Biomedical Microdevices最新文献

Flexible electronics offer a versatile, rapid, cost-effective and portable solution to monitor water contamination, which poses serious threat to the environment and human health. This review paper presents a comprehensive exploration of the versatile platforms of flexible electronics in the context of heavy metal ion detection in water systems. The review overviews of the fundamental principles of heavy metal ion detection, surveys the state-of-the-art materials and fabrication techniques for flexible sensors, analyses key performance metrics and limitations, and discusses future opportunities and challenges. By highlighting recent advances in nanomaterials, polymers, wireless integration, and sustainability, this review aims to serve as an essential resource for researchers, engineers, and policy makers seeking to address the critical challenge of heavy metal contamination in water resources. The versatile promise of flexible electronics is thoroughly elucidated to inspire continued innovation in this emerging technology arena.

Subcutaneous delivery of cell therapy is an appealing minimally-invasive strategy for the treatment of various diseases. However, the subdermal site is poorly vascularized making it inadequate for supporting engraftment, viability, and function of exogenous cells. In this study, we developed a 3D bioprinted scaffold composed of alginate/gelatin (Alg/Gel) embedded with mesenchymal stem cells (MSCs) to enhance vascularization and tissue ingrowth in a subcutaneous microenvironment. We identified bio-ink crosslinking conditions that optimally recapitulated the mechanical properties of subcutaneous tissue. We achieved controlled degradation of the Alg/Gel scaffold synchronous with host tissue ingrowth and remodeling. Further, in a rat model, the Alg/Gel scaffold was superior to MSC-embedded Pluronic hydrogel in supporting tissue development and vascularization of a subcutaneous site. While the scaffold alone promoted vascular tissue formation, the inclusion of MSCs in the bio-ink further enhanced angiogenesis. Our findings highlight the use of simple cell-laden degradable bioprinted structures to generate a supportive microenvironment for cell delivery.

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Microfluidic-based point-of-care diagnostics offer several unique advantages over existing bioanalytical solutions, such as automation, miniaturisation, and integration of sensors to rapidly detect on-site specific biomarkers. It is important to highlight that a microfluidic POC system needs to perform a number of steps, including sample preparation, nucleic acid extraction, amplification, and detection. Each of these stages involves mixing and elution to go from sample to result. To address these complex sample preparation procedures, a vast number of different approaches have been developed to solve the problem of reagent storage and delivery. However, to date, no universal method has been proposed that can be applied as a working solution for all cases. Herein, both current self-contained (stored within the chip) and off-chip (stored in a separate device and brought together at the point of use) are reviewed, and their merits and limitations are discussed. This review focuses on reagent storage devices that could be integrated with microfluidic devices, discussing further issues or merits of these storage solutions in two different sections: direct on-chip storage and external storage with their application devices. Furthermore, the different microvalves and micropumps are considered to provide guidelines for designing appropriate integrated microfluidic point-of-care devices.

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Biosensing for diagnostics has risen rapidly in popularity over the past decades. With the discovery of new nanomaterials and morphologies, sensitivity is being constantly improved enough for reliable detection of trace biomarkers in human samples, like serum or sweat. This precision has enabled detailed research on the efficacy of biosensors. However, current biosensors suffer from reduced speed of operation. To make better use of this sensitivity, the development of a conductometric biosensor with in-situ use of an Laser Emitting Device (LED) display can provide rapid determination of sample results, steadily pushing biosensors toward more clinical, point-of-care (POC) applications. In this research, a simple LED was used for facile optical determination and visual output of an ultrasensitive bio-signal amplification circuit was made to interface with a B-type Natriuretic Peptide (BNP) biosensor. Tuning circuit gain enables an elegant method for adjustable separation of concentrations into 3 discrete categories: sub-threshold, analog, and saturation regions. These regions corresponded to 0 < [C] < 500 pg/mL (25, 100, 250 pg/mL, LED off), 500 < [C] < 1000 pg/mL (LED varying intensity), and 1000 pg/mL < [C] (LED full intensity). System efficacy was tested using human blood serum samples from University of Pittsburgh Medical Center patients, which were able to be accurately detected and sorted for rapid low cost and power. determination without need for complex digital elements. Additional specificity testing suggests insignificant impact of non-target biomarkers.

Three-dimensional (3D) cell culture models have been extensively utilized in various mechanistic studies as well as for drug development studies as superior in vitro platforms than conventional two-dimensional (2D) cell culture models. This is especially the case in cancer biology, where 3D cancer models, such as spheroids or organoids, have been utilized extensively to understand the mechanisms of cancer development. Recently, many sophisticated 3D models such as organ-on-a-chip models are emerging as advanced in vitro models that can more accurately mimic the in vivo tissue functions. Despite such advancements, spheroids are still considered as a powerful 3D cancer model due to the relatively simple structure and compatibility with existing laboratory instruments, and also can provide orders of magnitude higher throughput than complex in vitro models, an extremely important aspects for drug development. However, creating well-defined spheroids remain challenging, both in terms of throughputs in generation as well as reproducibility in size and shape that can make it challenging for drug testing applications. In the past decades, droplet microfluidics utilizing hydrogels have been highlighted due to their potentials. Importantly, core-shell structured gel droplets can avoid spheroid-to-spheroid adhesion that can cause large variations in assays while also enabling long-term cultivation of spheroids with higher uniformity by protecting the core organoid area from external environment while the outer porous gel layer still allows nutrient exchange. Hence, core-shell gel droplet-based spheroid formation can improve the predictivity and reproducibility of drug screening assays. This review paper will focus on droplet microfluidics-based technologies for cancer spheroid production using various gel materials and structures. In addition, we will discuss emerging technologies that have the potential to advance the production of spheroids, prospects of such technologies, and remaining challenges.

