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Pathogenic bacteria are commonly found in food, water, and soil, posing significant public health challenges globally. Therefore, early, rapid, and highly sensitive strategies for monitoring the bacterial proliferation are crucial for ensuring public health, medical diagnosis, and food safety. Compared to traditional techniques, microfluidic platforms provide powerful detective tools characterized by high integration, high throughput, ease of operation, low reagent consumption, and high sensitivity. Driven by substantial commercial demand, research and development in microfluidic‐based rapid detection methods and technologies has progressed significantly derived by the interdisciplinary integration of multiple disciplines. In this review, progress in clinical detection of pathogenic bacteria with microfluidic biosensors, including microfluidic devices for point‐of‐care (POC) testing, is summarized. Strategies for pathogenic bacteria detection, containing their advantages and disadvantages are discussed in detail. Advanced platforms for capturing and detecting pathogenic bacteria, such as microchannels, microarrays, digital microfluidics (DMF) and paper‐based platforms, are highlighted. The accomplishments and shortcomings of these microfluidic devices are also summarized. Additionally, case studies of biosensor‑based microfluidic devices used for detecting diseases caused by bacterial imbalances are listed. Finally, possible research perspectives for further development in highly effective biosensor‑based microfluidics for clinical detection of pathogenic bacteria are proposed. [ABSTRACT FROM AUTHOR]

This study presents a novel microspectrometer-integrated microfluidic system for real-time protein concentration monitoring. The device employs electrokinetic principles for efficient protein preconcentration in a PDMS and Nafion film channel. Using FITC-labeled BSA as a model protein, the system demonstrated a linear correlation between protein concentration and absorbance at 491 nm. Notably, it achieved a 833-fold concentration increase from an initial 10 nM within 20 min. The compact microspectrometer system offers enhanced accuracy and sensitivity compared to traditional fluorescence microscopy methods. This innovation presents a promising solution for portable and point-of-care diagnostic applications, facilitating timely disease detection and monitoring. The findings highlight the potential for this technology to advance protein analysis and biomarker discovery in clinical settings, potentially improving patient outcomes through enhanced diagnostic capabilities. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is a malignant cancer affecting the brain. As per the WHO classifications, it is a grade IV glioma and is characterized by heterogenous histopathology, high recurrence rates, and a high median age of diagnosis. Most individuals diagnosed with GBM are aged between 50 and 64 years, and the prognosis is often poor. Untreated GBM patients have a median survival of 3 months, while treatments with Temozolomide (TMZ) and radiotherapy can improve the survival to 10–14 months. Tumor recurrence is common, owing to the inefficiency of surgical resection in removing microscopic tumor formations in the brain. A crucial component of GBM-related research is understanding the tumor microenvironment (TME) and its characteristics. The various cellular interactions in the TME contribute to the higher occurrence of malignancy, resistance to treatments, and difficulty in tumor resection and preventative care. Incomplete pictures of the TME have been obtained in 2D cultures, which fail to incorporate the ECM and other crucial components. Identifying the hallmarks of the TME and developing ex vivo and in vitro models can help study patient-specific symptoms, assess challenges, and develop courses of treatment in a timely manner which is more efficient than the current methods. Microfluidic models, which incorporate 3D cultures and co-culture models with various channel patterns, are capable of stimulating tumor conditions accurately and provide better responses to therapeutics as would be seen in the patient. This facilitates a more refined understanding of the potential treatment delivery systems, resistance mechanisms, and metastatic pathways. This review collates information on the application of such microfluidics-based systems to analyze the GBM TME and highlights the use of such systems in improving patient care and treatment options.

Cellular heterogeneity plays a significant role in understanding biological processes, such as cell cycle and disease progression. Microfluidics has emerged as a versatile tool for manipulating single cells and analyzing their heterogeneity with the merits of precise fluid control, small sample consumption, easy integration, and high throughput. Specifically, integrating microfluidics with electrical techniques provides a rapid, label-free, and non-invasive way to investigate cellular heterogeneity at the single-cell level. Here, we review the recent development of microfluidic-based electrical strategies for single-cell manipulation and analysis, including dielectrophoresis- and electroporation-based single-cell manipulation, impedance- and AC electrokinetic-based methods, and electrochemical-based single-cell detection methods. Finally, the challenges and future perspectives of the microfluidic-based electrical techniques for single-cell analysis are proposed. [ABSTRACT FROM AUTHOR]

The advent of single-molecule techniques has spurred rapid advancements in enzymology, revealing the individual behaviors of enzymes that are obscured by ensemble averages. Traditional enzyme evaluation methods, often based on Fluorescence Resonance Energy Transfer (FRET) technology, provide average-level information through platforms like enzyme-linked instruments, which do not allow for single-molecule rate assessments. In this research, we introduce a digital single-molecule enzymatic kinetics evaluation method based on a custom microfluidic biochip. By optimizing the reagent system and conducting kinetic studies at various template concentrations, we can assess the rate changes of individual phi29 DNA polymerases within tens of thousands of microwells using fluorescence intensity variations during Rolling Circle Amplification (RCA) reactions. This method, which also includes statistical distribution analysis, enhances the conformational kinetics research of phi29 DNA polymerase and offers new insights for single-molecule studies of other proteases or nucleases, with potential applications in real-time single-molecule sequencing and drug screening. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is a malignant cancer affecting the brain. As per the WHO classifications, it is a grade IV glioma and is characterized by heterogenous histopathology, high recurrence rates, and a high median age of diagnosis. Most individuals diagnosed with GBM are aged between 50 and 64 years, and the prognosis is often poor. Untreated GBM patients have a median survival of 3 months, while treatments with Temozolomide (TMZ) and radiotherapy can improve the survival to 10–14 months. Tumor recurrence is common, owing to the inefficiency of surgical resection in removing microscopic tumor formations in the brain. A crucial component of GBM-related research is understanding the tumor microenvironment (TME) and its characteristics. The various cellular interactions in the TME contribute to the higher occurrence of malignancy, resistance to treatments, and difficulty in tumor resection and preventative care. Incomplete pictures of the TME have been obtained in 2D cultures, which fail to incorporate the ECM and other crucial components. Identifying the hallmarks of the TME and developing ex vivo and in vitro models can help study patient-specific symptoms, assess challenges, and develop courses of treatment in a timely manner which is more efficient than the current methods. Microfluidic models, which incorporate 3D cultures and co-culture models with various channel patterns, are capable of stimulating tumor conditions accurately and provide better responses to therapeutics as would be seen in the patient. This facilitates a more refined understanding of the potential treatment delivery systems, resistance mechanisms, and metastatic pathways. This review collates information on the application of such microfluidics-based systems to analyze the GBM TME and highlights the use of such systems in improving patient care and treatment options. [ABSTRACT FROM AUTHOR]

