What is Microfluidics?

What is Microfluidics?

author:

Heeho Ryu

Posted On:

2024-07-10

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Microfluidics 101

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Introduction

Microfluidics is a fascinating and rapidly evolving field dealing with the behavior, control, and analysis of fluids at an extremely small scale (10 –9 to 10 –18 liters). That’s smaller than a single droplet! Think of microfluidics as plumbing on a tiny, almost microscopic level.

With roots in microelectronics, biodefense, and molecular biology and analysis, microfluidics arose from the need to conduct precise, sensitive, compact, and versatile chemical and biological analyses. Its application and relevance span across a diverse array of fields from diagnostics, drug discovery, biotechnology, environmental monitoring, food safety and science, materials production, and much more.

New and exciting possibilities in scientific research and development have been made possible thanks to microfluidics, and it has revolutionized the way we approach and solve complex scientific challenges. In essence, microfluidics is a tiny technology making huge splashes across the world.

How does it work?

At its core, microfluidics involves the movement of liquids through microchannels and chambers on custom chips and cartridges that range from submicron to few millimeters. Fluid dynamics and behaviour at this scale are quite different from those we experience in everyday life, and scientists and engineers take advantage of these differences to achieve precise control over the fluids Laminar flow, for instance, is a unique fluid property at small scales, where fluids move smoothly without mixing turbulently.

Microfluidic systems excel in manipulating multiphase flows to create uniform bubbles and droplets (Whites, 2006).

These tiny channels and reservoirs are molded, machined, or engraved into materials like glass, silicon, or polymers, and even paper, and directed using different methods (Sackmann 2014..?;). This includes pressure, electric fields, or capillary action (that’s the same principle of how plants draw water up from their roots) that can precisely move liquid in the chips and cartridges at a rate of 1-10,000 μL per minute.

Microelectronic and mechanical parts, particularly valves and pumps, are used for the pressure-driven flow, while sensors are used for monitoring and detection, and integrated software or firmware for the control of the microfluidic system. By intentionally designing and changing the shape and arrangement of the microchannels and electro-mechanical parts being used, the tiny fluids can be mixed, separated, and directed to react with each other (10), and even be linked to a macro-environment.

The fabrication of these devices leverages cost-effective methods such as wax printing, 3D printing, inkjet printing, screen printing, micromilling, laser cutting, and xurography. (Mesquita 2022)

What’s so great about microfluidics?

Microfluidics offers several key advantages that benefit multiple industries and sectors. These include:

  • Precision and Control: Greater control of flow allows the ability to precisely mix and separate fluids. Conduct controlled chemical reactions. You can precisely control and manipulate tiny amounts of liquids (Sackmann 2014), which is crucial in experiments and applications requiring high accuracy (2). High resolution and sensitivity in detecting and separating molecules. laminar or smooth flow of fluids in tiny channels allows greater flow control. greater control of experimental parameters and sample concentration at the micro scale. accurate measurement, increase measurement resolutions. Precise, automated processes that deliver high-yield results in real time. high-throughput, multiplexed, and highly parallelled assays.
  • Speed: Small volumes allow for rapid sample processing, meaning analyses can be done much faster. Quicker heating, cooling, and mixing of substances means shorter reactions and separation times.
  • Cost-Efficient: Using miniscule amounts of reagents and samples, rapid analysis times, and low energy consumption reduces costs, making experiments more economical and and ecological compared to huge machines in the lab.
  • Customizable: Microfluidic devices are highly customizable, where devices can be tailored to meet the specific needs of each user. Devices can be fabricated using a range of materials that is best suited for each application and manufacturing needs. Microfluidic systems can integrate multiple functions into a single device, and handle a range of fluidic operations, including mixing, separation, and detection.
  • Portability: Devices can be made compact and portable, leading to innovations in point-of-care applications and innovations like lab-on-a-chip technologies.
  • Safety: limits exposure to hazardous actors (i.e. antibodies and radiopharmaceuticals)
What are some examples of microfluidics in action?

Microfluidic systems and devices have a wide range of applications across various fields. Here are some of the most impactful ones:

  1. Lab-on-a-chip and Medical Diagnostics:
    Lab-on-a-chip (LOC) devices integrate and automate multiple laboratory functions into a single, tiny platform, allowing complex syntheses and analyses of various chemicals and fluids with high resolutions, and minimal sample preparation and reagent consumption. Microfluidics and LOC devices has revolutionized point-of-care testing, where small samples of blood, saliva, or other bodily fluids can be quickly analyzed to test for conditions like pregnancy and diabetes, as well as diagnose cancer and diseases such as HIV/AIDS, tuberculosis, malaria, COVID-19, and other emerging diseases.

