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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 -
Scientific Reports Aug 2022Droplet microfluidics has in recent years found a wide range of analytical and bioanalytical applications. In droplet microfluidics, the samples that are discretized...
Droplet microfluidics has in recent years found a wide range of analytical and bioanalytical applications. In droplet microfluidics, the samples that are discretized into droplets within the devices are predominantly loaded through tubings, but such tubing-based sample loading has drawbacks such as limited scalability for processing many samples, difficulty for automation, and sample wastage. While advances in autosamplers have alleviated some of these drawbacks, sample loading that can instead obviate tubings offers a potentially promising alternative but has been underexplored. To fill the gap, we introduce herein a droplet device that features a new Tubing Eliminated Sample Loading Interface (TESLI). TESLI integrates a network of programmable pneumatic microvalves that regulate vacuum and pressure sources so that successive sub-microliter samples can be directly spotted onto the open-to-atmosphere TESLI inlet, vacuumed into the device, and pressurized into nanoliter droplets within the device with minimal wastage. The same vacuum and pressure regulation also endows TESLI with cleaning and sample switching capabilities, thus enabling scalable processing of many samples in succession. Moreover, we implement a pair of TESLIs in our device to parallelize and alternate their operation as means to minimizing idle time. For demonstration, we use our device to successively process 44 samples into droplets-a number that can further scale. Our results demonstrate the feasibility of tubing-free sample loading and a promising approach for advancing droplet microfluidics.
Topics: Automation; Microfluidic Analytical Techniques; Microfluidics
PubMed: 35922529
DOI: 10.1038/s41598-022-17352-3 -
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 -
Nucleic Acids Research Feb 2016Microfluidics may revolutionize our ability to write synthetic DNA by addressing several fundamental limitations associated with generating novel genetic constructs....
Microfluidics may revolutionize our ability to write synthetic DNA by addressing several fundamental limitations associated with generating novel genetic constructs. Here we report the first de novo synthesis and cell-free cloning of custom DNA libraries in sub-microliter reaction droplets using programmable digital microfluidics. Specifically, we developed Programmable Order Polymerization (POP), Microfluidic Combinatorial Assembly of DNA (M-CAD) and Microfluidic In-vitro Cloning (MIC) and applied them to de novo synthesis, combinatorial assembly and cell-free cloning of genes, respectively. Proof-of-concept for these methods was demonstrated by programming an autonomous microfluidic system to construct and clone libraries of yeast ribosome binding sites and bacterial Azurine, which were then retrieved in individual droplets and validated. The ability to rapidly and robustly generate designer DNA molecules in an autonomous manner should have wide application in biological research and development.
Topics: Cell-Free System; Cloning, Molecular; DNA; Gene Library; Microfluidics
PubMed: 26481354
DOI: 10.1093/nar/gkv1087 -
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 -
Frontiers in Immunology 2018The field of immunoengineering aims to develop novel therapies and modern vaccines to manipulate and modulate the immune system and applies innovative technologies... (Review)
Review
The field of immunoengineering aims to develop novel therapies and modern vaccines to manipulate and modulate the immune system and applies innovative technologies toward improved understanding of the immune system in health and disease. Microfluidics has proven to be an excellent technology for analytics in biology and chemistry. From simple microsystem chips to complex microfluidic designs, these platforms have witnessed an immense growth over the last decades with frequent emergence of new designs. Microfluidics provides a highly robust and precise tool which led to its widespread application in single-cell analysis of immune cells. Single-cell analysis allows scientists to account for the heterogeneous behavior of immune cells which often gets overshadowed when conventional bulk study methods are used. Application of single-cell analysis using microfluidics has facilitated the identification of several novel functional immune cell subsets, quantification of signaling molecules, and understanding of cellular communication and signaling pathways. Single-cell analysis research in combination with microfluidics has paved the way for the development of novel therapies, point-of-care diagnostics, and even more complex microfluidic platforms that aid in creating cellular microenvironments for applications in drug and toxicity screening. In this review, we provide a comprehensive overview on the integration of microsystems and microfluidics with immunology and focus on different designs developed to decode single immune cell behavior and cellular communication. We have categorized the microfluidic designs in three specific categories: microfluidic chips with cell traps, valve-based microfluidics, and droplet microfluidics that have facilitated the ongoing research in the field of immunology at single-cell level.
Topics: Animals; Cell Communication; Humans; Immune System; Immunoassay; Microfluidic Analytical Techniques; Microfluidics; Single-Cell Analysis
PubMed: 30459757
DOI: 10.3389/fimmu.2018.02373 -
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 -
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 -
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 -
Cytometry. Part a : the Journal of the... Jul 2010Microfabricated flow cytometers can detect, count, and analyze cells or particles using microfluidics and electronics to give impedance-based characterization. Such... (Review)
Review
Microfabricated flow cytometers can detect, count, and analyze cells or particles using microfluidics and electronics to give impedance-based characterization. Such systems are being developed to provide simple, low-cost, label-free, and portable solutions for cell analysis. Recent work using microfabricated systems has demonstrated the capability to analyze micro-organisms, erythrocytes, leukocytes, and animal and human cell lines. Multifrequency impedance measurements can give multiparametric, high-content data that can be used to distinguish cell types. New combinations of microfluidic sample handling design and microscale flow phenomena have been used to focus and position cells within the channel for improved sensitivity. Robust designs will enable focusing at high flowrates while reducing requirements for control over multiple sample and sheath flows. Although microfluidic impedance-based flow cytometers have not yet or may never reach the extremely high throughput of conventional flow cytometers, the advantages of portability, simplicity, and ability to analyze single cells in small populations are, nevertheless, where chip-based cytometry can make a large impact.
Topics: Animals; Cell Death; Cell Differentiation; Cell Physiological Phenomena; Cell Survival; Electric Impedance; Equipment Design; Flow Cytometry; Humans; Microfluidics; Sensitivity and Specificity
PubMed: 20583276
DOI: 10.1002/cyto.a.20910