Controllable Emulsification And Point-Of-Care Assays Driven By Magnetic Induced Movement Of The Fluid

Tech ID: 26032 / UC Case 2016-228-0

Summary

UCLA researchers in the department of Bioengineering have developed a novel microfluidic droplet generation technique, where instead of pumps, only magnetic force is used for controllable emulsification of ferrofluid containing solutions. 

Background

  • Droplet or digital microfluidics is an emerging liquid-handling technology that enables individual control over droplets under a set of simple and well-defined operations, which offers significant advantage over conventional continuous-flow microfluidics. This technology has been a strong tool for a range of applications including genome profiling and high throughput digital assays. 
  • Traditionally, droplets are formed using bulky pressure driven or syringe pump driven flow systems, which has limited the ability to extend such assays to point-of-care formats. 
  • Ferrofluids are fluids that contain suspended magnetic nanoparticles. Recently, ferrofluids have been used in digital microfluidics to adjust flow rates and droplet sizes. However, accurate pumps are still needed for droplet generation in these systems. 

Innovation

  • To make these droplet generators portable for point-of-care applications, UCLA researchers in the department of Bioengineering developed a new technology for droplet formation based on magnetic induced flow of ferrofluid in a step emulsification device that operates without any pumps. 
  • Reagents mixed with ferrofluids can be introduced from two or more inlets and mixed prior to emulsification, allowing efficient mixing of reagents on chip and formation of compartmentalized droplets using only a small external magnet. 
  • Thus, this technology provides a complete solution to combine mixing of reagents, rapid droplet generation, and droplet control in a simple format driven by magnetic fields. 

Applications

  • Any assay conducted in confined volumes using other methods of forming droplets, could be performed in this system. Some examples are listed below.
  • Digital assays at point of care to replace PCR or other nucleic acid tests that require bulky and complex instruments
  • Single-cell whole genome amplification
  • Polymerize the droplets to make different types of magnetic polymers or hydrogel particles 
  • Active sorting of cells or particles encapsulated in droplets containing ferrofluid
  • Analyzing how pure a sample is or collecting only a fraction of droplets with particular reagents

Advantages

  • Uniform droplets can be generated at variable frequencies (1-100 Hz/channel) for long period of time (10s of minutes). Droplet size and generation rate can be easily adjusted. 
  • Pumps are not needed, making this device portable for point-of-care applications.
  • Small sample volume is required compared to pump-based systems which have large dead volume. 
  • The droplets generated are magnetic, allowing further manipulation for downstream experiments. 
  • On-chip mixing of different fluids and emulsification is easily achieved. When each reagents are mixed together the ratio can be precisely controlled, which makes it a good system for time-sensitive reactions.
  • Complexity of multiple assay steps/reagents is reduced.

State Of Development

  • Several setups with single and multiple inlets are fabricated and tested with 2 different aqueous ferrofluids, including biocompatible solutions.
  • A 10μL solution was emulsified to 125μm droplets in less than 10 minutes with a one-inlet device 
  • The relationship between droplet generation rate and magnet force is shown. The maximum droplet generation rate can be achieved with a permanent magnet of ~0.1 T surface B-field is about 12 droplets/second each channel. Parallelized designs allow generation of 100s of droplets/sec.
  • Demonstration of a digital nucleic acid amplification assay with the system.
  • A handheld device to achieve the combination of mixing of sample with ferrofluid followed by emulsification reaction and downstream detection is in development.

Patent Status

Patent Pending

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Inventors

  • Di Carlo, Dino

Other Information

Keywords

emulsification, magnetic nanoparticles, ferrofluid, droplets, microfluidics

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