Enabling Simultaneous Label-Free Sensing in Microfluidics

Posted 23rd November 2016 by Jane Williams

Microfluidics is a rapidly developing area of research and scientists are continually discovering the wide range of possibilities the technology can provide. Carolyn Ren is one such scientist. We spoke to Carolyn about her research around droplet microfluidics and how it enables high throughput screening analysis by utilising nanolitre-sized drops as mobilised test tubes.

What are the most exciting recent developments in microfluidics technology?
Microfluidic platforms integrated with microwave technology enable simultaneous label-free sensing, heating and manipulation of nanolitre-sized droplets. Droplet microfluidics is a promising alternative to microarray technology for combinatorial high-throughput screening, which is in high demand by many fields such as material synthesis, drug compound screening, cosmetics and chemical and biological reactions. Sensing is always challenging and largely relies on the use of labels, such as fluorescent dyes, which modify the working sample. Label-free sensing largely requires direct contact between the electrodes and working sample, which carries the risk of cross contamination and is not ideal for droplets which are encapsulated by an immiscible fluid. Therefore, remote sensing is urgently needed.

We developed capacitance sensing which is capable of detecting a droplets presence, speed and size. However, its sensitivity was not sufficient to differentiate droplets with subtle differences in their dielectric properties. We also developed microwave sensing which is capable of differentiating nanolitre-sized droplets dosed with materials with subtle differences in their conductivity and/or permittivity. Moreover, this sensor is capable of heating up individual droplets without influencing the surrounding media. Very recently, the entire system was miniaturised, which opens up the potential for point-of-care applications.

Our preliminary results show that heating enhances droplet mixing significantly, which eliminates the need for forcing droplets to travel through serpentines. It has the potential to be applied to single-phase microfluidics for molecular-based sensing and click chemistry reactions, because of the rapid mixing it enables and its fast heating (i.e. ~40oC over 15 ms).

What is the greatest challenge you currently face?
The biggest challenge is sorting and splitting droplets with high accuracy and speed. Sorting droplets using passive means does not need active control units to be integrated. However, it is too sensitive to any uncertainties such as fluctuations in pumping, defects in channel dimensions and other manipulation events. For example, merging and generation occurring in the channel network. Sorting using active means could be tuned for localised needs, but requires high throughput sensing and fast feedback control.

The same situation happens when splitting droplets. Splitting droplets is needed when controlling droplet content, for example, cleaning up waste and then perfusing with fresh media. Passive splitting by varying geometric conditions is possible in principle, but not practical. Any uncertainty in the applied pressures and surface properties would cause errors and it is too sensitive to other events in the flow channel network. Active means are possible but require fast data transport and accurate imaging in the first place.

How is microfluidics changing medical research?
Due to its small scale, microfluidics provides higher sensitivity because samples are confined and thus sensitivity can be increased. Microfluidics allows the integration of different label-free sensing mechanisms, such as microwave sensing, which avoids the use of fluorescent dyes that modify working samples. Its continuous flow processing allows different focusing mechanisms to be integrated, which will increase the separation capacity and sensitivity in proteomics.

Droplet microfluidics enables high throughput screening which is magnitudes higher than traditional high throughput systems, such as microarrays. In addition, the savings in cost of reagent use is significant. Therefore, with the advancement in sensing, heating and manipulation of individual droplets, droplet microfluidics would be the tool for screening drug compounds, providing personal medicine and manufacturing nanoparticles/quantum dots with controllable surface properties for disease diagnosis.

Carolyn Ren is a research chair in the Department of Mechanical and Mechatronics Engineering at University of Waterloo, Canada. She spoke at this year’s Microfluidics Congress: USA.

Take a look at what we’re planning for next year’s Microfluidics Congress: USA.

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