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Methods of Mixing a Large Volume of Liquid on a Droplet Actuator

IP.com Disclosure Number: IPCOM000237257D
Publication Date: 2014-Jun-10

Publishing Venue

The IP.com Prior Art Database

Abstract

The invention provides methods of mixing a relatively large volume of liquid on a droplet actuator. More specifically, the methods of the invention provide efficient mixing of a large volume of liquid (e.g., about 1 mL) in the absence of electrowetting. The large volume of liquid may be, for example, a sample liquid that contains a quantity of magnetically responsive beads. In one example, a magnetic stir bar(s) and a magnetic stirring device may be used to mix a large volume of a sample liquid and resuspend the magnetically responsive beads therein. In another example, a stream of air may be used to mix a large volume of a sample liquid and resuspend the magnetically responsive beads therein. In yet another example, a flexible filament may be used to physically mix a large volume of a sample liquid and resuspend the magnetically responsive beads therein. In yet another example, an ultrasonic module may be used to mix a large volume of a sample liquid and resuspend the magnetically responsive beads therein. In yet another example, micro-vibrations may be used to mix a large volume of a sample liquid and resuspend the magnetically responsive beads therein. In still another example, alternating current (AC) oscillation may be used to mix a large volume of a sample liquid.

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Methods of Mixing a Large Volume of Liquid on a Droplet Actuator

1 Background

A droplet actuator typically includes one or more substrates configured to form a surface or gap for conducting droplet operations. The one or more substrates establish a droplet operations surface or gap for conducting droplet operations and may also include electrodes arranged to conduct the droplet operations. The droplet operations substrate or the gap between the substrates may be coated or filled with a filler fluid that is immiscible with the liquid that forms the droplets.

In some applications of a droplet actuator there is a need for using a relatively large volume (e.g., about 1 mL) of liquid for various assays. In some cases, mixing the relatively large volume of liquid (e.g., a sample liquid) may be required at certain process steps of an assay. In one example, mixing may be used to provide a more homogenous distribution of one or more components (e.g., magnetically responsive beads and target substances) within a sample liquid. In another example, mixing may be used to facilitate extraction of target analytes in a large volume of sample liquid. While mixing a relatively small volume of liquid (e.g., a 2X droplet) is readily accomplished using droplet operations (i.e., electrowetting), mixing a larger volume of liquid is not. There is a need for improved methods for mixing a relatively large volume of liquid on a droplet actuator.


2 Definitions

As used herein, the following terms have the meanings indicated.

"Activate," with reference to one or more electrodes, means affecting a change in the electrical state of the one or more electrodes which, in the presence of a droplet, results in a droplet operation. Activation of an electrode can be accomplished using alternating or direct current. Any suitable voltage may be used. For example, an electrode may be activated using a voltage which is greater than about 150 V, or greater than about 200 V, or greater than about 250 V, or from about 275 V to about 1000 V, or about 300 V. Where alternating current is used, any suitable frequency may be employed. For example, an electrode may be activated using alternating current having a frequency from about 1 Hz to about 10 MHz, or from about 10 Hz to about 60 Hz, or from about 20 Hz to about 40 Hz, or about 30 Hz.


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"Bead," with respect to beads on a droplet actuator, means any bead or particle that is capable of interacting with a droplet on or in proximity with a droplet actuator. Beads may be any of a wide variety of shapes, such as spherical, generally spherical, egg shaped, disc shaped, cubical, amorphous and other three dimensional shapes. The bead may, for example, be capable of being subjected to a droplet operation in a droplet on a droplet actuator or otherwise configured with respect to a droplet actuator in a manner which permits a droplet on the droplet actuator to be brought into contact with the bead...