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Drug Metabolism and Pharmacokinetics Feb 2018Although animal experiments are indispensable for preclinical screening in the drug discovery process, various issues such as ethical considerations and species... (Review)
Review
Although animal experiments are indispensable for preclinical screening in the drug discovery process, various issues such as ethical considerations and species differences remain. To solve these issues, cell-based assays using human-derived cells have been actively pursued. However, it remains difficult to accurately predict drug efficacy, toxicity, and organs interactions, because cultivated cells often do not retain their original organ functions and morphologies in conventional in vitro cell culture systems. In the μTAS research field, which is a part of biochemical engineering, the technologies of organ-on-a-chip, based on microfluidic devices built using microfabrication, have been widely studied recently as a novel in vitro organ model. Since it is possible to physically and chemically mimic the in vitro environment by using microfluidic device technology, maintenance of cellular function and morphology, and replication of organ interactions can be realized using organ-on-a-chip devices. So far, functions of various organs and tissues, such as the lung, liver, kidney, and gut have been reproduced as in vitro models. Furthermore, a body-on-a-chip, integrating multi organ functions on a microfluidic device, has also been proposed for prediction of organ interactions. We herein provide a background of microfluidic systems, organ-on-a-chip, Body-on-a-chip technologies, and their challenges in the future.
Topics: Animals; Biochemical Phenomena; Drug Discovery; Humans; Lab-On-A-Chip Devices; Liver; Microfluidics; Pharmaceutical Preparations
PubMed: 29175062
DOI: 10.1016/j.dmpk.2017.11.003 -
Angiogenesis Nov 2022With recent progress in modeling liver organogenesis and regeneration, the lack of vasculature is becoming the bottleneck in progressing our ability to model human...
With recent progress in modeling liver organogenesis and regeneration, the lack of vasculature is becoming the bottleneck in progressing our ability to model human hepatic tissues in vitro. Here, we introduce a platform for routine grafting of liver and other tissues on an in vitro grown microvascular bed. The platform consists of 64 microfluidic chips patterned underneath a 384-well microtiter plate. Each chip allows the formation of a microvascular bed between two main lateral vessels by inducing angiogenesis. Chips consist of an open-top microfluidic chamber, which enables addition of a target tissue by manual or robotic pipetting. Upon grafting a liver microtissue, the microvascular bed undergoes anastomosis, resulting in a stable, perfusable vascular network. Interactions with vasculature were found in spheroids and organoids upon 7 days of co-culture with space of Disse-like architecture in between hepatocytes and endothelium. Veno-occlusive disease was induced by azathioprine exposure, leading to impeded perfusion of the vascularized spheroid. The platform holds the potential to replace animals with an in vitro alternative for routine grafting of spheroids, organoids, or (patient-derived) explants.
Topics: Animals; Azathioprine; Coculture Techniques; Humans; Liver; Microfluidics; Organoids
PubMed: 35704148
DOI: 10.1007/s10456-022-09842-9 -
Journal of Nanobiotechnology Mar 2023The advancement of microfluidics has enabled numerous discoveries and technologies in life sciences. However, due to the lack of industry standards and configurability,... (Review)
Review
The advancement of microfluidics has enabled numerous discoveries and technologies in life sciences. However, due to the lack of industry standards and configurability, the design and fabrication of microfluidic devices require highly skilled technicians. The diversity of microfluidic devices discourages biologists and chemists from applying this technique in their laboratories. Modular microfluidics, which integrates the standardized microfluidic modules into a whole, complex platform, brings the capability of configurability to conventional microfluidics. The exciting features, including portability, on-site deployability, and high customization motivate us to review the state-of-the-art modular microfluidics and discuss future perspectives. In this review, we first introduce the working mechanisms of the basic microfluidic modules and evaluate their feasibility as modular microfluidic components. Next, we explain the connection approaches among these microfluidic modules, and summarize the advantages of modular microfluidics over integrated microfluidics in biological applications. Finally, we discuss the challenge and future perspectives of modular microfluidics.
