Search

Alginate as a good drug delivery vehicle has excellent biocompatibility and biodegradability. In the ionic gelation process between alginate and Ca2+, the violent reaction is the absence of a well-controlled strategy in the synthesizing calcium alginate (CaA) microgels. In this study, a concentration-controlled microfluidic chip with central buffer flow was designed and 3D-printed to well-control the synthesis process of CaA microgels by the diffusion mixing pattern. The diffusion mixing pattern in the microfluidic chip can slow down the ionic gelation process in the central stream. The particle size can be influenced by channel length and flow rate ratio, which can be regulated to 448 nm in length and 235 nm in diameter. The delivery ratio of Doxorubicin (Dox) in CaA microgels are up to 90% based on the central stream strategy. CaA@Dox microgels with pH-dependent release property significantly enhances the cell killing rate against human breast cancer cells (MCF-7). The diffusion mixing pattern gives rise to well-controlled synthesis of CaA microgels, serving as a continuous and controllable production process for advanced drug delivery systems.

This protocol provides insights into the rapid, low-cost, and largescale fabrication of polymer microfluidic chips containing three-dimensional microstructures used in point-of-care devices for applications such as detection of pathogens via molecular diagnostic methods. The details of the fabrication methods are described in this paper. This study offers suggestions for researchers and experimentalists, both at university laboratories and in industrial companies, to prevent doom fabrication issues. For a demonstration of bio-application in point-of-care testing, the 3D microarrays fabricated are then employed in multiplexed detection of Salmonella (Salmonella Typhimurium and Salmonella Enteritidis), based on a molecular detection technique called solid-phase polymerase chain reaction (SP-PCR).

Abstract: Recently, a new observation method for monitoring of pH gradients in microfluidic free‐flow electrophoresis has emerged. It is based on the use of chip‐integrated fluorescent or luminescent micro sensor layers. These are able to monitor pH gradients in miniaturized separations in real time and spatially resolved; this is particularly useful in isoelectric focusing. Here these multifunctional microdevices that feature continuous separation, monitoring, and in some instances other functionalities, are reviewed. The employed microfabrication procedures to produce these devices are discussed and the different pH sensor matrices that were integrated and their applications in the separation of different types of biomolecules. The procedures for obtaining spatially resolved information about the separated molecules and the pH at the same time and different detection modalities to achieve this such as deep UV fluorescence as well as time‐resolved referenced pH sensing and the integration of a precolumn labeling step into these platforms are also highlighted. [ABSTRACT FROM AUTHOR]

Single-cell biology provides insights into some of the most fundamental processes in biology and promotes the understanding of life's mysteries. As the technologies to study single-cells expand, they will require sophisticated analytical tools to make sense of various behaviors and components of single-cells as well as their relations in the adherent tissue culture. In this paper, we revealed cell heterogeneity and uncovered the connections between cell adhesion strength and cell viability at single-cell resolution by extracting single adherent cells of interest from a standard tissue culture by using a microfluidic chip-based live single-cell extractor (LSCE). We believe that this method will provide a valuable new tool for single-cell biology. [ABSTRACT FROM AUTHOR]

Abstract: Next‐generation healthcare equipment and devices are in great demand for point‐of‐care testing (POCT), in view of their applications in rapid disease diagnosis, personalized medicine, portable or mobile health care, nontechnician assays, etc. Localized surface plasmon resonance (LSPR) biosensors, which are based on noble‐metal nanostructures and which provide fast, real‐time, nonlabeled, and sensitive biochemical detections, have become one of the leading candidates for POCT. The advances in nanofabrication, molecular biotechnology, and optoelectronics integration technology have promoted LSPR biosensing to low‐cost, easy‐to‐use, and on‐site POCT. Here, a synopsis of LSPR nano‐biosensors and LSPR‐based POCT devices is provided by delineating the fundamental principles of LSPR sensing, various metal nanostructures, the modification layers on LSPR nanostructures, and the integration of LSPR biosensors into devices. Examples of applications of existing LSPR‐based microfluidic platforms and POCT devices in healthcare, public security, environmental monitoring, and food safety, for example, are given. Finally, the challenges and perspectives of developing LSPR‐based POCT techniques are highlighted. A relatively complete and instructive summary is provided for the development of plasmonic nano‐biosensor‐based portable, mobile, and wearable POCT devices. [ABSTRACT FROM AUTHOR]