    LOC devices have made diagnostics not only faster and more efficient, but also more accessible. Portable and easy to use LOC devices play a crucial role in screening and monitoring treatments in remote and resource-limited settings, significantly enhancing global health outcomes by providing affordable and accessible diagnostic tools in developing countries where traditional laboratory infrastructure may not be available.
  2. Organs-on-chips and :
    Organs-on-chip (OoC) is 3D cell culture microdevices that aim to preproduce the key functions of living organs on a computer chip. These microfluidic devices are more efficient than conventional cell culture techniques as they are able to mimic microenvironments while influencing organ function. This allows for extensive research on human physiology for specific organs, leading to advancement in artificial disease models. Organs on chips use microfluidics and microfabrication technologies to better replicate the functionalities of living organs. Among them we can find models like gut on a chip, heart on a chip, liver on a chip, lung on a chip, tumor on a chip, muscle on a chip, multiple organs on a chip etc.

    the development of organ-on-a-chip systems has opened new avenues for creating more physiologically relevant in vitro models, which can mimic the functions of human organs and tissues. ((Sackmann 2014)

    Organ-on-a-chip: Cell culture and tissue engineering – microfluidics can simulate in vitro environment for applications that use live tissue, aiding lab-grown tissue development, building artificial structures that resembe and perfuse like the natural counterparts. organ-on-a-chip devices simulate the behaviour of an entire human organ. provide a more accurate model for drug development, disease modelling, and personalized medicine than existing conventional methods.

    Organs-on-chips represent a groundbreaking advancement in the field of drug discovery and development. These microengineered devices mimic the intricate structure and function of human organs, offering a more accurate and predictive platform for preclinical testing. The integration of cell biology, microfabrication, and microfluidics technologies allows these devices to recreate the complex 3D microarchitecture, tissue-tissue interfaces, and mechanical and biochemical microenvironments of human organs. (Esch 2015). The primary aim of organs-on-chips is to improve the accuracy of preclinical predictions regarding human drug responses, thereby reducing the high costs and failure rates associated with clinical trials. These devices have shown significant promise in various stages of drug discovery. For instance, they are used for target identification and validation, providing insights into interactions such as chemokine-mediated cancer metastasis. Additionally, they serve as effective platforms for drug screening, allowing researchers to test drug efficacy and toxicity in 3D models that better mimic human physiology compared to traditional 2D cell cultures or animal models. One of the notable advantages of organs-on-chips is their ability to provide real-time visualization and high-resolution analysis of biological processes, something that is often challenging with conventional models. This capability enhances our understanding of drug mechanisms and potential side effects, ultimately leading to more informed decisions in drug development.

    Organs-on-chips (OoCs) represent a significant advancement in the field of biomedical research, offering a new way to replicate human organ functions using microfluidic technology. These devices combine the latest developments in tissue engineering, microfabrication, and microfluidics to create systems that can guide and manipulate small volumes of fluids through networks of microchannels. By incorporating primary cells, stem cell-derived cells, and complex 3D cultures, OoCs can replicate key physiological and biochemical functions of human organs. The primary goal of OoCs is to provide a more accurate representation of human physiology than traditional in vitro models, which often fail to mimic the complexities of human organs. This enhanced mimicry is particularly valuable in drug discovery and development, where OoCs can provide more predictive data on human responses to new drugs. This reduces the reliance on animal testing and helps to identify potential side effects earlier in the drug development process. OoCs also hold great promise for disease modeling, allowing researchers to study disease mechanisms and test new treatments in a controlled environment that closely mimics human physiology. In toxicology, these devices can assess the safety and efficacy of new compounds, providing crucial information for regulatory approval. (Leung 2022)

