Performance Metrics for Droplet Microfluidics
Performance Metrics for Droplet Microfluidics
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Droplet microfluidics has enabled many recent applications in high-throughput screening and diagnostics. Little work has been done, however, to analyze the performance of droplet-based assays.
A recent review from Tang et al aimed to apply what is known in the literature to the analysis of the performance metrics of droplet-based assays. This work has specific relevance to diagnostic and biomedical applications based on two processes: enzymatic reactions and cell culture in droplets.
We spoke to Sindy Tang, Assistant Professor, Department of Mechanical Engineering, Stanford University, to understand more about droplet microfluidics and the benefits improved performance metrics offer.
AB: Why has there been such limited analysis of the performance of droplet-based assays?
Sindy Tang (ST): Droplet microfluidics is still relatively new – this sub-field of microfluidics started taking off only around 2003 when it was first shown that one can generate highly uniform droplet sizes in microfluidic channels at very high rates (> 1000 drops per second). Since then, the focus has been to develop different components to manipulate droplets on chip, and to demonstrate the feasibility of using droplets for a wide range of biochemical assays. In the last few years, it has become clear that the technology works so well that it could become a very competitive platform for the next-generation of ultrahigh throughput screening applications. The use of droplet microfluidics has already extended beyond academic labs into the commercial world (e.g., RainDance, QuantaLife (now part of BioRad)). As such, understanding the performance of the assay as a whole, and the ability to compare droplet microfluidics with other existing technologies (e.g., microtiter plates) will be the next necessary step.
AB: What benefits would increased understanding offer?
ST: Currently, microtiter plates are used everywhere in pharmaceutical and biotechnology companies; one of the keys to the wide adoption of microtiter plates was the standardization of the dimensions (e.g., diameter, depth, and spacing) of each well and each plate. There is a discrete set of well numbers and dimensions that are currently commercially available: 6, 12, 24, 48, 96, or 384 wells on each plate. Standardization of size is common for every mature field in biotechnology and engineering (e.g., in electronics, resistors and capacitors are manufactured in predefined discrete units).
As droplet microfluidics mature, the next relevant question is how do you standardize droplets? This question of standardization thus led us to consider the effect of droplet sizes and other parameters on the performance of droplet assays more carefully, before one could say anything about what should become the standard.
AB: In your article you state that droplet microfluidics holds great promise in high throughput screening applications. What are the features of this technique that makes it so suited to these applications?
The high throughput nature (~3 orders of magnitude faster than current 96 well plate technology), and the small volume per reaction (~ pL in droplets, v.s. 100 uL in wells) make droplet technology attractive to applications that require the screening of a large number of reactions or molecules (>10^6). Agresti et. al compared the time and cost needed for a directed evolution screen using traditional microtiter plate technology versus that using droplet microfluidics. The numbers are striking (see table 1 extracted from the Agresti paper below):
AB: Can you explain a little about the relationship between dimensions and the output characteristics of droplet-based assays?
ST: The physics of individual droplet manipulation processes have been established (e.g., the regimes where droplet generation is stable, and how droplet size and generation rate depend on the applied flow rate etc.). From these individual studies, one can extrapolate the relationship between droplet properties and output characteristics such as the ultimate throughput you can get.
AB: In your opinion what would be required to increase adoption of droplet microfluidics?
ST: Our work only pointed to how one might be able to go about standardizing droplet technology. The next step will require people in the field actually agreeing to some standard.