Collective cell migration is important in various physiological processes such as morphogenesis, cancer metastasis and cell regeneration. Such migration can be induced and guided by different chemical and physical cues. Electrotaxis, referring to the directional migration of adherent cells under stimulus of electric fields, is believed to be highly involved in the wound-healing process. Electrotactic experiments are conventionally conducted in Petri dishes or cover glasses wherein cells are cultured and electric fields are applied. However, these devices suffer from evaporation of the culture medium, non-uniformity of electric fields and low throughput. To overcome these drawbacks, micro-fabricated devices composed of micro-channels and fluidic components have lately been applied to electrotactic studies. Microfluidic devices are capable of providing cells with a precise micro-environment including pH, nutrition, temperature and various stimuli. Therefore, with the advantages of reduced cell/reagent consumption, reduced Joule heating and uniform and precise electric fields, microfluidic chips are perfect platforms for observing cell migration under applied electric fields. In this paper, I review recent developments in designing and fabricating microfluidic devices for studying electrotaxis, aiming to provide critical updates in this rapidly-growing, interdisciplinary field. [ABSTRACT FROM AUTHOR]

Simultaneous, sensitive and quantitative detection of biomarkers in infectious disease is crucial for guiding antimicrobial treatment and predicting prognosis. This work reported an ultrasensitive and quantitative microfluidic immunoassay combined with the streptavidin-biotin-peroxidase (SA-B-HRP) nanocomplex-signal amplification system (MIS) to detect two inflammatory biomarkers, procalcitonin (PCT, for discriminating bacterial infections from nonbacterial infections) and interleukin-6 (IL-6, for monitoring the kinetics of infectious disease) simultaneously. The amplification system was based on the one step self-assembly of SA and B-HRP to form the SA-B-HRP nanocomplex, which effectively amplified the chemiluminescent signals. The linear ranges for PCT and IL-6 detections by MIS were 250–1.28 × 10 5 pg mL −1 and 5–1280 pg mL −1 , and the limit of detection (LOD) were 48.9 pg mL −1 and 1.0 pg mL −1 , respectively, both of which were significantly improved compared with microfluidic immunoassays without amplification system (MI). More importantly, PCT and IL-6 in human serum could be simultaneously detected in the same run by MIS, which could greatly improve the detection efficiency and reduce the cost. Given the advantages of high sensitivity, multiplex and quantitative detection, MIS could be potentially applied for detection of biomarkers at low concentration in clinical diagnosis. [ABSTRACT FROM AUTHOR]

In vitro drug screening using reliable and predictable liver models remains a challenge. The identification of an ideal biological substrate is essential to maintain hepatocyte functions during in vitro culture. Here, we developed a fiber-embedded polydimethylsiloxane (PDMS) chip to culture hepatocytes. Hepatocyte spheroids formed in this device were subjected to different flow rates, of which a flow rate of 50 μL/min provided the optimal microenvironment for spheroid formation, maintained significantly higher rates of albumin and urea synthesis, yielded higher CYP3A1 (cytochrome P450 3A1) and CYP2C11 (cytochrome P450 2C11) enzyme activities for metabolism, and demonstrated higher expression levels of liver-specific genes. In vitro metabolism tests on tolbutamide and testosterone by hepatocytes indicated predicted clearance rates of 1.98 ± 0.43 and 40.80 ± 10.13 mL/min/kg, respectively, which showed a good in vitro–in vivo correspondence. These results indicate that this system provides a strategy for the construction of functional engineered liver tissue that can be used to study drug metabolism. [ABSTRACT FROM AUTHOR]

A novel method for the chemical manufacturing UV-curing assisted injection molding was proposed in this paper. A prototype of UV-curing injection molding apparatus has been manufactured. By using the prototype, we have successfully fabricated microfluidic chips, which can be practically applied in micro mixing experiments. Similar to the thermoplastic parts molded by traditional injection molding, the appearance defects such as bubbles also occurred on products fabricated by UV-curing injection molding. The generation process of bubble defect has been observed and captured through the visualization device. Because there is no gas produced in the polymerization chemical reaction, the shrinkage was considered to be the essential reason of bubble defect. In this paper, the solution of bubble defect was studied by employing single factor control variable method from the aspects of process parameters, materials, and mode of irradiation. It was noted that the bubble defect could be improved by increasing holding pressure, reducing irradiation intensity, and improving viscosity. Nevertheless, the achievement of process parameters was limited. On equal experimental conditions of process, equipment, and material, results revealed that the dynamic irradiation pattern can improve the feeding capacity significantly in UV-curing injection molding. It is further demonstrated that the bubble defect is caused by the polymerization shrinkage. Eventually, we obtained the microfluidic chips with good surface quality, high dimensional accuracy, and high transparency by UV curing injection molding. Moreover, it provides a feasible high efficiency and low cost manufacture technology for microfluidic chips in the future. [ABSTRACT FROM AUTHOR]

