Droplet-based microfluidics in drug discovery


Droplet-based microfluidics in drug discovery

Droplet-based microfluidics enables researchers to run thousands of samples per second while working with minimal material. Scientists can use this method in antibody screening, drug discovery, targeted genetic workflows, single-cell RNA sequencing, and many more.

Here we introduce you to this technique and its applications in drug discovery. We also show you how to use Cellix's 4U 4-channel Microfluidic Pump to help you get the best results possible.


Droplet Microfluidics

Droplet generation offers numerous advantages for drug discovery and biomedical research. This is mainly because you can perform large-scale studies using just a few microlitres of sample or a small number of cells. Droplet technology enables researchers to automate the process and analyse several cell-based assays in a single experiment, [1].

But before we dive deeper into the topic, let's first understand how the technique works.


What are microfluidic droplets?

Microfluidics is the technology that manipulates small amounts of fluids (10^-9 to 10^-18 litres) using very narrow channels. With this technology, scientists can control the concentrations of molecules in space and time, [2].

Droplet-based microfluidics is a type of microfluidics. Unlike continuous flow systems, it uses non-miscible phases (usually aqueous and oil-based) to create discrete volumes, i.e. droplets. With this technique, scientists generate and manipulate droplets using microfluidic pumps producing tiny droplets at high speed, [2].


What are the advantages of microfluidic droplets?

Droplet-based systems have particular characteristics such as a high surface area, short heat and mass transfer time, and fast reaction time. This technology allows you to control each droplet, generating individual micro-reactors, [2].

The principal advantages of this method are, [1]:

  • Requires very little sample volume

  • Enables a high degree of automation

  • Facilitates high throughput analysis

  • Cost-effective

Droplet microfluidics in drug discovery


Antibody Screening

Antibody screening is one possible application of droplet microfluidics technology. Research involving antibodies is bringing considerable advances in treating infectious diseases, cancer, and immune diseases. This industry is booming, demonstrating a need for more efficient screening methods, [1].

Typically, new antibodies are discovered using microtitre plates, immortalized hybridoma cells, and robotic technology. However, this technology usually produces a low output due to the low fusion efficiency of antibody-producing B cells and myeloma cells. Because of that, researchers can only screen a small fraction of the immune repertoire, [1].

One way of solving this problem is to use droplet microfluidics, which allows single-cell analysis at very high throughput. At low volumes, antibodies remain concentrated inside the droplets, bypassing clonal expansion, allowing detectable concentrations in microtitre plates, [1].


Direct screening for inhibition of enzymatic drug targets

In antibody screening, antibody-releasing cells are encapsulated into the droplets with the drug target and a fluorogenic substrate. If the antibody inhibits the enzymatic activity, the droplets show no fluorescence, [1].


Screening for antibody binding

Antibody-releasing cells are encapsulated into droplets with the antigen of interest and a secondary antibody. The binding of the primary antibody to the antigen causes a high-intensity fluorescence peak. If the primary antibody does not bind the antigen, it will result in a very weak fluorescence peak, [1].


Small molecules screening

With droplet microfluidics, scientists can run experiments using different drugs in parallel. For example, they can create a droplet drug library using multiple makers simultaneously and collect the resulting emulsions in a single tube. This requires labeling the droplets with different fluorescent stains. This approach can help researchers assess a drug's cytotoxicity in vitro, [1].


Another strategy is to generate concentration gradients to evaluate dose-response. Researchers can do this by continuously changing the relative flow rates of samples and buffer. They can also analyse more than one compound simultaneously. For example, this technique identifies optimal antibiotic concentrations and reveals antagonistic effects between the compounds, [1].


What do you need to get started?

If you're going to start your experiments with droplet generation, you'll need some basic materials. Cellix can supply the complete kit or just the components you wish.

The minimum set-up for droplet generation experiments is:

  • 2 or 3x Microfluidic pumps (or 3x channels on one pump)

to control the flow of the continuous (oil) phase and dispersed (water) phase. Depending on the application, we recommend the 4U pressure pump with 2x sample reservoirs or 2x (or 3x) ExiGo microfluidic syringe pumps. 4U pressure pump has a stable and accurate flow rate and enables independent control of 4 different channels, controlling both pressure and flow. You can program your flow profile and efficiently manage all the pump features using your smartphone.

  • 2 x Flow sensors to provide feedback of the flow control of both oil and water phases.

  • Microfluidic Chip with appropriate geometry creates droplets to ensure droplet size is optimal.


To learn more about our products or request a quote, contact Cellix.


References

  1. Shembekar, N., Chaipan, C., Utharala, R., & Merten, C. A. (2016). Droplet-based microfluidics in drug discovery, transcriptomics and high-throughput molecular genetics. Lab on a Chip, 16(8), 1314-1331.

  2. Sohrabi, S., & Moraveji, M. K. (2020). Droplet microfluidics: Fundamentals and its advanced applications. RSC Advances, 10(46), 27560-27574.


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