The present invention provides a hybrid digital and channel microfluidic device in the form of an integrated structure in which a droplet may be transported by a digital microfluidic array and transferred to a microfluidic channel. In one aspect of the invention, a hybrid device comprises a first substrate having a digital microfluidic array capable of transporting a droplet to a transfer location, and a second substrate having a microfluidic channel. The first and second substrates are affixed to form a hybrid device in which an opening in the microfluidic channel is positioned adjacent to the transfer location, so that a droplet transported to the transfer location contacts the channel opening and may enter the channel. The invention also provides methods of performing separations using a hybrid digital and channel microfluidic device and methods of assembling a hybrid digital microfluidic device.