About microfluidics

Lab-on-a-Chip and microfluidics in a nutshell

WHAT IS MICROFLUIDICS?

Minituarization is the key

Life sciences, medicine and diagnostics are currently undergoing a similar development as electronics did in the 1950s. The major trends driving this change are miniaturization and functional integration. The key principle enabling these advancements is microfluidics, which forms the fundamental basis for the development of µTAS (miniaturized total analysis systems) and complex Lab-on-a-Chip devices. These devices integrate multiple laboratory funtions into single systems.

Microfluidics is the science and technology of systems that process or manipulate extremely small volumes of fluids (10–6 to 10–12 liters), using channels with dimensions typically measured in tens to hundreds of micrometers.[1] This interdisciplinary field greatly impacts biology, chemistry, physics, and engineering, with wide-ranging applications across these areas.

Today, almost every product development in life sciences or diagnostics involves the integration of microfluidic functionality in one form or the other. This shift is driven by the numerous advantages that microfluidic technology offers over traditional equipment.

The major key in microfluidics is the principle of miniaturization. The ability to handle small liquid volumes allows for a reduction in sample and reagent volumes, which is important in case of limited sample availability (e.g. in neonatal diagnostics, protein analysis) and expensive reagents. Waste volume is reduced accordingly. Microfluidic systems facilitate highly precise liquid manipulation and sample detection with exceptional resolution and sensitivity. The reduced volumes not only accelerate reaction and analysis times but also facilitate high-throughput processing and parallelization. [1-3]

About microfluidics-1
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For commercial developments however, the most important aspect of this miniaturization is the possibility to integrate complex workflows (e.g. from molecular biology) into a single device, which allows for a hands-free sample-in result-out operation. The ability to create such integrated microfluidic cartridges and to manufacture them in high volumes has only recently been reached, which explains why the commercialization of microfluidics has been picking up speed for a few years.

microfluidic ChipShop offers you the tools and the infrastructure to fully utilize the advantages of the microfluidic technology described above for your product development.

About microfluidics-3

Advantages of microfluidics

Rapid analysis

Rapid Analysis

Saving costs

Saving Costs

Precision

High Precision

Automation

Automation & System Integration

Saving ressources

Saving Resources

Portable

Portability

The physics behind microfluidics

Understanding the science of fluids at the microscale

To understand the full benefit of microfluidic systems, it is important to first understand the physics of fluids on the microscale and how this affects their behavior.[3, 4] The effects that become dominant in microfluidics include laminar flow, diffusion, and surface tension.

Laminar Flow

The dimensionless Reynolds number (Re) describes the ratio of inertial forces to viscous forces in a fluid system and determines the flow regime—whether it is turbulent or laminar. It is defined by the equation:

Re = ρνL/µ

Here, ρ is the fluid density, ν is the flow velocity, L is the characteristic linear dimension of the system, and μ is the dynamic viscosity.

Thus, the reduction of the linear dimension L also reduces Re.

Due to the small dimensions of microchannels, flow in microfluidic systems is almost always laminar, typically with Re < 2000. Unlike turbulent flow, laminar flow is predictable and allows for precise control, which is a key advantage in microscale fluid manipulation.

In laminar flow, multiple streams can flow side by side without mixing. This is exploited in applications like hydrodynamic focusing or cell sorting.

Diffusion

One important consequence of laminar flow is that two or more fluids flowing in contact with each other will not mix, except by diffusion.

The diffusion time of a given molecule is highly reduced in a miniaturized system, leading to shorter reaction times compared to conventional systems. An approximation for diffusion time is calculated by:

t ≈ x2/2D               t ∝ x2

Here, t is the diffusion time (i.e. the time two molecules need to meet each other by random motion), D is the molecule-specific diffusion coefficient and x is the distance between these molecules (or typical length scale). If the distance x is reduced – for example, by a factor of 10 through miniaturization – the diffusion time decreases by a factor of 100.

To enhance mixing efficiency, specially designed mixing structures are used that disrupt the laminar flow and promote localized chaotic advection.