Humidity sensors deeply influence human manufacturing production and daily life, while researchers generally focus on developing humidity sensors with higher stability, higher linearity, rapid response time, etc. Yet, few people discuss measuring humidity in the microenvironment by miniaturizing sensor size into a microscale, in which the existing humidity sensors are difficult to reach. Accordingly, this study proposes a methodology for measuring relative humidity in the microscale by utilizing the distinctive morphologies of Equisetum spores across a range of relative humidities between 50% and 90%. Equisetum spores are responsive to changes in ambient relative humidity and remain in their original activities even after iron sputtering, which aims to endow the sensor with magnetic properties. The test performed in this study demonstrated a response time of 3.3 s and a recovery time of 3.6 s. In the first application, we employed such microscale sensors to work in the channel of the microfluidic chip or the cell migration microchip, as an example of working in the microenvironment. COMSOL Multiphysics 6.2 software was also used to simulate the change in relative humidity in such microchannels. Secondly, such microscale sensors are combined with smartphone-based microscopy to measure the humidity of the skin. These microscale sensors pave the new way to sensing humidity in microenvironments. [ABSTRACT FROM AUTHOR]

The potential threat posed by disease outbreaks to diagnostic instruments demands the development of more effective biosensor technologies to counteract the risks. Diseases like SARS-CoV-2, Ebola, malaria, cholera, and many more have demonstrated beyond the limits of health care that new advancements are required for early detection and diagnosis. The rising number of diseases outbreaks has led to an increasing demand for biosensors that are more effective and quicker to utilize in healthcare settings. A biosensor incorporated with microfluidic chips offers an improved detection compared to traditional or classical biosensors. Microfluidic chips improve the performance of the biosensors by allowing automation, mixing, separation, throughput processing, and transport of the analytes to desired reactors. A biosensor incorporated with a microfluidic chip has improved sensitivity, easy operation and can use small volumes of samples to process the results. The effectiveness of biosensors depends also on the materials used in its fabrication and there are many materials used for fabrication which are reviewed in this work. This paper reviews the potential advantages of the use of microfluidic chips to enhance the performance of biosensors, materials used to fabricate the chips, and potential electrodes incorporated into microfluidic chips which improve the detection time by shortening the processing time for biosensors at the point of care service. This work also reviews new technologies which are not previously addressed other reviews including, integration of cell-imprinted polymers with microfluidic sensors and delved into future technologies outlook.Article Highlights: Highlight 1: This work reviews biosensors integrated with microfluidic chips. Highlight 2: The work reviews different materials used to fabricate microfluidic chips and their impact on biosensing. Highlight 3: The works also highlight the integration of electrodes into microfluidic chips to improve biosensor performance. [ABSTRACT FROM AUTHOR]

Tumor‐derived extracellular vesicles (EVs) have attracted tremendous interest as one of the early cancer diagnostic markers. The major obstacle preventing EV‐based liquid biopsy is the efficient collection of EVs from the complex body fluid environment. This paper introduces a nanorod‐integrated microfluidic chip capable of immunoaffinity‐isolating EVs. Periodic silicon nanorod arrays in zigzag channels are prepared by nanosphere lithography. Nanorod sidewalls provide larger binding sites for antibodies, and their close interspacing to the EV sizes improves the binding probability. The fluid simulation results show that the significant increase in isolation efficiency also comes from the liquid perturbation enhanced by the particular nanorod arrangement. Under optimal operating conditions, plasma samples from patients (n = 14) with different types of cancers (hepatocellular carcinoma, colorectal cancer, and pancreatic adenocarcinoma) to the chip for EV isolation is applied. In this proof‐of‐concept study, the expression level of the epidermal growth factor receptor (EGFR) in isolated EVs is then quantified using droplet digital PCR, showing good diagnostic performance in cancer detection. [ABSTRACT FROM AUTHOR]

Single‐cell multiomic and exosome analyses are potent tools in various fields, such as cancer research, immunology, neuroscience, microbiology, and drug development. They facilitate the in‐depth exploration of biological systems, providing insights into disease mechanisms and aiding in treatment. Single‐cell isolation, which is crucial for single‐cell analysis, ensures reliable cell isolation and quality control for further downstream analyses. Microfluidic chips are small lightweight systems that facilitate efficient and high‐throughput single‐cell isolation and real‐time single‐cell analysis on‐ or off‐chip. Therefore, most current single‐cell isolation and analysis technologies are based on the single‐cell microfluidic technology. This review offers comprehensive guidance to researchers across different fields on the selection of appropriate microfluidic chip technologies for single‐cell isolation and analysis. This review describes the design principles, separation mechanisms, chip characteristics, and cellular effects of various microfluidic chips available for single‐cell isolation. Moreover, this review highlights the implications of using this technology for subsequent analyses, including single‐cell multiomic and exosome analyses. Finally, the current challenges and future prospects of microfluidic chip technology are outlined for multiplex single‐cell isolation and multiomic and exosome analyses. [ABSTRACT FROM AUTHOR]

