Interfacing Digital Microfluidics with Ambient Mass Spectrometry Using SU-8 as Dielectric Layer

Abstract

This work describes the interfacing of electrowetting-on-dielectric based digital microfluidic (DMF) sample preparation devices with ambient mass spectrometry (MS) via desorption atmospheric pressure photoionization (DAPPI). The DMF droplet manipulation technique was adopted to facilitate drug distribution and metabolism assays in droplet scale, while ambient mass spectrometry (MS) was exploited for the analysis of dried samples directly on the surface of the DMF device. Although ambient MS is well-established for bio- and forensic analyses directly on surfaces, its interfacing with DMF is scarce and requires careful optimization of the surface-sensitive processes, such as sample precipitation and the subsequent desorption/ionization. These technical challenges were addressed and resolved in this study by making use of the high mechanical, thermal, and chemical stability of SU-8. In our assay design, SU-8 served as the dielectric layer for DMF as well as the substrate material for DAPPI-MS. The feasibility of SU-8 based DMF devices for DAPPI-MS was demonstrated in the analysis of selected pharmaceuticals following on-chip liquid-liquid extraction or an enzymatic dealkylation reaction. The lower limits of detection were in the range of 1–10 pmol per droplet (0.25–1.0 µg/mL) for all pharmaceuticals tested.

Affordable Fabrication of Conductive Electrodes and Dielectric Films for a Paper-Based Digital Microfluidic Chip

“…The intervening dielectric thin film allows the use of high voltages for inducing a stronger electrowetting force so that the shape of the drop can be sufficiently deformed, and the drop can eventually move [3]. However, since Berge introduced an excellent dielectric material, parylene-C, which has a very high electrical breakdown voltage (200 V/μm), new attempts to obtain alternative dielectrics have been surprisingly rare, except for a few materials, such as Teflon, SU-8, CYTOP, and polydimethylsiloxane (PDMS) [3,19,23,24,25,26]. Even worse, most thin-film deposition methods, such as CVD for parylene-C and spin-coating for Teflon, require heavy instruments, including gas- and temperature-control systems on a lab-scale, which is a severe obstacle to the affordable fabrication of DMF chips.…”

Role of Digital Microfluidics in Enabling Access to Laboratory Automation and Making Biology Programmable

“…Some studies have also focused on directly integrating MS with the DMF platform without the need for intermediate equipment. For example, Sathyanarayanan et al 97 show in their work a DMF device integrated MS via desorption atmospheric pressure photoionization (DAPPI-MS). The device was developed for the implementation and in situ quantification of an on-chip drug distribution and drug metabolism assay while minimizing sample loss.…”

A Digital‐to‐Channel Microfluidic Interface via Inkjet Printing of Silver and UV Curing of Thiol–Enes

“…DMF driving electrodes are typically defined on a glass substrate by photolithography. Recently, increasing effort has been put into fabrication of electrodes by rapid inkjet prototyping techniques [ 11 ] as well as by using mass manufacturing techniques, such as printed circuit board (PCB) processing [ 23 ] or microcontact printing. [ 24 ] The dielectric coating typically relies on chemical vapor deposition (CVD) of Parylene C because its deposition quality is often superior (defect‐free) compared with, for instance, spin‐coated dielectric layers.…”

“…[ 1 ] With automated droplet actuation, [ 2 ] multiple individual droplets can be dispensed, mixed, and split in parallel to perform sequential sample manipulation protocols, such as rinsing, preconcentration, reaction, and extraction. Interfacing of DMF with a range of optical, [ 3,4 ] electrochemical, [ 5–7 ] and mass spectrometric detection [ 8–11 ] methods is well established and the fabrication of the devices has already been pushed toward low‐cost cleanroom‐free techniques. [ 12,13 ] As a result, DMF is a robust and cost‐effective technology for miniaturization of various biochemical assays including but not limited to immunological, [ 14 ] enzymatic, [ 15 ] cell‐based, [ 16 ] PCR, [ 17 ] drug, [ 18 ] and biopsy [ 19 ] screening assays.…”