate various particles, a systematic study on the separation of microplastics from blood samples has not been previously reported. Specifically, the theoretical values of the acoustic radiation factor for various types of microplastics and blood cells were investigated. The significant differences in resonant frequencies indicated the feasibility of separating microplastics of different sizes and types from blood cells. Experimental validation was performed using a polydimethylsiloxane microfluidic device on a piezoelectric lithium niobate substrate. The device successfully separated 5- and 10-micrometer polystyrene microplastics from blood samples. The effects of power and flow rate on separation efficiency were also systematically investigated. This study provides a novel approach for the effective separation of microplastics from blood, contributing to the assessment of their distribution and potential health impacts.

Glioblastoma multiforme (GBM) is the most severe form of brain cancer in adults, characterized by its complex vascular network that contributes to resistance to conventional therapies. Thermal therapies, such as magnetic hyperthermia (MHT), emerge as promising alternatives, using heat to selectively target tumor cells while minimizing damage to healthy tissues. The organ-on-a-chip can replicate this complex vascular network of GBM, allowing for detailed investigations of heat dissipation in MHT, while computational simulations refine treatment parameters. In this in silico study, tumor-on-a-chip models were used to optimize MHT therapy by comparing heat dissipation in normal and abnormal vascular networks, considering geometries, flow rates, and concentrations of magnetic nanoparticles (MNPs). In the high vascular complexity model, the maximum velocity was 19 times lower than in the normal vasculature model and 4 times lower than in the low-complexity tumor model, highlighting the influence of vascular complexity on velocity and temperature distribution. The MHT simulation showed greater heat intensity in the central region, with a flow rate of 1 µL/min and 0.5 mg/mL of MNPs being the best conditions to achieve the therapeutic temperature. The complex vasculature model had the lowest heat dissipation, reaching 44.15 °C, compared to 42.01 °C in the low-complexity model and 37.80 °C in the normal model. These results show that greater vascular complexity improves heat retention, making it essential to consider this heterogeneity to optimize MHT treatment. Therefore, for an efficient MHT process, it is necessary to simulate ideal blood flow and MNP conditions to ensure heat retention at the tumor site, considering its irregular vascularization and heat dissipation for effective destruction. [ABSTRACT FROM AUTHOR]

In recent years, many researchers have proposed biohybrid systems that integrate biological materials, especially cells or cultured tissues formed by in vitro cell culture, and microdevices to utilize the functions of cultured cellular tissues in an engineering way. In this paper, we focus on microphysiological systems composed of microfluidic channels or microdevices and cells or cultured tissues and introduce the functional characteristics of these microphysiological systems. In the microphysiological system, we can adjust cell culture conditions under mechanical stress control and bring out the dynamic performance of the cultured tissue. The systems can be applied not only to drug development to replace laboratory animals, but also to the development of advanced robots with cellular functions. Therefore, we believe that the biohybrid systems are a promising technology to apply cells and cultured tissues in various fields. [ABSTRACT FROM AUTHOR]

The high prevalence of diabetes requires simple, continuous, and accurate monitoring of glucose level for diabetic patients in daily life. Recent researches have been geared toward flexible and wearable sensors to realize non-invasive detection and continuous glucose monitoring from body fluids, such as sweat, saliva, and tears. This review mainly summarizes the recent development of textile-based glucose sensors using silk, cotton, and synthetic polymers and fabrics as substrates and discusses their fabrication processes and working mechanism. In particular, the characteristics of these textile-based glucose sensors are analyzed and the sensing performances are compared. Based on this review, the challenges and prospects of textile-based glucose sensors are also proposed. Although the textile-based glucose sensors still have some problems, they show great application potential, which also presents new challenges and development directions for the application of the textiles. [ABSTRACT FROM AUTHOR]