    OOACs are microfluidic devices that replicate the structure and function of human organs, providing a more accurate representation of human physiology compared to traditional 2D cultures and animal models. By combining cell biology, engineering, and biomaterials, these devices create a microenvironment that simulates human organ systems, allowing for precise control and monitoring of physiological processes. One of the primary applications of OOAC technology is in drug development. These devices are used to test the efficacy and toxicity of new drugs, providing valuable data that can help reduce the reliance on animal testing and improve the accuracy of preclinical predictions. Additionally, OOAC models are instrumental in disease modeling, enabling researchers to study specific disease mechanisms and test potential therapies in a controlled environment. OOACs offer several key benefits over traditional models. They mimic human organ function more closely, allowing for real-time observation and analysis of biological processes. This capability is particularly valuable for studying dynamic interactions and responses within the human body. (Wu 2020)’on-a-chip’ biomimetic systems that contain living human stem cells that replicate human physiology – kidneys, livers, lungs, and hearts have already been successfully transferred to organ-on-a-chip devices in lab settings, while tumor-on-a-chip platforms diligently monitor cancer progression and test the effectivenes of certain therapies. this technology can provide personalized treatments, more accurate models for drug development, and disease modelling, and reduce animal testing.
  3. Drug Discovery and Development: Pharmaceutical companies use microfluidics to screen thousands of drug candidates rapidly. This technology helps in identifying promising drugs more quickly and efficiently (7) – mimicking in vivo conditions, labs-on-a-chip enable how cell type interacts with certain drugs and the efficacy of that drug before its even prescribed to the patient
  4. Biotechnology: Scientists use microfluidics for tasks like DNA analysis, cell sorting, and studying biochemical reactions in real-time. This helps in understanding complex biological processes and developing new therapies (8).
  5. Therapeutic applications include screening candidate antibodies, testing drug toxicity, and developing lipid nanoparticles for drug delivery, providing numerous opportunities for therapeutic discovery and validation. (Battat 2022)
  6. Food science: monitor quality of perishables in food and beverage industry; Microfluidics also plays a crucial role in food and consumer product safety. It helps detect foodborne pathogens, ensures proper food labelling, and maintains quality control. In materials production, microfluidic devices enable the continuous synthesis of chemicals, the creation of core-shell particles, and the development of advanced drug delivery systems. (Battat 2022)

  1. DNA sequencing – which looks at the order in which the 4 building blocks – adenine, cytosine, guanine, and thymine, make up an individual molecule, microfluidics is used to pair individual cells with tiny DNA barcoded ‘gel beads’ for single-cell sequencing. DNA sequencing and genomic single-cell analysis.
  2. Gene editing: help downsize and automate gene-editing workflow; the miniature, droplet-based mechanisms deliver gene-editing materials directly to a cell, where it can insert, replace, or delete parts of a DNA sequence with precision and accuracy. This practice would be used to correct known mutations that cause cancers and other genetic diseases.
  3. Environmental Monitoring: Microfluidic devices can detect pollutants in water and air, providing real-time data to monitor environmental health (9). – identify contaminants in drinking sources, track biothreats in national defense,

    Microfluidic systems, or lab-on-a-chip (LOC) devices, are miniaturized platforms that incorporate various analytical techniques, such as chromatography, electrophoresis, and flow injection analysis. These systems are designed to detect a wide range of environmental pollutants, including heavy metals, volatile organic compounds (VOCs), ions, fine particulate matter, and microorganisms in both water and air samples. The integration of these techniques into LOC systems allows for rapid and efficient analysis with minimal sample preparation. In addition to detection, microfluidic technologies also play a crucial role in environmental remediation. Droplet-based microfluidics, for example, enables the production of functional materials that can separate and remove pollutants. Photocatalytic microreactors, which utilize visible light to decompose organic pollutants in water, are one such example. Droplet-based systems can also fabricate emulsions and microparticles with precise control over their size and morphology, enhancing their effectiveness in pollutant removal. Innovations in droplet-based microfluidics have led to the development of monodisperse emulsions and functional microparticles. Materials like chitosan, carbon nanotubes, and microporous polymers are being used to create advanced adsorbents for pollutant removal. These materials offer high surface areas and customizable properties, making them highly effective for environmental applications.(Yew 2019)

