What is a Microfluidic Chip: How It Works, Fabrication, and More

Curious about how microfluidic chip technology is revolutionizing diagnostics? This article unpacks the definition of a microfluidic chip, how it works, how to fabricate it, and why it’s becoming a game-changer in medicine, research, and beyond. Get ready to explore the future—tiny but mighty!

What is a Microfluidic Chip? How Does a Microfluidic Chip Work?

A microfluidic chip, sometimes referred to as a lab-on-a-chip when integrating multiple functions, is a compact platform that manipulates and analyzes tiny fluid volumes, typically ranging from microliters to picoliters. At its heart, there is a network of tiny, interconnected channels and chambers—each carefully designed to perform specific tasks.

These channels are only a few micrometers wide and can be customized for a wide range of applications, including mixing chemicals, culturing cells, analyzing DNA, generating droplets, or even mimicking entire organs in organ-on-a-chip studies. This built-in design allows complex lab procedures to be carried out on a small, portable chip.

To use the chip, fluids such as samples, reagents, or gases are introduced through small inlet ports and exit through outlet ports after processing. These ports serve as the connection between the chip and the external world, typically through flexible tubing. The design ensures that fluids can enter and leave the system in a controlled manner, keeping everything clean and contained.

Then, the fluids inside the chip need to move through the microchannels in a controlled way. This can be done either actively or passively. In active systems, external devices like syringe pumps, peristaltic pumps, or pressure controllers are used to push or pull fluids through the chip. On the other hand, passive methods rely on natural forces, such as gravity (hydrostatic pressure) or capillary action (how water moves through a paper towel), to move the fluids.

These passive flows are simpler and don’t require external equipment, making the chip more compact and efficient.

What makes microfluidic chips especially powerful is how fluids behave at the microscale. 

When fluids flow through such tiny channels, they exhibit laminar flow, meaning the layers of liquid move smoothly in parallel without mixing on their own. This allows for greater precision in experiments. Also, the small size of the channels means that heat and molecules move quickly across short distances, speeding up reactions and improving efficiency.

Development of Microfluidics

The origins of microfluidics date back to the mid-20th century. During this time, scientists began using micro-sized channels in tools like gas chromatography and capillary electrophoresis to handle tiny fluid samples. In the 1950s, the invention of semiconductors and the first transistors laid important groundwork. By the late 1960s, microelectromechanical systems (MEMS) emerged, allowing mechanical systems to be miniaturized using silicon-based technology.

In the 1980s, researchers began adapting techniques from the microelectronics industry, such as silicon etching and micromachining, to develop devices with microscale mechanical components. This gave rise to MEMs, which were initially used in industrial applications like pressure sensors and inkjet printer heads. Around the same time, innovative fabrication methods like the LIGA process allowed for the precise creation of 3D structures using lithography and electroplating, laying further groundwork for microscale systems. Patents began to emerge describing how to guide and control fluids in these miniaturized environments, signaling the early steps toward integrated microfluidic systems.

The 1990s marked a pivotal shift as scientists started applying MEMS technology to biology and chemistry. This transition introduced a new need: precise manipulation of fluids at the microscale for tasks like sample preparation, mixing, and analysis. The concept of lab-on-a-chip began to gain traction, representing compact systems capable of performing multiple laboratory functions. A landmark moment came in 1990, when Andreas Manz and colleagues proposed the idea of miniaturized total chemical analysis systems (μTAS), which are chips that could handle every step of a chemical or biological assay, from sample input to detection.

The 2000s ushered in a boom in microfluidics research, thanks to the development of low-cost, easy-to-make chips using soft materials like PDMS (polydimethylsiloxane, a type of silicone). This made it easier for more labs to explore microfluidic applications in biology, chemistry, and medicine. Key breakthroughs followed: PCR (a DNA analysis technique) was successfully performed on a chip in 1998, and organ-on-a-chip technologies began to emerge in the 2010s. In 2015, the drop-sequencing technique, used for genetic analysis, was introduced. Since then, microfluidics has grown rapidly, powering new tools like point-of-care diagnostic devices, 3D cell culture platforms, and flexible lab-on-a-chip systems.

