High Speed Droplet-based Delivery System for Passive Pumping in Microfluidic Devices
September 2nd, 2009
A novel microfluidic system has been developed using the phenomenon of passive pumping and a user controlled fluid delivery system. This microfluidic system has the potential to be used in a wide variety of biological applications given its low cost, ease of use, volumetric precision, high speed, repeatability and automation.
Passive pumping requires a big drop placed in the outlet and a small one placed at the inlet. This will cause the pressure difference needed to drive flow. Alternating drops of different fluids will cause packets to be flown in the channel and eventually be collected at the outlet.
High flow rates can be achieved by delivering low volume droplets at a frequency high enough to achieve a stable fluid shell at the inlet. Hi, I'm Pedro Reto from the Justin Williams lab in the Department of Biomedical Engineering at the University of Wisconsin Medicine. And I'm Brian Mogan, also from the Williams lab.
And I'm Aaron Burier from Professor S Lab, also in the biomedical engineering department at a W Medicine. Today we're gonna show you a procedure to do passive pumping in microfluidic devices. In our lab, we use this procedure to study flow within micro channels and to study fluidic exchange within the channel for biological applications.
So let's get started. First, using the soft lithography technique, create a microfluidic device using polymethyl suboxone. Next, cut out the device and then reversibly.
Attach the PDMS device to a glass slide by pressing it onto the slide and squeezing out any air bubbles. A reversible attachment allows the device to be reused multiple times. Now fill the device with liquid.
We use water with food coloring. If the liquid does not go into the channel by itself, put a drop of liquid at the inlet and use a pipette at the opposite end to suck the liquid through the channel. After filling the device with liquid, place a small drop on the inlet and a bigger drop on the outlet.
Make sure that fluid is moving by watching the small drop at the inlet collapse while the outlet drop gets bigger. Before we go any further, let's explain the basic relationships of passive pumping. Dynamics of pumped drops depend on several things, channel dimensions with height and length, and on the size of the drop that is placed at the inlet.
To give you a better idea of how these factors impact flow, we will give a few examples. Let's start out with two similar channels. They have the same width and height, but one is longer than the other.
Now we place drops of the same size at the inlet of each channel. Watch how the shorter channels inlet drop collapses faster than the longer channels drop. This is because a longer channel has greater fluidic resistance and flow inside of it is slower.
Next, let's explore two more channels with the same length and height, but different widths. Let's place identical drops at the inlet of each channel and watch them collapse. See how the thinner channel takes longer to collapse the inlet drop?
This is because the thinner channel possesses larger fluidic resistance than the wider channel. Lastly, let's take two identical channels and place different size drops at the inlet of each. Notice how the larger inlet drop takes longer to collapse than the smaller inlet drop.
This is because a smaller drop has less volume and greater inner pressure than the larger one. Knowing that smaller drops are better than larger ones. And having observed how fast these small drops can collapse, we now ask ourselves how to deliver volumetrically precise drops to the inlet of a channel in such a way that we can do biological experiments.
Using the Lee Company's micro dispensing starting kit, put together one or more valves each consisting of the vol valve, a nozzle with orifice size of 0.0100 inches, and a soft tube adapter. So here we have the valve connected to the control box via the tube valve connectors, which we did in the previous step. And then we have a spike voltage source, which is this root over here.
And then we have our control voltage source, followed by the hold voltage source. And finally, in connection to ground To hold the valves in place while aiming at the inlet. Use bioscience tools, miniature holders.
These provide a way to precisely aim and hold the valve at a certain position. During experimentation, using three quarter ounce syringes, make a reservoir system to be placed a few feet above the PDMS device. The reservoir provides a pressure head to drive the nozzles.
Attach a syringe needle to the syringe. Now attach the syringe needle to 1.14 millimeter inner tubing, and then attach that to 1.58 millimeter inner diameter tubing. Using PDMS as a sealant.
