Taming Conductive Droplets. Guest Post
Last year I talked about one of the most interesting microdevices – a lab-on-a-chip. In essence, it is a small (literally a few centimeters) chip with a developed network of channels that are filled with various liquids. The volume of the channels is several microliters. Such a chip easily replaces an entire laboratory not only with equipment, but also with trained personnel. A lab-on-a-chip is just one of the practical implementations of microfluidics – a scientific discipline that studies the behavior of small-volume liquids.
Microfluidics (in Soviet and some Russian sources also called “microfluidics”) is gaining popularity today. In this article, we will try not only to consider the application options for microfluidics and beautiful gifs (and videos), but also talk about how difficult it is to reproduce devices based on microfluidics, as well as how digitalization is proceeding in this science. All interested people are welcome to the world of microscopic flows and reactions!
According to data Data Bridge Market Research The global microfluidic technology market size was $23.17 billion in 2022 and is expected to grow to $70.93 billion by 2030. Currently, the fastest growing fluidic technology market is in Asia (as expected), and the largest is in North America. The outlook is exciting: a CAGR of 15.01% is projected. So why is this industry booming?
If a new technology is in demand, it usually receives support. And such demand usually arises for two reasons – if it satisfies pressing needs in itself or creates preconditions for the dissemination of other technologies that allow these needs to be met. Let's consider how microfluidics fits into this picture.
Molecular diagnostics usually require a serious, well-equipped laboratory and trained personnel. Microfluidics, in turn, greatly reduces the cost and simplifies molecular diagnostics. Microfluidic devices are several times cheaper than traditional ones and can be used outside the laboratory. The results are better, there is less defect, stability from launch to launch – please. You can proudly go to the buffet near the lab! An elementary example of practical implementation in medicine – blood sugar meter. This is the one. futuristic microfluidicswhich is adjacent to the biosensor industry.
Fluidics is used in the analysis of substances in materials science. This technology allows for express diagnostics of a substance by modeling processes that occur under conditions that would take much longer to create in the macro world. For example, technologies are currently being created to model diffuse soil properties to assess its oil drainage features. Moreover, directly at the site of the field development.
It allows you to model biological organ systems. In essence, this is a new direction; before the development of fluidics, similar problems were solved by torturing laboratory animals. For example, in fluidics, the properties of membrane complexes, vessels, etc. are tested, whereas previously animal tissues were used for the same purposes. (By the way, laboratory animals will be used later, but in much smaller quantities, until in vivo modeling is surpassed)
Allows functional reproduction of processes that require 100-1000 times less reagents. This means lower service costs and the ability to spend savings on something else.
This is just great. Here I would like to pay tribute to ordinary scientific employees. Many of them work frankly for the idea, and not for money (not all, but we are talking about those who do not go into the industry). Finally, the whimsical running drops are simply beautiful.
Currently, automated diagnostic systems based on robotics are actively used in laboratories all over the world. Robotic manipulatorsprobably doesn't surprise anyone. Spectrometersmultiparameter analyzers of blood and other fluids, etc. But why was it easier to make such complex, weighty structures than glass or plastic with a bunch of wells and channels for the same purposes?
It's all about size. The complexity of the new world that prevails in the pores and channels of a microfluidic device. Fluids in such small volumes begin to be significantly affected by forces that are not noticeable in larger volumes. And it's not just significant. It's too significant.
Let me give you an example.
You throw a sugar cube into a cup of coffee. Then you take a spoon and stir it. Is the coffee sweet and hot? Convenient? Yes. What happens if you don't stir the sugar and wait for it to dissolve on its own? Most likely, the sugar cube will turn into a pile of sugar that will settle at the bottom, and the coffee will cool down.
Now let's try adding milk. How long will it take for the mixture to become homogeneous? By the way, pay attention to the ratio of the diameter of the cylinder formed by the mug, compared to the height of the cylinder (spoiler: very long). And if the height of the mug is 100 times greater than its diameter? Or 1000 times? Such ratios are normal for the channels inside the microfluidic chip. As you understand, it is very difficult to mix anything there. Although it is possible. This is achieved by creating, for example, a large number of angles and turns of the channel, which force the liquid to mix.
So we come to the first limitation. This is complex geometry.
The second limitation is physics. There are many forces and different quantities that, with the slightest changes, will have a strong influence up to a change in the result. Let's look at the main ones.