Microplastics have emerged as ubiquitous contaminants, attracting increasing global attention. Recent evidence confirms the presence of microplastics in human blood, suggesting their potential to interact with cells and induce adverse physiological reactions in various organs as blood circulates. To quantify the distribution of microplastics and assess their potential effects on human health, the effective separation of microplastics from blood is crucial. However, current methods for separating microplastics from blood are limited in effectiveness and simplicity. This study proposes a microfluidic device that utilizes traveling surface acoustic waves to separate microplastics from blood. While traveling surface acoustic waves have been employed to separate various particles, a systematic study on the separation of microplastics from blood samples has not been previously reported. Specifically, the theoretical values of the acoustic radiation factor for various types of microplastics and blood cells were investigated. The significant differences in resonant frequencies indicated the feasibility of separating microplastics of different sizes and types from blood cells. Experimental validation was performed using a polydimethylsiloxane microfluidic device on a piezoelectric lithium niobate substrate. The device successfully separated 5- and 10-micrometer polystyrene microplastics from blood samples. The effects of power and flow rate on separation efficiency were also systematically investigated. This study provides a novel approach for the effective separation of microplastics from blood, contributing to the assessment of their distribution and potential health impacts. [ABSTRACT FROM AUTHOR]

Among human CD8+ T cells, senescent cells are marked by the expression of CD57. The frequency of senescent CD57+CD8+ T cells is significantly correlated with aging and age-associated disorders, and it can be measured by multi-color flow cytometry. However, multi-color flow cytometry presents challenges in terms of accessibility and requires significant resource allocation. Therefore, developing a rapid and straightforward method for quantifying CD57+CD8+ T cells remains a key challenge. This study introduces a microfluidic device composed of a PDMS microfluidic channel with a pre-modified glass substrate for anti-CD8 antibody immobilization. This design allows blood samples to flow through, enabling the selective capture of CD8+ T cells while minimizing the required blood sample volume. This technology enables accurate and reliable quantification of CD57+ cells among captured CD8+ T cells through fluorescence image analysis. The ability of the device to easily quantify senescent CD57+CD8+ T cells is anticipated to contribute significantly to both immunological research and clinical applications. [ABSTRACT FROM AUTHOR]

Background: The prognostic value of circulating tumor cells (CTCs) in metastatic breast cancer (MBC) has been extensively studied and verified by the CellSearch® system. Varieties of microfluidic systems have been developed to improve capture efficiency with the lack of standardization and automation. This study systematically verified the positive threshold for prognosis and its guidance value in anti-HER2 therapy based on a novel automated microfluidic system OmiCell®. Methods: CTCs isolation, enumeration and labeling were performed using the OmiCell® system. CTCs identification and reporting were performed using the DeepSight® scanning system. Results: The capture efficiency and specificity of OmiCell® system was 91.9% and 90%, respectively. Then, 65 MBC patients with known HER2 status of their metastatic tumors were enrolled. In the cohort, we detected ≥ 1 CTCs in 59 patients (90.8%, range: 1–55 CTCs, median = 6), < 8 CTCs in 45 (69.2%) and ≥ 8 CTCs in 20 (30.8%) patients at baseline. The patients with < 8 CTCs had longer PFS than ≥ 8 CTCs (median, 7 vs. 4.4 months, p = 0.028). CTC enumeration was found to be an independent prognostic factor in our cohort. Moreover, we found a weak concordance between tissue HER2 (tHER2) status and the corresponding CTCs (k = 0.16, p = 0.266). The patients with tHER2 positive and cHER2 negative had better PFS compared with patients with both tHER2 and cHER2 positive (median, 8.2 vs. 3.3 months, p = 0.022). Conclusions: This clinical study shows the prognosis value of a new threshold of CTC number and meanwhile the guidance value of cHER2 status in anti-HER2 therapy. [ABSTRACT FROM AUTHOR]

Although methods for generating human induced pluripotent stem cell (hiPSC)-derived motor nerve organoids are well established, those for sensory nerve organoids are not. Therefore, this study investigated the feasibility of generating sensory nerve organoids composed of hiPSC-derived sensory neurons using a microfluidic approach. Notably, sensory neuronal axons from neurospheres containing 100,000 cells were unidirectionally elongated to form sensory nerve organoids over 6 mm long axon bundles within 14 days using I-shaped microchannels in microfluidic devices composed of polydimethylsiloxane (PDMS) chips and glass substrates. Additionally, the organoids were successfully cultured for more than 60 days by exchanging the culture medium. The percentage of nuclei located in the distal part of the axon bundles (the region 3−6 mm from the entrance of the microchannel) compared to the total number of cells in the neurosphere was 0.005% for live cells and 0.008% for dead cells. Molecular characterization confirmed the presence of the sensory neuron marker ISL LIM homeobox 1 (ISL1) and the capsaicin receptor transient receptor potential vanilloid 1 (TRPV1). Moreover, capsaicin stimulation activated TRPV1 in organoids, as evidenced by significant calcium ion influx. Conclusively, this study demonstrated the feasibility of long-term organoid culture and the potential applications of sensory nerve organoids in bioengineered nociceptive sensors. [ABSTRACT FROM AUTHOR]