Circulating tumor cells (CTCs) present in the blood of patients with non-hematological cancers are accessible sources for diagnosis and monitoring of cancers. By the aid of the ability of the anti-EpCAM antibody to recognize the epithelial cells, microsystem-based technologies provide robust means for effectively detecting CTCs in vitro . Considering the EpCAM expression is down-regulated during epithelial-mesenchymal transition (EMT) process, the amount of CTCs detected based on anti-EpCAM antibody is underestimated. In our study, the A549 cells targeting peptide (A-1 peptide), as the substitute of anti-EpCAM antibody, was introduced to microfluidic chip to capture A549 cells. Our results showed that both epithelial-like and mesenchymal-like A549 cells could efficiently be captured by the A-1 peptide modified microfluidic chip, and the capture efficiency for epithelial-like cells is comparable to that captured by the EpCAM antibody. Thus, we concluded that the peptide could be a better supplement to the EpCAM antibody for capturing CTCs in microfluidic system with broader spectrum. [ABSTRACT FROM AUTHOR]

In the development of microfluidic chips, conventional 2D processing technologies contribute to the manufacturing of basic microchannel networks. Nevertheless, in the pursuit of versatile microfluidic chips, flexible integration of multifunctional components within a tiny chip is still challenging because a chip containing micro-channels is a non-flat substrate. Recently, on-chip laser processing (OCLP) technology has emerged as an appealing alternative to achieve chip functionalization through in situ fabrication of 3D microstructures. Here, the recent development of OCLP-enabled multifunctional microfluidic chips, including several accessible photochemical/photophysical schemes, and photosensitive materials permiting OCLP, is reviewed. To demonstrate the capability of OCLP technology, a series of typical micro-components fabricated using OCLP are introduced. The prospects and current challenges of this field are discussed. [ABSTRACT FROM AUTHOR]

Cell migration is an essential bioactive ceramics property and critical for bone induction, clinical application, and mechanism research. Standardized cell migration detection methods have many limitations, including a lack of dynamic fluid circulation and the inability to simulate cell behavior in vivo. Microfluidic chip technology, which mimics the human microenvironment and provides controlled dynamic fluid cycling, has the potential to solve these questions and generate reliable models of cell migration in vitro. In this study, a microfluidic chip is reconstructed to integrate the bioactive ceramic into the microfluidic chip structure to constitute a ceramic microbridge microfluidic chip system. Migration differences in the chip system are measured. By combining conventional detection methods with new biotechnology to analyze the causes of cell migration differences, it is found that the concentration gradients of ions and proteins adsorbed on the microbridge materials are directly related to the occurrence of cell migration behavior, which is consistent with previous reports and demonstrates the effectiveness of the microfluidic chip model. This model provides in vivo environment simulation and controllability of input and output conditions superior to standardized cell migration detection methods. The microfluidic chip system provides a new approach to studying and evaluating bioactive ceramics., (© 2023 Wiley-VCH GmbH.)

Microfluidic devices are used in a myriad of biomedical applications such as cancer screening, drug testing, and point-of-care diagnostics. Three-dimensional (3D) printing offers a low-cost, rapid prototyping, efficient fabrication method, as compared to the costly—in terms of time, labor, and resources—traditional fabrication method of soft lithography of poly(dimethylsiloxane) (PDMS). Various 3D printing methods are applicable, including fused deposition modeling, stereolithography, and photopolymer inkjet printing. Additionally, several materials are available that have low-viscosity in their raw form and, after printing and curing, exhibit high material strength, optical transparency, and biocompatibility. These features make 3D-printed microfluidic chips ideal for biomedical applications. However, for developing devices capable of long-term use, fouling—by nonspecific protein absorption and bacterial adhesion due to the intrinsic hydrophobicity of most 3D-printed materials—presents a barrier to reusability. For this reason, there is a growing interest in anti-fouling methods and materials. Traditional and emerging approaches to anti-fouling are presented in regard to their applicability to microfluidic chips, with a particular interest in approaches compatible with 3D-printed chips.