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Particle classification plays a crucial role in various scientific and technological applications, such as differentiating between bacteria and viruses in healthcare applications or identifying and classifying cancer cells. This technique requires accurate and efficient analysis of particle properties. In this study, we investigated the integration of electrical and optical features through a multimodal approach for particle classification. Machine learning classifier algorithms were applied to evaluate the impact of combining these measurements. Our results demonstrate the superiority of the multimodal approach over analyzing electrical or optical features independently. We achieved an average test accuracy of 94.9% by integrating both modalities, compared to 66.4% for electrical features alone and 90.7% for optical features alone. This highlights the complementary nature of electrical and optical information and its potential for enhancing classification performance. By leveraging electrical sensing and optical imaging techniques, our multimodal approach provides deeper insights into particle properties and offers a more comprehensive understanding of complex biological systems.

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We report the fabrication and characterisation of magnetic liquid beads with a solid magnetic shell and liquid core using microfluidic techniques. The liquid beads consist of a fluorinated oil core and a polymer shell with magnetite particles. The beads are generated in a flow-focusing polydimethylsiloxane (PDMS) device and cured by photo polymerisation. We investigated the response of the liquid beads to an external magnetic field by characterising their motion towards a permanent magnet. Magnetic sorting of liquid beads in a channel was achieved with 90% efficiency. The results show that the liquid beads can be controlled magnetically and have potential applications in digital microfluidics including nucleic acid amplification, drug delivery, cell culture, sensing, and tissue engineering. The present paper also discusses the magnetophoretic behaviour of the liquid bead by varying its mass and magnetite concentration in the shell. We also demonstrated the two-dimensional self-assembly of magnetic liquid beads for potential use in digital polymerase chain reaction and digital loop mediated isothermal amplification.

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Millions of people are subject to infertility worldwide and one in every six people, regardless of gender, experiences infertility at some period in their life, according to the World Health Organization. Assisted reproductive technologies are defined as a set of procedures that can address the infertility issue among couples, culminating in the alleviation of the condition. However, the costly conventional procedures of assisted reproduction and the inherent vagaries of the processes involved represent a setback for its successful implementation. Microfluidics, an emerging tool for processing low-volume samples, have recently started to play a role in infertility diagnosis and treatment. Given its host of benefits, including manipulating cells at the microscale, repeatability, automation, and superior biocompatibility, microfluidics have been adopted for various procedures in assisted reproduction, ranging from sperm sorting and analysis to more advanced processes such as IVF-on-a-chip. In this review, we try to adopt a more holistic approach and cover different uses of microfluidics for a variety of applications, specifically aimed at sperm separation and analysis. We present various sperm separation microfluidic techniques, categorized as natural and non-natural methods. A few of the recent developments in on-chip fertilization are also discussed.

We report a centrifugal microfluidic device that automatically performs sample preparation under steady-state rotation for clinical applications using mass spectrometry. The autonomous microfluidic device was designed for the control of liquid operation on centrifugal hydrokinetics (CLOCK) paradigm. The reported device was highly stable, with less than 7% variation with respect to the time of each unit operation (sample extraction, mixing, and supernatant extraction) in the preparation process. An agitation mechanism with bubbling was used to mix the sample and organic solvent in this device. We confirmed that the device effectively removed the protein aggregates from the sample, and the performance was comparable to those of conventional manual sample preparation procedures that use high-speed centrifugation. In addition, probe electrospray ionization mass spectrometry (PESI-MS) was performed to compare the device-treated and manually treated samples. The obtained PESI-MS spectra were analyzed by partial least squares discriminant analysis, and the preparation capability of the device was found to be equivalent to that of the conventional method.

Kirigami is one of the interesting paper art forms and the modified sub-class of origami. Kirigami paper art is widely employed in a variety of applications, and it is currently being used in biosensors because of its outstanding advantages. This is the first study on the use of a Kirigami-based aptasensor for DENV (Dengue virus)-antigen detection. In this study, the kirigami approach has been utilized to develop a stretchable, movable, and flexible sensor. The constructed stretchable-kirigami electrode helps in adjusting the connection of electrodes without disturbing the electrochemical cell zone during the experiment. To increase the sensitivity of this biosensor we have synthesized Ag-NPs (Silver nanoparticles) via chemical methods and characterized their results with the help of TEM & UV-Vis Spectroscopy. Different electrochemical approaches were used to validate the sensor response i.e., CV (Cyclic voltammetry) and LSV (Linear sweep voltammetry), which exhibited great detection capability towards dengue virus with the range of 0.1 µg/ml to 1000 µg/ml along with a detection limit of 0.1 µg/ml and showing no reactivity to the chikungunya virus antigen, making it more specific to the DENV antigen. Serum (healthy-human) was also successfully applied to validate the results of the constructed aptasensor. Integration of the Kirigami approach form with the electrochemical aptasensor that utilizes a 3-E setup (three-electrode setup) which is referred to as a tripod and collectively called Kirigami-tripod-based aptasensor. Thus, the developed integrated platform improves the sensors capabilities in terms of cost efficiency, high stretchability, and sensitivity.

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