Radioimmunoconjugates (RICs) composed of tumor‐targeting monoclonal antibodies and radionuclides have been developed for diagnostic and therapeutic application. A new radiolabeling method using microfluidic devices is expected to facilitate simpler and more rapid synthesis of RICs. In the microfluidic method, microfluidic chips can promote the reaction between reactants by mixing them efficiently, and pumping systems enable automated synthesis. In this study, we synthesized RICs by the pre‐labeling method, in which the radiometal is coordinated to the chelator and then the radiolabeled chelator is incorporated into the antibodies, using microfluidic devices for the first time. As a result of examining the reaction parameters including the material of mixing units, reaction temperature, and flow rate, RICs with radiochemical purity (RCP) exceeding 90% were obtained. These high‐purity RICs were successfully synthesized without any purification simply by pumping three solutions of a chelating agent, radiometal, and antibody into microfluidic devices. Under the same conditions, the RCP of RICs labeled by conventional methods was below 50%. These findings indicate the utility of microfluidic devices for automatic and rapid synthesis of high‐quality RICs. [ABSTRACT FROM AUTHOR]

In order to extract pure cell populations from multiple cell populations or to extract the required components from complex samples, a novel regulation method of induced‑charge electro‑osmotic (ICEO) is proposed, based on the superposition effect of dual electric fields, to study the remodeling mechanism of the ICEO vortex and its particle control performance. Firstly, a multi‑physical coupling simulation model is established and the asymmetric evolution mechanism is studied. Secondly, the particle control device is designed and processed, and the particle control experimental system is built. Then, the aggregation and longitudinal migration characteristics of single particle induced by asymmetrically ICEO vortices at different voltages are studied. Finally, aggregation and separation characteristics of various particles within the asymmetric ICEO vortices are explored. The results show that this method can achieve the aggregation, migration and separation of micro‑scale particles in a simple control way, and it has great application potential in the field of environmental detection and disease diagnosis. [ABSTRACT FROM AUTHOR]

The aim of this study was to prepare, characterize and evaluate liposomes co-encapsulated with curcumin and quercetin using a droplet-based microfluidic device. Curcumin and quercetin co-encapsulated liposomes made of phosphatidylcholine and cholesterol were synthesized using a droplet-based microfluidic device with different flow rate ratios of 9:1, 6:1, 3:1 and 1:1 of the aqueous to organic phase at 100 to 160 µl/min flow rate. The dynamic light scattering technique showed that 9:1 and 6:1 flow rate ratios at 140 and 160 µl/min flow rates, respectively provide desired particle size range of 200–250 nm and 0.17–0.23 polydispersity index. The greatest encapsulation and loading efficiency achieved for curcumin and quercetin was 68 ± 9.2%, 14 ± 1.8%, and 36 ± 2.7%, 7.2 ± 0.5%, respectively with 6:1 flow rate ratio. Cell uptake studies performed on human oral carcinoma cells, FaDu using confocal laser scanning microscopy showed that the liposomes were taken up within 2 h. Clathrin and caveolin-mediated pathways contribute to the cell uptake of liposomes. The FaDu cell viability was reduced to 49 ± 2.2, 69 ± 1.5 and 47 ± 3.5% after incubation with liposomes containing curcumin (80 µM), quercetin (86 µM) and combination (32 µM of curcumin and 26 µM of quercetin), respectively. Apoptosis assay showed that the combination liposomes inhibit FaDu cell growth through apoptosis induced cell death. In conclusion, co-encapsulated liposomes can be prepared by microfluidics-based method and curcumin and quercetin combination liposomes are effective against oral carcinoma. [ABSTRACT FROM AUTHOR]