Organoid technology offers sophisticated in vitro human models for basic research and drug development. However, low batch-to-batch reproducibility and high cost due to laborious procedures and materials prevent organoid culture standardization for automation and high-throughput applications. Here, using a novel platform based on the findings that Pluronic F-127 (PF-127) could trigger highly uniform spheroid assembly through a mechanism different from plate coating, we develop a one-pot organoid differentiation strategy. Using our strategy, we successfully generate cortical, nephron, hepatic, and lung organoids with improved reproducibility compared to previous methods while reducing the original costs by 80%-95%. In addition, we adapt our platform to microfluidic chips allowing automated culture. We showcase that our platform can be applied to tissue-specific screening, such as drug toxicity and transfection reagents testing. Finally, we generate NEAT1 knockout tissue-specific organoids and show NEAT1 modulates multiple signaling pathways fine-tuning the differentiation of nephron and hepatic organoids and suppresses immune responses in cortical organoids. In summary, our strategy provides a powerful platform for advancing organoid research and studying human development and diseases., (Creative Commons Attribution license.)

Super-resolution microscopy is rapidly developed in recent years, allowing biologists to extract more quantitative information on subcellular processes in live cells that is usually not accessible with conventional techniques. However, super-resolution imaging is not fully exploited because of the lack of an appropriate and multifunctional experimental platform. As an important tool in life sciences, microfluidics is capable of cell manipulation and the regulation of the cellular environment because of its superior flexibility and biocompatibility. The combination of microfluidics and super-resolution microscopy revolutionizes the study of complex cellular properties and dynamics, providing valuable insights into cellular structure and biological functions at the single-molecule level. In this perspective, an overview of the main advantages of microfluidic technology that are essential to the performance of super-resolution microscopy are offered. The main benefits of performing super-resolution imaging with microfluidic devices are highlighted and perspectives on the diverse applications that are facilitated by combining these two powerful techniques are provided., (© 2023 Wiley-VCH GmbH.)

We designed one type of microfluidic chip integrated with Au microelectrodes to detect target CCRF-CEM cells based on the electrochemical oxidation of hydrazine catalyzed by Pt nanoparticles (NPs). The microelectrode can improve the sensitivity of detection, with a low background signal and decreased nonspecific adsorption. Applying the cell aptamer as the sensing element, this method exhibits good selectivity. Owing to the strong catalytic ability of Pt NPs for the electrochemical oxidation of hydrazine, the limit of detection of this method is ten cells. By adjusting the detection area of Au microelectrodes, this chip can detect a wide range of target cells. Besides, this method successfully detected the target cells doped in blood samples, indicating its potential application in clinical diagnosis. [ABSTRACT FROM AUTHOR]

A new method to integrate poly-DL-lactide (PLA) patterned electrospun fibers with a polydimethylsiloxane (PDMS) microfluidic chip was successfully developed via lithography. Hepatocyte behavior under static and dynamic conditions was investigated. Immunohistochemical analyses indicated good hepatocyte survival under the dynamic culture system with effective hepatocyte spheroid formation in the patterned microfluidic chip vs. static culture conditions and tissue culture plate (TCP). In particular, hepatocytes seeded in this microfluidic chip under a flow rate of 10 μL/min could re-establish hepatocyte polarity to support biliary excretion and were able to maintain high levels of albumin and urea secretion over 15 days. Furthermore, the optimized system could produce sensitive and consistent responses to nano-Ag-induced hepatotoxicity during culture. Thus, this microfluidic chip device provides a new means of fabricating complex liver tissue-engineered scaffolds, and may be of considerable utility in the toxicity screening of nanoparticles. [ABSTRACT FROM AUTHOR]

The detection of bacterial pathogens from complex sample matrices by PCR requires efficient DNA extraction. In this study, a protocol for extraction and purification of DNA from swabs, air, and water samples using a microfluidic chip system was established. The optimized protocol includes a combination of thermal, chemical and enzymatic lysis followed by chip-based DNA purification using magnetic particles. The procedure was tested using Gram-positive Bacillus thuringiensis Berliner var. kurstaki as a model organism for Bacillus anthracis and the attenuated live vaccine strain of Francisella tularensis subsp. holarctica as Gram-negative bacterium. The detection limits corresponded to 10 3 genome equivalents per milliliter (GE/ml) for surface water samples spiked with F. tularensis and 10 2 GE/ml for B. thuringiensis . In air, 10 GE of F. tularensis per 10 L and 1 GE of B. thuringiensis per 10 L were detectable. For swab samples obtained from artificially contaminated surfaces the detection limits were 4 × 10 3 GE/cm 2 for F. tularensis and 4 × 10 2 GE/cm 2 for B. thuringiensis . Suitability of the chip-assisted procedure for DNA preparation of real samples was demonstrated using livestock samples. The presence of thermophilic Campylobacter spp. DNA could be confirmed in air samples collected on pig and broiler farms. [ABSTRACT FROM AUTHOR]