From its origins in semiconductor engineering to its transformation into a cornerstone of modern bioscience, microfluidics has evolved into a powerful platform for innovation over the past 30 years. Today, the field stands at an exciting crossroads, where cutting-edge trends like ultrasound integration, artificial cell systems, and machine learning are redefining what microfluidic chips can do. As advances in scalable manufacturing and system integration continue, microfluidics is poised to move beyond the lab and into widespread real-world use.

How to Build a Microfluidic Chip: Fabrication

The fabrication of microfluidic chips involves several key steps, from designing the tiny fluid channels to choosing the right materials and assembling the final device. Each step must be carefully planned based on the chip’s intended application. Let’s learn more about its fabrication process!

Material Selection

The first step is choosing the right material. This decision depends on what the chip will be used for, how harsh the working conditions are, and how important factors like cost, transparency, or chemical resistance are. Here are some common materials used:

• Glass is prized for its chemical inertness, high thermal and mechanical stability, excellent optical transparency, and compatibility with surface treatments. It supports applications requiring high precision and harsh environments, such as optical detection or high-pressure reactions. However, glass processing typically requires cleanroom facilities and longer production times, making it costlier.

• Silicon offers high-resolution patterning and excellent mechanical strength. It’s compatible with established MEMS processes such as photolithography, reactive ion etching (RIE), and micromachining. Silicon chips are ideal for integration with sensors or actuators, but are opaque, limiting their use in optically-based applications.

• Polymers (like PDMS) are widely used because they’re cheap, easy to mold, and can be mass-produced. They also work well for biological tests since they’re often transparent and biocompatible.

• Other materials, such as metals, ceramics, and hydrogels, are used for specialized applications. Metals and ceramics offer robustness for electrochemical or high-temperature environments, while hydrogels are employed for cell-laden platforms due to their permeability and biocompatibility. Increasingly, hybrid microfluidic devices combine different materials to leverage multiple functional advantages.

Designing the Microchannels

The process then begins with the design of the microchannel layout using CAD (Computer-Aided Design) software. The design dictates the geometry, depth, and connectivity of channels tailored for tasks such as mixing, sorting, droplet formation, or cell culture.

Once finalized, the design is transferred to a photomask, typically a chrome-coated glass or printed polymer film. The photomask acts as a template to define the areas to be developed or etched during the fabrication process.

Making the Microchannel Mold

For polymer-based chips (especially PDMS), photolithography is used to create a mold:

1. A negative photoresist (commonly SU-8) is spin-coated onto a silicon wafer to the desired thickness.

2. UV light is projected through the photomask onto the photoresist. The exposed areas harden.

3. The wafer is developed in a solvent, washing away unexposed areas and leaving a raised mold.

4. The mold is treated with a silanizing agent to ease demolding in the next step.

   
   

In glass or silicon chips, the photomask is used for etching:

• Wet etching (e.g., with hydrofluoric acid for glass) offers high-speed material removal but produces rounded profiles.

• Dry etching (e.g., Reactive-Ion Etching, the RIE) provides anisotropic, highly defined channel geometries but is more time-consuming.

Molding and Curing the Chip (for Polymer Replication)

For soft lithography, a liquid polymer mixture (e.g., PDMS base and curing agent) is poured over the master mold and degassed to remove air bubbles. It is then:

• Cured at elevated temperatures (e.g., 60–80°C) to solidify the structure.

• Demolded carefully to extract the replica.

• Ported by punching holes to create inlets and outlets for fluid flow.

Sealing the Chip

The last step is bonding the patterned layer to a flat base (usually glass or another layer of polymer) to seal the channels. This is often done with plasma treatment, which makes the surfaces temporarily sticky at a chemical level, forming a strong permanent bond when pressed together. Different bonding methods, like thermal bonding or adhesives, are used depending on the materials involved.

Benefits of Microfluidic Chips

Microfluidic chips have revolutionized various scientific and industrial fields by enabling precise control and manipulation of small fluid volumes. Their integration into laboratory and diagnostic settings offers numerous advantages, enhancing efficiency, accuracy, and portability. Below are some key benefits:​

Low Sample Volume Requirement

One of the biggest perks of microfluidic chips is that they need only tiny amounts of liquid, sometimes just a few nanoliters or even picoliters. This means you can do experiments or run tests with much fewer samples and reagents than you’d need in traditional labs. It’s a huge cost-saver and especially helpful when your samples are rare, expensive, or hard to get.