    low-cost microfluidic technologies for environmental applications. These technologies aim to provide affordable and efficient tools for monitoring and assessing environmental quality, particularly in water, air, and soil. One of the primary applications of these low-cost microfluidic devices is in water quality monitoring. They are used to detect various contaminants, including heavy metals like lead, mercury, and silver, as well as non-metal pollutants such as pesticides, pharmaceutical residues, and microplastics. Additionally, these devices can identify waterborne microorganisms like E. coli and SARS-CoV-2, making them valuable for public health monitoring. In air quality monitoring, microfluidic devices detect airborne trace metals and non-metal pollutants, as well as airborne microorganisms. For soil quality monitoring, they are used to detect heavy metals and non-metallic pollutants and to extract and identify contaminants such as pyrene and pesticides. (Mesquita 2022).
  4. Water Quality Analysis: Traditional, labor-intensive methods of water quality analysis — such as collecting samples from different locations, delivering them to a lab, then running them through tests — pale in comparison to microfluidic alternatives that can deliver on-site results in real time. A range of tools, from electrode systems to paper test strips, can be used to detect and quantify pollutants and contaminants in a water source.
  5. Air Quality Analysis: Microfluidic devices can be used to detect particulate matter in the air as well as gaseous pollutants, like a carbon monoxide detector. Some models may even be equipped to monitor the presence of airborne pathogens or allergens by capturing floating microorganisms, such as bacteria or mold spores, then reporting its air-quality findings via a readout.
  6. Microplastic Pollution: Given its molecular-level sorting capabilities, microfluidics may be a viable filtering method to combing out microplastics from the ecosystem. A 2023 study published in the journal Biosensors outlines several proven methods of using microfluidics as a separation tool, ranging from acoustic forces activated by piezoelectric actuators to electrical and mass-based approaches.

Flow Cytometry

Mass spectometry

PCR Amplification

immuno assays

research into antibiotic drug resistant bacteria, nanoparticle transport in blood, observation of chemical reaction kinetics

mesuring molecular diffusion coefficients, fluid viscosity, pH, and chemical binding coefficient

Future of Microfluidics

Microfluidics might sound like science fiction, but it’s very much a part of our present reality, revolutionizing fields from healthcare, food and beverage, and research, to environmental science. By understanding and manipulating fluids on a microscopic scale, researchers and engineers are creating powerful tools that are making our world healthier, cleaner, and more efficient. Whether it’s diagnosing diseases faster, developing new drugs, or monitoring the environment, microfluidics is a tiny technology with a huge impact.

Partner with DropLab today to find out how microfluidics can revolutionize your work.

References and Further Reading
  1. Whitesides GM. The origins and the future of microfluidics. Nature. 2006;442(7101):368-373.
  2. Sackmann EK, Fulton AL, Beebe DJ. The present and future role of microfluidics in biomedical research. Nature. 2014;507(7491):181-189.
  3. Battat S, Weitz DA, Whitesides GM. An outlook on microfluidics: the promise and the challenge.
  4. Squires TM, Quake SR. Microfluidics: Fluid physics at the nanoliter scale. Rev Mod Phys. 2005;77(3):977-1026.
  5. Yager P, et al. Microfluidic diagnostic technologies for global public health. Nature. 2006;442(7101):412-418.
  6. Chin CD, et al. Microfluidics-based diagnostics of infectious diseases in the developing world. Nat Med. 2011;17(8):1015-1019.
  7. Wang C, et al. Point-of-care diagnostics for infectious diseases: From methods to devices. Nano Today. 2021;37:101092.
  8. Neil C, Nikolaj G. 30 years of microfluidics. 2019.
  9. Esch 2015. Organs-on-chips at the frontiers of drug discovery
  10. Leung 2022. A guide to the organ-on-a-chip
  11. Wu 2022. Organ-on-a-chip: recent breakthroughs and future prospects
  12. Yew 2019. A review of state-of-the-art microfluidic technologies for environmental applications: detection and remediation.
  13. Mesquita 2022. Low-cost microfluidics.

Mark D, et al. Microfluidic lab-on-a-chip platforms: requirements, characteristics and applications. Chem Soc Rev. 2010;39(3):1153-1182.

Dittrich PS, Manz A. Lab-on-a-chip: microfluidics in drug discovery. Nat Rev Drug Discov. 2006;5(3):210-218.

Neuzil P, et al. Revisiting lab-on-a-chip technology for drug discovery. Nat Rev Drug Discov. 2012;11(8):620-632.

Wu M-H, Huang S-B, Lee G-B. Microfluidic cell culture systems for drug research. Lab Chip. 2010;10(8):939-956.

Weibel DB, DiLuzio WR, Whitesides GM. Microfabrication meets microbiology. Nat Rev Microbiol. 2007;5(3):209-218.

Stone HA, Stroock AD, Ajdari A. Engineering flows in small devices: microfluidics toward a lab-on-a-chip. Annu Rev Fluid Mech. 2004;36:381-411.

Martin CJ, et al. Integration of microfluidics with proteomics: a review. Proteomics. 2013;13(3-4):335-352.

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