By combining a chemiluminescence immunoassay with microfluidic chip technology, a simple assay was established for the sensitive detection of cloxacillin in poultry samples. The chip used in this approach was composed of an upper microchannel layer and a lower flat base layer. Each of the formed microchannels has a volume of 18 μL, thus enabling a considerable reduction of reagent consumption as well as sample size needed for analysis by the indirect competitive immunoassay. To obtain labeled antigens for coating, the active ester method was employed to couple cloxacillin to glucose oxidase (GlcOx). The immobilized GlcOx-cloxacillin conjugate on the base layer competed with residues of cloxacillin in samples for binding sites of the monoclonal antibodies (mAb) against cloxacillin. Horseradish peroxidase-labeled anti-mouse IgG antibodies and chemiluminescent substrate were used for signal generation. Under optimized conditions, the IC and the limit of detection (LOD) of the assay were at 96.5 ± 9.37 and 0.92 ± 0.07 ng/mL, respectively, and thus well below the maximum residue level of 300 ng/mL set by the European Commission. Recoveries for spiked chicken and duck samples were in the range from 94 to 118 % with relative standard deviations lower than 11 %. The results demonstrate that the microfluidic chip-based immunoassay can be used as a rapid and reliable platform for determination of cloxacillin in poultry. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) printing, also called additive manufacturing (AM) or rapid prototyping (RP), is a layer by layer manufacturing method and now has been widely used in many areas such as organ printing, aerospace and industrial design. Now 3D printed microfluidics attract more and more interests for its rapid printing in the lab. In this review, we focused on the advances of 3D printed microfluidic chips especially the use in the chemistry and biology (vascularization and organs on chips). Based on the brief review of different 3D printing methods, we discussed how to choose the suitable 3D printing methods to print the desired microfluidics. We predict that microfluidics will be evolved from 2D chips to 3D cubes, printed hydrogel-based microfluidics will be reported and widely used, sensors & actuators could be integrated in the microfluidics during printing, and rapid assembling chips with printed microfluidic modules will be popular in the near future. [ABSTRACT FROM AUTHOR]

We consider the basic principles, instruments, problems, and examples of application of thermal lens spectroscopy and microscopy, highly sensitive force methods of molecular absorption spectroscopy, in various embodiments of electromigration methods of analysis, particularly, capillary electrophoresis and microfluidic chip electrophoresis. Examples illustrating the sensitivity and selectivity of the combined methods are presented. [ABSTRACT FROM AUTHOR]

The advent of chemical sensors and biosensors has drawn tremendous attention particularly in the inspection of food quality. Array-based sensors take advantage of the integration of multiple recognition elements on a single microdetector, and the ability to recognize a myriad of molecular targets from complex samples. With the continuous advancement in lab-on-a-chip technology, microfluidic-based techniques have enabled rapid and portable monitoring of multiple nutritional or harmful substances that provide high sensitivity, high throughput, and low sample consumption. In this article, the latest progress in array-based chemical sensors and biosensors is carefully reviewed. Several major chemometric methods for handling high-dimensional data, including hierarchical cluster analysis, principal component analysis, and support vector machine, are introduced and commented of reference to their use primarily in the detection of foodborne hazardous species or contaminants. Finally, special insights are given into the development of miniaturized, sensitive, and selective sensors as the next generation of point-of-care tools. [Display omitted] • Array-based chemical or biological sensors are able to recognize multiple targets from complex samples. • Microfluidic chip is a powerful platform for the construction of sensor arrays with microscale components. • Chemometrics enhance the performance of sensor arrays through the analysis of high dimensional data. • Array-based sensors display great potentials in food safety screening and quality control. [ABSTRACT FROM AUTHOR]