Surface tension – molecular pressure on the liquid. The molecules of the surface layer of the liquid are attracted to the molecules inside the liquid and to each other. And this attraction causes additional potential energy of the molecules on the surface of the liquid. As a result, an elastic film is formed on the surface. It is the surface tension that makes the liquid take the shape of a ball and takes part in the creation capillary phenomena.
The stronger the surface tension, the lower the density and the narrower the capillary, the stronger the capillary effect.
It is necessary to carefully monitor the tension and turn its effect to your advantage. For example, with the help of tension you can accurately dose liquids (well, also with the help of viscosity, about it below), control the flow of liquid in the channels (this is achieved, among other things, by the geometry of the microfluidic device) and separate the liquid into separate droplets of different sizes or by density. Also, by controlling the surface tension (increasing and decreasing it), we can control the distribution of liquid in the channel. Low surface tension promotes good wetting, and high – vice versa. You can regulate the value of surface tension by changing the temperature – the higher it is, the lower the value of surface tension. But it is also worth paying attention to the temperature at which the reactions in the device should take place. In this case, you can use surfactants And PIVwhich reduce or increase surface tension.
You can conduct a small experiment yourself, demonstrating the various capillary properties of liquids. To do this, take two identical pieces of paper and hang them by a string. So that the sheets of paper hang perpendicular to the ground.
Then prepare a few milliliters of water and alcohol. You can paint them in different colors with food coloring, brilliant green or other alcohol/water-soluble paints. After that, dip both leaves into the prepared liquids.
It will quickly become apparent that the level of liquid rise will vary on different sheets of paper. This will depend on the density of the liquid and the strength of the surface tension.
By the way. A similar method is widely used in analytical chemistry and biology. It allows one to determine the difference between different compounds and even to separate them spatially from one solution. This method is called “paper chromatography“, it is built precisely on such capillary effects.
Liquid dispersion
It may not be immediately clear what kind of energy we are talking about and why it needs to be dissipated. There are different types of energy, electrical, kinetic, potential, etc. In microfluidic systems, three types of energy are very important. These are kinetic energy of the liquid, kinetic energy of the molecules of this liquid (heat) and energy of chemical bonds.
What do these energies have to do with it? In essence, it's only a matter of isochoric process. Remember it? I don't either. I'll write down its property for all of us here: “In an isochoric process pressure ideal gas directly proportional to it temperature “And what does this mean? Well, if we do not control the temperature of the liquid and gas inside this very microfluidics, they will eventually lead to an increase in pressure inside the fluidic channels. This in turn can affect the chemical processes that should occur at a constant temperature. And it can also lead to a breakdown of the cartridge or an incorrect interpretation of the data from it. Temperature measurement can occur both due to friction of the liquid against the walls of the cartridge, and due to exothermic chemical reactions. Well, or endothermic. These reactions, as you understand, can heat or cool liquids, which will change their density, properties, reaction kinetics (Van't Hoff's rule where the speed delta is 2-4 times dependent on the increase in the temperature delta by 10 degrees). In fact, most reactions are like this. What to do with it? That's right. Control the dissipation of this very heat. So that the liquid has time to cool down, or heat up faster than the reaction takes place, which has time to significantly change the properties of the liquid.
To control thermal and mechanical dissipation in microfluidics, the following can be used:
1) materials with a low coefficient of friction: This allows to reduce energy losses when liquid moves through microchannels.
2) Optimizing channel geometry: Designing microfluidic devices with optimal channel geometry (again, we run into the first limitation) can help reduce mechanical dispersion. Smooth curves, shorter channel lengths, and minimizing diameter differences can reduce friction and drag during fluid flow.
3) Flow rate control: allows for optimized heat transfer and minimized fluid heating in microfluidic devices.
4) Use of thermal insulation materials
5) Flow parameter control: Control of flow parameters such as pressure, temperature and flow rate allows optimization of heat transfer and mechanical dissipation processes in microfluidic devices.
Liquid resistance
The fluid resists flow. During the flow, turbulent flows (and the flow in microfluidic channels is usually laminar), elastic deformations of the walls or gas may occur in the liquid. As noted earlier, for uniform mixing, it is necessary to create many bulges, angles and turns along the channel. However, such solutions create additional hydrodynamic resistance. This resistance may require additional operating conditions, connections, pumps and valves used in the fluid system.
