Microfluidics

Microfluidics is the scientific field dealing with the manipulation and control of tiny amounts of fluid. The fluids (usually liquids and sometimes gases) used in microfluidics are usually measured in microliters or picoliters. Scientists isolate and experiment with fluids at the micro-scale using chips, usually made from silicone, with tiny channels measuring tens to hundreds of micrometers in diameter. Scientists study the liquids at the micro-level because experiments conducted at this scale are more cost-efficient, more efficient, and quicker than those conducted at the macro-level. Scientists can also run multiple experiments simultaneously using microfluidics. Furthermore, conditions at the micro-level make fluids behave differently than they do at the macro-level, so scientists receive unique insight by studying them at this level. The term microfluidics can also be used to describe the technology used to manufacture the devices, such as chips, that are used in the study of microfluidics.

Background

Microfluidics became an established field in the 1990s, but its roots started in the 1950s. The first transistor, which was also the first invention in the field of microtechnology, was created in the 1950s. During the 1960s, the budget for the Apollo space program allowed for the funding of research info mini-computers that would be used to guide space travel. The research led to the production of the first integrated circuits and the first microprocessors. Also during this decade, scientists created inkjet printhead technology, which forces fluids through tiny channels to print images. In the 1960s and 1970s, microtechnology advanced, and technologies such as photolithography were developed. Scientists used microtechnology advancements to create capillary electrophoresis and other technologies.

In the 1980s, silicon etching procedures were developed for the microelectronics industry. This enabled the production of the first device using a mechanical microelement on a silicon wafer.

In the 1990s, microfluidics became its own field. Scientists created technology for microfluidics based on microelectromechanical systems (MEMS) technology. The silicone used in MEMS technology became a model for microfluidics chips. The first microfluidics experiments were conducted mostly in biology, chemistry, and biomedicine. In the 2000s, more scientists began studying microfluidics as the price for developing chips and the time it took to make them decreased.

By the early 2000s, microfluidics had been hailed as an advancement that would forever change science and technology. Many scientists thought great advancements would be made in the medical field because of microfluidics. However, the benefits of microfluidics in the 2000s and 2010s were less significant than scientists had anticipated. For example, in 2005 the biotechnology company Theranos designed what was supposed to be a device that could perform hundreds of tests on tiny blood samples. However, Theranos’s design was not functional and the company lost millions of dollars in funding. Despite the difference between the hopes for the technology and the actual outcomes, microfluidics has helped create several important devices. For example, microfluidics helped the company Abbott Laboratories create a blood analyzer that is used for clinical diagnostics. This machine can analyze blood using only a few drops. The field has also produced advances in computer printing, cosmetic formulation, and other types of diagnostic devices.

Overview

Microfluidics studies minuscule volumes of fluids, and fluids at these volumes behave differently than fluids at the macro-level. For example, they move in a laminar flow instead of turbulent flow. A turbulent flow is the type of liquid flow that people often observe in everyday life. A turbulent flow includes constant changes in the pressure and velocity of the liquid movement. So, two liquids in a turbulent flow mix together easily. A drop of food coloring easily mixing into a glass of water is an example of turbulent flow. Liquids used in microfluidics exhibit a laminar flow, fluid flows in parallel layers and no mixing occurs between the layers. This laminar flow allows scientists to put two liquids beside each other without having them mix, which is helpful for microfluidics experiments. Viscosity is the reason that laminar flow exists in microfluidics. Liquids change their flow depending on viscosity and inertia. Viscosity is a liquid’s ability to resist flow. Inertia is the likelihood that a liquid will continue to flow in the same direction. If viscosity is the more dominant force, the flow will be laminar. If inertia is the more dominant force, the flow will be turbulent. Viscosity increases at a very small scale, so viscosity is the dominant force in microfluidics.

Fluids at this level also behave differently because capillary forces acting on the fluids begin to dominate gravitational forces. Capillary forces allow fluids to more easily travel through a porous material. A final way that fluids are different at the micro-level is that the surface tension changes.

Scientists study microfluidics by constructing chips that allow them to manipulate and move fluids in specific ways. They create specific chips for different experiments and needs. All the fluids used in microfluidics are measured in extremely small volumes such as femtoliters (fL). One femtoliter is a quadrillionth of a liter. Microfluidics also has a very low energy consumption because of the extremely low volume of fluids.

The chips used in microfluidics get their name because they were originally made using the same methods as computer microchips. The chips that are used in microfluidics are often meant to mimic objects and systems that people use for experiments at the macro-level. Most microfluidics chips measure only a few square millimeters in size. They are often made from glass and silicone. The chips have channels, pumps, inlets, and outlets—this is like plumbing at a micro-level. Not all chips used in microfluidics have pumps, inlets, and channels that are designed the same way. Scientists design chips specifically for their projects and experiments. They must design a chip before creating it. Creating inlets, pumps, and channels at the micro-level (with them all being no larger than the diameter of a human hair) must be done following specific procedures. Often, scientists use a method called micromolding to design the chips. In this method, a mold is created with raised areas where the inlets and valves should be. To create the mold, scientists use a method called photolithography. They pour resin on a silicone surface. Then they shine a special light onto the resin, but the light shines only on the parts of the resin that will be the hard part of the mold. The parts of the resin that are shielded from light remain soft. Scientists wear away this part of the resin, making the mold. Then they pour plastic over the mold, which gives the plastic indentations that create the inlets, valves, and tubes. Scientists then glue the plastic to the glass slide, creating completely enclosed microtubes through which the liquids will flow.