The large-scale use of antibiotics and the resulting drug residues poses a significant threat to global human health. Waste discharge and biological chain transmission are closely linked to residual antibiotic pollution in the fields of medicine, environmental monitoring, and food safety. Monitoring drug dosage in medicines and the detection of trace antibiotic residues in environmental and food matrices is therefore especially important. Microfluidic technology allows manipulation and flexible design of micro/nanofluids and is thus an essential means of antibiotic detection and analysis. Herein, we review recent progress in the design and applications of microfluidic chips as biosensors for the analysis of antibiotic residue analysis over the past five years. The types of chip materials and combination of microfluidic chips with essential technologies involving optics, electrochemistry, and mass spectrometry are introduced, and the critical principles of antibiotic microfluidic analysis and its application in the three aforementioned fields are summarized. [Display omitted] • The types of microfluidic chips used for analysis of antibiotics were described. • Described and summarized the important principles applied by microfluidic biosensors in antibiotic assays. • Described the progress of detection techniques for antibiotic microfluidic biosensing analysis in the last five years. • Summarized the application of microfluidic biosensing analysis of antibiotic detection in three major fields. [ABSTRACT FROM AUTHOR]

The Coronavirus disease 2019 (COVID-19) outbreak has urged the establishment of a global-wide rapid diagnostic system. Current widely-used tests for COVID-19 include nucleic acid assays, immunoassays, and radiological imaging. Immunoassays play an irreplaceable role in rapidly diagnosing COVID-19 and monitoring the patients for the assessment of their severity, risks of the immune storm, and prediction of treatment outcomes. Despite of the enormous needs for immunoassays, the widespread use of traditional immunoassay platforms is still limited by high cost and low automation, which are currently not suitable for point-of-care tests (POCTs). Microfluidic chips with the features of low consumption, high throughput, and integration, provide the potential to enable immunoassays for POCTs, especially in remote areas. Meanwhile, luminescence detection can be merged with immunoassays on microfluidic platforms for their good performance in quantification, sensitivity, and specificity. This review introduces both homogenous and heterogenous luminescence immunoassays with various microfluidic platforms. We also summarize the strengths and weaknesses of the categorized methods, highlighting their recent typical progress. Additionally, different microfluidic platforms are described for comparison. The latest advances in combining luminescence immunoassays with microfluidic platforms for POCTs of COVID-19 are further explained with antigens, antibodies, and related cytokines. Finally, challenges and future perspectives were discussed. • Immunological signatures of the life cycles of COVID-19 are introduced. • Luminescence immunoassays on microfluidic chips for point-of-care (POC) diagnosis of COVID-19 are well detailed. • Existent challenges and future perspectives for POC immunoassays are further discussed. [ABSTRACT FROM AUTHOR]

Exosomes are promising new biomarkers for colorectal cancer (CRC) diagnosis, due to their rich biological fingerprints and high level of stability. However, the accurate detection of exosomes with specific surface receptors is limited to clinical application. Herein, an exosome enrichment platform on a 3D porous sponge microfluidic chip is constructed and the exosome capture efficiency of this chip is ≈90%. Also, deep mass spectrometry analysis followed by multi-level expression screenings revealed a CRC-specific exosome membrane protein (SORL1). A method of SORL1 detection by specific quantum dot labeling is further designed and the ensemble classification system is established by extracting features from 64-patched fluorescence images. Importantly, the area under the curve (AUC) using this system is 0.99, which is significantly higher (p < 0.001) than that using a conventional biomarker (carcinoembryonic antigen (CEA), AUC of 0.71). The above system showed similar diagnostic performance, dealing with early-stage CRC, young CRC, and CEA-negative CRC patients., (© 2023 Wiley-VCH GmbH.)

Introduction: Pancreatic ductal adenocarcinoma presents with a dismal prognosis. Personalized therapy is urgently warranted to overcome the treatment limitations of the 'one-size-fits-all' scheme. Organoids have emerged as fundamental novel tools to study tumor biology and heterogeneity, hence overcoming limitations of other model systems by better-reflecting tissue heterogeneity and recapitulating in-vivo processes. Besides their crucial role in basic research, they have evolved as tools for translational drug discovery and patient stratification., Areas Covered: This review highlights the achievements of an organoid-based drug investigation and discovery. The authors present an overview of studies using organoids for drug testing. Further, they pinpoint studies correlating the in vitro prediction of organoids to the actual patient`s response. Furthermore, the authors describe novel model systems and take a thorough overlook of microfluidic chips, synthetic matrices, multicellular systems, bioprinting, and stem cell-derived pancreatic organoid systems., Expert Opinion: Organoid systems promise great potential for future clinical applications. Indeed, they may be implemented into informed decision-making for guiding therapies. However, validation by randomized trials is mandatory. Additionally, organoids in combination with other cellular compartments may be exploited for drug discovery by studying niche-tumor interaction. Yet, several precautions must be kept in mind, such as standardization and reproducibility.

