Electrochemical chip

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. 

Fig. 12.1 Images of the electrochemical chip, (a) Silicon chip contains an array of eight miniaturized electrochemical ceUs with external pads, (b) The electrodes without the top layer (SU-8). Each electrochemical-ceU consists of three circular-shaped electrodes gold working and counter electrodes and Ag/AgCl reference electrode...

The treated cells were placed into the electrochemical chambers and the substrate PAPP was added to a 1 mg/ml final concentration at a total volume of 100 nL. Alkaline phosphatase activity was measured by monitored the PAP oxidation current. The electrochemical chips are disposable and were replaced every experiment. 

Chen, C.M. Chang, GL. Lin, C.H. Performance evaluation of a capillary electrophoresis electrochemical chip integrated with gold nanoelectrode ensemble working and decoupler electrodes. J. Chromatogr. A, 2008,1194 (2), 231-236. 

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... 

Nakayama, M. Electrochemical chip or biosensor and electrochemically active substances for detection of biological molecule such as nucleic acid, protein, carbohydrate and lipid in medical, food or environmental field. PCX Int. Appl. WO 2008096757, 2008 Chem. Abstr. 2008, 149, 262178. 

Ino, K., Nishijo, T., Aral, T. etal. 2012. Local redox-cycling-based electrochemical chip device with deep microweUs for evaluation of embryoid bodies. Angew. Chem. Int. Ed. 51 6648-6652. 

Technical grade DMF is available from the Grasselli Chemicals Department of E. I. duPont de Nemours and Company. The 1,4-dichlorobutane was obtained from the Electrochemicals Department, E. I. duPont de Nemours and Company. Technical Baker and Adamson fused chip sodium sulfide assaying 60% sodium sulfide was used. The checkers obtained somewhat lower yields when the appropriate amount of reagent grade Na2S OHjO was employed instead of the technical material. 

Manipulation of a droplet on a solid surface is of growing interest because it is a key technology to construct lab-on-a-chip systems. The imbalance of surface tensions is known to cause spontaneous motion of a droplet on the surface, as mentioned above. The wetting gradient causing liquid motion has been prepared by chemical [32], thermal [37], electrochemical [3] and photochemical [38-40] methods. 

On the way to more reliability in device fabrication, Kronholz et al. reported on the reproducible fabrication of protected metal nanoelectrodes on silicon chips with <30nm gap width and their electrochemical characterization [33]. For the fabrication of the chips, an optical lithography step and two electron-beam steps are combined (Figure 18). 

M. Okochi, H. Ohta, T. Tanaka, and T. Matsunaga, Electrochemical probe for on-chip type flow immunoassay immunoglobulin G labeled with ferrocenecarboaldehyde. Biotechnol. Bioeng. 90, 14-19 (2005). 

C.M. Ruan, L. Yang, and Y. Li, Immunobiosensor chips for detection of Escherichia coliO 51 Wl using electrochemical impedance spectroscopy. Anal. Chem. 74, 4814-4820 (2002). 

L. Nyholm, Electrochemical techniques for lab-on-a-chip applications. Analyst 130, 599-605 (2005). 

T.K. Lim, H. Ohta, and T. Matsunaga, Microfabricated on-chip-type electrochemical flow immunoassay system for the detection of histamine released in whole blood samples. Anal. Chem. 75, 3316-3321 (2003). 

Many naturally occurring substances, in particular the oxide films that form spontaneously on some metals, are semiconductors. Also, electrochemical reactions are used in the production of semiconductor chips, and recently semiconductors have been used in the construction of electrochemical photocells. So there are good technological reasons to study the interface between a semiconductor and an electrolyte. Our main interest, however, lies in more fundamental questions How does the electronic structure of the electrode influence the properties of the electrochemical interface, and how does it affect electrochemical reactions What new processes can occur at semiconductors that are not known from metals ... 

With the introduction of modern electronics, inexpensive computers, and new materials there is a resurgence of voltammetric techniques in various branches of science as evident in hundreds of new publications. Now, voltammetry can be performed with a nano-electrode for the detection of single molecular events [1], similar electrodes can be used to monitor the activity of neurotransmitter in a single living cell in subnanoliter volume electrochemical cell [2], measurement of fast electron transfer kinetics, trace metal analysis, etc. Voltammetric sensors are now commonplace in gas sensors (home CO sensor), biomedical sensors (blood glucose meter), and detectors for liquid chromatography. Voltammetric sensors appear to be an ideal candidate for miniaturization and mass production. This is evident in the development of lab-on-chip... 

Fig. 18b.1. Electrochemical cells and representative cell configurations, (a) Schematic diagram of a cell-potentiostat system, (b) Typical laboratory cell with Hg-drop electrode and drop knocker, (c) Voltammetric cell as detector at the end of a high-performance liquid chromatographic column, (d) A two-electrode (graphite) chip cell for biosensor development, (e) Three-electrode chip cells on a ceramic substrate for bioanalytical work.

A.T. Wooley, K. Lao, A.N. Glazer and R.A. Mathias, Capillary electrophoresis chip with integrated electrochemical detection, Anal. Chem.,... 

A. Hilmi and J.H.T. Luong, Micromachined electrophoresis chip with electrochemical detectors for analysis of explosive compounds in soil and groundwater, Environ. Sci. Technol., 34 (2000) 3046-3050. 

J. Rossier and H. Girault, Enzyme linked immunoabsorbent assay on a microchip with electrochemical detection, Lab on a Chip, 1 (2001) 153-157. 

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