-
Current Opinion in Structural Biology Oct 2021Microfluidic systems under laminar flow conditions provide in-solution information about species size and binding affinities at very modest sample costs. Flow-induced... (Review)
Review
Microfluidic systems under laminar flow conditions provide in-solution information about species size and binding affinities at very modest sample costs. Flow-induced dispersion analysis directly measures the spread of the analyte profile using Taylor dispersion analysis, whereas microfluidic diffusional sizing quantifies the transfer of analyte from one phase to another. Species of sizes between 0.5 and 1000 nm can be analyzed, and different populations resolved. Both techniques also allow analysis in complex media and medium throughput analysis. These properties make them valuable complements to existing approaches to measure biomolecular interactions.
Topics: Diffusion; Microfluidics
PubMed: 33831785
DOI: 10.1016/j.sbi.2021.02.006 -
Current Neuropharmacology 2016Dissociated primary neuronal cell culture remains an indispensable approach for neurobiology research in order to investigate basic mechanisms underlying diverse... (Review)
Review
Dissociated primary neuronal cell culture remains an indispensable approach for neurobiology research in order to investigate basic mechanisms underlying diverse neuronal functions, drug screening and pharmacological investigation. Compartmentalization, a widely adopted technique since its emergence in 1970s enables spatial segregation of neuronal segments and detailed investigation that is otherwise limited with traditional culture methods. Although these compartmental chambers (e.g. Campenot chamber) have been proven valuable for the investigation of Peripheral Nervous System (PNS) neurons and to some extent within Central Nervous System (CNS) neurons, their utility has remained limited given the arduous manufacturing process, incompatibility with high-resolution optical imaging and limited throughput. The development in the area of microfabrication and microfluidics has enabled creation of next generation compartmentalized devices that are cheap, easy to manufacture, require reduced sample volumes, enable precise control over the cellular microenvironment both spatially as well as temporally, and permit highthroughput testing. In this review we briefly evaluate the various compartmentalization tools used for neurobiological research, and highlight application of the emerging microfluidic platforms towards in vitro single cell neurobiology.
Topics: Animals; Biomedical Research; Cell Culture Techniques; Drug Evaluation, Preclinical; Humans; Microfluidics; Neurons; Pharmaceutical Preparations
PubMed: 26813122
DOI: 10.2174/1570159x13666150516000957 -
Lab on a Chip Feb 2024Microbial life is at the heart of many diverse environments and regulates most natural processes, from the functioning of animal organs to the cycling of global carbon.... (Review)
Review
Microbial life is at the heart of many diverse environments and regulates most natural processes, from the functioning of animal organs to the cycling of global carbon. Yet, the study of microbial ecology is often limited by challenges in visualizing microbial processes and replicating the environmental conditions under which they unfold. Microfluidics operates at the characteristic scale at which microorganisms live and perform their functions, thus allowing for the observation and quantification of behaviors such as growth, motility, and responses to external cues, often with greater detail than classical techniques. By enabling a high degree of control in space and time of environmental conditions such as nutrient gradients, pH levels, and fluid flow patterns, microfluidics further provides the opportunity to study microbial processes in conditions that mimic the natural settings harboring microbial life. In this review, we describe how recent applications of microfluidic systems to microbial ecology have enriched our understanding of microbial life and microbial communities. We highlight discoveries enabled by microfluidic approaches ranging from single-cell behaviors to the functioning of multi-cellular communities, and we indicate potential future opportunities to use microfluidics to further advance our understanding of microbial processes and their implications.