Now connect the 1.58 millimeter inner diameter tubing to the soft tube adapter of the valve. Now that there is a line between the syringe needle and the valve, fill the syringe reservoirs with liquid to purge the valves and allow the tubing to be filled with water. Place a magnet to the side of the valve and watch liquid begin to flow from the reservoir through the valve and out the 0.01 inch nozzle.
We control this system with a computer using lab view and the Lee Company's spike and hold control box. To calibrate the system, aim one valve to a Petri dish or a whey boat for weighing. Now open the valve for whatever amount of time you choose and weigh the total volume of water coming out of the nozzle.
Divide this volume by the total open time of the system. This calibration allows the user to find the volume of water that shoots out of the nozzle for any given period of time. Having calibrated the system, aim the nozzle to the inlet of a channel based on the previous calibration shoot from the nozzle, a volume such that a drop is shot at the inlet of the channel without being too big to cause a mess or too small to be unnoticed.
Remember to remove bubbles between experiments. Now that the basic principles of passive pumping are understood and system calibration has been explained, let's look at what a user should see if things are going right. The following video is a flow through a microfluidic channel going from higher volumes at lower frequencies to low volumes at high frequencies.
This should give the user an understanding of the capabilities of past pumping along with an automated fluidic delivery system. The device dimensions being used in the following videos are 2.22 millimeter width, 10 millimeter length and 260 micrometer. Height inlet and outlet diameters are 1.78 millimeter and 5.11 millimeter respectively.
Two or more valves are necessary to create alternating flows as shown up. Next is a video showing the maximum flow rate possible out of the current device being used. A single valve is used to deliver fluid in this case.
To maintain system balance, it is important to aim the valve directly from the top of the inlet. Notice the shell that the drop forms at the inlet. This represents the constant pressure maintained by delivering water to the inlet as fast as the device can passively pump it through.
Also, notice how the inlet drop overflows at some point. This is most likely caused by perturbing, the outlet drop. By removing the overflow at the inlet, the system regains equilibrium and flow continues.
Normally, We've just shown you how to set up, calibrate and operate a passive pumping system using commercially available micro nozzles. When doing these experiments is always important to remember to have a steady pressure source to avoid bubbles getting into your channel, to know the trade-offs between channel geometry, drop size in order to achieve the desired flows and exchanges. To not let the outlet drop get too big, for example, it'll make a mess or reach your inlet and to keep your PDMS devices clean and dry.
So that's it. Thank you for watching and good luck for your experiments.
View the full transcript and gain access to thousands of scientific videos
Overview
A novel microfluidic system has been developed that utilizes passive pumping and a user-controlled fluid delivery system. This system is designed for various biological applications due to its low cost, ease of use, and high precision.
Key Study Components
Area of Science
- Microfluidics
- Biomedical Engineering
- Fluid Dynamics
Background
- Passive pumping involves creating a pressure difference using droplets.
- Alternating fluid droplets can create flow packets in microchannels.
- High flow rates can be achieved with low volume droplets.
- This technology can enhance biological experimentation and analysis.
Purpose of Study
- To develop a cost-effective microfluidic system.
- To improve fluid delivery precision in biological applications.
- To automate processes for better repeatability and speed.
Methods Used
- Design of a microfluidic system utilizing passive pumping.
- Implementation of a user-controlled fluid delivery mechanism.
- Testing of flow rates with varying droplet sizes.
- Evaluation of system performance in biological contexts.
Main Results
- The system demonstrated high volumetric precision.
- Flow rates were significantly improved with the new design.
- Automation led to enhanced repeatability in experiments.
- The system is adaptable for various biological applications.
Conclusions
- The developed microfluidic system offers a promising tool for researchers.
- Its low cost and ease of use make it accessible for various labs.
- Future applications could expand into multiple areas of biological research.
