The Next Wave of Devices are Liquids: Microfluidics

Over the course of history, our interest in the fundamentals of biology, especially proteomics — the study of all the proteins in the human body — has been completely reliant on expensive testing. Despite this, we’ve been able to make considerable advances in the fields of drug development to cellular microbiology.

As our development of biological products become increasingly prolific, we’re seeing that our previous environmental and in-vivo testing mechanisms are much too expensive and impractical, and even oftentimes inaccurate.

Think about it like this: would you want your barber to treat your lice? Would you have a veterinarian give you surgery or prescribe medication to you? No. These roles are similar but they’re flip flopped in a way that doesn’t make sense. They just don’t fit, and won’t work.

Currently, we’re using similar environments and organs to see cellular behaviors and drug interactions, but they’re not correct. This is why so many drugs are failing, and we can’t seem to understand cells.

What if we could design exactly what we needed, except using less resources, less money, and get more use and practicality?

Well we can, and it’s thanks to a technology called microfluidics.

Microfluidics is an interdisciplinary bio-technique that represents the culmination of engineering, chemistry, nanotechnology, physics, biology & biochemistry, and biotechnology to develop and control small amounts of fluid, and leverage them in a variety of ways. Not only is it much cheaper and scaleable, but its also more refined and accurate.

Interestingly, microfluidics have applications in a variety of applications, from telecommunications to screening during drug development. The overarching idea is that small liquid environments, that use up much less money, space, and time, can be used to replace their more expensive counterparts.

There are a variety of microfluid types, but they generally have the same look.

A microfluidic device can be easily recognized through its appearance, though since their introduction in the late 1980s by Frederick Stanley Kipping, microfluidic devices have undergone radical expansion in terms of customization, and diversification of use. That being said, they do have some invariable characteristics, including multiple thin layers/membrane of clear materials, a very flat, board-like look, pathways on the surface, and some accessories— chips, pumps, sensors, valves, and/or connectors.

Though microfluidics describe the actual liquid manipulation, the overall use of it is as a microfluidic chip, or a multilayer network of fluids and other miniature components to create a sort of environment to accomplish all sorts of biochemical testing in. These devices are intuitive, requiring no engineering background to use, allowing researchers of other disciplines to leverage their micro-environments.

Form Factor of Microfluidic Chips.

The structure of a microfluidic chip is rather plain. The first layer is a material (glass, polymer — like PDMS (Polydimethylsiloxane), or silicon), that has a set of microchannels, or pathways, that are connected together to create a microchip feature.

assay: the testing of a metal or ore to determine its ingredients and quality; to assay/determine the content or quality of (a metal or ore)

The inputs and outputs are poked through the chip to create an interface between the small and large. The small openings allow for different injections into the chip to create different solutions.

TL;DR: microfluidic structure can be described as
1. Silicon and Glass
2. Paper
3. Polymers
4. Hydrogels

The accessory and material used is heavily dependent on the device itself. There are multiple classifications of microfluidics:

  1. Open Microfluidics — The fluid is exposed by the removal of at least one boundary, and the liquid then interacts with another interface, like air or some other fluid.
  2. Continuous-flow Microfluidics — This is a steady state liquid flow moving through slim microchannels with applied pressure from an internal or external source. Despite being difficult to integrate or scale, CF microfluid chips are very commonly used because of their simple capabilities in biochemistry.
  3. Droplet Microfluidics —These are microfluidic devices that manipulate miniscule volumes of fluids in phases that can’t mix, and how with low Reynolds number and dominated by laminar flow regimes.
    What this means is that predicted fluid flow behavior is expeted to be very sheet like! Because of their applications in devices such as sensors, these have become increasingly popular.
  4. Digital Microfluidics — Super specific lab-on-a-chip technology. They deal with nanoliter measures of droplets to preform laboratory experiments. roplets are dispensed, moved, stored, mixed, reacted, or analyzed on a platform with a set of insulated electrodes.
    Procedures such as mass spectrometry, colorimetry, electrochemical, and electrochemiluminescense can be done by combining analyses with digital microfluidics.
  5. Paper Microfluidics — These are my personal favorites, and they describe using paper to make cheaper medical devices, such as centrifuges! They rely on the porous and capillary behaviors of the media, and can use up to 2 or 3 dimensions, and the topology/geometry of the devices accommodate for different reactions.

