PortaDrop: A portable digital microfluidic platform providing versatile opportunities for Lab-On-A-Chip applications

Electrowetting-on-dielectric is a decent technique to manipulate discrete volumes of liquid in form of droplets. In the last decade, electrowetting-on-dielectric systems, also called digital microfluidic systems, became more frequently used for a variety of applications because of their high flexibility and reconfigurability. Thus, one design can be adapted to different assays by only reprogramming. However, this flexibility can only be useful if the entire system is portable and easy to use. This paper presents the development of a portable, stand-alone digital microfluidic system based on a Linux-based operating system running on a Raspberry Pi, which is unique. We present “PortaDrop” exhibiting the following key features: (1) an “all-in-one box” approach, (2) a user-friendly, self-explaining graphical user interface and easy handling, (3) the ability of integrated electrochemical measurements, (4) the ease to implement additional lab equipment via Universal Serial Bus and the General Purpose Interface Bus as well as (5) a standardized experiment documentation. We propose that PortaDrop can be used to carry out experiments in different applications, where small sample volumes in the nanoliter to picoliter range need to be handled an analyzed automatically. As a first application, we present a protocol, where a droplet is consequently exchanged by droplets of another medium using passive dispensing. The exchange is monitored by electrical impedance spectroscopy. It is the first time, the media exchange caused by passive dispensing is characterized by electrochemical impedance spectroscopy. Summarizing, PortaDrop allows easy combination of fluid handling by means of electrowetting and additional sensing.


S1 Fig. Switching delay H-bridge.
(a) 5 V rectangle signal at a frequency of 1 kHz and the inverted signal for the control of the H-bridge (b) Magnification of the change between HIGH and LOW and vice versa. The implemented delay corresponds to one processor cycle. For this time period, both signals are LOW and thus the connected optotriacs are turned off. Hence, a short between VOut and GND is avoided. Fig. I2C level shifter. a) Schematic of the I 2 C level shifter. The Raspberry Pi operates with 3.3 V representing a logical HIGH and is the master of the I 2 C bus while the AVR microcontrollers serving as the slaves detect 5 V as HIGH level. The level shifter is working bi-directional on the two wires of the I 2 C bus SDA and SCL. b) Level conversion from 5 V to 3.3 V running at the standard I 2 C frequency of 100 kHz.

S3 Fig. Overview of the relays controlling the proper routing of the signals for EWOD and EIS operation. (a)
The relays connected to the input and output of the boost converter disable or enable the boost converter, respectively. When the boost converter is enabled, the input terminal of the H-bridge is connected. In addition, an external voltage supply can be connected to the H-bridge. Two relays between the output of the H-bridge and the AC+ and AC-connectors allow to disconnect the voltage, thus the semiconductor switches boards are galvanically isolated. For EWOD operation both need to be connected to the blocks in (b), where the mode of operation can be switched from EWOD to EIS. Relays can therefore connect the electrodes on the top chip attached to the SMA connectors to the internal and external measurement devices and change the wire mode to 2-, 3-or 4-point measurement. At the same time the high-voltage is decoupled from the system to avoid damage of the devices as well as hydrolysis in the droplet.       The voltage can be generated automatically using the boost converter (internal) or an external source can be used. During the execution, the user is asked to change the voltage to the defined set point.

S15 Fig. GUI tab "Add Task/Spectrometer Task".
Allows the use of the optical spectrometer (Ocean Optics HR2000+). The integration time per taken spectrum and the number of spectra for computing an average spectrum can be defined.

S16 Fig. GUI tab "Add Task/Pad Task".
Overview of the used EWOD chip allowing to (1) immediately activate pads for the set time and (2) to add the task to the current recipe. The latter allows to specify sequences of activated path electrodes in a certain order.      The outer area is covered with ITO and a hydrophobic Teflon layer, patterned circularly to allow access of the media to the sensor. The impedance between the star-shaped electrode and the three sector electrodes connected all together is measured.

Important: The µC itself limits the voltage to stay in the specs of all circuit elements, when the voltage increases to undesired values. The button 'Set
Frequency' adjusts the frequency of the PWM signal for the boost converter.
• Frequency Generator: Shows the actual frequency of the rectifier circuit. The value can be updated using the 'refresh' button. To change the frequency, a value for the new frequency can be entered and set using 'set Frequency'. o Pad Task: Adds specified EWOD pads, which are turned on for a specified time to the recipe. Therefore, an overview of the path electrodes is depicted in the GUI. Multiple steps stringed together allow droplet movement over certain path electrodes. In addition, path electrodes can be activated manually to move droplets by hand.
o Imp Task: Adds an EIS measurement to the current recipe. Correct connection of the utilized instruments will be checked at the start of the recipe. The settings available are depicted in S16 Fig.
• Log: All status messages given by the software are recorded and shown here.
The log file content during one experiment is also saved to the project folder.
• Preferences: Allows path settings to the project folder and the recipe folder.