Topics: Animals; Microfluidics; Ecology
PubMed: 38344937
DOI: 10.1039/d3lc00784g -
Theranostics 2023There has been a long-standing interest in point-of-care (POC) diagnostics as a tool to improve patient care because it can provide rapid, actionable results near the... (Review)
Review
There has been a long-standing interest in point-of-care (POC) diagnostics as a tool to improve patient care because it can provide rapid, actionable results near the patient. Some of the successful examples of POC testing include lateral flow assays, urine dipsticks, and glucometers. Unfortunately, POC analysis is somewhat limited by the ability to manufacture simple devices to selectively measure disease specific biomarkers and the need for invasive biological sampling. Next generation POCs are being developed that make use of microfluidic devices to detect biomarkers in biological fluids in a non-invasive manner, addressing the above-mentioned limitations. Microfluidic devices are desirable because they can provide the ability to perform additional sample processing steps not available in existing commercial diagnostics. As a result, they can provide more sensitive and selective analysis. While most POC methods make use of blood or urine as a sample matrix, there has been a growing push to use saliva as a diagnostic medium. Saliva represents an ideal non-invasive biofluid for detecting biomarkers because it is readily available in large quantities and analyte levels reflect those in blood. However, using saliva in microfluidic devices for POC diagnostics is a relatively new and an emerging field. The overarching aim of this review is to provide an update on recent literature focused on the use of saliva as a biological sample matrix in microfluidic devices. We will first cover the characteristics of saliva as a sample medium and then review microfluidic devices that are developed for the analysis of salivary biomarkers.
Topics: Humans; Microfluidics; Point-of-Care Systems; Saliva; Point-of-Care Testing; Lab-On-A-Chip Devices; Biomarkers
PubMed: 36793864
DOI: 10.7150/thno.78872 -
Nature Reviews. Molecular Cell Biology Sep 2015The underlying physical properties of microfluidic tools have led to new biological insights through the development of microsystems that can manipulate, mimic and... (Review)
Review
The underlying physical properties of microfluidic tools have led to new biological insights through the development of microsystems that can manipulate, mimic and measure biology at a resolution that has not been possible with macroscale tools. Microsystems readily handle sub-microlitre volumes, precisely route predictable laminar fluid flows and match both perturbations and measurements to the length scales and timescales of biological systems. The advent of fabrication techniques that do not require highly specialized engineering facilities is fuelling the broad dissemination of microfluidic systems and their adaptation to specific biological questions. We describe how our understanding of molecular and cell biology is being and will continue to be advanced by precision microfluidic approaches and posit that microfluidic tools - in conjunction with advanced imaging, bioinformatics and molecular biology approaches - will transform biology into a precision science.
Topics: Animals; Biological Assay; Gene Expression Profiling; Genomics; Humans; Microfluidic Analytical Techniques; Microfluidics; Models, Biological; Single-Cell Analysis
PubMed: 26296163
DOI: 10.1038/nrm4041 -
Nature Communications Jun 2020Non-invasive and label-free calorimetry could become a disruptive technique to study single cell metabolic heat production without altering the cell behavior, but it is...
Non-invasive and label-free calorimetry could become a disruptive technique to study single cell metabolic heat production without altering the cell behavior, but it is currently limited by insufficient sensitivity. Here, we demonstrate microfluidic single-cell calorimetry with 0.2-nW sensitivity, representing more than ten-fold enhancement over previous record, which is enabled by (i) a low-noise thermometry platform with ultralow long-term (10-h) temperature noise (80 μK) and (ii) a microfluidic channel-in-vacuum design allowing cell flow and nutrient delivery while maintaining a low thermal conductance of 2.5 μW K. Using Tetrahymena thermophila as an example, we demonstrate on-chip single-cell calorimetry measurement with metabolic heat rates ranging from 1 to 4 nW, which are found to correlate well with the cell size. Finally, we perform real-time monitoring of metabolic rate stimulation by introducing a mitochondrial uncoupling agent to the microchannel, enabling determination of the spare respiratory capacity of the cells.