Topics: Microfluidics; Biological Science Disciplines; Lab-On-A-Chip Devices
PubMed: 36906553
DOI: 10.1186/s12951-023-01846-x -
Nature Communications Jun 2022New microfluidic systems for whole organism analysis and experimentation are catalyzing biological breakthroughs across many fields, from human health to fundamental... (Review)
Review
New microfluidic systems for whole organism analysis and experimentation are catalyzing biological breakthroughs across many fields, from human health to fundamental biology principles. This perspective discusses recent microfluidic tools to study intact model organisms to demonstrate the tremendous potential for these integrated approaches now and into the future. We describe these microsystems' technical features and highlight the unique advantages for precise manipulation in areas including immobilization, automated alignment, sorting, sensory, mechanical and chemical stimulation, and genetic and thermal perturbation. Our aim is to familiarize technologically focused researchers with microfluidics applications in biology research, while providing biologists an entrée to advanced microengineering techniques for model organisms.
Topics: Humans; Microfluidic Analytical Techniques; Microfluidics
PubMed: 35680898
DOI: 10.1038/s41467-022-30814-6 -
Trends in Biotechnology Jan 2023Enzymes have essential roles in catalyzing biological reactions and maintaining metabolic systems. Many in vitro enzymatic bioassays have been developed for use in... (Review)
Review
Enzymes have essential roles in catalyzing biological reactions and maintaining metabolic systems. Many in vitro enzymatic bioassays have been developed for use in industrial and research fields, such as cell biology, enzyme engineering, drug screening, and biofuel production. Of note, many of these require the use of high-throughput platforms. Although the microtiter plate remains the standard for high-throughput enzymatic bioassays, microfluidic arrays and droplet microfluidics represent emerging methods. Each has seen significant advances and offers distinct advantages; however, drawbacks in key performance metrics, including reagent consumption, reaction manipulation, reaction recovery, real-time measurement, concentration gradient range, and multiplexity, remain. Herein, we compare recent high-throughput platforms using the aforementioned metrics as criteria and provide insights into remaining challenges and future research trends.
Topics: Microfluidics; High-Throughput Screening Assays; Drug Evaluation, Preclinical; Biological Assay; Microfluidic Analytical Techniques
PubMed: 35863950
DOI: 10.1016/j.tibtech.2022.06.006 -
Advanced Science (Weinheim,... Aug 2021Innate cell function can be artificially engineered and reprogrammed by introducing biomolecules, such as DNAs, RNAs, plasmid DNAs, proteins, or nanomaterials, into the... (Review)
Review
Innate cell function can be artificially engineered and reprogrammed by introducing biomolecules, such as DNAs, RNAs, plasmid DNAs, proteins, or nanomaterials, into the cytosol or nucleus. This process of delivering exogenous cargos into living cells is referred to as intracellular delivery. For instance, clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 gene editing begins with internalizing Cas9 protein and guide RNA into cells, and chimeric antigen receptor-T (CAR-T) cells are prepared by delivering CAR genes into T lymphocytes for cancer immunotherapies. To deliver external biomolecules into cells, tools, including viral vectors, and electroporation have been traditionally used; however, they are suboptimal for achieving high levels of intracellular delivery while preserving cell viability, phenotype, and function. Notably, as emerging solutions, microfluidic and nanofluidic approaches have shown remarkable potential for addressing this open challenge. This review provides an overview of recent advances in microfluidic and nanofluidic intracellular delivery strategies and discusses new opportunities and challenges for clinical applications. Furthermore, key considerations for future efforts to develop microfluidics- and nanofluidics-enabled next-generation intracellular delivery platforms are outlined.
Topics: Gene Editing; Gene Transfer Techniques; Genetic Therapy; Humans; Microfluidics; Nanotechnology
PubMed: 34096197
DOI: 10.1002/advs.202004595 -
Lab on a Chip Oct 2022Microphysiological systems (MPSs), also known as organ-on-a-chip models, aim to recapitulate the functional components of human tissues or organs . Over the last decade,... (Review)
Review
Microphysiological systems (MPSs), also known as organ-on-a-chip models, aim to recapitulate the functional components of human tissues or organs . Over the last decade, with the advances in biomaterials, 3D bioprinting, and microfluidics, numerous MPSs have emerged with applications to study diseased and healthy tissue models. Various organs have been modeled using MPS technology, such as the heart, liver, lung, and blood-brain barrier. An important aspect of modeling is the accurate phenotypical and functional characterization of the modeled organ. However, most conventional characterization methods are invasive and destructive and do not allow continuous monitoring of the cells in culture. On the other hand, microfluidic biosensors enable in-line, real-time sensing of target molecules with an excellent limit of detection and in a non-invasive manner, thereby effectively overcoming the limitation of the traditional techniques. Consequently, microfluidic biosensors have been increasingly integrated into MPSs and used for in-line target detection. This review discusses the state-of-the-art microfluidic biosensors by providing specific examples, detailing their main advantages in monitoring MPSs, and highlighting current developments in this field. Finally, we describe the remaining challenges and potential future developments to advance the current state-of-the-art in integrated microfluidic biosensors.