Surface tension

The behavior of a fluid’s surface differs significantly between the macroscale and the microscale. At small scales, surface tension, interfacial tension, and capillary forces become dominant, whereas gravity, the main driving force at the macroscale, becomes negligible.

As a result, fluid motion in microfluidic systems can often be driven entirely by capillary action. This principle has been successfully applied in the design of passive, pump-free analytical devices, such as blood glucose meters, lateral flow assays, and paper-based microfluidic platforms used in point-of-care diagnostics.

A specialized area of microfluidics, digital microfluidics, takes advantage of surface tension and immiscibility between fluids to generate and manipulate discrete droplets. These droplets act as isolated microreactors, enabling high-throughput screening, single-cell analysis and more.

Applications in Microfluidics

For diagnostics, biotech, and chemical innovation

Cell Culture on Chip

Cell Culture

Droplet Generation

Droplet Generation

PCR

PCR

Cell Sorting

Cell Sorting

Sample Filtration

Sample Filtration

Fluorescence Detection

Fluorescence Detection

Organ-on-a-Chip

Organ-on-a-Chip

LNP Production

LNP production

Cell-based Immunoassays

Immunoassays

Mixing

Mixing

Chemotaxis

Chemotaxis

Integrated Chips

Integrated Assays

Manufacturing Technologies for Polymer-Based Microfluidic Devices

Our CSO Holger Becker takes you on a tour through microfluidics

A Brief History of Microfluidics

How it all started

Microfluidics emerged at the intersection of molecular analysis, microelectronics, biodefense, and molecular biology. [1]

Its origins can be traced back to early microanalytical techniques such as gas chromatography and capillary electrophoresis, which transformed chemical analysis by enabling high-resolution results from minimal sample volumes.

In the 1980s, advancements in microfabrication were driven by technologies developed in the semiconductor industry. Photolithography, originally used for fabricating microelectronic circuits, was adapted to create the first microfluidic devices from glass and silicon.[5] A pioneering work came in 1979, when Terry et al. developed a miniaturized gas chromatograph on a silicon chip—one of the first examples of a “lab-on-a-chip.”[6]

In 1990, Manz et al. introduced the concept of “miniaturized total chemical analysis systems” (µTAS), which aimed to integrate all steps of chemical analysis into a single chip. [7]

The field advanced further in the 1990s with the development of soft lithography. This technology enabled the use of polydimethylsiloxane (PDMS) for microfluidics fabrication, a flexible and biocompatible material, making microfluidics more accessible for biological applications. [8, 9]

Microfluidics Timeline (adapted from Hajam, M.I. et al. [2] and Convery, N. et al. [3])
Microfluidics Timeline (adapted from Hajam, M.I. et al. [2] and Convery, N. et al. [3])

A lesser-known driver of microfluidics development was biodefense. In the 1990s, the Defense Advanced Research Projects Agency (DARPA) funded microfluidics for portable biodefense diagnostics and greatly contributed to the growth of microelectromechanical systems (MEMS).[1, 3] At the same time, the Human Genome Project accelerated demand for sensitive analysis in molecular biology.[3]

Despite the great potential of PDMS and soft lithography for rapid prototyping, they were not well translatable to high-volume production. To meet industrial demands, injection molding of thermoplastic materials became increasingly important. Injection molding evolved into a highly efficient and scalable method for producing microfluidic components with high precision and reproducibility.[3] Moreover, the broad range of thermoplastics available allows developers to select materials suited for nearly any application.[10]

Since the early 2000s, microfluidics has expanded rapidly. Innovations include paper-based microfluidics for low-cost diagnostics, [11] droplet microfluidics for high-throughput biological assays, [12, 13] and organ-on-a-chip systems that replicate human physiological processes. [2, 14] Most recently, the COVID-19 pandemic significantly accelerated innovation in microfluidics.[2] In particular, microfluidic platforms enabled the scalable and precise production of lipid nanoparticles (LNPs)—a core technology for the formulation and delivery of mRNA vaccines. [15]

Today, microfluidics is a key enabler of innovation across healthcare, diagnostics, drug development, and life sciences. The adoption of scalable, cost-effective manufacturing methods, such as injection molding, continues to enhance design flexibility and broaden the impact of microfluidic technologies.

