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TA : Pelin Kübra İşgör |
Topics covered:
Microfluidic systems
Droplet generation devices
Fabrication of microfluidic devices
Introduction to Elveflow pressure pump and Microqubic 3D digital microscope
Droplet generation at varying sizes
Droplet detection using via video/image processing
Experiment details:
DROPLET GENERATION EXPERIMENT
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Microfluidics is the key science and technology that enables fluid manipulation and control in channels that have dimensions on the order of micrometers (Fig.1). The change in fluid physics in microscale ensures novel use of microfluidic systems. Although the first microfluidic device was a gas chromatograph invented in 1975, these systems have not used for biological or chemical applications since 1990s [41]. Microfluidic device fabrication technology was derived from microelectromechanical system (MEMS) technology.
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Paper-based microfluidic systems are considered Microfluidics 2.0. This method is inexpensive and easy-to-use. Changing hydrophobicity of the paper at different zones using a printer and wax, channels are fabricated [54]. Printing reagents and other materials to the test zones makes microfluidic paper-based analytical devices (µPADs) cheaper point-of-care diagnostic devices. Being user-friendly and cheap, paper-based microfluidic systems are developed for disease diagnostics in third world countries [65].
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Glass, Si and polymers are the three main materials for fabricating microchannels. According to application, any of these three materials can be used. Si wafer is not a suitable material for optical measurement techniques due to its opacity. Glass is a fragile material and etching it rather difficult than etching a Si wafer. The bonding process requires high voltages or temperatures. Also, a clean room was needed for the fabrication process [76]. The dimensions of polymers change when they interact with some chemicals such as alcohols. Silicon can be used for applications requiring high temperatures such as quantum dot synthesis [87]. Glass microchannels are resistant to chemicals and reusable. A polymer type, polymethylmethacrylate (PMMA), is suitable for high volume production of cartridges. On the other hand, polydimethylsiloxane (PDMS), is the "working horse" of scientists, since it is a non-toxic, opaque material and can be cured at low temperatures. PDMS is a rather cheap material and fabrication of a microfluidic device becomes quite easy with soft lithography techniques. Microfluidic systems are integrated with different components to operate properly. Pumps, valves, mixers, pressure and flow sensors are some of the fluidic components that are integrated with microfluidic systems.
Microfluidic systems or lab-on-a-chip technologies generate, manipulate and process small liquid volumes. Due to their miniaturized nature, microfluidic systems especially microdroplet based microfluidic systems provide several advantages such as, enhanced analytical performance with respect to macroscale techniques, low cost and ability to process large libraries of samples in a short amount of time (high throughput). Nowadays, these platforms are used for DNA sequencing, chemical and biochemical screening, PCR (polymerase chain reaction), protein crystallization, directed evolution of proteins, detection of rare diseases, cell-cell interactions, single cell analysis [98]–[1514].
Droplet generation
In the literature, there are two main passive droplet formation generators, T-junction ;
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Two immiscible fluids are driven from two separate channels and meet at a junction that is determined by the specific geometry of the channels. In 2001, Thorsen et al. published an article titled "Dynamic pattern formation in a Vesicle-Generating Microfluidic Device" [1615]. For the first time, they accomplished droplet generation with two immiscible fluids using a T-junction. Both water and oil were continuously driven to the microchannel (Fig.3). The water obstructs the main channel at the junction, while oil flows through the channel. At this moment, high shear forces occur. The flow is not linear and static due to interactions between the boundary of two liquids. This instability arises from the competition between surface tension and shear forces. The competition generates droplets. The size and speed of droplets are finely tuned by adjusting water and oil flow rates or pressures.
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Anna et al. used flow-focusing technique in a planar microchannel to form droplets [1716]. In this technique, two immiscible phases are driven to the one orifice, where the outer channel carries oil, and the inner channel carries water. These three channels form a cross at the intersection. The oil comes from two sides of the water and applies pressure to it so that water breaks into droplets. Using this technique, varying size of droplets can be generated at very high speeds. Three regimes occur during droplet formation depending on physical properties of fluids and external variables. These regimes are categorized as squeezing, dripping and jetting [1817]. The physical properties of liquids such as interfacial tensions, viscosities, and external variables as flow rates of fluids, channel dimensions and geometry are used to categorize droplet formations [1918]. The dimensionless numbers originated from aforementioned variables determine these regimes. Capillary (Ca) number is the most important dimensionless number for droplet formation and its value varies between 10-3 and 10 (Eq. 1). In Eq. 1, µ is the dynamic viscosity of the fluid, V is velocity of the fluid and is interfacial tension between two liquids. Capillary number relates viscous forces with interfacial tension.
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Abate et al. stated that monodisperse droplets are generated at low capillary numbers for T-junctions and at high capillary numbers for flow-focusing devices [1918]. In a T-junction two regimes occur: squeezing and dripping. When dispersed phase (water) completely blocks the mainstream channel and there is pressure drop along the droplet due to channel blockage, the regime is called squeezing regime. In dripping regime, droplets do not completely block the main channel and are smaller than the dimension of the main channel. In a flow-focusing device dripping and jetting are two regimes that occur during droplet formation. In dripping regime, the dispersed phase breaks now it enters the junction and turns into droplets. These droplets are immediately carried away by continuous phase. In jetting regime, dispersed phase goes into continuous phase and for a while they co-exist in the main channel [1817].
How do we use Navier-Stokes eqn for microfluidics?
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Switch on Elveflow pump. Make sure inlet ports are closed.
Open vacuum source.
Open ESI software. Click on Calibration button. Let the system calibrate itself. Calibrate the system twice.
Switch on Microqubic 3D digital microscope.
Open Microqubic software. Choose See3Cam camera.
Under camera options adjust Exposure, set it to Auto.
Put your microfluidic chip on the stage.
Using joystick adjust focus until you observe microfluidic channels.
Connect DI and silicone oil vial to the inlets of pump.
Never let fluid to go inside pressure line.
On ESI software, click Stop All button.
Give 10 mbar pressure to the DI line. Wait until fluid comes at the edge of the precision tip.
Insert DI precision tip to the DI inlet on the microfluidic chip.
Close pressure.
Give 50 mbar pressure to the silicone oil line. Wait until fluid comes at the edge of the precision tip.
Insert DI precision tip to the DI inlet on the microfluidic chip.
Close pressure.
Go to DI inlet. Increase pressure to 20 mbar. Watch for the fluid while it is going through the microchannel. At this point you can lower the pressure, because DI should not go into the silicone oil channel. The reverse is also valid.
Go to silicone oil inlet. Increase pressure to 40 mbar. Watch for the fluid while it is going through the microchannel. At this point you can lower the pressure, because silicone oil should not go into the DI channel.
Using microscope joystick, go to the junction where droplet will be generated.
Adjust pressures accordingly until you observe droplet generation.
After droplet generation is observed, increase pressure of DI and silicone oil proportionally to observe varying size and speed droplets.
Take a note of pressure values for both DI and silicone oil.
Take a video using Microqubic software.
Use this video for image processing to determine droplet sizes (Code will be provided).
Report requirements:
The report for this part is expected to include:
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Please plot silicone pressure value vs. Droplet size for 10 different silicone oil pressure values while fixing DI pressure. Do not forget to include units.
References
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