Electrochemistry and Microfluidics : A short review
Introduction to electrochemistry
Electrochemistry is schematically the relationship between chemical transformations and electrical current flows. Electrochemistry studies the chemical reactions occuring at the interface of an electron conductor (a metallic or semi-conductor electrode) and an ionic solution and which involve electrons transfers from or to the species in solution through the application of an external voltage.
Electrochemistry is at the interface of various domains of chemistry and physics: hydrodynamic, thermodynamics, kinetics, molecular chemistry,… and develops more and more interactions with biology and nanosciences. Electrochemistry has numerous applications especially in analytical chemistry with the emergence of electrochemical sensors, lab-on-a-chip and biosensors.
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Electrochemistry and microfluidics
In microfluidics, major efforts have been made to develop lab-on-a-chip, that is to say a microfluidic device that integrates all the manipulations usually made in a laboratory. For applications in analytical chemistry, one challenge is the integration of detection components in the device. Electrochemical detection is particularly suitable for lab-on-a-chip integration due to the versatility of size, geometry and nature of electrodes that can be integrated within a microfluidic platform, and to the minimum instrumentation it requires. Moreover electrochemical detection is reliable, selective and highly sensitive.
Electrochemical sensors and biosensors
A sensor is schematically composed of two parts: a receptor which recognizes the species to detect with high specificity and selectivity, and a transducer which translates the event of recognition into a measurable physical signal i.e. an electrical signal in the case of electrochemical sensors.
Fig 1. Principe of a biosensor
The receptor has to be specific to the target thus it depends on the target nature. Single stranded DNA complementary to a single stranded DNA target are used in the case of DNA electrochemical sensor; enzyme can be used if the target is its substrate; for proteins and small molecules antibodies or aptamers can be used. Aptamers are synthetic short single stranded DNA/RNA (selected in vitro by the SELEX method) or synthetic short peptide. Nucleic acid aptamer are thus able to hybridize with complementary single stranded DNA. Peptide aptamer can recognize proteins or small molecules with a selectivity that can compete with antibodies.
Two cases have to be distinguished: the event of recognition implies an electronic transfer or not. If it does not imply an electronic transfer, the detection is challenging: how to transduce a recognition event which implies no electronic transfer? One strategy is the “sandwich approach” in which the target is recognized by a first specific receptor immobilized on the surface of an electrode, then by a second receptor, modified with an electroactive tag. In that case, the recognition event is transduced by an electrochemical signal occurring via an electronic transfer between the redox tag and the electrode surface. The alternative is to use a target modified with an electroactive tag but the drawbacks of this strategy are that the target is modified and therefore the pre-treatment of the sample is more complex.
Fig 2. Three cases of electrochemical sensors (a) the event of recognition implies an electronic transfer (b) the “sandwich approach” (c) the target is marked with an electroactive tag
A few examples of microfluidic electrochemical sensors
An electrochemical glucose sensor usually implies the use of an enzyme oxido-reductase, i.e glucose oxidase, which catalyses the oxidation of glucose into hydrogen peroxide and D-glucono-δ-lactone. Hydrogen peroxide can be detected electrochemically on a polarized platinum electrode and its concentration can be related to the concentration of glucose.
Fig 3 Principle of detection of glucose using glucose oxidase enzyme.
Suzuki et al  used this approach to develop a complex microfluidic lab-on-a-chip able to detect various species and parameters such as glucose, lactate using the “enzyme approach”.
Fig 4 : Microfluidic lab-on-a-chip allowing electrochemical glucose detection (from )
Ferguson et al  developed a microfluidic electrochemical DNA sensor which combines PCR amplification and electrochemical detection in a glass/PDMS chip. In this approach, the electrochemical detection was realised using a single-stranded DNA probe which has a hairpin structure, i.e. two regions of the same strand that hybridize to form a double helix that ends in an unpaired loop. The DNA probe is grafted on the surface of an electrode at one side, the other side is modified with an electroactive methylene blue tag. Without the DNA target, the DNA probe has the hairpin structure and the electroactive tag is close to the surface. Therefore an electronic transfer can occur between the tag and the electrode surface resulting in an amperometric current. In the presence of the DNA target, hybridization occurs and the rigid duplex moves away the electroactive tag from the electrode surface so less current is observed. A detection limit < 10 aM was achieved.
Fig 5 A) A glass/PDMS chip with a PCR chamber and a detection compartment with a system of electrodes B) the detection strategy using a hairpin DNA probe modified with an electroactive tag. The detection of the target implies a decrease of the current (from ref ).
Plaxco et al  developed an electrochemical cocaine sensor based on the use of a cocaine-binding aptamer immobilized on the surface of an electrode by one extremity. At the end of its other extremity, the aptamer is modified by an electroactive tag. Without cocaine, the redox tag is “far” from the electrode surface so the electronic transfer between the redox tag and the surface is low. In the presence of cocaine, the aptamer binds with the target and adopts a specific conformation. Therefore the redox tag is brought close to the surface and the electronic transfer in higher in this case. Micromolar concentration was achieved in undiluted serum.
Fig 6. A) Strategy of detection using an electroactive modified aptamer. B) Glass chip with an electrodes system comprising 3 working electrodes, a reference and a counter electrodes. C) Electrochemical signal obtained whithout cocaine and with 250 µM of cocaine (from ref ).
As an example, Liu et al.  developed a microfluidic electrochemical sandwich-type aptasensor for the detection of thrombin in human serum sample. They used the “sandwich approach” described previously (see fig 2) with aptamers as receptors 1 and 2. The secondary aptamer was modified with a phosphatate enzyme which catalyses the reaction of a substrate, 4-aminophenyl phosphate, into an electroactive product. A detection of 1 pM was achieved with a three macroscopic electrodes system present at the end of a PMMA microchannel (see Fig B).
Fig 7. A) Differential pulse voltammograms (DPV) of the microfluidic aptasensor with different concentrations of thrombin: (a) 0 pM, (b) 40 pM, (c) 100 pM, (d) 200 pM, and (e) 1000 pM. B) PMMA chip with a three electrodes system at the end of the microfluidic channel (from ref ).
For more tutorial about microfluidics, please visit our other tutorials here: «Microfluidics tutorials». The photos in this article come from the Elveflow® data bank, Wikipedia or elsewhere if precised. Article written by Grégory March, Klearia team and Timothée Houssin.
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 Wataru Satoh, Hiroki Hosono, Hiroomi Yokomaku, Katsuya Morimoto, Sanjay Upadhyay and Hiroaki Suzuki, Sensors 2008, 8, 1111-1127
 Brian S. Ferguson, Steven F. Buchsbaum, James S. Swensen, Kuangwen Hsieh, Xinhui Lou, and H. Tom Soh, Anal. Chem. 2009, 81, 6503–6508
 Swensen JS, Xiao Y, Ferguson BS, Lubin AA, Lai RY, Heeger AJ, et al. Continuous, Real-Time Monitoring of Cocaine in Undiluted Blood Serum via a Microfluidic, Electrochemical Aptamer-Based Sensor. J Am Chem Soc. 2009;131(12):4262‑6.
 Huixiang Wang, Yun Liu, Chengcheng Liu, Jingyu Huang, Pengyuan Yang, Baohong Liu, Electrochemistry Communications 12 (2010) 258–261