Overview: LOC Devices and Fabrication of PDMS Microfluidic Chips

Posted by Nazım Yılmaz on

 Microfluidics is a science at the microscopic scale. But it's also mature technology that has already been applied to everyday objects such as inkjet printers, and LOC devices that can shrink a whole laboratory down to a few square inches. It can be found everywhere in nature as well. Blood flow in capillaries, and spiders spreading their webs. The question is why would the size of these systems alone give them interesting properties? To answer this consider scaling laws. A scaling law is a very broad way of describing the variation of the physical quantity as a function of the size of the system. As known, simple scaling laws are the area of an object scales like the square of its length and the volume scales like the cube of its length. For large objects, the volume should matter more than the surface whereas for small objects it should be the other way around. Interactions between objects usually depend either on their volume or their area which can lead to surprising results. An example – two balls of modeling made of the same mass for these objects the three dimensions are a comparable size which makes them volumic. If turn one of these balls into a thin sheet, there are virtually only two dimensions left and we've created a surface object. The question is that what happens when it puts these two objects in the water. The behavior depends not only on the mass but also the shape of the object on the relationship between the surface and the volume.

 In the microscopic world, surface effects matter more which leads to seemingly counterintuitive situations. Surface and volume are not the only physical quantities to behave weirdly. Scales like the size of the object in contact with the liquid two the power of one. On the other hand, gravity is proportional to the mass and therefore to the volume which means that it goes from the size of the object two the power of three. For instance, in the case of insects, weight isn't that important to prepare for surface tension. Having hydrophobic legs is enough to walk on the water. Another phenomenon is heat transfer. Let’s think about the lightest mammal on earth. Animals eat to get energy and the heavier the animal the more food it needs. On the other hand, a golden retriever roughly two times the size of a poodle needs to take twice as much and since mass is proportional to volume the energy intake per unit time goes like the cube of the animals' size but mammals like all warm-blooded animals lose energy all the time by heat transfer from their body to the surrounding environment. This energy loss scales like the size to the power of one, as a result, the smaller the animal the higher the energy loss compared to the food intake which means that small animals have to eat more often less they freeze to death. So basically mammals can't exist below a certain size and the tiniest have spent all their time eating. All of these examples show that the microscopic has many interesting properties surprising for us but unnoticeable for insects, but can we use those characteristics to work at the microscopic scale? Well, yes since we've made 2,000 years. Insects are no longer the only ones able to play with micrometric physics. Many objects have been designed at the scale such as beams, springs, motors, guitars, and even rivers.

 Microfluidics is at the microscopic scale and fluid dynamics is the science of flows. So what we want is to make liquid flow at the microscale and how do we do that? In the microfluidic system, you often find the same components; pumps, valves, pipes, and all of these are no larger than air. It's micro plumbing. So what do need? First of all, we need to make several different liquids enter the system, then it needs to build channels to make them, therefore it can be built the whole circuit in the first place so the liquids interact. Finally, we need to analyze or collect the volumes it has transformed and the goal is to make all of it hold on a glass flight like this one. It's enough only a few square centimeters.

                   Overview: LOC Devices and Fabrication of PDMS Microfluidic Chips


Lab-on-a-chip and fabrication steps

 What it's called a LOC device? For example, let's say we want to create a microfluidic circuit that produces water droplets in oil to do that using a well-known technique flow focusing. There's going to be a channel where we're going to make the water flow and putting two channels transporting oil which will connect with the water channel at a right angle. The oil is going to pinch the water and fragment it into small drops and we'll collect them in a big pool. So there we have the outline of our circuit. How it is done? It is by micro molding. A creating the mold based on the outline on that mold will pour plastic will turn the plastic into a solid take away the mold and glue the plastic on a glass slide. Now have a design where it drew channels. First of all, how do make the mold that uses the technique called photolithography? With engrave a pattern on a substrate with the use of light, a create a mask.  It can imprint the negative of the channels pattern on a transparent sheet of plastic then we'll need a silicon wafer of our support and a layer of resin which will spread on the support. If this resin is exposed to light when heated it can't be dissolved in a solvent so if it's lit up through the mask, the zones corresponding to the channels are the only one which becomes insoluble, it can get rid of the rest of the resin by immersing it into a solvent called the developer and now have a mold.