Thermal gradient‐driven fluid motion, also known as thermal convection, is a common and significant phenomenon in nature. The utilization of localized thermal gradients to induce convection has emerged as a competitive approach in microfluidic chips. This technique enables the long‐distance transportation of substances under the influence of low‐power lasers. In this paper, an innovative optofluidic micro‐platform is presented that possesses a simple structure, easy operation, and excellent expandability. A UV nanosecond laser is utilized to create a high photothermal conversion region (HPCR) within the carbon nanotube‐doped PDMS substrate. Subsequently, the HPCR is subjected to irradiation for generating localized thermal gradients in the microfluidic chip. This resulted in Rayleigh–Bernard convection formation and facilitated long‐range transport and control of fluids and particles. Under low‐power laser irradiation, particles can be transported at speeds up to 0.18 mm s−1. In addition, the optofluidic platform shows significant potential for a range of functionalities, including fluid mixing and material sorting. The methodology described here allows for the rapid integration of new functionalities into existing chips while maintaining cost effectiveness and efficiency. This technique holds great promise for expanding the use of microfluidic devices in diverse fields, including chemistry, health sciences, materials science, and biomedicine. [ABSTRACT FROM AUTHOR]

This study presents a novel microspectrometer-integrated microfluidic system for real-time protein concentration monitoring. The device employs electrokinetic principles for efficient protein preconcentration in a PDMS and Nafion film channel. Using FITC-labeled BSA as a model protein, the system demonstrated a linear correlation between protein concentration and absorbance at 491 nm. Notably, it achieved a 833-fold concentration increase from an initial 10 nM within 20 min. The compact microspectrometer system offers enhanced accuracy and sensitivity compared to traditional fluorescence microscopy methods. This innovation presents a promising solution for portable and point-of-care diagnostic applications, facilitating timely disease detection and monitoring. The findings highlight the potential for this technology to advance protein analysis and biomarker discovery in clinical settings, potentially improving patient outcomes through enhanced diagnostic capabilities.

Hepatocellular carcinoma (HCC) is a highly lethal malignant tumor, and the current non‐invasive diagnosis method based on serum markers, such as α‐fetoprotein (AFP), and des‐γ‐carboxy‐prothrombin (DCP), has limited efficacy in detecting it. Therefore, there is a critical need to develop novel biomarkers for HCC. Recent studies have highlighted the potential of exosomes as biomarkers. To enhance exosome enrichment, a silicon dioxide (SiO2) microsphere‐coated three‐dimensional (3D) hierarchical porous chip, named a SiO2‐chip is designed. The features of the chip, including its continuous porous 3D scaffold, large surface area, and nanopores between the SiO2 microspheres, synergistically improved the exosome capture efficiency. Exosomes from both non‐HCC and HCC subjects are enriched using an SiO2‐chip and performed RNA sequencing to identify HCC‐related long non‐coding RNAs (lncRNAs) in the exosomes. This study analysis reveales that LUCAT‐1 and EGFR‐AS‐1 are two HCC‐related lncRNAs. To further detect dual lncRNAs in exosomes, quantitative real time polymerase chain reaction (qRT‐PCR) is employed. The integration of dual lncRNAs with AFP and DCP significantly improves the diagnostic accuracy. Furthermore, the integration of dual lncRNAs with DCP effectively monitors the prognosis of patients with HCC and detects disease progression. In this study, a liquid biopsy‐based approach for noninvasive and reliable HCC detection is developed. [ABSTRACT FROM AUTHOR]

The intricate tapestry of biomarkers, including proteins, lipids, carbohydrates, vesicles, and nucleic acids within sweat, exhibits a profound correlation with the ones in the bloodstream. The facile extraction of samples from sweat glands has recently positioned sweat sampling at the forefront of non-invasive health monitoring and diagnostics. While extant platforms for sweat analysis exist, the imperative for portability, cost-effectiveness, ease of manufacture, and expeditious turnaround underscores the necessity for parameters that transcend conventional considerations. In this regard, 3D printed microfluidic devices emerge as promising systems, offering a harmonious fusion of attributes such as multifunctional integration, flexibility, biocompatibility, a controlled closed environment, and a minimal requisite analyte volume—features that leverage their prominence in the realm of sweat analysis. However, formidable challenges, including high throughput demands, chemical interactions intrinsic to the printing materials, size constraints, and durability concerns, beset the landscape of 3D printed microfluidic devices. Within this paradigm, we expound upon the foundational aspects of 3D printed microfluidic devices and proffer a distinctive perspective by delving into the computational study of printing materials utilizing density functional theory (DFT) and molecular dynamics (MD) methodologies. This multifaceted approach serves manifold purposes: (i) understanding the complexity of microfluidic systems, (ii) facilitating comprehensive analyses, (iii) saving both cost and time, (iv) improving design optimization, and (v) augmenting resolution. In a nutshell, the allure of 3D printing lies in its capacity for affordable and expeditious production, offering seamless integration of diverse components into microfluidic devices—a testament to their inherent utility in the domain of sweat analysis. The synergistic fusion of computational assessment methodologies with materials science not only optimizes analysis and production processes, but also expedites their widespread accessibility, ensuring continuous biomarker monitoring from sweat for end-users. [ABSTRACT FROM AUTHOR]

The intestine is the main site of oral drug absorption, and the epithelial cells of the intestine contain villi and microvilli, which promote secretion, cell adhesion, and absorption by increasing surface area and other factors. Traditional twodimensional/three-dimensional (2D/3D) cell culture models and animal models have played an important role in studying drug absorption, but their application is limited due to the lack of sufficient predictability of human pharmacokinetics or ethical issues, etc. Therefore, mimicking the core structure and key functions of the human intestine based on in vitro live cells has been the focus of research on constructing a microfluidic chip-based intestinal model. The model is a microfluidic chip bionic system that simulates the complex microstructure, microenvironment, and physiological functions of the human intestine using microfabrication technology. Compared with 2D cell culture and animal experiments, the intestinal microarray model can effectively simulate the human in vivo environment and is more specific in drug screening. The research progress and applications in disease modeling, drug absorption and transport of intestinal microarray models and intestine-related multi-organ coupled microarray models at home and abroad were reviewed in this paper. The current challenges of intestinal chip simulating intestinal homeostasis and diseases were summarized，in order to provide reference for the further establishment of a more reliable in vitro intestinal chip model. [ABSTRACT FROM AUTHOR]

