Integration and detection of biochemical assays in digital microfluidic LOC devices

Abstract

The ambition of lab-on-a-chip (LOC) systems to achieve chip-level integration of a complete analytical process capable of performing a complex set of biomedical protocols is hindered by the absence of standard fluidic components able to be assembled. As a result, most microfluidic platforms built to date are highly specialized and designed to fulfill the requirements of a single particular application within a limited set of operations. Electrowetting-on-dielectric (EWOD) digital microfluidic technology has been recently introduced as a new methodology in the quest for LOC systems. Herein, unit volume droplets are manipulated along electrode arrays, allowing a microfluidic function to be reduced to a set of basic operations. The highly reprogrammable architecture of these systems can satisfy the needs of a diverse set of biochemical assays and ensure reconfigurability, flexibility and portability between different categories of applications and requirements. While important progress was made over past years in the fabrication, miniaturization and function programming of the basic EWOD fluidic operations, the success of this technology will in great part depend on the ability of researchers to couple or integrate digital microfluidics to detection approaches that can make the system competitive for LOC applications. The detection techniques should be able to circumvent the limitations of hydrophobic surfaces and exploit the advantages of the array format, high droplet transport speeds and rapid mixing schemes. This review provides an in-depth look at recent developments for the coupling and integration of detection techniques with digital microfluidic platforms for bio-chemical applications.

Advanced EWOD-based digital microfluidic system for multiplexed analysis of biomolecular interactions

“…We believe that the developed technology proposed herein provides a highly flexible tool for the rapid analysis of biomolecular interactions under numerous different conditions. Work is underway to integrate these devices with label-free detection systems [2] and various biological species (DNA, RNA, proteins, cells, etc.). …”

“…Among the various types of microfluidic devices developed in the past years, digital microfluidics (DMF) has emerged as a promising technology that offers key advantages to perform miniaturized bioassays [2][3][4]. In DMF devices, nl-size liquid droplets are manipulated at will on a 2D surface using electrowetting-ondielectric (EWOD) forces applied with an array of computer-controlled electrodes (figure 1).…”

Recent Advances in Nanobiotechnology and High-Throughput Molecular Techniques for Systems Biomedicine

“…The transcriptional heterogeneity of monoclonal human colon cancer (Dalerba et al, 2011) and circulating tumor cells (Powell et al, 2012) were revealed by commercially available qRT-PCR equipment in microfluidic platform. Another common approach involves a series of components which integrate various steps in metering, formulation, mixing, analysis, and storage (Malic et al, 2010;Mark et al, 2010). One module which arises repeatedly in high-throughput analysis is storage.…”

An intelligent digital microfluidic system with fuzzy-enhanced feedback for multi-droplet manipulation

“…16 Reliability and robustness are still great challenges of DMFbased micro-reactors [9][10][11][12][13][14] due to the co-existence of different sorts of chemical reagents and biological species. It is particularly true for those containing sticky constituents, and the various irregular sample-originated surface damages, adsorption, and aging effects 17 of the insulation and hydrophobic materials of the DMF chip. For instance, in a sequential reaction, a droplet sample may fail to reach the expected destination due to a premature charging time, halting the entire system.…”