Shorter Analysis Time

Because everything happens on such a small scale, fluids mix, heat up, and react faster inside microfluidic chips. That means you can run tests and get results much quicker than with traditional setups. This speed is a big advantage in places like hospitals or research labs where time matters.

Cost-Effective Production

Microfluidic devices can be made at a lower cost compared to traditional laboratory equipment. Techniques such as soft lithography and injection molding allow for the mass production of disposable chips, reducing costs, materials, and fabrication. That’s great news for researchers, startups, and even healthcare providers looking to lower testing costs without sacrificing quality.

Portability and Integration

The compact size of microfluidic chips makes it possible to develop portable diagnostic devices used for point-of-care testing and on-site analysis. Their ability to integrate multiple laboratory functions onto a single chip makes complex experiments easier, faster, and more accessible in diverse environments, such as fieldwork or even at home.

Key Applications of Microfluidic Chips

Since their emergence in the 1990s, microfluidic chips have become essential tools in both scientific research and industry. Below are some of the most prominent fields where microfluidic chips are making an impact:

Pharmaceutical Analysis and Drug Development

Microfluidic technology plays a key role in modern drug research and development. It allows researchers to screen drugs, test their activity, and study how they are metabolized—all at a fraction of the time and cost of traditional methods. These chips are well-suited for high-throughput drug screening, as well as for preparing drug nanoparticles, encapsulating drugs, and controlling drug delivery.

Advanced systems like organs-on-chips (e.g., liver-, kidney-, or bone marrow-on-a-chip) are used to simulate human organ functions for drug toxicity testing, reducing the need for animal experiments.

Biomedical Research and Diagnostics

Microfluidic chips help miniaturize and automate medical testing. Their small channels, often similar in size to human cells, make them perfect for cell analysis, separation, culture, and treatment. Researchers use them for single-cell studies and rapid drug-switching experiments in cell biology.

They are widely used in diagnostic techniques like PCR, DNA analysis, immunoassays, and mass spectrometry sample preparation. One powerful use is digital PCR for early, non-invasive detection of genetic disorders like fetal aneuploidy. Forensic labs also use integrated microfluidic chips for fast human identification using STR (short tandem repeat) analysis.

Point-of-care diagnostics is another key application. These chips are behind at-home pregnancy tests, blood glucose monitors, and rapid virus testing, including for COVID-19 and HIV. They're also used to detect pathogens and monitor biomarkers with built-in biosensors.

Nanomaterial Synthesis

In the field of nanotechnology, microfluidic chips act as miniature chemical reactors. Thanks to their controlled environments, such as laminar flow and enhanced mass/heat transfer, researchers can fine-tune the properties of nanoparticles. These particles are used in medicine, energy storage, electronics, and biotechnology. Microfluidic platforms allow for the consistent, scalable synthesis of nanomaterials, often yielding more uniform particles compared to bulk methods.

Molsentech: Redefining Diagnostics Through BioFET and Microfluidic Synergy

While microfluidic chips expertly control fluid flow at the microscale, their true potential shines when combined with advanced sensing technologies, especially biosensors based on field-effect transistors (BioFETs). BioFETs transform biological interactions into fast, measurable electrical signals with exceptional sensitivity when integrated into a microfluidic platform. This powerful fusion results in a compact, highly efficient lab-on-a-chip system, ideal for real-time, point-of-care diagnostics.

As a leading manufacturer of microfluidic chips and BioFET-based biosensing chips through strategic fabrication partnerships, Molsentech is redefining biomedical detection. We are not simply fabricating microchannels; we deliver highly integrated semiconductor chip systems, merging state-of-the-art molecular biosensing, microfluidics, and AI technology.

Our next-generation BioFET chips demonstrated exceptional performance during the COVID-19 pandemic, offering high sensitivity and rapid detection. Today, Molsentech's technology is driving new breakthroughs in diagnostics for Alzheimer’s disease, cancer, and a wide range of infectious diseases.

Whether you're aiming to accelerate early disease detection, improve diagnostic accuracy, or build smarter healthcare solutions, Molsentech’s platform is ready to power your innovation. Let’s shape the future of diagnostics. Contact us today and discover what our technology can do for you.