Precise detection involving droplets based on functional surfaces is promising for the parallelization and miniaturization of platforms and is significant in epidemic investigation, analyte recognition, environmental simulation, combinatorial chemistry, etc. However, a challenging and considerable task is obtaining mutually independent droplet arrays without cross-contamination and simultaneously avoiding droplet evaporation-caused quick reagent loss, inaccuracy, and failure. Herein, a strategy to generate mutually independent and hardly-volatile capsular droplet arrays using innovative mosaic patterned surfaces is developed. The evaporation suppression of the capsular droplet arrays is 1712 times higher than the naked droplet. The high evaporation suppression of the capsular droplet arrays on the surfaces is attributed to synergistic blocking of the upper oil and bottom mosaic gasproof layer. The scale-up of the capsular droplet arrays, the flexibility in shape, size, component (including aqueous, colloidal, acid, and alkali solutions), liquid volume, and the high-precision hazardous substance testing proves the concept's high compatibility and practicability. The mutually independent capsular droplet arrays with amazingly high evaporation suppression are essential for the new generation of high-performance open-surface microfluidic chips used in COVID-19 diagnosis and investigation, primary screening, in vitro enzyme reactions, environmental monitoring, nanomaterial synthesis, etc., (© 2023 Wiley-VCH GmbH.)

Solvent bonding represents a joining method for thermoplastic materials that results in high bond strength, with short process times. However, there is a challenge in bonding micro-channeled substrates for microfluidic devices due to excessive channel clogging and distortion. In this work, a simple design method to fuse poly(methyl methacrylate) microfluidic chips with solvents without micro-channel clogging is demonstrated. The joining process is improvised improved by subjecting the chip to a vacuum during the bonding process, whereby the undesired excess solvent between the microfluidic chip and cover can be removed. The microfluidic devices that were bonded using this method exceeded the application requirements, in particular transparency and internal back pressure requirements. [ABSTRACT FROM AUTHOR]

A catalytic polymer multilayer shell motor has been developed, which effects fast motion-based separation of charged organics in water. The shell motors are fabricated by sputtering platinum onto the exposed surface of silica templates embedded in Parafilm, followed by layer-by-layer assembly of polyelectrolyte multilayers to the templates. The catalytic shell motors display high bubble propulsion with speeds of up to 260 μm s−1 (13 body lengths per second). Moreover, the polyelectrolyte multilayers assembled at high pH (pH>9.0) adsorb approximately 89 % of dye molecules from water, owing to the electrostatic interaction between the positively charged polymers and the anionic dye molecules, and subsequently release them at neutral pH in a microfluidic device. The efficient propulsion coupled with the effective adsorption behavior of the catalytic shell motors in a microfluidic device results in accelerated separation of organics in water and thus holds considerable promise for water analysis. [ABSTRACT FROM AUTHOR]

The basic structural and functional unit of a living organism is a single cell. To understand the variability and to improve the biomedical requirement of a single cell, its analysis has become a key technique in biological and biomedical research. With a physical boundary of microchannels and microstructures, single cells are efficiently captured and analyzed, whereas electric forces sort and position single cells. Various microfluidic techniques have been exploited to manipulate single cells through hydrodynamic and electric forces. Digital microfluidics (DMF), the manipulation of individual droplets holding minute reagents and cells of interest by electric forces, has received more attention recently. Because of ease of fabrication, compactness and prospective automation, DMF has become a powerful approach for biological application. We review recent developments of various microfluidic chips for analysis of a single cell and for efficient genetic screening. In addition, perspectives to develop analysis of single cells based on DMF and emerging functionality with high throughput are discussed. [ABSTRACT FROM AUTHOR]

