This paper presents a novel technique based on plasma etching for the mass production of polymer microchip devices. The method consists of the patterning of a photo-resist by a high resolution printer on a foil composed of three layers (5 microm copper/50 microm polyimide/5 microm copper). After this step, both copper layers are chemically etched in order to serve as a contact mask on the polyimide surface so as to produce the desired microstructure pattern. The foil is placed into a reactive plasma chamber in order to etch the exposed polyimide by means of an oxidizing plasma. The method enables holes, lines or larger areas to be etched, thereby generating either microholes, microchannels or electrodes in the plastic material. The copper can then be chemically removed or further patterned to produce conductive pads which are further electroplated with gold. The microchannel is then covered with a polyethylene terephthalate/polyethylene (PET/PE) lamination. The strength of this technology is that access holes for the fluid inlet and outlet, as well as gold coated electrodes can be fabricated without post-processing in a batch process. Demonstration of the application of such microelectrochemical systems is shown here by voltammetric detection inside a 60 nL microchannel, which presents the special feature of linear depletion of the analytes in the direction parallel to the microchannel.

A micro-analytical system for rapid and quantitative analysis by inhibition immunoassay is presented and applied to the detection of folic acid. Eight polymer microchannels of 65-nL volume each and containing microelectrodes are embedded in a cartridge so that they can be operated simultaneously. All fluidic steps as well as the amperometric detection in the channels are operated by an instrument and software developed in-house. The fluidic steps of the immunoassay occur through hydrodynamic loading of the different solutions through the channels. The speed and duration of the flow and incubation parameters can thus be adapted to the biological and testing requirements. The effectiveness of the system was demonstrated by analysing folic acid concentrations in real infant formula samples within 5 min. In an effort to get a fully monitored assay, each fluidic step is monitored thanks to continuous amperometric detection of oxygen in the microchannel.

A way of using gravity flow to induce a linear convection within a microfluidic system is presented. It is shown and mathematically supported that tilting a 1 cm long covered microchannel is enough to generate flow rates up to 1000 nL.min(-1), which represents a linear velocity of 2.4 mm.s(-1). This paper also presents a method to monitor the microfluidic events occurring in a covered microchannel when a difference of pressure is applied to force a solution to flow in said covered microchannel, thanks to electrodes inserted in the microfluidic device. Gravity-induced flow monitored electrochemically is applied to the performance of a parallel-microchannel enzyme-linked immunosorbent assay (ELISA) of the thyroid-stimulating hormone (TSH) with electrochemical detection. A simple method for generating and monitoring fluid flows is described, which can, for instance, be used for controlling parallel assays in microsystems.

G RAVI, presented here in its automated version, is a new bench-top sized immunoassay platform combining the advantages of microfluidics with those of simplified robotics. Characterized by dramatically reduced time to result (!10 min) and significantly decreased sample/reagent consumption, the cost-efficient biosensor instrumentation allows performing multimenu analysis with minimal laboratory infrastructure.Coupled to a robotic liquid handler, the system dispenses samples and reagents from conventional plates or tubes into microchannels of a microchip (GRAVI-Chip), in which assays are processed and results readout. As in conventional 96-well microtiter plates, the microchannels have a standard spacing of 9 mm to facilitate automation.With solely gravity and capillary force-driven fluidics within the microchannels, liquids are free to flow while magnetic beads, functionalized with the antibody of choice, are trapped nearby incorporated electrodes by virtue of a magnet array. Following assay performance and electrochemical signal detection in the parallel microchannels, chips are regenerated by magnet release and rinsing of beads out from the microchannels.Applicability of the presented immunoassay platform, delivering 100 results per hour, is exemplified here with results from the validation of an immunoglobulin assay for antibody quantification in mammalian cell cultures. Adapted to run on the GRAVI platform, this competitive assay covers a dynamic range of two orders of magnitude.

This article describes the preparation of tosyl-activated nonmagnetic poly(2-hydroxyethyl methacrylate-co-glycidyl methacrylate) [P(HEMA-GMA)] microspheres by dispersion polymerization and tosyl-activated magnetic poly(2-hydroxyethyl methacrylate-co-ethylene dimethacrylate) [P(HEMA-EDMA)] microspheres by multistep swelling polymerization method and precipitation of iron oxide inside the pores. These new approaches show that monodisperse microspheres, 2.3 µm, respectively 4.1 µm, in diameter can be produced in high yields avoiding aggregation and with the advantage of being free of aromatic moieties. To demonstrate their potential for diagnostic applications, both types of microparticles have been coated with capture and detection antibodies (DAs), respectively. Immunoassay protocols have then been developed for the dosage of ferritin using an automated affinity platform combining microchannel chips and electrochemical detection. The assay performance using the above magnetic microspheres has been compared with that obtained with commercial tosyl-activated beads. Finally, the possibility to combine functionalized magnetic and nonmagnetic microspheres has been evaluated in view of amplifying the number of enzymatic labels in the immuno-complex. At a ferritin concentration of 119.6 ng/mL, a signal-to-noise ratio of 150.5 is obtained using 0.2 mg/mL of anti-ferritin-coated P(HEMA-GMA)-DA microspheres against a value of 158.8 using free DA in solution.