Robust Multi-Target Sample Preparation on MEDA Biochips Obviating Waste Production

What is it about?

In this work, we present an error-free sample preparation technique for guaranteeing the correctness of the resulting concentration factor of a sample without performing any additional roll-back or roll-forward action. To the best of our knowledge, we are the first to present a solution strategy for tackling dispensing errors during sample preparation. We use micro-electrode-dot-array biochips that offer the advantages of manipulating fractional volumes of droplets (aliquots) for navigation,as well as mix-split operations. Instead of performing traditional mix-and-split steps with integral-volume droplets, we execute only an aliquoting-and-mix sequence using differential-size aliquots. Thus, all split operations, which are the main source of errors in conventional digital microfluidic biochips, are completely eliminated, and hence neither sensing nor any correcting action is needed, and further, no management of intermediate waste droplets is needed. Additionally, the procedure can be fully parallelized for accurately producing multiple dilutions of a sample.

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Why is it important?

Most of the errors in sample preparation are attributed to volume variation in droplets, which are caused by mix-split operations resulting in a change in the desired concentration factor of the target solution. Volumetric imbalance among daughter droplets is inherent to a “split” operation,which is an essential primitive in droplet-based microfluidics. Such errors are caused by random events and cannot be rectified so easily on a DMFB platform. Traditional recovery processes include invoking of either “roll-back” or “roll-forward” action when such errors are sensed online.Both of them cause an increase in reactant cost or assay completion time. In this work, we present a fundamentally different approach to robust sample preparation that eliminates the need for any droplet-splitting operation. Instead of using conventional mix-split sequences, we recast sample preparation algorithms from a new perspective that rely on using only “aliquots-and-mix” and utilize the granularity of MEDA chips to implement the procedure. As a spin-off of this method,multiple target-CFs can also be produced in parallel on a MEDA-based DMFB.

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