Microfluidic systems have important application value in biology and medicine research. However, a major challenge in Microfluidic based cell analysis is to automatically segment touching cells in the microscopic images. In this paper, we propose a novel automatic cell segment method based on concave point detection and matching. On the basis of high-quality image deblurring, we adopt a UNet++ based deep neural network to accurately extract cell contours by taking as input both bright and dark-field images, and trained with a Dice loss based objective function. Then, we propose a method that extracts concave points from the contours by detecting the convex hull defects, and the issue of missing concave points is addressed by considering the distance between the starting and the ending point of defect. Finally, to overcome the limitation of existing methods that the accuracy of segmentation is highly dependent on the accuracy of concave point detection, we propose a concave points matching condition based on compactness to obtain the concave point pairs for segmentation. Experimental results show that our method can effectively segment touching cells with high accuracy, and is robust to different cell concentration levels. • Propose a novel deep learning based cell segmentation method for microfluidic chips. • Both the bright and dark field information is used in contour extraction. • Novel concave point detection and matching algorithms are proposed. • Achieve over 90% accuracy on most experiments of different concentration levels. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a global health problem resulting from islet dysfunction or insulin resistance. The mechanisms of islet dysfunction are still under investigation. Islet hormone secretion is the main function of islets, and serves an important role in the homeostasis of blood glucose. Elucidating the detailed mechanism of islet hormone secretome distortion can provide clues for the treatment of diabetes. Therefore, it is crucial to develop accurate, real-time, labor-saving, high-throughput, automated, and cost-effective techniques for the sensing of islet secretome. Microfluidic chips, an elegant platform that combines biology, engineering, computer science, and biomaterials, have attracted tremendous interest from scientists in the field of diabetes worldwide. These tiny devices are miniatures of traditional experimental systems with more advantages of time-saving, reagent-minimization, automation, high-throughput, and online detection. These features of microfluidic chips meet the demands of islet secretome analysis and a variety of chips have been designed in the past 20 years. In this review, we present a brief introduction of microfluidic chips, and three microfluidic chips-based islet hormone sensing techniques. We focus mainly on the theory of these techniques, and provide detailed examples based on these theories with the hope of providing some insights into the design of future chips or whole detection systems., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Near-infrared spectroscopy (NIRS) is a non-invasive optical method for monitoring cerebral oxygenation. Changes in regional blood flow and oxygenation due to neurovascular coupling are important biomarkers of neuronal activation. So far, there has been little research on multilayer tissue phantoms with tuneable blood flow, blood volume, and optical properties to simulate local changes in oxygenation at different depths. The aim of this study is to design, fabricate and characterize a complex dynamic phantom based on multilayer microfluidics with controllable blood flow, blood volume, and optical properties for testing NIRS instruments. We developed a phantom prototype with two microfluidic chips embedded at two depths inside a solid silicone phantom to mimic the vessels in the scalp and in the cortex. To simulate the oxygenation and perfusion of tissue, a solution with blood-like optical properties was sent into the microchannels by a pump with a programmable pressure controller. The pressure adjusted the volume of the microfluidic chips representing a distension of blood vessels. The optical changes in the superficial and deep layers were measured by a commercially available frequency domain NIRS instrument. The NIRS successfully detected the changes in light intensity elicited by the changes in the pressure input to the two layers. In conclusion, the microfluidics-based imaging phantom was successfully designed and fabricated and mimics brain functional activity. This technique has great potential for testing other optical devices, e.g., diffuse correlation spectroscopy, pulse oximetry, and optical coherence tomography., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

This paper reports design, fabrication, and characterization of liquid metal-based microheaters. Liquid metal microheaters designed via finite element simulation were fabricated by simply injecting eutectic gallium indium into polydimethylsiloxane (PDMS) microfluidic chips bonded to either silicon or PDMS substrates. Considering the net positive volume change of the microheater upon heating, both nonpressurized and pressurized contacts between the power supply and the liquid metal wires were investigated. The pressurized contact was found to provide more reliable electrical connection, thus more stable long-term operation than the nonpressurized contact. Due to higher thermal conductivity, liquid metal microheaters with silicon substrate exhibit better temperature uniformity than ones with PDMS substrate. However, liquid metal microheaters with PDMS substrate are flexible and deformable, thus more suitable than ones with silicon substrate when microheaters should be applied to nonflat objects. [ABSTRACT FROM AUTHOR]

Detection of the droplet contents is a key function for droplet-based microfluidic systems. This paper presents a polystyrene microfluidic device integrated with droplet generator and micro film electrodes for direct amperometric detection of droplet contents without droplet desegmentation and phase separation. The method for fabrication of the full polystyrene micro chip was presented, and the behaviors of the developed polystyrene chip for generation and stabilization of water in n-octanol droplets, and detection of H2O2 in droplets were examined. The influences of electrode architecture and flow conditions on the electrochemical signals were studied in detail. With the developed chip, a sensitivity of 0.12Amol-1Lcm-2 and a detection limit of 10.0μmolL-1 were observed for the determination of droplet contained H2O2. The achieved precision for the detection of 21 droplets containing 250μmolL-1 H2O2 was 3.8% in relative standard deviation. The way for the aqueous droplets encapsulated by the oil-carrier to contact sensing electrodes was discussed based on the experimental observations, and the potential approaches for further improving the analytical performance were suggested. [ABSTRACT FROM AUTHOR]