Organ-on-a-chip (OOC) facilitates precise manipulation of fluids in microfluidic chips and simulation of the physiological, chemical, and mechanical characteristics of tissues, thus providing a promising tool for in vitro drug screening and physiological modeling. In recent decades, this technology has advanced rapidly because of the development of various three-dimensional (3D) printing techniques. 3D printing can not only fabricate microfluidic chips using materials such as resins and polydimethylsiloxane but also construct biomimetic tissues using bioinks such as cell-loaded hydrogels. In this review, recent advances in 3D-printing-based OOC are systematically summarized based on materials used for direct or indirect 3D printing of OOC, 3D printing techniques for the construction of OOC, and applications of 3D-printing-based OOC in models of the heart, blood vessels, intestines, liver, and kidney. Moreover, the paper outlines prospective vistas and hurdles within the field, intended to catalyze innovative use of 3D printing methodologies to propel OOC advancements.

Age-related macular degeneration(ARMD)is the primary cause of severe visual impairment and blindness in people over 60 years old. With the aging of the global population, the incidence of the disease is also rising year by year. However, the pathogenesis and treatment strategy of ARMD need to be further explored. As a cutting-edge science and technology, microfluidic chips can build a comprehensive microsystem that simulates the condition and function of human tissues and organs, which has the advantages of less sample consumption and short analysis time. In recent years, many studies have confirmed that microfluidic chips can bring brand new technology solutions to the basic and clinical research of ARMD. This article will discuss and review the application progress of microfluidic chips in the areas of ARMD mechanism research, drug evaluation and clinical translation, providing a theoretical reference for further research on the diagnosis and treatment of ARMD.

Persistent HPV infection is a major risk factor for the subsequent development of cervical cancer. LAMP is simple and suitable for field detection in the resource-limited settings. In this study, hydroxy naphthol blue (HNB)-based visual LAMP and evagreen-based fluorescent LAMP coupled with a microfluidic chip (LAMP-chip) were established for the field detection of seven subtypes of HPV. The analytical sensitivity was 19–233 copies/reaction. The overall clinical sensitivity was 97.35% for visual LAMP and 98.23% for LAMP-chip. Both LAMP assays exhibited 100% specificity and were completed in less than 50 min. Additionally, both assays did not require complicated nucleic acid extraction and purification steps. A complete quality control monitoring system (including internal control, positive quality control and negative control) in the LAMP assays further ensured the credibility of the results. Our findings demonstrated that the proposed LAMP assays have the potential to be applied in the testing of common HPV DNA in field investigations (visual LAMP) or within communities and primary health centers (LAMP-chip).

Humidity sensors deeply influence human manufacturing production and daily life, while researchers generally focus on developing humidity sensors with higher stability, higher linearity, rapid response time, etc. Yet, few people discuss measuring humidity in the microenvironment by miniaturizing sensor size into a microscale, in which the existing humidity sensors are difficult to reach. Accordingly, this study proposes a methodology for measuring relative humidity in the microscale by utilizing the distinctive morphologies of Equisetum spores across a range of relative humidities between 50% and 90%. Equisetum spores are responsive to changes in ambient relative humidity and remain in their original activities even after iron sputtering, which aims to endow the sensor with magnetic properties. The test performed in this study demonstrated a response time of 3.3 s and a recovery time of 3.6 s. In the first application, we employed such microscale sensors to work in the channel of the microfluidic chip or the cell migration microchip, as an example of working in the microenvironment. COMSOL Multiphysics 6.2 software was also used to simulate the change in relative humidity in such microchannels. Secondly, such microscale sensors are combined with smartphone-based microscopy to measure the humidity of the skin. These microscale sensors pave the new way to sensing humidity in microenvironments.

This paper presents the results of the full-scale verification and validation of the mathematical model and numerical algorithm for the network computation of a single-phase flow in a highly branched pipeline chain. The essential difference of this work from others is that highly branched hydraulic networks with homogeneous and non-uniform permeability, containing more than 70 thousand branches, are considered. Such branched networks are important in many applications. Therefore, the development of algorithms for calculating flows in such networks is very important. The network model is based on hydraulic theory, and the numerical algorithm relies on the network analogue of the well-known control volume method. At the same time, obtaining reliable experimental data for testing models for calculating very branched hydraulic networks is very difficult. In this work, microfluidic technologies are used to solve this problem. Data of laboratory experiments, obtained using microfluidic models of branched networks with homogeneous and heterogeneous permeability, containing several tens of thousands of branches, as well as CFD simulation results in full 3D formulation employing the fine computational grids were used to validate the model. The Reynolds number ranged from 0.81 to 13. Conducted validation has shown a good qualitative and quantitative concordance of the results of network and hydrodynamic simulation, as well as the data of the microfluidic experiments. The error in determining the total pressure drop in the branched hydraulic network with heterogeneous permeability, containing 37,855 nodes and 74,900 branches, did not exceed 5%. It has been demonstrated that the speed of solving a single-phase flow problem in a highly branched chain using network simulation techniques is 60 times more of magnitude higher as compared to CFD simulation at virtually the same accuracy.

High-quality bonding of microfluidic chips is essential for driving the rapid marketization of microfluidic devices. While thermocompression bonding is known for its simplicity, challenges such as high deformation and low bond strength persist. In this paper, we conducted micro-scale compression creep experiments to address the coexistence problem between low deformation and high bond strength during the thermocompression bonding process. Accurate creep models were constructed based on the experimental results, achieving an improved simulation accuracy of 95% for microchannel deformation in thermocompression bonding. Additionally, a finite element simulation model was developed to simulate microchannel deformation during the thermocompression process. To enhance bond strength and minimize microchannel deformation, we propose two methods: microchannel height compensation and cross-size microchannel coordination. Results demonstrate a remarkable 200% improvement in bond strength with reduced microchannel deformation under the same bonding conditions. The findings of this study offer valuable insights and serve as a process reference and design basis for enhancing the quality of microfluidic chip products.