The promise of microlfuidic devices is immense. There are even microfluidic devices that can detect particles in fluids!

However, most promising are the different types of devices that can be made using them. This post will highlight three primary ones:

1 Microfluidic Diagnostics.These are the primary medical applications of microfluidic devices for diagnosis and lab experiments.

2Microfluidic Chips. Also known as “lab” or “organ” — on-a-chip technologies, microfluidic chips are the most versatile devices.

3Microfluidic Sensors. These are smaller, cost effective devices for monitory different states, or conducting a variety of experiments.

Let’s delve into it.

1. Microfluidic Diagnostics

The promise of using chemical analyses with small liquid volumes also has implications in medicine, as I briefly mentioned. The chief application is in diagnosis, which includes a variety of subcategories and complex biochemical procedures to determine the presence and virulence of a disease/infection.

The typical form factor of a microfluidic diagnostic device is standard fabrication devices, also known as lab-on-a-chip devices that can be made from different materials to lower cost or increase efficiency; these are unfortunately typically inversely proportional.

The manufacturing dependency for ensuring the reliability of the microfluid diagnostic typically falls on precision die cutting, or the cutting and molding of the laminate into specific shapes for use as a mini-lab on a chip. Because microfluidic chips can be produced in bulk for high-throughput diagnosis, it is imperative that the devices’ channels are modeled and produced correctly to conduct diagnostic experiments.

The devices offer cartridges through which biological material can be filtered, and the substance is run through a small chemical test to isolate a specific factor. A majority of the difficulty in later steps is primarily concerned with the level of intuition involved in interpreting the results.

For example, to diagnose COVID using microfluids, researchers leveraged the polymerase chain reaction, DNA sequencing, Enzyme-linked immunosorbent assay (ELISA) to model COVID-19 disease and diagnose it on a microscale sample of a human organ using a microfluidic chip.

PCR: A reaction that uses enzymatic replications to create a bulk sample of DNA from a much smaller sample (copying)
DNA Sequencing: The process of determining what sequences of nucleic acids (A, T, C, G) make up strands of DNA
ELISA: Plate-based assay technique for finding soluble substances and determining what they are (hormones, peptides, etc.)
Check out my other articles for a more in-depth description of these techniques!

However, even with the possibility of faster, and less resource-intensive diagnosis using microfluidics, manufacturing millions of these chips to diagnose diseases isn’t necessarily the easiest task. Not only would the construction of them be difficult due to their microscopic features, but using a large amount of sheeted materials may turn out to be an extremely wasteful process, depending on the ratio of defective devices produced.

Even when using automation that’s DFM, companies and medical institutions are going to have to be very careful. Imagine how much scrutiny will be required for a machine to make hundreds of thousands of 30-layer microfluidic chips that can conduct multiple tests! Fortunately, multi-use microfluidics are on the rise, and they’re outpacing many other diagnostic devices on the market.

A fully controlled environment — a cleanroom with controlled temperature/humidity and monitored air particles — is mandatory when creating nearly any medical device, including microfluidics. And adhesives must be selected specifically to be used near fluids; hydrophilic, hydrophobic, etc.

This means that there are very specific sterile conditions needed to manufacture these devices, which will increase production costs, and the cost of the devices themselves. Even with that possibility though, microfluidics are already significantly cheaper than their larger, more complex counterparts.

All that’s left is to develop these tiny diagnostic fluid machines further! Ultimately, the use of microfluidic chips for a speedy diagnosis will also lead to earlier treatments and swift productions, which saves lives. There’s massive potential in this technology; its way less invasive, too.

2. Microfluidic Chips

Microfluidic chips are considered the most exciting development in microfluidics. I’ve begun getting in on the action myself with some new projects 👀. Their potential primarily stems from the fact that you can develop real human organs or bio-environments using small volumes of enzymes, cell culture, drugs, etc. — any substance that’s being tested or used, which makes them extremely viable.

As we know, microfluidic chips are also at the center of not only this article, but also all of the possible uses of microfluidics in other fashions, such as diagnosis or sensors.