Topics: Biocompatible Materials; Biosensing Techniques; Humans; Lab-On-A-Chip Devices; Liver; Microfluidics
PubMed: 36074812
DOI: 10.1039/d2lc00262k -
Small (Weinheim An Der Bergstrasse,... Apr 2018Contact lens is a ubiquitous technology used for vision correction and cosmetics. Sensing in contact lenses has emerged as a potential platform for minimally invasive...
Contact lens is a ubiquitous technology used for vision correction and cosmetics. Sensing in contact lenses has emerged as a potential platform for minimally invasive point-of-care diagnostics. Here, a microlithography method is developed to fabricate microconcavities and microchannels in a hydrogel-based contact lens via a combination of laser patterning and embedded templating. Optical microlithography parameters influencing the formation of microconcavities including ablation power (4.3 W) and beam speed (50 mm s ) are optimized to control the microconcavity depth (100 µm) and diameter (1.5 mm). The fiber templating method allows the production of microchannels having a diameter range of 100-150 µm. Leak-proof microchannel and microconcavity connections in contact lenses are validated through flow testing of artificial tear containing fluorescent microbeads (Ø = 1-2 µm). The microconcavities of contact lenses are functionalized with multiplexed fluorophores (2 µL) to demonstrate optical excitation and emission capability within the visible spectrum. The fabricated microfluidic contact lenses may have applications in ophthalmic monitoring of metabolic disorders at point-of-care settings and controlled drug release for therapeutics.
Topics: Contact Lenses; Microfluidics; Photography
PubMed: 29521022
DOI: 10.1002/smll.201704363 -
Trends in Microbiology Nov 2020While conventional in vitro culture systems and animal models have been used to study the pathogenesis of viral infections and to facilitate development of vaccines and... (Review)
Review
While conventional in vitro culture systems and animal models have been used to study the pathogenesis of viral infections and to facilitate development of vaccines and therapeutics for viral diseases, models that can accurately recapitulate human responses to infection are still lacking. Human organ-on-a-chip (Organ Chip) microfluidic culture devices that recapitulate tissue-tissue interfaces, fluid flows, mechanical cues, and organ-level physiology have been developed to narrow the gap between in vitro experimental models and human pathophysiology. Here, we describe how recent developments in Organ Chips have enabled re-creation of complex pathophysiological features of human viral infections in vitro.
Topics: Animals; Humans; Microfluidics; Organ Culture Techniques; Virology; Virus Diseases; Virus Physiological Phenomena; Viruses
PubMed: 32674988
DOI: 10.1016/j.tim.2020.06.005 -
Molecules (Basel, Switzerland) Feb 2020Haemostatic disorders are both complex and costly in relation to both their treatment and subsequent management. As leading causes of mortality worldwide, there is an... (Review)
Review
Haemostatic disorders are both complex and costly in relation to both their treatment and subsequent management. As leading causes of mortality worldwide, there is an ever-increasing drive to improve the diagnosis and prevention of haemostatic disorders. The field of microfluidic and Lab on a Chip (LOC) technologies is rapidly advancing and the important role of miniaturised diagnostics is becoming more evident in the healthcare system, with particular importance in near patient testing (NPT) and point of care (POC) settings. Microfluidic technologies present innovative solutions to diagnostic and clinical challenges which have the knock-on effect of improving health care and quality of life. In this review, both advanced microfluidic devices (R&D) and commercially available devices for the diagnosis and monitoring of haemostasis-related disorders and antithrombotic therapies, respectively, are discussed. Innovative design specifications, fabrication techniques, and modes of detection in addition to the materials used in developing micro-channels are reviewed in the context of application to the field of haemostasis.
Topics: Biosensing Techniques; Hemostasis; Hemostatic Disorders; Humans; Lab-On-A-Chip Devices; Microfluidics; Point-of-Care Systems; Quality of Life
PubMed: 32075008
DOI: 10.3390/molecules25040833