The morphology of catalysts in microchannels plays a crucial role in the orbital maneuvering and networking applications of micro/nano satellites using hydrogen peroxide as a unit propellant. In this paper, a microfluidic reaction chip was designed and fabricated to detect the reaction rate of the catalytic decomposition of hydrogen peroxide solution by a microchannel catalytic bed. In addition, a silver thin film prepared by constant-current electroplating was used as a substrate for the microchannel catalyst. The results show that the ratio of surface area to area of silver film and the average particle size of silver particles have a significant positive correlation on the reaction rate of catalytic decomposition, while the thickness, silver content, and surface roughness of the silver film have no significant effect on the reaction rate of catalytic decomposition. The catalytic performance of the microchannel catalytic bed of silver thin film is greatly influenced by the conditions of electroplating, namely, the electroplating temperature (T), time (t), and current (I). And when I = 0.3 mA, t = 180 s, and T = 60 °C, the microchannel catalytic bed of the silver film prepared by electroplating reaches the optimal reaction rate for the catalytic decomposition of hydrogen peroxide solution. This study has the best process parameters for the design and optimization of heterogeneous catalysts applied to microfluidic reactors. [ABSTRACT FROM AUTHOR]

Microfluidic chips have shown their potential for applications in fields such as chemistry and biology, and 3D printing is increasingly utilized as the fabrication method for microfluidic chips. To address key issues such as the long printing time for conventional 3D printing of a single chip and the demand for rapid response in individualized microfluidic chip customization, we have optimized the use of DLP (digital light processing) technology, which offers faster printing speeds due to its surface exposure method. In this study, we specifically focused on developing a fast-manufacturing process for directly printing microfluidic chips, addressing the high cost of traditional microfabrication processes and the lengthy production times associated with other 3D printing methods for microfluidic chips. Based on the designed three-dimensional chip model, we utilized a DLP-based printer to directly print two-dimensional and three-dimensional microfluidic chips with photosensitive resin. To overcome the challenge of clogging in printing microchannels, we proposed a printing method that combined an open-channel design with transparent adhesive tape sealing. This method enables the rapid printing of microfluidic chips with complex and intricate microstructures. This research provides a crucial foundation for the development of microfluidic chips in biomedical research. [ABSTRACT FROM AUTHOR]

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Thermoplastic microfluidic chips show broad development prospects in biomedicine, point-of-care testing, healthcare, environmental monitoring, etc. However, improving the production efficiency of microfluidic chips remains a key industrial challenge to promote rapid popularization. In this work, we proposed a novel method for rapid and mass production of microfluidic chips based on a highly dynamic tempered in-mold thermocompression bonding (HD-IMTCB) process. The bonding temperature was tuned by a highly dynamic local variotherm technology based on thick film heaters. The results show that bonding temperature was the most significant factor for the bonding strength, and bonding time was the lowest one, which can be primarily optimized. With the bonding temperature reaching Vicat Softening Temperature and Glass Transition Temperature, the micro-channel deformation and bonding strength increased exponentially successively. The stable bonding strength reached 560–640 kPa with a microchannel deformation of less than 15%. The well-bonded thermoplastic microfluidic chips have been manufactured by the HD-IMTCB process from raw materials within 5 min, which not only improves the thermocompression bonding from a low-scale to a high-scale production model but also provides a blueprint for commercialization.

Abstract Chimeric antigen receptor (CAR) T cells are widely used to treat hematological tumors due to their powerful ability to target and kill cancer cells, of which accurate function evaluation at the single‐cell level is crucial to ensuring the efficacy of diagnosis and treatment. Currently, a universal platform to evaluate the efficacy of immune single cells rapidly, efficiently, and systematically is urgently needed. Here, the cytotoxicity, proliferative potential, and persistence of TIM3/CD28‐modified CD19 CAR‐T cells are evaluated in comparison with ordinary CD19 CAR‐T cells through high‐performance and throughput graphene oxide quantum dot (GOQD)‐based single‐cell microfluidic chips. Overall secretory factor expression, immune‐therapy effect of different effector‐target ratios, spatial immune‐therapy effects, and subgroup type profiling are demonstrated to explicit the immunotherapy effect of TIM3/CD28‐modified CD19 CAR‐T cells. TIM3/CD28‐modified CD19 CAR‐T cells show stronger anti‐tumor ability and maintain excellent immunotherapy effects even at low effector‐target ratios and remote distances. TIM3/CD28 also strengthens the local targeting ability of TIM3/CD28‐modified CD19 CAR‐T. Importantly, TIM3/CD28‐modified CD19 CAR‐T exhibits more distinct Th1/Th2 long‐term persistent and potent killer subgroups, which is very helpful for personalized therapy. Overall, this study provides a valuable approach that can be widely implemented to analyze current CAR‐T combinations and evaluate the function of innovative CAR treatments in the future.

