Microfluidics? What's That? A Beginner's Guide

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Microfluidic chemostat used to study microbes

Microfluidic chemostat used to study microbes

I don’t quite have the resources to poll the United States and the rest of the world, but if I did, this is what I’d ask:

  1. Do you know what microfluidics is?
  2. Can you explain it to me?
  3. Do you currently use anything with this technology?

We may never know the results of the poll, but I think I'd hear "No" and "What is microfluidics?" Have no fear, because today you’re lucky enough to read my Beginner’s Guide to Microfluidics.

To start with, let’s look at the word itself. It is the word fluidics with the prefix micro- strapped onto the front. Thus, we’re looking at the manipulation of fluid at the micro scale, often flowing through channels. There isn't a strict definition, but some like to refer to flow with a channel dimension less than 1,000 µm as microfluidics. It's more complicated than that, so to guide us, I’ll be referencing heavily from a review article George M Whitesides wrote in 2006, “The origins and the future of microfluidics.” For those unfamiliar with Dr. Whitesides, he is a legend in many spheres including microfluidics, and if you are reading a paper on microfluidics, it most likely either cites him, or can be traced to something that does. In this particular article, he looks at four “parents” of microfluidics that have brought us to the technology we have today:

  1. Microanalytical methods
  2. Biodefense
  3. Molecular biology
  4. Microelectronics

Microfluidics’ Loving Parents

Microanalysis

Microanalysis is the chemical analysis and identification of small amounts of matter, such as capillary electrophoresis. First developed in the 1960s, it is a method to separate ionic species using their size to charge ratio. Capillary electrophoresis is still used today, showing that microanalysis not only provided needs for microfluidics to meet, but it also provided some techniques.

Biodefense

Awareness of chemical and biological warfare escalated after the Cold War, fueling the United States’ Defense Advanced Research Projects Agency (DARPA) to heavily fund microfluidics research in the 1990s. Biodefense remains a major area or research in homeland defense as demonstrated by the recently unveiled microfluidics-based device that detects anthrax or other suspect DNA. The suitcase-sized system recovers cells from a sample and analyzes the DNA in less than an hour, while it currently takes 1 to 3 days in the lab. 

Molecular Biology

In the past few decades, genomics activity has progressed quickly and has demanded newer technology to grow even further. Microfluidics had the opportunity to process DNA faster, cheaper and more precisely. Stephen Quake, a professor at Stanford University, has been leading cutting-edge research in sequencing. The ability to sequence DNA in weeks rather than months has allowed him to start a company, Helicos, implementing microfluidic methods. There have been several microfluidic applications for sequencing as researchers and companies race to sequence a human genome for only $1,000.

Microelectronics

While the three previous “parents” have provided some tools and needs for microfluidics, the final “parent” helped it find its form and substance. Microelectronics was also developing at the time (although it was further along), and people saw a way to manufacture micro-sized structures precisely. Microfluidic components were first made of silicon and glass with microelectronics techniques such as photolithography. Eventually, silicon was replaced by materials with more suitable properties. Silicon is not durable, cheap nor transparent to visible or ultraviolet light. This is important because light is often used to either determine the results of a test, or to or to provide excitation energy. The most popular substitute material has been PDMS (polydimethylsiloxane). PDMS is a soft, transparent elastic polymer that is permeable to carbon dioxide and oxygen, making it useful for housing cells. Other cheaper, alternative materials have also been developed, such as thermoplastics, paper and string.

Advantages of Microfluidics

These four parents have given birth to a field that focuses on biochemical and medical applications, and with good reason. While everyone loves small things (I’m sure that micro is sad that it never got its time in the sun before the world became obsessed with nano), there’s more to it than that. A microfluidic device does have a smaller footprint than a huge machine in a lab, but it also uses a lot less fluid too. Why would you make a whole pot of soup just to taste and then dump it down the drain? On the other hand, I would make as little as I could and still taste it. So we can see that microfluidics is beneficial because it uses less costly chemicals and reagents, but it's also attractive due to the physics happening at the micro scale. Now, we’re not talking about leaving the world of classical physics and entering quantum physics, but matter does behave differently, most evidently in the way liquids flow.

Turbulent flow vs Laminar flow

Turbulent flow vs Laminar flow

Laminar flow around air bubbles (source)

Laminar flow around air bubbles (source)

In fluid mechanics, there are two main types of flow: laminar and turbulent. Turbulent flow is just how it sounds, violent and chaotic. Laminar flow is peaceful, and particles will basically maintain their course without mixing. The state of a flowing liquid is determined by its Reynolds number. This is proportional to the dimensions of the channel and the velocity of the liquid. Slower liquids travelling in narrower channels are more likely to be laminar. This not only makes pretty images like those from Albert Folch’s lab, it gives a new level of control to researchers. Two laminar fluids flowing side-by-side will only slowly mix by diffusion, rather than convection. This allows us to do some clever manipulations, like selectively inserting components to induce mixing in some of the streams in a multi-stream channel. Other techniques exist to create droplets, which allow for controlled mixing, and capillary action is utilized to eliminate the need for pumps.

Microfluidic Applications and Issues

Paul Yager with a lab-on-a-chip that detects malaria

Paul Yager with a lab-on-a-chip that detects malaria

Microfluidics can be incorporated into a lab-on-a-chip which is used as an assay or diagnostic test and replaces its large, costly full-size lab counterpart. This has three basic components, a sample, a process and a validation method. For example, you might input a fluid such as saliva or blood to be analyzed. Next, you’ll have to process this blood mechanically or chemically. This may mean mixing it or applying filters to isolate what you want, and then introducing a possible chemical reaction. Even so, what good is this reaction if you can’t tell if it happened? You may be able to see a change in color, or look at it under a fluorescent microscope. These three components can be fulfilled in dozens of ways to create whichever test you so desire.

You must be saying to yourself, “Wow! What a technology! So why haven’t I heard more about this if it can do so many magical things?” Well, space travel is cool too, but when was the last time that you were out in space? Microfluidics just hasn’t made its breakthrough to the rest of us consumers. We can create some pretty cool applications with it, but how often can those prototypes be easily mass-produced? And how easy will they be able to use and troubleshoot and fix? Both concerns are even more important for point-of-care applications. Point-of-care refers to a medical application that is being used right where the caregiver meets the patient. In the developed world, this means that your samples don’t have to be sent to a lab somewhere to be processed, and in the developing world, this gives access to life-saving diagnostics that are normally too expensive to purchase and operate. More importantly, the quick response time of the devices would provide results to people who have travelled to a far-away clinic and need to return home again. No matter how elegant or complex a microfluidic device is, it must be easy and cheap to make, simple to use and durable.

Now, I don’t want it to seem like there are no companies producing microfluidics-based technologies. Some relevant ones are Helicos, FluidigmClaros DiagnosticsMicroFluidic Systems, Affymetrix and Advanced Liquid Logic. If you want to see a more complete list, check out the one at FluidicMems. I hope that I’ve helped you to understand the basics of microfluidics, and you can continue to learn about the field on this site. Oh, and if you were wondering how long it will be until you can get your hands on some microfluidic tech, you probably already have: your inkjet printhead incorporates microfluidics!

This is one part of my Microfluidics Beginner’s Guide. Check out the rest of it and keep learning!

Reference:

ResearchBlogging.org Whitesides, G. (2006). The origins and the future of microfluidics Nature, 442 (7101), 368-373 DOI: 10.1038/nature05058