[1] Whitesides, G. The origins and the future of microfluidics. Nature 442, 368–373 (2006), https://doi.org/10.1038/nature05058

[2] Hajam, M.I.; Khan, M.M. Microfluidics: a concise review of the history principles, design, applications, and future outlook. Biomaterial Science 12, 218–251 (2024), https://doi.org/10.1039/D3BM01463K

[3] Convery, N.; Gadegaard, N. 30 years of microfluidics. Micro and Nano Engineering 2, 76–91 (2019), https://doi.org/10.1016/j.mne.2019.01.003

[4] Beebe D.J., Mensing G.A., Walker G.M. Physics and applications of microfluidics in biology. Annual Reviews Biomedical Engineering 4, 261–286 (2002), https://doi.org/10.1146/annurev.bioeng.4.112601.125916

[5] Lathrop J.W. The Diamond Ordnance Fuze Laboratory’s Photolithographic Approach to Microcircuits. IEEE Annals of the History of Computing, 35, 48–55 (2011), https://doi.org/10.1109/MAHC.2011.83

[6] Terry, S.C.; Herman, J.H.; Angell, J.B. A gas chromatographic air analyzer fabricated on a silicon wafer, IEEE Trans Electron Devices 26, 1880–1886 (1979), https://doi.org/10.1109/T-ED.1979.19791

[7] Manz, A.; Graber, N.; Widmer, H.M. Miniaturized total chemical analysis systems: a novel concept for chemical sensing, Sensors actuators B Chemical 1, 244–248 (1990), https://doi.org/10.1016/0925-4005(90)80209-I

[8] (a) McDonald, J.C.; Whitesides, G.M. Poly(dimethylsiloxane) as a material for fabricating microfluidic devices, Account of Chemical Research Journal 35, 491–499 (2002), https://doi.org/10.1021/ar010110q. (b) Xia Y., Whitesides, G.M. Soft Lithography. Angewandte Chemie International Edition 37 550–575 (1998), doi:10.1002/(SICI)1521-3773(19980316)37:5<550::AID-ANIE550>3.0.CO;2-G. (c) Duffy, D.C.; McDonald, J.C.; Schueller, O.J.A.; Whitesides, G.M. Analytical Chemistry 70, 4974-4984 (1998), doi: https://pubs.acs.org/doi/10.1021/ac980656z

[9] Unger, M.A.; Chou, H.-P.; Thorsen, T.; et al. Monolithic microfabricated valves and pumps by multilayer soft lithography, Science 288, 113–116 (2000), https://doi.org/10.1126/science.288.5463.113

[10] Heckele, M.; Schomburg, W.K. Review on micro molding of thermoplastic polymers, Journal of Micromechanics and Microengineering 14, R1 (2003), https://doi.org/10.1088/0960-1317/14/3/R01

[11] Martinez, A.W.; Phillips, S.T.; Butte, M.J.; et al. Patterned paper as a platform for inexpensive, low-volume, portable bioassays Angewandte Chemie, International Edition 46, 1318–1320 (2007), https://doi.org/10.1002/anie.200603817

[12] Tawfik, D.S.; Griffiths, A.D. Man-made cell-like compartments for molecular evolution, Nature Biotechnology 16, 652–656 (1998), https://doi.org/10.1038/nbt0798-652

[13] Markey, A.L.; Mohr, S.; Day, P.J.R. High-throughput droplet PCR, Methods 50, 277–281 (2010), https://doi.org/10.1016/j.ymeth.2010.01.030

[14] Zhang, C.; Zhao, Z.; Rahim, N.A.A.; et al. Towards a human-on-chip: culturing multiple cell types on a chip with compartmentalized microenvironments Lab on a Chip 9, 3185–3192 (2009), https://doi.org/10.1039/B915147H

[15] Shepherd, S.J.; Han, X.; Mukalel, A.J.; et al. Throughput-scalable manufacturing of SARS-CoV-2 mRNA lipid nanoparticle vaccines, Proceedings of the National Academy of Sciences of the United States of America 120, e2303567120 (2023), https://doi.org/10.1073/pnas.2303567120

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