The present work extends a previous paper where an agent-based and two-dimensional partial differential diffusion model was introduced for describing immune cell dynamics (leukocytes) in cancer-on-chip experiments. In the present work, new features are introduced for the dynamics of leukocytes and for their interactions with tumor cells, improving the adherence of the model to what is observed in laboratory experiments. Each system's solution realization is a family of biased random walk trajectories, affected by the chemotactic gradients and in turn affecting them. A sensitivity analysis with respect to the model parameters is performed in order to assess the effect of their variation on both tumor cells and on leukocyte dynamics. [ABSTRACT FROM AUTHOR]

Cancer is a fatal disease and a significant cause of millions of deaths. Traditional methods for cancer detection often have limitations in identifying the disease in its early stages, and they can be expensive and time-consuming. Since cancer typically lacks symptoms and is often only detected at advanced stages, it is crucial to use affordable technologies that can provide quick results at the point of care for early diagnosis. Biosensors that target specific biomarkers associated with different types of cancer offer an alternative diagnostic approach at the point of care. Recent advancements in manufacturing and design technologies have enabled the miniaturization and cost reduction of point-of-care devices, making them practical for diagnosing various cancer diseases. Furthermore, machine learning (ML) algorithms have been employed to analyze sensor data and extract valuable information through the use of statistical techniques. In this review paper, we provide details on how various machine learning algorithms contribute to the ongoing development of advanced data processing techniques for biosensors, which are continually emerging. We also provide information on the various technologies used in point-of-care cancer diagnostic biosensors, along with a comparison of the performance of different ML algorithms and sensing modalities in terms of classification accuracy. [ABSTRACT FROM AUTHOR]

(1) Background: Microfluidic chips have found extensive applications in multiple fields due to their excellent analytical performance. As an important platform for micro-mixing, the performance of micromixers has a significant impact on analysis accuracy and rate. However, existing micromixers with high mixing efficiency are accompanied by high pressure drop, which is not conducive to the integration of micro-reaction systems; (2) Methods: This paper proposed a novel "Tai Chi"-shaped planar passive micromixer with high efficiency and low pressure drop. The effect of different structural parameters was investigated, and an optimal structure was obtained. Simulations on the proposed micromixer and two other micromixers were carried out while mixing experiments on the proposed micromixer were performed. The experimental and simulation results were compared; (3) Results: The optimized values of the parameters were that the straight channel width w, ratio K of the outer and inner walls of the circular cavity, width ratio w1/w2 of the arc channel, and number N of mixing units were 200 μm, 2.9, 1/2, and 6, respectively. Moreover, the excellent performance of the proposed micromixer was verified when compared with the other two micromixers; (4) Conclusions: The mixing efficiency M at all Re studied was more than 50%, and at most Re, the M was nearly 100%. Moreover, the pressure drop was less than 18,000 Pa. [ABSTRACT FROM AUTHOR]

The microfluidic production of simple (microspheres) and core–shell (microcapsules) polymer microparticles, often called microencapsulation, has been the scope of several research works since the 1980s. It is a fast, thrifty, and efficient process because of its controlled properties, tuneability, and yield, which can reach 100%. However, the question of its greenness, sustainability, and scalability remains unclear, and more awareness/education is required in this field. The sustainability of production processes using microfluidic techniques can be realized/discussed based on three pillars: (i) waste generation, (ii) the solvents employed, and (iii) raw materials. On the other hand, although the scaling-up of these processes was reported on in several papers as procedures in which hundreds or thousands of microfluidic chips are set in parallel, the sustainability of this scale-up has not been addressed to our knowledge. This opinion paper highlights the advantages of microfluidic encapsulation processes, their greenness according to the above-mentioned pillars, (i–iii) and the necessary considerations to scale them up while preserving their sustainability. [ABSTRACT FROM AUTHOR]

In this study, the electrical conductivity of low‐volume samples was measured using a prototype microfluidic chip with electrodes. We were able to show the difference of electrical conductivity in the samples of saline solution (0.9w/v% NaCl solution) with sucrose. The correlation between the electrical conductivity and the viscosity evaluated by the capillary method was shown. This correlation was shown that it is possible to evaluate viscosity based on the Walden's rule with our chip. [ABSTRACT FROM AUTHOR]

Abstract Zinc oxide nanorods have been extensively studied for the specific killing of breast cancer (BC) cells, and their killing mechanism and anticancer effects have been initially demonstrated. However, systematic studies at the single‐cell level are still necessary to explore cellular functions in detail. In this work, a hydrothermal method was used to synthesize zinc oxide nanorod arrays (ZnO NRs). Their effect on BC cells was demonstrated at single‐cell resolution for the first time through microfluidic chips and a single‐cell analysis platform. The inhibitory effects of ZnO NRs were observed. First, ZnO NRs suppressed cell proliferation and migration abilities. Moreover, Interferon‐γ, Tumor Necrosis Factor‐α, and Granzyme B in BC cells turned out to be antitumor instead of tumorigenic under ZnO NRs stimulation. Furthermore, ZnO NRs inhibition altered cellular functions and thus weakened intercellular and intercluster correlations. More importantly, MDA‐MB‐231 cells (strongly metastatic) showed much greater resistance to ZnO NRs than MCF‐7 cells (nonmetastatic). The experiments complemented the findings at the single‐cell level and provided a more comprehensive consideration of the potential risks and applications of ZnO NRs in breast cancer therapy, which is of great importance for biomedical research on nanomaterials.

Tumor evolution is the accumulation of various tumor cell behaviors from tumorigenesis to tumor metastasis and is regulated by the tumor microenvironment (TME). However, the mechanism of solid tumor progression has not been completely elucidated, and thus, the development of tumor therapy is still limited. Recently, Tumor chips constructed by culturing tumor cells and stromal cells on microfluidic chips have demonstrated great potential in modeling solid tumors and visualizing tumor cell behaviors to exploit tumor progression. Herein, we review the methods of developing engineered solid tumors on microfluidic chips in terms of tumor types, cell resources and patterns, the extracellular matrix and the components of the TME, and summarize the recent advances of microfluidic chips in demonstrating tumor cell behaviors, including proliferation, epithelial-to-mesenchymal transition, migration, intravasation, extravasation and immune escape of tumor cells. We also outline the combination of tumor organoids and microfluidic chips to elaborate tumor organoid-on-a-chip platforms, as well as the practical limitations that must be overcome.