Frequently Asked Questions
Executive Industry Relevance
This droplet-based microfluidic system enables precise, high-frequency fluid delivery for biological applications by combining passive pumping with automated droplet generation. It supports reproducible reagent dosing and dynamic fluid exchange in microchannels, addressing key challenges in assay development and target validation workflows. The technology enhances predictive confidence in early discovery by providing controllable fluid dynamics for drug-cell interaction studies and mechanistic screening.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Scientific Value: Enables interrogation of therapeutic hypotheses through controlled fluid exchange and droplet-mediated mixing at microfluidic inlets.
- Operational Value: Provides volumetrically precise droplet delivery via voltage-controlled valves, supporting reproducible compound dosing in microfluidic assays.
- Predictive Value: Facilitates dynamic fluid exchange in channels as fast as eight milliseconds, allowing rapid perturbation and readout in target engagement studies.
Screening & Assay Development
- Scientific Value: Supports preparation of stable fluid shells at channel inlets through high-frequency droplet delivery, enabling consistent baseline conditions for screening.
- Operational Value: Achieves flow rates up to 4 mL/min in 2.2mm x 260µm channels, enabling high-throughput fluid exchange and reagent replenishment in microfluidic formats.
- Scalability: Uses commercially available micro-nozzles and control systems, allowing platform reuse across multiple microfluidic device designs.
Translational & Preclinical Research
- Translational Continuity: Enables drug-cell studies by controlling flow characteristics and momentum-driven mixing at microfluidic inlets, relevant to pharmacokinetic and pharmacodynamic modeling.
- Mechanistic De-risking: Allows study of interplay between droplet momentum and surface tension, providing insight into fluidic behavior that affects reagent delivery and cellular response.
- Predictive Confidence: Offers a disease-relevant system for studying fluid-mediated biological processes under controlled hydrodynamic conditions.
Pipeline & Workflow Integration
The system integrates into early discovery workflows by enabling precise fluid manipulation for target validation and assay readiness, bridging droplet-based delivery with passive pumping for continuous microfluidic operation.
- Discovery Biology: Supports hypothesis testing via controlled droplet delivery and fluid exchange, allowing researchers to probe target dynamics under defined flow conditions.
- Screening: Enables assay readiness through stable fluid shell formation at inlets via high-frequency droplet delivery, improving reproducibility in compound screening.
- Analytics: Provides quantitative fluid exchange measurements (e.g., 8 ms exchange time) that help teams compare conditions and assess kinetic responses in microfluidic formats.
- Translational Research: Connects to preclinical continuity by enabling drug-cell studies under controlled flow, relevant to modeling in vivo-like fluid dynamics.
- Enterprise Reuse: Leverages a reusable microfluidic device with reversible PDMS-glass attachment, supporting repeated use across multiple experiments and teams.
Operational & Enterprise Impact
- Scientific Value: Reduces mechanistic ambiguity in fluid-driven biological responses by enabling precise control over droplet momentum and surface tension equilibration.
- Operational Value: Ensures standardization and reproducibility through calibrated, voltage-controlled droplet delivery and reversible device attachment.
- Strategic Value: Improves go/no-go decisions by providing reliable fluid exchange kinetics and mixing capabilities for early-stage biological assessment.
- Portfolio Impact: Supports risk-adjusted prioritization through quantifiable fluid dynamics outputs that inform assay design and target validation confidence.
Implementation Considerations
- Requires expertise in microfluidic device fabrication, passive pumping principles, and voltage-controlled fluid delivery systems.
- Needs instrumentation including micro-dispensing valves, control boxes (spike/hold), pressure reservoirs, and microscopy for flow observation.
- Demands cross-team standardization of droplet volume calibration, nozzle positioning, and reservoir setup to ensure consistent performance.
- Involves adaptation considerations for different channel geometries, fluid viscosities, and droplet angles to avoid inlet overflow or unstable flow shells.
- Includes practical limitations such as bubble formation risk if pressure head is unstable, and the need to manage outlet drop size to prevent backflow or inlet perturbation.