Microfluidic chips ensure that resources aren’t wasted. They even have potential in immunotherapy testing as well. Researchers — including myself :) — have modeled for organic structures such as the blood brain barrier, the liver, lungs, the mucus lining of the small intestine, the heart, and even animal parts, as well as constructed different pH materials from a single substance.

They’re also very simple, which makes them quite the accessible piece of technology. Here’s an example of what a homemade microfluidic chip looks like:

It’s a series of connectors, nylon, tape…

Not to complex whatsoever, yet it created a small sample of a real human organ. I’m currently working on replication full scale tissues and membrane to do some testing for a drug discovery project.

There are a lot of applications with the microfluidic chip, but the accessibility of the chip itself is what makes it so powerful. These low cost devices are extremely scalable. Because they don’t always require intricate microscope engravings, they can actually be produced by hand, or even faster (up to 200–10,000+ per hour) by machines and laser cutters.

At the same time, financial burden is heavily minimized, screening and diagnostic machines can cost up to $100,000, and perhaps even more, while a simple, multiple-time use microfluidic chip costs around $150–200. Mine costs around $220! There’s a company that sells them for cheap as well, which is extremely useful if you need a general or specialized chip for an experiment or for product testing.

Microfluidic chips have a promising future as a technology for biochemical testing, and perhaps even experimentations. They’re so impactful, having uses in everything from supercapacitors to vaccination tests.

3. Microfluidic Sensors

Microfluidic sensors represent a huge advancement in fabrication and detection systems, and they’re one of my personal favorite applications in the field of microfluidics. One of the disciplines heavily involved in the structure, design, and usability of microfluidics is microelectromechanical systems (MEMS), which describes the moving parts of microscope technologies, and how their dynamics influence the function of the devices themselves.

Interestingly, a large part of the fabrication systems were initially based on semiconductive materials, such as silicon, though since the rise of polymer-based substitutes in the industry, polymer-based microfluidic sensors have become extremely popular.

Microfluidic devices can combine with microcontrollers and small measuring units for detecting different amounts, such as pressures, liquid volumes, or air that could either trigger a reaction, or release a signal to notify the user of a specific detection. Darwin Microfluidics makes devices like these.

Basing the microfluidic sensors on MEMS technology makes them highly sensitive to chemio-physical and bio-physical changes or presence, which makes them highly accurate and “aware”, if you will, devices.

The extent of manufacturing and production is quite similar to previous sections, though it does differentiate via the use of MEMS, which may reduce complications in productions. As the technology continues to develop, we can see microfluidic sensor technology (MSTs, perhaps?!) becoming a standalone discipline, or a larger sub-application of MEMS.

With the rise of other microfluidic devices, sensors are even more important for regulatory purposes. We also have devices like the Arduino and Raspberry Pi, which could create a pretty cool amalgamation of this tech!

The really economical and empirical usage of these sensors is their form factor. Microfluidic sensors can be engineered with more pliable and smaller designs in mind, making them optimal as wearables to monitor different substance contents, or to determine and map substrate activity, for example.

Overall, microfluidics is an exciting, fresh innovation that will impact so many fields, from CAR T-Cell therapy, to robotics, to drug discovery, and beyond. However, we must remember that the excitement comes with drawbacks: there’s no guarantee that this technology will pan out down the line as we make more complex systems; the efficiency could decrease, which would be dangerous. However, keeping that in mind, there’s so much we could do with just some miniature ounces of fluid.

After all,

Great things come in small packages.

Keep that in mind the next time you come up with an idea, and make sure to keep microfluidics in mind!

Before you go…

Thanks so much for being curious and actually reading through this article. It was a lot of fun to make (and “research”, so I’m really glad you made it through! If you like waterslides, drinking water, fluids, or anything liquid related (everyone), you should love this article… just kidding — though I still hope you liked it!

My name’s Okezue, a developer and researcher obsessed with learning and building things, especially when it involves any biology or computer science. Check out my socials here, or contact me: i@okezuebell.com.

I write something new every day/week, so I hope to see you again soon! Make sure you comment, and leave some claps on this too — especially if you liked it! I sure enjoyed writing it!

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© 2020 by Okezue Bell. All Rights Reserved.

Applied Biology @theksociety, Currently focusing on Alternative Protein x Artificial Intelligence. AI + Security @Fidutam

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