Topics: Basal Metabolism; Calorimetry; Microfluidic Analytical Techniques; Microfluidics; Mitochondria; Oxygen Consumption; Single-Cell Analysis; Temperature; Tetrahymena thermophila; Thermal Conductivity
PubMed: 32532969
DOI: 10.1038/s41467-020-16697-5 -
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 -
Lab on a Chip May 2016In the last two decades, the vast majority of microfluidic systems have been built in poly(dimethylsiloxane) (PDMS) by soft lithography, a technique based on PDMS... (Review)
Review
In the last two decades, the vast majority of microfluidic systems have been built in poly(dimethylsiloxane) (PDMS) by soft lithography, a technique based on PDMS micromolding. A long list of key PDMS properties have contributed to the success of soft lithography: PDMS is biocompatible, elastomeric, transparent, gas-permeable, water-impermeable, fairly inexpensive, copyright-free, and rapidly prototyped with high precision using simple procedures. However, the fabrication process typically involves substantial human labor, which tends to make PDMS devices difficult to disseminate outside of research labs, and the layered molding limits the 3D complexity of the devices that can be produced. 3D-printing has recently attracted attention as a way to fabricate microfluidic systems due to its automated, assembly-free 3D fabrication, rapidly decreasing costs, and fast-improving resolution and throughput. Resins with properties approaching those of PDMS are being developed. Here we review past and recent efforts in 3D-printing of microfluidic systems. We compare the salient features of PDMS molding with those of 3D-printing and we give an overview of the critical barriers that have prevented the adoption of 3D-printing by microfluidic developers, namely resolution, throughput, and resin biocompatibility. We also evaluate the various forces that are persuading researchers to abandon PDMS molding in favor of 3D-printing in growing numbers.
Topics: Dimethylpolysiloxanes; Equipment Design; Lab-On-A-Chip Devices; Microfluidics; Printing, Three-Dimensional
PubMed: 27101171
DOI: 10.1039/c6lc00163g -
Cytometry. Part a : the Journal of the... Oct 2018Last decade's advancements in optofluidics allowed obtaining an ever increasing integration of different functionalities in lab on chip devices to culture, analyze, and... (Review)
Review
Last decade's advancements in optofluidics allowed obtaining an ever increasing integration of different functionalities in lab on chip devices to culture, analyze, and manipulate single cells and entire biological specimens. Despite the importance of optical imaging for biological sample monitoring in microfluidics, imaging is traditionally achieved by placing microfluidics channels in standard bench-top optical microscopes. Recently, the development of either integrated optical elements or lensless imaging methods allowed optical imaging techniques to be implemented in lab on chip systems, thus increasing their automation, compactness, and portability. In this review, we discuss known solutions to implement microscopes on chip that exploit different optical methods such as bright-field, phase contrast, holographic, and fluorescence microscopy.
Topics: Automation; Holography; Humans; Lab-On-A-Chip Devices; Microfluidic Analytical Techniques; Microfluidics; Microscopy; Optical Imaging
PubMed: 30211977
DOI: 10.1002/cyto.a.23589 -
Biosensors & Bioelectronics Feb 2023The effective analysis of the basic structure and functional information of bioparticles are of great significance for the early diagnosis of diseases. The synergism... (Review)
Review
The effective analysis of the basic structure and functional information of bioparticles are of great significance for the early diagnosis of diseases. The synergism between microfluidics and particle manipulation/detection technologies offers enhanced system integration capability and test accuracy for the detection of various bioparticles. Most microfluidic detection platforms are based on optical strategies such as fluorescence, absorbance, and image recognition. Although optical microfluidic platforms have proven their capabilities in the practical clinical detection of bioparticles, shortcomings such as expensive components and whole bulky devices have limited their practicality in the development of point-of-care testing (POCT) systems to be used in remote and underdeveloped areas. Therefore, there is an urgent need to develop cost-effective non-optical microfluidic platforms for bioparticle detection that can act as alternatives to optical counterparts. In this review, we first briefly summarise passive and active methods for bioparticle manipulation in microfluidics. Then, we survey the latest progress in non-optical microfluidic strategies based on electrical, magnetic, and acoustic techniques for bioparticle detection. Finally, a perspective is offered, clarifying challenges faced by current non-optical platforms in developing practical POCT devices and clinical applications.
Topics: Microfluidics; Biosensing Techniques; Point-of-Care Testing; Point-of-Care Systems; Microfluidic Analytical Techniques; Lab-On-A-Chip Devices
PubMed: 36470061
DOI: 10.1016/j.bios.2022.114944