Monitoring the properties of fluids in microfluidic chips often requires complex open-space optics technology and expensive equipment. In this work, we introduce dual-parameter optical sensors with fiber tips into the microfluidic chip. Multiple sensors were distributed in each channel of the chip, which enabled the real-time monitoring of the concentration and temperature of the microfluidics. The temperature sensitivity and glucose concentration sensitivity could reach 314 pm/°C and −0.678 dB/(g/L), respectively. The hemispherical probe hardly affected the microfluidic flow field. The integrated technology combined the optical fiber sensor with the microfluidic chip and was low cost with high performance. Therefore, we believe that the proposed microfluidic chip integrated with the optical sensor is beneficial for drug discovery, pathological research and material science investigation. The integrated technology has great application potential for micro total analysis systems (μ-TAS). [ABSTRACT FROM AUTHOR]

Electrochemical surface‐enhanced Raman scattering (EC‐SERS) is a promising technique for the diagnosis of trace amounts of neurotransmitters, because it can elucidate neurotransmitters' behavior on electrodes to deduce their functions in the human body. However, the current EC‐SERS devices need several tens of milliliters of analyte solution to collect enough signal for analysis. Miniaturization of EC‐SERS devices is crucial for the early diagnosis of disease and point‐of‐care testing. Herein, a new type of EC‐SERS sensor based on 3D microfluidic chips for the analysis of neurotransmitters in ultrasmall volumes is proposed. The microfluidic EC‐SERS chip is fabricated by a ship‐in‐a‐bottle technique based on hybrid laser processing. The working electrode is modified using silver/zinc oxide materials, enabling the formation of a unique "candy apple" structure. To assess the fabricated microfluidic EC‐SERS chips, ascorbic acid is analyzed using the ingenious microfluidic EC‐SERS chips to elucidate its redox reaction by EC‐SERS spectroscopy. Significantly, a sub‐10 μL volume of analyte solution is sufficient for EC‐SERS analysis, which is several orders smaller in volume than the requirements of current EC‐SERS devices. The unprecedented microfluidic EC‐SERS chips fabricated by the ship‐in‐a‐bottle integration technique can be used in portable and smart analyzers for next‐generation biomedicines and catalysts. [ABSTRACT FROM AUTHOR]

Real-time polymerase chain reaction (real-time PCR) tests were successfully conducted in an aluminum-based microfluidic chip developed in this work. The reaction chamber was coated with silicone-modified epoxy resin to isolate the reaction system from metal surfaces, preventing the metal ions from interfering with the reaction process. The patterned aluminum substrate was bonded with a hydroxylated glass mask using silicone sealant at room temperature. The effect of thermal expansion was counteracted by the elasticity of cured silicone. With the heating process closely monitored, real-time PCR testing in reaction chambers proceeded smoothly, and the results show similar quantification cycle values to those of traditional test sets. Scanning electron microscope (SEM) and atomic force microscopy (AFM) images showed that the surface of the reaction chamber was smoothly coated, illustrating the promising coating and isolating properties. Energy-dispersive X-ray spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), and inductively coupled plasma-optical emission spectrometer (ICP-OES) showed that no metal ions escaped from the metal to the chip surface. Fourier-transform infrared spectroscopy (FTIR) was used to check the surface chemical state before and after tests, and the unchanged infrared absorption peaks indicated the unreacted, antifouling surface. The limit of detection (LOD) of at least two copies can be obtained in this chip. [ABSTRACT FROM AUTHOR]

Opioids are widely used in clinical practice, but drug overdoses can lead to many adverse reactions, and even endanger life. Therefore, it is essential to implement real-time measurement of drug concentrations to adjust the dosage given during treatment, keeping drug levels within therapeutic levels. Metal-Organic frameworks (MOFs) and their composite materials modified bare electrode electrochemical sensors have the advantages of fast production, low cost, high sensitivity, and low detection limit in the detection of opioids. In this review, MOFs and MOFs composites, electrochemical sensors modified with MOFs for the detection of opioids, as well as the application of microfluidic chips in combination with electrochemical methods are all reviewed, and the potential for the development of microfluidic chips electrochemical methods with MOFs surface modifications for the detection of opioids is also prospected. We hope that this review will provide contributions to the study of electrochemical sensors modified with MOFs for the detection of opioids. [ABSTRACT FROM AUTHOR]

• Address application limitations of traditional focus variation microscopy. • Determine the optimal parameters for active illumination mode. • Measurement noise immunity enhanced from 8.7 nm to 1.1 nm (50 × objective). • Reconstruct the surface topography of microchannels through transparent encapsulation layer. Optical measurement methods for surface topography offer the advantages of high accuracy, rapid measurement, and non-destructiveness. Each method has its own suitable application scenarios. Among them, focus variation microscopy is extensively employed in precision manufacturing, aerospace, and medical industries due to its ability to measure rough and large slopes surfaces. However, since the measurement depends on local grayscale differences between focused and blurred images, it cannot measure surfaces with low reflectivity or insufficient texture information. In this work, we propose an active illumination mode for focus variation method that utilizes a digital micromirror device (DMD) to generate a checkerboard pattern. This method introduces additional texture information, resulting in a usable local gradient of image grayscale. Additionally, we analyze the selection criteria for the checkerboard pattern parameters, including the period and light-dark ratio. Furthermore, measurements of two standard steps with different heights demonstrate that the measurement repeatability of the proposed method can reach the nanometer level, rendering it suitable for high-precision measurements. More importantly, the measurement noise results indicate significantly superior performance of active illumination mode compared to the uniform illumination mode. Finally, we reconstruct the surface topography of the microchannels in a microfluidic chip through the encapsulation layer, demonstrating the feasibility of the proposed method. [ABSTRACT FROM AUTHOR]

Co-culture spheroids mimic tumor architecture more accurately than traditional 2D cell cultures, but non-invasive, long-term tracking of live cells within these 3D models remains a challenge. This study addresses this critical need by developing a novel approach for live cell imaging in U-87/HUF co-culture spheroids. We introduce water-soluble, biocompatible red carbon dots (R-CDs) exhibiting exceptional stability and brightness (21% quantum yield) specifically designed for imaging within these 3D models. Furthermore, we designed a microfluidic chip with ellipsoid-shaped microwells to efficiently generate two distinct co-culture spheroid types: direct mixing and core-shell. R-CDs enabled non-invasive tracking of U-87 cancer cell location within these 3D models demonstrating their efficacy for long-term monitoring of live cells in cancer research. This R-CD and microfluidic technology has the potential to accelerate cancer drug discovery by enabling live cell studies in 3D tumor models. [Display omitted] [ABSTRACT FROM AUTHOR]

