**Bioelectronics for Amperometric Biosensors**

Jaime Punter Villagrasa, Jordi Colomer-Farrarons and Pere Ll. Miribel

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/52248

**1. Introduction**

The Discrete-to-Integrated Electronics group (D2In), at the University of Barcelona, in partnership with the Bioelectronics and Nanobioengineering Group (SICBIO), is researching Smart Self-Powered Bio-Electronic Systems. Our interest is focused on the development of custom built electronic solutions for bio-electronics applications, from discrete devices to Application-specific integrated circuit (ASIC) solutions.

The integration of medical and electronic technologies allows the development of biomedical devices able to diagnose and/or treat pathologies by detecting and/or monitoring pathogens, multiple ions, PH changes, and so on. Currently this integration enables advances in various areas such as microelectronics, microfluidics, microsensors and bio-compatible materials which open the door to developing human body Lab-on-a-Chip implantable devices, Pointof-Care in vitro devices, etc.

In this chapter the main attention is focused on the design of instrumentation related to amperometrics biosensor: biopotentiostat amplifiers and lock-in amplifiers. A potentiostat is a useful tool in many fields of investigation and industry performing electrochemical trials [1], so the quantity and variety of them is very extensive. Since they can be used in studies and targets as different as the study of chemical metal conversions [2] or carcinogenic cells detection, neuronal activity detection or Deoxyribonucleic acid (DNA) recognition, their characteristics are very varied.

For chemical measurement systems in biological applications, potentiostat amplifiers [3] are the electronic interface to a large category of amperometric chemical sensors which are capable of managing many biologically and environmentally important analyses. This characteristic gives us the possibility of building an extremely versatile tool with other interesting specs: portability, accuracy and reliability.

© 2013 Villagrasa et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 Villagrasa et al.; licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Demand for increased functionality, smaller systems, with smaller electrodes, for ultra-low current detection and versatility will force potentiostat amplifiers to be designed on a systemon-chip (SoC), combining single to multi-sensor measurements, to be implemented in ad‐ vanced Complementary metal–oxide–semiconductor (CMOS) processes. The scaled supply voltages in these processes [4-8], however, seriously limit the chemical analysis range.

Interesting approaches have been designed in terms of the instrumentation [9-13], attempting to work with low-voltages and low-currents, these electronics are integrated with autonomous powering. In [10] the authors propose an interesting low-power concept of a two-electrodes approach with the capability to measure from 1pA to 200nA with a simple Analog-to-Digital (ADC) approach, but operating at 5V. [11] presents a nice approach based on a Sigma-Delta modulator with the capability to check currents with a sensitivity of 50fA with a power dissipation of 12 µW, operating at 3.3V in this case, but with all the processing electronics being external to the prototype. In [12] a Complementary metal–oxide–semiconductor (CMOS) approach is presented for electrochemical arrays, operating with a bias of 5V, where the array (5X5) is placed in the same substrate with the amperometric detector. The design works in an unipolar fashion detecting pA, with a maximum operating frequency @ 2kHz. Good approach is also presented in [13] where a current-mirror circuit is implemented for three-electrode amperometric electrochemical sensors. There the system has an accuracy of 1%, with a range of currents of 1nA to1µA, operating at 1.8V with a power consumption of70µW. [14] present a 5V, 0.6mA amperometric electrochemical microsystem array (4X4), with a range between 6pA to10µA, where full electronics and array are placed on-chip, also working with an unipolar approach, with a chip size of 2.3X2.2 mm, with the electrode array implemented with electro‐ des of 2mm of diameter. Also in [15] a similar approach is derived, with an array of 8X8, with circular electrodes of 6µm, and a second implementation with the array implemented in-chip with the electronics. First Cyclic voltammetry (CV) approaches are presented with a typical range between 0.1V to 0.8V, detection currents from-1.5µA to 1.5µA.

Latest advances have been reported in [16] and in [17]. In [16], the novelty resides in the technological approach for the electronics design. Generally, all the implementations are based on silicon electronics, looking for a cheapest massive production and good properties. In this case Poly-Si Thin-Film transistors are used, ideal for their flexibility. In this particular work the system it is just conceived for a single three-based electrode for a cyclic voltammetry to detect diabetes. Electronic performances are not significantly inferior to those based on a CMOS solution. The system operates at 1.2V, working between 0.111V to 0.679V, but not reference is addressed to the power consumption and current range. The last example [17] is quite interesting and a great approach to our concept, but also is an excellent example of the challenge of the present proposal. This system has the capability to define different stimulus for the amperometric and electrochemical measurement. It provides linear sweep, constant potential, cyclic and pulse voltammetry, with enough smart facilities, but the system presents a fixed clock and a maximum power dissipation of 22.5mW, for an array of just 2X2 electrodes. The budget of 22.5mW is a lot of power for the present concept. As a readout circuit, it has good performances, between±47µA, with a linear resolution of 0.5pA.

In terms of the Lock-In Amplifiers, the measurement must be processed in order to extract the impedance variation of the cell. In an electrochemical cell, electrode kinetics, redox reactions, diffusion phenomena and molecular interactions at the electrode surface can be considered analogous to the above components that impede the flow of electrons in an ac circuit. The simplest electrical modelization is based on an equivalent RC circuit, also called a Randles circuit.

In order to proceed with the signal processing there are two main approaches: a) the Fast Fourier Transform (FFT) [18], and b) the Frequency Response Analyzer (FRA) [19]. In the case of the FFT, a pulse, or a step, -the approach to be followed is the ideal Dirac function-, is applied to the sample because it contains a wide frequency content. Then, the response of the sample is digitized and processed in a digital processor, for instance a DSP (Digital Signal Processor), and using the FFT algorithm, the different frequency components are obtained for their analysis. Another possibility is the logarithmic sampling in the DFFT calculus, reducing the data required in the process.

A simpler solution is based on the FRA approach. In this case a sine and cosine signals are adopted and using two multipliers and a filter stage the real and imaginary components of the response are obtained. This measurement must be done for each frequency. Working with just one sensor and in terms of the size of the final product, the FFT option could be adopted, because the response for several frequencies is obtained. The FRA solution is a solution more oriented to multi-sensor approaches but also in the case of single sensors it is also a good option, in terms of the trade-off between complexity and speed, if not too low frequencies are to be measured. This lock-in approach is more feasible.

The perturbation signal provided by the instrumentation system – following the FRA approach – generally uses a sinus wave as the input voltage.

The chapter would present the state-of-the art in the conception of the involved electronics for the potentiostat amplifier instrumentation and EIS approaches, analogue and digital.