In the microworld, the properties of the liquids themselves also change. For example, Reynolds number becomes low and the liquids no longer mix. More precisely, they do not mix in the usual sense. The flow of liquids in microfluidics becomes laminarand not turbulentand therefore the transfer of molecules during “mixing” occurs due to diffusion and the molecules’ own movement (not from the outside).
It is precisely according to the principle of laminar flow that the movement of blood through blood vessels occurs, which is why it is easy and pleasant to model the circulatory system with microfluidics.
However, at low Reynolds numbers, the mixing process may be ineffective, especially on a large scale or when rapid and uniform mixing is required. In such cases, additional methods and devices (e.g., mixers, agitators, etc.) may be used to speed up the mixing process and ensure the required intensity and uniformity of mixing.
Viscosity of liquids
However, if the viscosity of the liquid is high, there is a chance of transition to turbulent flow even in microchannels. And the particles in this case will not mix diffusely, but chaotically. Like when we mix sugar or milk in coffee. Is the result worse? If there is no help in the form of mechanical mixing or changing temperature conditions/pressure, then yes. However, not without a nuance. High viscosity can prevent effective heat exchange, which may require additional efforts to control the temperature and optimize the heating and cooling processes.
Moreover, the higher the viscosity, the greater the resistance and energy required to move the fluid through the channels. Therefore, it is necessary to carefully study and consider the aspects of the fluids with which the device will work.
Formation of gas locks
The channels are small. Therefore, even small impacts can lead to large limitations. For example, air gets into the channel. At the same time, the device is designed to perform PCR. The stages of annealing, denaturation and elongation occur at elevated temperatures. And then again this isochoric process. There will be bam. And all that is left of the reagents and the reaction will spread throughout the lab, the lab coats and the sad faces of those who started the device. Well, in general, the cartridge will burst. It is not rubber…
It seems that the basics are clear, everything is complicated, but interesting. However, there is a nuance. In essence, microfluidics, which will lie on the shelves, which will be placed in all sorts of distribution companies, is a dish. Yes, it is a piece of glass or plastic (up to with complex geometry, but no more), in which reactions occur. Initially, there are no drops in it, no liquids. However, in order for a reaction to occur in the dish and an incredible fascinating microworld to appear, it is necessary to create all the conditions. To check the compliance of the conditions, it will be necessary to hang various sensors: pressure, temperature, strain gauges; electrodes; spectrometers.
Therefore, electronics also have their place in microfluidics. They are needed in order to:
1) create conditions for reactions to occur
2) count the signals and show that we have achieved the desired result.
In biological equipment, electronics occupy an honorable and important place with the same functionality as in microfluidic devices. And again, a nuance. The fact is that sensors and microcontrollers have certain dimensions. And they can also detect certain volumes, concentrations and control certain flow rates. Therefore, we get another limitation on the development of microfluidics. However, enthusiasm and ambitions are in the first place and there are already examples of overcoming such limitations. In order to control liquids in microfluidics, pneumatic, hydrodynamic (piston), piezoelectric, and electrohydrodynamic systems are used. By the way, inkjet printing is the very first microfluidic device using piezoelectric systems. Above the nozzle of the print head is a piezoelectric crystal, which bends under the influence of electric current and pushes an ink drop from the nozzle onto the paper.
Something is too complicated with capillaries, labyrinths and all these… Researchers and developers could well think so. Simply because the design of such a device takes a lot of effort, requires attention and perseverance. But not everyone is ready for such a development. Especially for different applications to sit and draw grooves. Then digital microfluidics comes to replace conventional microfluidics. Its main difference is in the mechanism of droplet movement. If in the case of conventional microfluidics the liquid flows through the channels under the influence of gravity and mechanics, then in digital microfluidics electrowettability prevails. That is, under the influence of an electric field and a change in the wetting angle, the trajectory of the droplet movement changes. This phenomenon fascinates scientists, perhaps, even more. Probably, it is even more aesthetic.
You can read more about digital microfluidics here.
Well, microfluidics is complex, beautiful and incredibly attractive with its “inner” microworld. I think the analysts' expectations will be justified and it will take its place of honor in distribution companies along with laboratory centrifuges and analyzers. We will follow the development. And beautiful videos with the movement of drops. Probably, such videos and excursions to such devices will become a real sensation not only for scientists, but also for everyone who wants to.