 That was theory how does it work in practice? If the person doesn't make channels in the proper environment it only takes a single grain of dust in the channels to block them. This means it has to work in an extremely clean room. It's called a cleanroom and since doing photolithography there not going to choose the color of the lighting at random. It's going to light the cleanroom in orange. The resin is sensitive to green light if a person shines this color on it, that would be a parasitic exposure that's why people use orange which happens to be a color that does not contain any green. It's kind of like developing analog photos. Taking a silicon wafer and pour resin on top. The researcher spread it by spinning it very fast and heat it to solidify the resin then he/she takes the mask and puts it in the lithography machine. After, put the wafer with the resin it light it up to take the resin back out. At this point, heat it and develop it to get rid of the non-lit-up parts with the solvent should clean it and the mold is ready.

Molding the circuit into PDMS

 Most of the time, its being use poly dimethyl siloxane also known as PDMS when but it looks like a transparent and viscous liquid but it can easily be solidified thanks to a compound called cross-linker which creates chemical bonds between the PDMS chains. So really all that needs to be done is pouring it on the mold when it's liquid then hardening it and that's what going to do. Let's start by surrounding the mold with aluminum. We take liquid PDMS then some crosslinker mixes them and pours the mixture on the mold. The whole setup is put under a vacuum bail to eliminate air bubbles and finally wait for about 10 minutes, once the bubbles are gone it takes the PDMS and puts it in a heated enclosure to speed up cross-linking. After an hour, can take out the PDMS which has become solid it takes away the aluminum in the mold and cut out of the PDMS the area around the circuit that wanted. Now just need to make holes with a punch for the liquids inlets and outlets.

 At this point, almost done steps. There is a molded-in PDMS but still, open on one side. It’s going to close them by sticking them to glass and the glue is nothing less than the plasma and putting the chip and a glass slide in an atmosphere of extremely energetic pure dioxygen. It will make every exposed surface is very reactive all it takes is putting the poly dimethyl siloxane on the slides for chemical bonds to form.

Using the chip and output: microdroplets!

 With using the microfluidic chip to produce water droplets in oil, will need to see what's happening in the chip. That means, the microscope is needed, then oil and water will be put in using syringe pumps that very precisely control the flow rates of the liquids. A blue dye is added to the water so can see it more easily, it's filtered to prevent impurities from clogging up the chip, then the inlets will be connected to the two syringes and the outlets will be connected to a bootle from which droplets are collected. It will start by sending the oil in. This is what's happening through the microscope. The oil pushes the air out of the channel it fills and flow-focusing takes place here. It can be seen that the oil comes from the two side channels and then invades everything below the channel where the water will flow and above the large chamber where the droplets will be collected. Now that the oil has been taken care of, only water needs to be brought in. This is where the pipe connects to the channel and the water has to come in at any time and there it just has to come back to the area where it meets the oil and there are droplets.

 In microfluidics, there is no time to understand what is happening at what velocity in the liquid. Then a high-speed camera is used. It can be seen that the oil compresses the water and then leaves one droplet and another hundred times per second. Another thing is that once the droplets are formed they don't coalesce because the molecules have been added. These molecules, like both oil and water, will insert themselves at the interface between the two liquids, which will make our droplets hold, then what happens to our droplets once they're created? They will travel in the chamber until the exit of the chip, and this can be seen if we stop looking through the microscope. And now all that remains is to collect them after a while. It is waited for one hour to fill drop by drop and microdroplets are obtained.

 Why is creating microdroplets so interesting for research experiments or industrial applications? The main point is that a drop is a small enclosed volume. That means it can easily manipulate it, for example, we know how to split a drop into or emerge two drops. Very small volumes can be used if two chemical components are desired to react in this way. They are mixed quickly, which makes the reaction much more efficient, and their concentration can be changed from one drop to another by changing the flow rates of liquids, allowing many different experimental conditions to be automatically discovered. It’s also known that how to put objects inside the droplets, such as cells, for example. The droplet can be used as a carrier, a cell is placed inside, the droplet goes to the desired location and the cell is released. The droplets can also be used as many Petri dishes in which cell culture can be made, and recently it has even been possible to separate droplets by color.


 Microfluidics is at the microscopic scale and fluid dynamics is the science of flows. It needs to make several different liquids enter the system, then it needs to build channels to make them, therefore it can be built the whole circuit in the first place so the liquids interact. Finally, we need to analyze or collect the volumes it has transformed and the goal is to make all of it hold on a glass flight like this one. Also, the range of controlling the liquid flows depends on applications of the microfluidic system. It can be adjusted by changing the size of the channel valve.

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