Summary: Backgrounds: Detecting free cancer cells from ascites and peritoneal lavages is crucial for diagnosing gastric cancer (GC). However, traditional methods are limited for early-stage diagnosis due to their low sensitivity. Methods: A label-free, rapid, and high-throughput technique was developed for separating cancer cells from ascites and peritoneal lavages using an integrated microfluidic device, taking advantage of dean flow fractionation and deterministic lateral displacement. Afterward, separated cells were analyzed using a microfluidic single-cell trapping array chip (SCTA-chip). In situ immunofluorescence for EpCAM, YAP-1, HER-2, CD45 molecular expressions, and Wright-Giemsa staining were performed for cells in SCTA-chips. At last, YAP1 and HER-2 expression in tissues was analyzed by immunohistochemistry. Findings: Through integrated microfluidic device, cancer cells were successfully separated from simulated peritoneal lavages containing 1/10,000 cancer cells with recovery rate of 84.8% and purity of 72.4%. Afterward, cancer cells were isolated from 12 patients’ ascites samples. Cytological examinations showed cancer cells were efficiently enriched with background cells excluded. Afterwards, separated cells from ascites were analyzed by SCTA-chips, and recognized as cancer cells through EpCAM+/CD45− expression and Wright-Giemsa staining. Interestingly, 8 out of 12 ascites samples showed HER-2+ cancer cells. At last, the results through a serial expression analysis showed that YAP1 and HER-2 have discordant expression during metastasis. Interpretation: Microfluidic Chips developed in our study could not only rapidly detect label-free free GC cells in ascites and peritoneal lavages with high-throughput, they could also analyze ascites cancer cells at the single-cell level, improving peritoneal metastasis diagnosis and investigation of therapeutic targets. Funding: This research was supported by National Natural Science Foundation of China (22134004, U1908207, 91859111); Natural Science Foundation of Shandong Province of China (ZR2019JQ06); Taishan Scholars Program of Shandong Province tsqn (201909077); Local Science and Technology Development Fund Guided by the Central Government (YDZX20203700002568); Applied Basic Research Program of Liaoning Province (2022020284-JH2/1013).

Microfluidic devices made from polydimethylsiloxane (PDMS) have diverse biomedical applications. However, due to the poor printability of PDMS, current 3D printing techniques are rarely used to fabricate microfluidic devices. This study aims to investigate a fumed silica-PDMS suspension that can function as a matrix bath for embedded 3D printing (e-3DP) purposes, making it technically feasible to print microfluidic chips with complex embedded channels via low-cost extrusion 3D printing. The rheological properties, mechanical properties, transparency, and filament fidelity of the fumed silica-PDMS suspension have been systematically studied. It is found that the addition of fumed silica particles can effectively change PDMS from a viscous solution to a yield-stress suspension with suitable rheological properties for e-3DP. Also, the mechanical properties of the crosslinked fumed silica-PDMS are enhanced with an increased concentration of fumed silica. Although the transparency of PDMS has been lessened by mixing it with fumed silica particles, the visibility of the printed microfluidic chips is still acceptable. The filament fidelity has been studied by embedded printing filaments using a sacrificial ink in the fumed silica-PDMS suspension. Finally, two representative microfluidic chips for biomedical applications have been successfully printed to validate the effectiveness of the proposed fumed silica-PDMS suspension-enabled e-3DP method. [ABSTRACT FROM AUTHOR]

BACKGROUND: Microalgae is an important natural resource with extensive applications in various fields, such as health products, animal feed, biopharmaceuticals, and clean energy. However, before the research and utilization of microalgae resources, the microalgae cells of interest must be separated from hybrid strains and bacteria. The traditional method of microalgae separation requires manual labor under the microscope that is time‐consuming and labor‐intensive. RESULTS: Herein, a novel microalgae cell separation method based on the dielectrophoresis (DEP) technique was proposed. A unique DEP separation chip with a 3D electrode was designed. Chlorella and Closterium were used as the experimental samples to verify the effectiveness of the proposed method because they have similar volumes and very different electrical properties. Within a certain frequency range, Chlorella suffers from negative dielectrophoresis (nDEP) force and Closterium suffers from positive dielectrophoresis (pDEP) force, so their separation can be achieved. The separation efficiency exceeded 90%. In addition, the DEP response of the Chlorella and Closterium were studied, and the DEP spectra of the two microalgae cells were obtained. Moreover, the effects of DEP force on cell viability under different voltages and frequencies were experimentally analyzed. CONCLUSION: These findings will contribute to DEP technology, to the portable and harmless separation of microalgae, and to research on the dielectric properties of microalgae cells. © 2022 Society of Chemical Industry (SCI). [ABSTRACT FROM AUTHOR]

Macrophages and fibroblasts are two types of important cells in wound healing. The development of novel platforms for studying the interrelationship between these two cells is crucial for the exploration of wound-healing mechanisms and drug development. In this study, a microfluidic chip composed of two layers was designed for the co-culturing of these two cells. An air valve was employed to isolate fibroblasts to simulate the wound-healing microenvironment. The confluence rate of fibroblasts in the co-culture system with different macrophages was explored to reflect the role of different macrophages in wound healing. It was demonstrated that M2-type macrophages could promote the activation and migration of fibroblasts and it can be inferred that they could promote the wound-healing process. The proposed microfluidic co-culture system was designed for non-contact cell–cell interactions, which has potential significance for the study of cell–cell interactions in biological processes such as wound healing, tumor microenvironment, and embryonic development. [ABSTRACT FROM AUTHOR]