Microfluidic electrochemical immunoassay

As an example of microchip-based electrochemical immunoassays, we describe here the protocol established for the analysis of interleukin IB by enzyme linked immunosorbent assay (ELISA) with amperometric detection at the sub-pM level in DiagnoSwiss microfluidic chip called Immuchip . 

Zang DJ, Ge L, Van M, Song XR, Yu JH (2012) Electrochemical immunoassay on a 3D microfluidic paper-based device. Chem Common 48(39) 4683-4685... 

Heinemann et al. pioneered electrochemical immunoassays prior to the nanoparticle era [25]. His team s systems involve sandwich immunoassays using the enzyme label alkaline phosphatase which produces electroactive products that are transported by a chromatographic or fluidic system to an electrode detector [26,27]. Recent advances have interfaced this approach into microfluidic devices [28]. Interdigitated electrodes have provided the highest sensitivity [29]. 

Hervas, M., L6pez, M.A., and Escarpa, A. (2011) Integrated electrokinetic magnetic bead-based electrochemical immunoassay on microfluidic chips for reliable control of permitted levels of zearalenone in infant foods. Analyst, 136, 2131-2138. 

Electrochemical immunoassays were pioneered in the 1980s by Heineman, Halsall, and coworkers.23-29 Early in their studies, they employed voltammetric and amperometric techniques to measure proteins and small biologically important molecules, such as hormones, via competitive and sandwich-type immunoassays. Heineman and Halsall and other researchers explored many different measurement techniques and incorporated microfluidics, - reagent delivery systems, interdigitated electrode arrays, b34-36 magnetic beads ° b33,35-37 various designs to improve... 

Dong H, Li C-M, Zhang Y-F, Cao X-D, Gan Y (2007) Screen-printed microfluidic device for electrochemical immunoassay. Lab Chip 7 1752-1758... 

This chapter presents an approach to perform enzyme linked immunosorbent assays (ELISA) in a microfluidic format with electrochemical detection. This field of analytical chemistry has shown a strong activity in recent years, and many reports have presented the use of capillary-sized reactors for running immunoassays either in homogeneous format (where the antigen-antibody complex and the labelled revelation reagents are separated prior to detection, as for instance by capillary electrophoresis [1-3]) or in heterogeneous format (where the antibody is immobilised on the inner surface of the microsensor device [4] or on microbeads [5,6]). 

The use of ELISA is broad and it finds applications in many biological laboratories over the last 30 years many tests have been developed and vahdated in different domains such as clinical diagnostics, pharmaceutical research, industrial control or food and feed analytics for instance. Our work has been to redesign the standard ELISA test to fit in a microfluidic system with disposable electrochemical chips. Many applications are foreseen since the biochemical reagents are directly amenable from a conventional microtitre plate to our microfluidic system. For instance, in the last 5 years, we have reported previous works with this concept of microchannel ELISA for the detection of thromboembolic event marker (D-Dimer) [4], hormones (TSH) [18], or vitamin (folic acid) [24], It is expected that similar technical developments in the future may broaden the use of electroanalytical chemistry in the field of clinical tests as has been the case for glucose monitoring. This work also contributes to the novel analytical trend to reduce the volume and time consumption in analytical labs using lab-on-a-chip devices. Not only can an electrophoretic-driven system benefit from the miniaturisation but also affinity assays and in particularly immunoassays with electrochemical detection. 

Nonoptical detection is another important branch in the microfluidic immunoassay [22, 23], especially the electrochemical detection... 

Microfluidics coupled to bioanalytical devices has the potential to improve multiplexing and signal/noise, consume less expensive reagents and provide a degree of automation. In this section, we briefly summarize recent efforts to couple microfluidics to nanoparticle-based protein immunoassays for multiplexed biomarker detection. A recent example involves a 16-sensor electrochemical chip... 

Lateral flow immunoassay (LFIA) is a special type of microfluidic test strip in which flow of liquid is governed by capillary forces. The chemicals required for detection are preimmobilized on the test strip and the detection is usually colorimetric, so that the results are visible using the naked eye. Because colorimetry provides qualitative results, electrochemical and other optical transductions have been used for quantitative detection of analytes. 

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