A digital microfluidic device with integrated nanostructured microelectrodes for electrochemical immunoassays

Abstract

Nanostructured microelectrodes (NMEs) are three-dimensional electrodes that have superb sensitivity for electroanalysis. Here we report the integration of NMEs with the versatile fluid-handling system digital microfluidics (DMF), for eventual application to distributed diagnostics outside of the laboratory. In the new methods reported here, indium tin oxide DMF top plates were modified to include Au NMEs as well as counter and pseudoreference electrodes. The new system was observed to outperform planar sensing electrodes of the type that are typically integrated with DMF. A rubella virus (RV) IgG immunoassay was developed to evaluate the diagnostic potential for the new system, relying on magnetic microparticles coated with RV particles and analysis by differential pulse voltammetry. The limit of detection of the assay (0.07 IU mL(-1)) was >100× below the World Health Organization defined cut-off for rubella immunity. The sensitivity of the integrated device and its small size suggest future utility for distributed diagnostics.

DStat: A Versatile, Open-Source Potentiostat for Electroanalysis and Integration

“…A video demonstration of combined droplet manipulation and electrochemical measurement can be found in S1 Video with experimental details in S5 Supporting Information . Thus, the extensibility of DStat makes it an attractive tool for the burgeoning area of digital microfluidic electrochemistry [ 29 – 33 ].…”

Pre-concentration by liquid intake by paper (P-CLIP): a new technique for large volumes and digital microfluidics

“…20 While surface-binding on magnetic microparticles can be a versatile pre-concentration technique, a disadvantage is the risk of clogging when used with microchannel systems. 21 "Open"-format microfluidic systems such as those powered by digital microfluidics (DMF) eliminate the problem of clogging and have proven particularly useful for handling magnetic micro-particles 22 for the analysis of small molecules, 23,24 proteins, [25][26][27][28][29][30][31] and nucleic acids. 32,33 In the most common DMF device format, discrete droplets of liquid are sandwiched between two plates: the bottom plate comprises an array of electrodes that is covered by an insulating dielectric layer and a hydrophobic layer, and the top plate comprises a ground electrode that is covered with a hydrophobic layer.…”

“…In this two-plate format, droplets cannot be manipulated in the z-axis but are unrestricted by any walls or barriers in the xy-plane. 34 Despite its proven utility in handling magnetic microparticles, [22][23][24][25][26][27][28][29][30][31][32][33] DMF is limited in its ability to effect preconcentrations of significant magnitude. Specifically, the difference between the smallest and largest volumes that can be (practically) manipulated on most DMF devices is often quite smalle.g., in the devices used here, this range runs from ∼0.9 μL (a "unit" droplet covering one electrode) to ∼9 μL (a droplet covering 10 electrodes; volumes larger than this are impractical to use).…”

“…More generally, the new technique should be incorporated in any DMF assay relying on functionalized magnetic microparticles. [22][23][24][25][26][27][28][29][30][31][32][33]…”

An inkjet printed, roll-coated digital microfluidic device for inexpensive, miniaturized diagnostic assays

“…Complex multi-step operations (e.g., washing, 15 solvent exchanges, 16 and extractions 17 ) can be performed in an automated fashion, and since droplets are individually addressable on a generic device geometry, experiments can be reconfigured on-the-fly. These properties (and others) are making DMF an increasingly popular tool for miniaturizing applications ranging from chemical synthesis, [18][19][20][21] to chemical analysis, [22][23][24][25] and cell culture. [26][27][28][29] While DMF has proven to be a useful technology, one of its leading challenges is fabrication -devices are typically manufactured on glass substrates with slow and expensive photolithography, wet-etching, vapour deposition, and spincoating techniques (often requiring a clean room facility).…”