Evaporation management in digital microfluidic devices
Described herein are digital microfluidic (DMF) devices and corresponding methods for managing reagent solution evaporation during a reaction. Reactions on the DMF devices described here are performed in an air or gas matrix. The DMF devices include a means for performing reactions at different temperatures. To address the issue of evaporation of the reaction droplet especially when the reaction is performed at higher temperatures, a means for introducing a replenishing droplet has been incorporated into the DMF device. A replenishing droplet is introduced every time when it has been determined that the reaction droplet has fallen below a threshold volume. Detection and monitoring of the reaction droplet may be through visual, optical, fluorescence, colorimetric, and/or electrical means.
1. A method of replenishing a reaction droplet within an air gap region of a microfluidic apparatus to correct for evaporation, the method comprising:
monitoring a reaction droplet in the air gap of the microfluidic apparatus for a change in an optical intensity;
determining, based on the change in the optical intensity, when a volume of the reaction droplet falls below a threshold, wherein the reaction droplet comprises a solvent and reaction reagents;
introducing a replenishing droplet into the air gap of the microfluidic apparatus, wherein the replenishing droplet consists of solvent; and
combining the replenishing droplet with the reaction droplet after the volume of the reaction droplet falls beneath the threshold.
2. The method of claim 1 , wherein combining comprises moving the replenishing droplet, the reaction droplet, or both the replenishing droplet and the reaction droplet by applying energy to electrodes adjacent to the replenishing droplet, the reaction droplet or both the replenishing droplet and the reaction droplet.
3. The method of claim 1 , wherein monitoring comprises determining a change in the volume of the reaction droplet.
4. The method of claim 1 , wherein the threshold of a change in volume of the reaction droplet is a change of 30% or more.
5. The method of claim 1 , further comprising heating the reaction droplet in a thermal zone of the air gap region of the microfluidic apparatus.
6. The method of claim 1 , wherein introducing the replenishing droplet comprises introducing a replenishing droplet having a volume of between 10% and 50% the volume of the reaction droplet.
7. The method of claim 1 , wherein monitoring the reaction droplet in the air gap of the microfluid apparatus for a change in optical intensity includes monitoring the reaction droplet for an increase in colorimetric intensity of the reaction droplet.
8. A method of replenishing a reaction droplet in an air gap region of a microfluidic apparatus to correct for evaporation, the method comprising:
optically monitoring the reaction droplet by using a camera to image the droplet in the air gap region of the microfluidic apparatus;
determining a volume of the reaction droplet by from the image of the droplet;
determining when the volume of the reaction droplet falls below a threshold, wherein the reaction droplet comprises a solvent and reaction reagents;
introducing a replenishing droplet into the air gap region of the microfluidic apparatus, wherein the replenishing droplet consists of solvent; and
combining the replenishing droplet with the reaction droplet after the volume of the reaction droplet falls beneath the threshold.
9. The method of claim 8 , wherein introducing the replenishing droplet includes adjusting a temperature by holding the replenishing droplet at a region that is adjacent to a reaction droplet and in thermal communication with a region beneath the reaction droplet.
10. The method of claim 8 , wherein introducing the replenishing droplet includes adjusting a temperature of the replenishing droplet by holding the replenishing droplet at a thermal zone and adjusting a temperature of the thermal zone to match the temperature of the reaction droplet.
11. The method of claim 8 , wherein combining comprises moving the replenishing droplet, the reaction droplet, or both the replenishing droplet and the reaction droplet by applying energy to electrodes adjacent to the replenishing droplet, the reaction droplet or both the replenishing droplet and the reaction droplet.
12. The method of claim 8 , wherein the threshold of a change in volume of the reaction droplet is a change of 30% or more.
13. The method of claim 8 , further comprising heating the reaction droplet in a thermal zone of the air gap region of the microfluidic apparatus.
14. The method of claim 8 , wherein introducing the replenishing droplet comprises introducing a replenishing droplet having a volume of between 10% and 50% of the volume of the reaction droplet.
15. A method of replenishing a reaction droplet within an air gap region of a microfluidic apparatus to correct for evaporation, the method comprising:
monitoring, with a camera, a size of a reaction droplet in the air gap of the microfluidic apparatus;
determining when the size of the reaction droplet falls below a threshold, wherein the reaction droplet comprises a solvent and reaction reagents;
introducing a replenishing droplet into the air gap of the microfluidic apparatus, wherein the replenishing droplet consists of solvent; and
combining the replenishing droplet with the reaction droplet after the size of the reaction droplet falls beneath the threshold by applying electrical energy to move the replenishing droplet into contact with the reaction droplet by electrowetting.