Microbubble-mediated sonothrombolysis has been proven to be a non-invasive and efficient method for thrombolysis. Nevertheless, there is a potential risk that the thrombus debris generated during the dissolution of the original thrombus are too large and can lead to hazardous emboli. Using a sonothrombolysis microfluidic platform, we investigated the effects of ultrasound power, thrombolytic agent and microbubble concentration on the size of thrombus debris with the example of microbubble-mediated sonothrombolysis of arterial thrombus. Additionally, we studied the effects of ultrasound power on the size and shape of thrombus debris produced by acute and chronic arterial sonothrombolysis. In acute arterial sonothrombolysis, ultrasound power has significant effect on the size of thrombus debris and steadily increases with the increase of ultrasound power. Conversely, in chronic arterial sonothrombolysis, the size of thrombus debris is minimally affected by ultrasound power. Using the sonothrombolysis microfluidic platform, the relationship between ultrasound power and the safety of sonothrombolysis has been illustrated, and the sonothrombolysis microfluidic platform is demonstrated to be a promising tool for further studies on the process of sonothrombolysis. Highlights: The effect of ultrasound power on the size and morphological characteristics of thrombus debris was studied in a microfluidic device. The sonothrombolysis process of acute and chronic arterial thrombosis is emphasized. The mechanical action of ultrasound and the biochemical action of thrombolytic agents are matched in different ways, resulting in debris of different composition and size. This study may also help to implement safer thrombolysis strategies. [ABSTRACT FROM AUTHOR]

Microfluidic systems have become integral for lab‐on‐a‐chip and organ‐on‐a‐chip applications across numerous disciplines. These systems, typically fabricated using polydimethylsiloxane (PDMS) chips on glass substrates, lack the bioactivity required for such applications. To overcome this, biomolecules are immobilized using either oxygen (O2) plasma treatment or chemical reagents like amino silanes. However, O2 plasma treatments are unstable and cannot covalently immobilize biomolecules, while wet‐chemistry approaches are toxic, time‐consuming, and expensive. A novel microfluidic platform that combines two plasma surface treatments: Plasma‐activated coating (PAC) and atmospheric pressure plasma jet (APPJ), to enable reagent‐free covalent immobilization of biomolecules is described here. These surface treatments, unlike O2 plasma, covalently immobilized fibronectin on PDMS and glass, and significantly improved endothelial cell attachment and proliferation. By combining PAC and APPJ, a hybrid microfluidic platform with equivalent bond strength to standard O2 plasma devices, but with significantly enhanced endothelial cell growth in and artery‐on‐a‐chip model, is developed. This platform is also amenable to high‐shear applications such as coronary shear, with endothelial cells aligning with flow, as seen in human arteries. By providing reagent‐free covalent immobilization of biomolecules within a microfluidic system, this technology has the potential to radically improve organ‐on‐a‐chip development as well as lab‐on‐a‐chip systems, point‐of‐care diagnostics, and sensors. [ABSTRACT FROM AUTHOR]

We propose a nucleic acids dilution-induced assembly (NADIA) method for the preparation of lipid nanoparticles. In the conventional method, water-soluble polymers such as nucleic acids and proteins are mixed in the aqueous phase. In contrast, the NADIA method, in which self-assembly is triggered upon dilution, requires dispersion in an alcohol phase without precipitation. We then investigated several alcohols and discovered that propylene glycol combined with sodium chloride enabled the dispersion of plasmid DNA and protamine sulfate in the alcohol phase. The streamlined characteristics of the NADIA method enable the preparation of extracellular vesicles-mimicking lipid nanoparticles (ELNPs). Among the mixing methods using a micropipette, a syringe pump, and a microfluidic device, the lattermost was the best for decreasing batch-to-batch differences in size, polydispersity index, and transfection efficiency in HepG2 cells. Although ELNPs possessed negative ζ-potentials and did not have surface antigens, their transfection efficiency was comparable to that of cationic lipoplexes. We observed that lipid raft-mediated endocytosis and macropinocytosis contributed to the transfection of ELNPs. Our strategy may overcome the hurdles linked to supply and quality owing to the low abundance and heterogeneity in cell-based extracellular vesicles production, making it a reliable and scalable method for the pharmaceutical manufacture of such complex formulations. [ABSTRACT FROM AUTHOR]