Sometimes scientists also use chips made out of paper to conduct experiments. Paper chips are extremely cheap to produce. They are also easy to keep in stock and inexpensive to transport. Furthermore, paper chips are more environmentally friendly than glass-and-silicone chips. However, paper chips also have some drawbacks. For example, creating a pattern on the chips can be a very complex process.

Scientists must also consider the purpose of the experiment when they design their chips. One common chip type is the lab-on-a-chip device. Scientists use this type of chip when they want to perform an experiment that they would normally do in a lab at the macro-scale. Scientists use microfluidics in this way so they can save money, as reagents and other materials used in experiments can be costly; dramatically reducing the amount of fluid needed for an experiment saves money. Scientists can also run multiple experiments at one time because they have more space, resources, and time.

Scientists also use organ-on-a-chip devices, which are meant to mimic human and animal organs. They use these chips to better understand the function of organs and other biological systems. The organ-on-a-chip devices are similar to other microfluidics chips but are also lined with living human organ-specific cells and human endothelial cells. Furthermore, depending on the purpose of the chip, scientists can exert mechanical forces on the chips to mimic living organs (e.g., breathing motions on a chip with lung cells). Organ chips may help scientists replace animal testing, which has long been seen as a necessary but inhumane part of medical research. These organ chips help scientists study at the cellular level and also learn about human organ function, diseases, and new therapeutics.

Once scientists have created chips, they can begin their experiments. They need a sample, a process, and a validation method to conduct experiments. The fluid can be a liquid or a gas. For example, blood could be used as a fluid. Scientists also need a process, which is the experiment or system to test or observe the fluid. The process could include a chemical reaction by adding a chemical to the fluid being tested. The process could also include manipulating the fluid mechanically. Scientists then observe the fluid during the experiment. Because microfluidics is done on an extremely small scale, the events taking place during microfluidics experiments and projects happen extremely quickly. Therefore, scientists often record the actions using high-speed cameras. Then, they replay the recording at a much slower speed. This helps them validate the findings and report on what they find.

Microfluidic experiments have numerous benefits including giving scientists the ability to save money and conduct multiple experiments simultaneously. These experiments are also useful because scientists have a great deal of control over the microenvironment, making the observations from these experiments generally very reliable. These experiments can also detect small changes, making them very precise. Furthermore, microfluidics experiments are often easy to automate so that scientists do not have to be physically involved in every step of the process.

Microfluidics encompasses various types of experiments and branches of study. In a constant flow experiment, the fluid passes through the channels throughout the experiment. Scientists can manipulate the flow through pumps, inlets, outlets, and other micro-devices. During digital microfluidics, which is also called droplet microfluidics, scientists use electrical charges to manipulate droplets in the system. This manipulation helps them reproduce the same size droplets over and over again. Optofluidics is a field in microfluidic that uses light to help control fluids. Acoustofluidics is a field that combines microfluidics, acoustics, and fluid dynamics. Electrophoresis is another field that can be used along with microfluidics and helps scientists separate molecules in microfluidics by size, electrical charge, and shape.

Bibliography

Cheriyedath, Susha. “What Is Microfluidics?” News-Medical.Net, 26 Feb. 2019, www.news-medical.net/life-sciences/What-is-Microfluidics.aspx. Accessed 10 Sept. 2020.

Ingber, Donald E. “Developmentally Inspired Human ‘Organs on Chips.’” Development, 2018, dev.biologists.org/content/145/16/dev156125. Accessed 10 Sept. 2020.

Jennifer Chu. “Microfluidics from LEGO Bricks.” MIT News Office, 30 Jan. 2018, news.mit.edu/2018/microfluidics-lego-bricks-0131. Accessed 10 Sept. 2020.

“Laminar and Turbulent Flow.” Vapourtec Ltd., www.vapourtec.com/flow-chemistry/laminar-turbulent/. Accessed 10 Sept. 2020.

“Microfluidics Definitions and Advantages.” Fluigent, www.fluigent.com/microfluidic-expertise/what-is-microfluidic/microfluidic-definitions-and-advantages/#:~:text=Microfluidics%20is%20the%20science%20of,1990’s%20and%20has%20grown%20exponentially. Accessed 10 Sept. 2020.

“Microfluidics: A General Overview of Microfluidics.” Elveflow, www.elveflow.com/microfluidic-reviews/general-microfluidics/a-general-overview-of-microfluidics/. Accessed 10 Sept. 2020.

Pflanzer, Lydia Ramsey. “The Rise and Fall of Theranos, the Blood-Testing Startup that Went from Silicon Valley Darling to Facing Fraud Charges.” Business Insider, 11 Apr. 2019, www.businessinsider.com/the-history-of-silicon-valley-unicorn-theranos-and-ceo-elizabeth-holmes-2018-5#the-initial-design-for-the-theranos-device-in-2005-was-a-cartridge-and-reader-system-that-was-dependent-on-microfluidics-and-biochemistry-this-prototype-was-dubbed-the-theranos-10-and-the-company-had-plans-to-license-the-technology-out-to-pharmaceutical-firms-to-help-them-catch-side-effects-during-drug-trials-5. Accessed 10 Sept. 2020.

Whitesides, George M. “The Origins and the Future of Microfluidics.” Nature, vol. 442, 2006, pp. 368–373.